Life doi: 10.3390/life14030404
Authors: Yingmei Yang Jie Zhang Jiduo Yan Lianjin Zhao Li Luo Chengyun Li Genhua Yang
Rhizoctonia solani AG-3 TB primarily causes tobacco target spot disease by producing a large number of sexual spores. However, inducing sexual spore formation under in vitro conditions has been challenging, impeding further research on its control. In this study, field experiments were conducted to assess the effects of different concentrations of chemical and biological fungicides on the production of sexual spores of R. solani AG-3 TB on tobacco plants. The results demonstrated that four chemical fungicides (propiconazole-morpholine guanidine, bordeaux mixture, thiophanate-methyl, and mancozeb) significantly induced sexual spore formation. Among them, increasing the concentrations of the first three fungicides resulted in an increase in the number of sexual spores, while increasing the concentration of mancozeb led to a decrease in spore count. The pathogenic fungus produced more sexual spores during the night than during the day. Temperature, humidity, and light conditions influenced spore production. Additionally, the infection rate of sexual spores was directly proportional to their concentration and inoculation time, but their survival time did not exceed 6 h in vitro. Importantly, Streptomyces rectiolaceus A8 significantly suppressed sexual spore formation, achieving an 83.63% control efficacy in the field and producing antimicrobial substances against R. solani AG-3 TB. In conclusion, appropriate concentrations of chemical fungicides can induce sexual spore formation, while A8 can inhibit their production, showing potential value for controlling tobacco target spot disease.
]]>Life doi: 10.3390/life14030403
Authors: Rossana Soloperto Federica Magni Anita Farinella Elisa Gouvea Bogossian Lorenzo Peluso Nicola De Luca Fabio Silvio Taccone Filippo Annoni
We investigated independent factors predicting neurological outcome and death, comparing in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) patients. The study was conducted in the mixed 34-bed Intensive Care Department at the Hôpital Universitaire de Bruxelles (HUB), Belgium. All adult consecutive cardiac arrest (CA) survivors were included between 2004 and 2022. For all patients, demographic data, medical comorbidities, CA baseline characteristics, treatments received during Intensive Care Unit stay, in-hospital major complications, and neurological outcome at three months after CA, using the Cerebral Performance Category (CPC) scale, were collected. In the multivariable analysis, in the IHCA group (n = 540), time to return of spontaneous circulation (ROSC), older age, unwitnessed CA, higher lactate on admission, asystole as initial rhythm, a non-cardiac cause of CA, the occurrence of shock, the occurrence of acute kidney injury (AKI), and the presence of previous neurological disease and of liver cirrhosis were independent predictors of an unfavorable neurological outcome. Among patients with OHCA (n = 567), time to ROSC, older age, higher lactate level on admission, unwitnessed CA, asystole or pulseless electrical activity (PEA) as initial rhythm, the occurrence of shock, a non-cardiac cause of CA, and a previous neurological disease were independent predictors of an unfavorable neurological outcome. To conclude, in our large cohort of mixed IHCA and OHCA patients, we observed numerous factors independently associated with a poor neurological outcome, with minimal differences between the two groups, reflecting the greater vulnerability of hospitalized patients.
]]>Life doi: 10.3390/life14030402
Authors: Anca-Narcisa Neagu Taniya Jayaweera Lilian Corrice Kaya Johnson Costel C. Darie
We are exposed to a mixture of environmental man-made and natural xenobiotics. We experience a wide spectrum of environmental exposure in our lifetime, including the effects of xenobiotics on gametogenesis and gametes that undergo fertilization as the starting point of individual development and, moreover, in utero exposure, which can itself cause the first somatic or germline mutation necessary for breast cancer (BC) initiation. Most xenobiotics are metabolized or/and bioaccumulate and biomagnify in our tissues and cells, including breast tissues, so the xenobiotic metabolism plays an important role in BC initiation and progression. Many considerations necessitate a more valuable explanation regarding the molecular mechanisms of action of xenobiotics which act as genotoxic and epigenetic carcinogens. Thus, exposomics and the exposome concept are based on the diversity and range of exposures to physical factors, synthetic chemicals, dietary components, and psychosocial stressors, as well as their associated biologic processes and molecular pathways. Existing evidence for BC risk (BCR) suggests that food-borne chemical carcinogens, air pollution, ionizing radiation, and socioeconomic status are closely related to breast carcinogenesis. The aim of this review was to depict the dynamics and kinetics of several xenobiotics involved in BC development, emphasizing the role of new omics fields related to BC exposomics, such as environmental toxicogenomics, epigenomics and interactomics, metagenomics, nutrigenomics, nutriproteomics, and nutrimiRomics. We are mainly focused on food and nutrition, as well as endocrine-disrupting chemicals (EDCs), involved in BC development. Overall, cell and tissue accumulation and xenobiotic metabolism or biotransformation can lead to modifications in breast tissue composition and breast cell morphology, DNA damage and genomic instability, epimutations, RNA-mediated and extracellular vesicle effects, aberrant blood methylation, stimulation of epithelial–mesenchymal transition (EMT), disruption of cell–cell junctions, reorganization of the actin cytoskeleton, metabolic reprogramming, and overexpression of mesenchymal genes. Moreover, the metabolism of xenobiotics into BC cells impacts almost all known carcinogenic pathways. Conversely, in our food, there are many bioactive compounds with anti-cancer potential, exerting pro-apoptotic roles, inhibiting cell cycle progression and proliferation, migration, invasion, DNA damage, and cell stress conditions. We can conclude that exposomics has a high potential to demonstrate how environmental exposure to xenobiotics acts as a double-edged sword, promoting or suppressing tumorigenesis in BC.
]]>Life doi: 10.3390/life14030401
Authors: Michael Bordonaro Darina Lazarova
Primary tumors can inhibit the growth of secondary lesions, particularly metastases, in a phenomenon termed “concomitant resistance”. Several mechanisms have been proposed for this effect, each supported by experimental data. In this paper, we hypothesize that concomitant resistance is a form of hormesis, a biphasic dose response in which a stimulus has a positive and/or stimulatory effect at low dosages and a negative, inhibitory, and/or toxic effect at higher dosages. When this paradigm applies to tumorigenesis, it is referred to as “cancer hormesis”. Thus, low numbers of benign neoplastic cells or less tumorigenic malignant cells may result in resistance to the development of malignant neoplasms, including metastases. A host containing a number of (less tumorigenic) neoplastic cells may exhibit greater protection against more tumorigenic malignant neoplasms than a host who lacks neoplastic cells, or who has too few neoplastic cells to stimulate a protective response. As a theoretical endeavor, this paper also proposes that cancer hormesis can be leveraged for therapeutic purposes, by the implantation of safely controlled, benign artificial tumors in high-risk patients. These tumors would prevent the development of endogenous malignant neoplasms by creating an inhibitory environment for such growth. Strategies for testing the hypothesis are proposed.
]]>Life doi: 10.3390/life14030399
Authors: Aleksandra Pilśniak Anastazja Szlauer-Stefańska Andrzej Tukiendorf Tomasz Rutkowski Krzysztof Składowski Grażyna Kamińska-Winciorek
Radiotherapy (RT) is an integral part of many cancer treatment protocols. Chronic radiation-induced dermatitis (CRD) is a cutaneous toxicity that occurs in one-third of all patients treated with this method. CRD is usually observed several months after completion of treatment. Typical symptoms of CRD are telangiectasia, skin discoloration, atrophy, thickening, and cutaneous fibrosis. There are currently no data in the literature on the evaluation of the dermoscopic features of CRD. The aim of this prospective study was the identification of clinical and dermoscopic features in a group of 32 patients with head and neck cancer (HNC) in whom CRD developed after RT. CRD was assessed at 3, 6, and 12 months after RT in 16, 10, and 10 patients, respectively. CRD was assessed at one time point and two time points in 28 and 4 patients, respectively. The control included skin areas of the same patient not exposed to RT. The dataset consisted of 36 clinical and 216 dermoscopic photos. Clinical evaluation was performed according to the RTOG/EORTC radiation-induced dermatitis scale. The highest score was grade 2 observed in 21 patients. Clinical observations revealed the presence of slight and patchy atrophy, pigmentation change, moderate telangiectasias, and some and total hair loss. Dotted vessels, clustered vessel distribution, white patchy scale, perifollicular white color, white structureless areas, brown dots and globules, and white lines were the most frequently noted features in dermoscopy. Three independent risk factors for chronic toxicity, such as age, gender, and surgery before RT, were identified. The dermoscopic features that had been shown in our study reflect the biological reaction of the skin towards radiation and may be used for the parametrization of CRD regarding its intensity and any other clinical consequences in the future.
]]>Life doi: 10.3390/life14030400
Authors: Nicholas G. Kounis Ming-Yow Hung Cesare de Gregorio Virginia Mplani Christos Gogos Stelios F. Assimakopoulos Panagiotis Plotas Periklis Dousdampanis Sophia N. Kouni Anastasopoulou Maria Grigorios Tsigkas Ioanna Koniari
Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even at very low medication dosages, and can present as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome, and myocarditis caused by cancer therapy.
]]>Life doi: 10.3390/life14030398
Authors: Aikaterina L. Stefi Konstantina Mitsigiorgi Nikolaos S. Christodoulakis
The seeds, roots, leaves, flowers and fruits of the critically endangered (CR) species Saponaria jagelii Phitos & Greuter (Caryophyllaceae) were studied. The morphology of the seeds was investigated with scanning electron microscopy. The seeds were imbibed, germinated and developed into young plants. These plants, along with strictly selected wild-growing plants, were used for optical microscopic observations. The leaves and flowers were observed with scanning electron microscopy as well. At least two types of active glandular trichomes were detected on both the leaves and the calyxes of the flowers. The structures of the primary and secondary roots were also investigated. The roots turned into secondary structures very quickly and very close to the root tip. Light microscopy and histochemical reagents were employed to detect secondary metabolites of interest in the leaves. All the metabolites detected were already reported to be synthesized in stressed plants. Distribution data are presented. Conservation actions based on the habitat morphology and the human activities within it, such as the limitation of beach access during the seed-dispersing period and the prohibition of vehicle usage, are recommended in order to protect this tolerant yet severely stressed plant species.
]]>Life doi: 10.3390/life14030397
Authors: Paula Recacha-Ponce Pablo Baliño Remiro Laura García-Rayo-Reolid Violeta Dominguez-Gomez María Pilar Suárez-Alcázar Ana Folch-Ayora Pablo Salas-Medina Eladio Joaquin Collado-Boira
Background and Aims: Efforts to humanize childbirth focus on promoting skin-to-skin contact, labor accompaniment, and breastfeeding. Despite these advancements, cesarean sections often lack a consideration of immediate mother–child contact, early breastfeeding initiation, and follow-up. This underscores the need for a ‘natural’ approach to cesarean sections, aiming to ‘humanize’ the procedure and emulate some aspects of vaginal birth. Materials and Methods: An observational longitudinal cohort study was conducted, involving pregnant women scheduled for a cesarean section. Two comparison groups were established: one undergoing conventional cesarean sections and the other receiving a humanization intervention. While in “conventional cesarean sections,” newborns are separated from mothers at birth, preventing actions such as early breastfeeding or skin-to-skin contact, and maternal companionship is lacking in the operating room, the intervention of cesarean section humanization was based on avoiding the separation of the mother and newborn, promoting skin-to-skin contact, early breastfeeding, and maternal accompaniment during surgery. Descriptive data on maternal and neonatal variables, including breastfeeding initiation, maintenance, and baby weight trends, were collected. Additionally, a validated survey assessed the pain, satisfaction, and anxiety among the 73 participating women. Results: Women undergoing natural cesarean sections reported higher satisfaction, lower anxiety, and reduced postoperative pain, requiring less analgesia. Although their exclusive breastfeeding rates at 10 days postpartum showed no significant difference, statistically significant differences favored natural cesarean sections at 3 months (67.5% vs. 25%) and 6 months (50% vs. 4.5%). Neonates in the natural cesarean group exhibited greater weight gain at 10 days postpartum compared to those delivered conventionally (+49.90 g vs. −39.52 g). No significant differences in blood counts were observed between the groups. Conclusions: This study underscores the manifold advantages offered by the natural cesarean procedure compared to the conventional cesarean approach. Notably, a NC demonstrates superior outcomes in terms of heightened maternal satisfaction with the obstetric process, the enhanced sustainability of exclusive breastfeeding, and augmented neonatal weight gain.
]]>Life doi: 10.3390/life14030396
Authors: Carla Pais-Vieira José Gabriel Figueiredo André Perrotta Demétrio Matos Mafalda Aguiar Júlia Ramos Márcia Gato Tânia Poleri Miguel Pais-Vieira
Brain–computer interfaces (BCIs) that integrate virtual reality with tactile feedback are increasingly relevant for neurorehabilitation in spinal cord injury (SCI). In our previous case study employing a BCI-based virtual reality neurorehabilitation protocol, a patient with complete T4 SCI experienced reduced pain and emergence of non-spastic lower limb movements after 10 sessions. However, it is still unclear whether these effects can be sustained, enhanced, and replicated, as well as the neural mechanisms that underlie them. The present report outlines the outcomes of extending the previous protocol with 24 more sessions (14 months, in total). Clinical, behavioral, and neurophysiological data were analyzed. The protocol maintained or reduced pain levels, increased self-reported quality of life, and was frequently associated with the appearance of non-spastic lower limb movements when the patient was engaged and not experiencing stressful events. Neural activity analysis revealed that changes in pain were encoded in the theta frequency band by the left frontal electrode F3. Examination of the lower limbs revealed alternating movements resembling a gait pattern. These results suggest that sustained use of this BCI protocol leads to enhanced quality of life, reduced and stable pain levels, and may result in the emergence of rhythmic patterns of lower limb muscle activity reminiscent of gait.
]]>Life doi: 10.3390/life14030395
Authors: Prisca Guerra Antonella Di Cesare Elia Rosi Ilaria Scandagli Gianmarco Silvi Giulia Nunziati Francesca Prignano
Apremilast, a phosphodiesterase-4 inhibitor, has shown promise to have a potential beneficial metabolic effect. We conducted a single-centre retrospective study on adult patients with moderate-to-severe psoriasis who underwent apremilast treatment over at least 12 and 52 weeks, respectively. Baseline characteristics, weight, lipid profile, and fasting glucose levels were collected at baseline and at 12, 24, and 52 weeks. Furthermore, we conducted a narrative review of the current scientific knowledge on the metabolic effects of apremilast in patients with psoriasis and psoriatic arthritis. We observed a significant reduction in average weight and body mass index (BMI) in patients treated with apremilast in both the initial and the subgroup analysis, a significant reduction in triglycerides levels at 24 and 52 weeks, and a significant increase in high-density lipoprotein (HDL) levels at 52 weeks, whereas there were no significant changes in total cholesterol or low-density lipoprotein (LDL) concentrations over the 52-week treatment period. These findings suggest a potential positive impact of apremilast on both weight management and lipid profile in individuals with moderate-to-severe psoriasis in the medium–long term.
]]>Life doi: 10.3390/life14030394
Authors: Valentina Cioffi Giulia Di Napoli Pierfrancesco Tozzi Sabina Martelli Katia Bruno Andrea Longo Helena Buso Francesco Pugliese Cinzia Milito
Ustekinumab is a monoclonal antibody targeting the p40 subunit of IL-12 and IL-23, approved for treating psoriasis, psoriatic arthritis, and inflammatory bowel disease. Despite a remarkable success in treating chronic inflammatory conditions and a generally favorable safety profile, its role in inducing rare adverse events, such as interstitial pneumonia and acute respiratory distress syndrome (ARDS), remains largely uncharted. We report a case of a 66-year-old male patient treated with Ustekinumab for severe psoriasis who, after almost two years of treatment, developed dyspnea, asthenia, and fever progressing to non-infectious pneumonia and ARDS leading to ICU admission. Moreover, we conducted a literature review on Ustekinumab-associated pulmonary complications. Our case underscores the importance of appropriate and long-term clinical monitoring in patients on Ustekinumab treatment, particularly considering the potential lung complications. The possibility of non-infectious pneumonitis should be considered alongside infectious causes, facilitating prompt management in the case of negative infectious screening. Additionally, the severity of ARDS underscores the importance of timely recognition and proper management. Further investigations are recommended to investigate the immunological basis of Ustekinumab-induced ARDS for designing appropriate monitoring strategies.
]]>Life doi: 10.3390/life14030393
Authors: Eman N. Chaudhri Ayman Salman Khalid Awartani Zaraq Khan Shahrukh K. Hashmi
Current advances in cancer therapy have increased survival, emphasizing the need for life quality improvement. Fertility loss is common post-chemotherapy. Current guidelines establish embryo and oocyte cryopreservation to address premature ovarian insufficiency (POI). Ovarian tissue cryopreservation has also recently become an acceptable option for fertility preservation, particularly as it is the only option for pre-pubertal patients. Few definitions for optimum fertility outcomes, and few systematic reviews comparing embryo, oocyte, and ovarian tissue cryopreservation as a means of fertility preservation (FP) in pre- and post-pubertal female cancer patients exist. This systematic review aims to improve understanding of gonadotoxic effects of chemoradiation therapy in cancer patients, to analyze the different fertility preservation techniques and procedures available to women with chemoradiation induced ovarian insufficiency, and to compare and recognize the benefits of each technique in restoring fertility, sexual hormone function, and quality of life. Searches were conducted electronically on PubMed, Cochrane, and EBSCOHost, including clinical trials, prospective, and retrospective studies of female cancer patients undergoing anti-cancer therapy, with predefined MeSH terminology. Data were collected, analyzed, and compared. Non-randomized clinical studies were evaluated for risk bias through the Newcastle–Ottawa Scale. In total, 23 studies were included. From there, 647 patients opted for oocyte cryopreservation, 267 for embryo cryopreservation, and 1382 for ovarian tissue cryopreservation (OTC). A total of 175, 18, and 121 live births resulted respectively from oocyte, embryo, and OTC, respectively. Studies without live births discussed other fertility markers as indicators of improvement in sexual hormone function and fertility. The gonadotoxic effects of chemotherapy call for FP intervention. Oocyte and embryo cryopreservation/implantation are well-established procedures. With changing trends and life quality consideration, OTC is a promising interventional method for pre-pubertal patients facing the prospect of fertility loss.
]]>Life doi: 10.3390/life14030392
Authors: Luana Nosetti Marco Zaffanello Giorgio Piacentini Francesca De Bernardi Cristina Cappelluti Camilla Sangiorgio Massimo Agosti
Background: Brief Resolved Unexplained Events (BRUEs), formerly known as Apparent Life-Threatening Events (ALTEs), are concerning episodes of short duration (typically <1 min) characterized by a change in breathing, consciousness, muscle tone, and/or skin color. In some cases, SARS-CoV-2 infection has been associated with episodes of BRUEs in previously healthy children. This study aimed to compare the demographic, respiratory, perinatal, and infectious characteristics in children affected by BRUEs before the COVID-19 pandemic and after the spread of SARS-CoV-2. Methods: We conducted a retrospective observational study covering January 2018 to March 2020 (pre-COVID-19) and April 2023 (during the ongoing COVID-19 pandemic). Collected variables included clinical information during pregnancy and neonatal details of children with BRUEs. Results: The number of children in the pre-COVID-19 period was 186 (41%); after the emergence and spread of SARS-CoV-2 this number was 268 (59%). The risk of infection at birth for children developing BRUEs was higher during the pandemic. Children were less likely to have ongoing symptomatic infection during BRUEs during the pandemic (coefficient B = 0.783; p = 0.009). Respiratory symptoms during BRUEs were more frequent during the pandemic (coefficient B = 0.654; p = 0.052). Fever during BRUEs was less likely during the pandemic (coefficient B = −0.465, p = 0.046). Conclusions: These findings could have significant clinical implications for managing children with BRUEs during the COVID-19 pandemic.
]]>Life doi: 10.3390/life14030391
Authors: Tisa Hodnik Stiven Roytman Nico I. Bohnen Uros Marusic
Phase-amplitude coupling (PAC) describes the interaction of two separate frequencies in which the lower frequency phase acts as a carrier frequency of the higher frequency amplitude. It is a means of carrying integrated streams of information between micro- and macroscale systems in the brain, allowing for coordinated activity of separate brain regions. A beta–gamma PAC increase over the sensorimotor cortex has been observed consistently in people with Parkinson’s disease (PD). Its cause is attributed to neural entrainment in the basal ganglia, caused by pathological degeneration characteristic of PD. Disruptions in this phenomenon in PD patients have been observed in the resting state as well as during movement recordings and have reliably distinguished patients from healthy participants. The changes can be detected non-invasively with the electroencephalogram (EEG). They correspond to the severity of the motor symptoms and the medication status of people with PD. Furthermore, a medication-induced decrease in PAC in PD correlates with the alleviation of motor symptoms measured by assessment scales. A beta–gamma PAC increase has, therefore, been explored as a possible means of quantifying motor pathology in PD. The application of this parameter to closed-loop deep brain stimulation could serve as a self-adaptation measure of such treatment, responding to fluctuations of motor symptom severity in PD. Furthermore, phase-dependent stimulation provides a new precise method for modulating PAC increases in the cortex. This review offers a comprehensive synthesis of the current EEG-based evidence on PAC fluctuations in PD, explores the potential practical utility of this biomarker, and provides recommendations for future research.
]]>Life doi: 10.3390/life14030390
Authors: Angelika Pointner Ulrike D. B. Krammer Elena Tomeva Ulrich Magnet Berit Hippe Ursula Jacob Alexander G. Haslberger
The importance of diet and lifestyle in maintaining overall health has long been recognised. MicroRNAs (miRNAs) have emerged as key players in the intricate interplay between health and disease. This study, including 305 participants, examined the role of miRNAs from capillary blood as indicators of individual physiological characteristics, diet, and lifestyle influences. Key findings include specific miRNAs associated with inflammatory processes and dietary patterns. Notably, miR-155 was associated with subjects with metabolic diseases and upregulated in age. Additionally, the study revealed diet-related miRNA expressions: high consumption of vegetables, fruits, and whole grains correlated with increased levels of miR-let-7a and miR-328, both implicated in anti-inflammatory pathways, and decreased expression of pro-inflammatory miR-21. In the context of smoking, we found a significant decrease in miRNA-142, known for its downregulation in lung cancer. We observed a sex-biased expression of various miRNAs with significant upregulation of miR-151a in females and a higher expression of miR-155 in ageing females, representing a possible mechanism for the increased susceptibility to autoimmune diseases. In conclusion, the study underscores the significant influence of lifestyle, nutrition, and sex on miRNA profiles. Circulating miRNAs demonstrate significant potential as biomarkers in personalized medicine, highlighting their utility in tailoring healthcare to individual needs.
]]>Life doi: 10.3390/life14030389
Authors: Yuichi Horigome Kazuhito Suzuki Takahiro Suzuki
Remarkable advancements have been made in the treatment outcomes of multiple myeloma (MM) patients; however, for frail elderly patients, these treatment outcomes are still insufficient. Elderly MM patients are increasing, as are their treatment regimens. There is a heightened demand to assess these patients in order to provide optimized treatments. While continuous treatment is more common for MM patients when compared to fixed-duration treatment, due to the risk of treatment interruption causing reduced survival rates, effectiveness and safety are essential. Treatment goals vary for each patient, but must preserve their quality of life (QOL). When planning treatments for these patients, frailty evaluation is increasingly emphasized as a stratification factor which helps develop accurate screening tools. Daratumumab (DARA) therapy, used globally, is not only effective in frail elderly MM patients, but also has QOL benefits. Proficiency in utilizing DARA regimens is potentially advantageous for patients not included in clinical trials, and innovative usage can further broaden its scope. The development of tools to accurately assess frailty and the establishment of optimal treatments for frail elderly MM patients are imperative. This review is an overview, challenging the frailty assessments for MM patients, re-examining the evidence for DARA regimens in frail elderly MM patients, and discussing potential areas for improvement.
]]>Life doi: 10.3390/life14030388
Authors: Yongwook Kim
Morton’s foot syndrome (MFS) is characterized by a distally longer head of the second metatarsal bone compared to the head of the first metatarsal bone. Few studies have investigated the effects of a foot orthosis on kinetic characteristics, such as ground reaction force (GRF), during walking in individuals with MFS. This study aimed to verify dynamic GRF using a 3D motion analysis system, including two platforms with and without a foot orthosis condition. Kinetic GRF data of 26 participants with MFS were collected using a motion analysis system and a force platform. Participants were asked to walk wearing standard shoes or shoes with a pad-type foot orthosis. Repeated-measures analysis of variance (ANOVA) was used to compare the kinetic GRF data in the stance phase during gait according to the side of the leg and orthotic conditions for MFS. The late sagittal and frontal peak forces showed that the presence of a foot orthosis condition significantly increased the GRF when compared with the absence of a foot orthosis condition for both sides of the feet (p < 0.05). In addition, the second vertical peak force of the GRF showed that the presence of a foot orthosis condition significantly increased the GFR when compared with the absence of a foot orthosis condition on the side of the right foot (p = 0.023). Significant effects were observed in the late sagittal and frontal peak GRFs when wearing the pad-type foot orthosis in individuals with MFS during gait. Thus, even if there are no signs and symptoms of MFS in patients diagnosed with the disease condition, clinical interventions, such as a foot orthosis, that can be simply applied to shoe insoles are needed to manage and prevent various musculoskeletal disorders that may develop in the future. It was hypothesized that when wearing a foot orthosis, the participants would walk with increased GRF during gait compared to those without an orthosis.
]]>Life doi: 10.3390/life14030387
Authors: Ozlen Saglam
The previous endometrial cancer (EC) FIGO staging primarily relied on the extent of the disease spread into the anatomical sites at diagnosis. The most recent one (2023) incorporates clinicopathological features such as histological subtype, tumor grade, the extent of lymphovascular space invasion (LVI), and, when available, molecular subtypes of EC. The emphasis on accurate histological typing, tumor grading, and the molecular features of the cancer is stronger than ever. This review addresses challenging diagnostic patterns in the histologic subtyping and grading EC under five categories: 1. EC with spindle cells, 2. EC with clear cells, 3. EC with a papillary architecture, 4. EC with a biphasic morphology, and 5. EC with a microglandular architecture. The morphological features differentiating low- and high-grade cancers are discussed, along with relevant clinical work-ups. Recent molecular genetic findings regarding the diagnosis and prognosis of the disease and the results of related clinical trials are summarized. The potential challenges in the evaluation of LVI follow these sections. The final section of the review includes an overview of the literature on incorporating molecular subtypes of EC into clinical practice.
]]>Life doi: 10.3390/life14030386
Authors: Francisco Javier De la Torre-Gomar Jose María Llamas-Molina Maria Dolores Pegalajar-García Carmen Pérez-Valencia Alejandro Carrero-Castaño Ricardo Ruiz-Villaverde
The association between Primary cutaneous CD4 small/medium T-cell lymphoproliferative disorder (PCSM-TCLPD) and COVID-19 immunization has been sparsely documented in the medical literature. Reviewing the literature, albeit infrequently, we can find cases of the recurrence and new onset of lymphoproliferative processes and cutaneous lymphomas following the COVID-19 vaccine. Many of the entities we encounter are classified as cutaneous lymphoproliferative disorders. The prevailing hypothesis suggests that the predominant cutaneous reactions to SARS-CoV-2 vaccines may stem from T-cell-mediated immune activation responses to vaccine components, notably messenger RNA (mRNA). Specifically, it is posited that the presence of cutaneous lymphoid infiltrates may be linked to immune system stimulation, supported by the absence, to date, of instances of primary cutaneous B-cell lymphoma following mRNA vaccination. Within this context, it is imperative to underscore that the etiological association between PCSM-TCLPD and COVID-19 vaccination should not discourage vaccination efforts. Instead, it underscores the necessity for continuous surveillance, in-depth investigation, and comprehensive follow-up studies to delineate the specific attributes and underlying mechanisms of such cutaneous manifestations post vaccination.
]]>Life doi: 10.3390/life14030385
Authors: Suvitesh Luthra Hannah Masraf Mostafa Elbadry Mohamed Pietro G. Malvindi Davorin Sef Szabolcs Miskolczi Theodore Velissaris
Background: This study compared perioperative outcomes and long-term survival of saphenous vein grafts (SVGs) versus left internal thoracic artery (LITA) to left anterior descending artery (LAD) in isolated coronary artery bypass graft surgery (CABG). Methods: In this retrospective, single-centre study, we included patients with primary isolated CABG from January 2001 to July 2022. Baseline demographics were compared between SVG-LAD and LITA-LAD. Univariable and multivariable regressions were performed for predictors of in-hospital death. Propensity score matching was performed for LITA-LAD vs. SVG-LAD. Kaplan–Meier survival curves were generated for comparison of survival. Cox proportional hazards model was used for predictors of survival. Results: A total of 8237 patients (1602 SVG-LAD/6725 LITA-LAD) were included. Median age was 67.9 years (LITA-LAD; 67.1 years vs. SVG-LAD; 71.7 years, p < 0.01). A total of 1270 pairs of SVG-LAD were propensity-matched to LITA-LAD. In matched cohorts, in-hospital mortality (0.8% vs. 1.6%, LITA-LAD and SVG-LAD respectively; p = 0.07), deep sternal wound infection, new cerebrovascular events, renal replacement therapy and hospital stay >30 days were similar. SVG-LAD did not adversely affect in-hospital mortality (OR; 2.03, CI; 0.91, 4.54, p = 0.08). Median long-term survival was similar between the groups (13.7 years vs. 13.1 years for LITA-LAD and SVG-LAD respectively, log rank p < 0.31). SVG-LAD was not a predictor of adverse long-term survival. (HR; 1.06, 95% CI; 0.92, 1.22, p < 0.40). Long-term survival was better with LITA-LAD for LVEF <30% (log rank p < 0.03). Conclusions: There was no difference in the propensity-matched cohorts for use of SVG vs. LITA to the LAD. Further contemporary long-term studies are needed for substantiation.
]]>Life doi: 10.3390/life14030384
Authors: Hamid Ehsan Myra Robinson Peter M. Voorhees Kristen Cassetta Shanice Borden Shebli Atrash Manisha Bhutani Cindy Varga Mauricio Pineda-Roman Reed Friend Barry A. Paul
Selinexor (Seli) is a first-in-class, oral selective inhibitor of the nuclear export protein, exportin-1 (XPO1). Seli exhibits its antitumor effect through the blockage of XPO1, which increases nuclear retention of tumor suppressor proteins (TSPs), including p53, thereby limiting the translation of oncogenes, triggering cell cycle arrest and the death of malignant cells. Multiple Myeloma (MM) patients with del17p are deficient in TP53 and have a particularly poor prognosis. Given its unique mechanism of action, we investigated whether Seli has increased efficacy in RRMM patients with del17p compared to other high-risk cytogenetics (OHRC). This is an IRB-approved observational study of RRMM patients with high-risk cytogenetics (del17p, t (4;14), t (14;16) or gain 1q) or standard-risk cytogenetics treated at the Levine Cancer Institute (LCI) with a Seli-based regimen between January 2019 and December 2022. Time-to-event endpoints (PFS, OS) were evaluated using Kaplan–Meier (KM) methods. Log-rank tests compared time-to-event endpoints between cohorts [del17p vs. OHRC vs. standard risk]. We identified 40 RRMM patients with high-risk cytogenetics, including 16 patients with del17p and 24 patients with OHRC, as well as 20 with standard-risk cytogenetics. The median age was 62.5 vs. 69 vs. 65.5 years (del17p group vs. OHRC vs. standard risk). The median prior line of therapies was five (range: 3–16) with similar rates of prior autologous stem cell transplant in all arms (68.8% vs. 62.5% vs. 70.0%). The most frequently used regimens were Seli–Pomalidomide–dexamethasone(dex) or Seli–Carfilzomib–dex (Seli-Kd) in the del17p group and Seli-Kd in the OHRC and standard-risk groups. The median time to start the Seli-based regimen after initial MM diagnosis was 5.6 years for the del17p group, 4.1 years in OHRC, and 4.8 years in the standard-risk group. The median follow-up time after the start of the Seli-based regimen was 10.5 months (mos) in the del17p group, 8.4 mos in OHRC, and 10.3 mos in the standard-risk group. In the del17p group, 50% had an objective response, 41.7% in the OHRC, and 35% in the standard-risk group (p = 0.71). Depth of response was also similar across the arms (12.5% vs. 12.5% vs. 10.0% VGPR p = 0.99). The median OS was 10.9 mos in the del17p group, 10.3 mos in the OHRC, and 10.3 mos in the standard-risk group (p = 0.92). The median OS was 15.5 mos for patients who received Seli as a bridging therapy versus 9 mos for Seli use for other reasons rather than as a bridge. Overall, Seli-based regimens showed promising responses even in this heavily pretreated population. Our analysis suggests that Seli-based regimens lead to similar outcomes among RRMM patients with del17p, OHRC, and standard-risk cytogenetics. This contrasts with previously reported outcomes using combinations of novel therapies in this population, where the del17p patients often have a poorer prognosis. Interestingly, our data suggest that Seli is a particularly effective bridging modality for patients preparing for CAR-T cell therapies in our population. Further investigation into this population is warranted, including in earlier lines of therapy, in hopes of seeing a more durable response.
]]>Life doi: 10.3390/life14030383
Authors: Joaquim Ruiz
Quinolone resistance has been largely related to the presence of specific point mutations in chromosomal targets, with an accessory role of impaired uptake and enhanced pump-out. Meanwhile the relevance of transferable mechanisms of resistance able to protect the target of pump-out or inactivate quinolones has been increasingly reported since 1998. Nevertheless, bacteria have other strategies and mechanisms allowing them to survive and even proliferate in the presence of quinolones, which might be qualified as resistance or resilience mechanisms. These include decreasing levels of quinolone target production, transient amoeba protection, benthonic lifestyle, nutrient-independent slow growth, activation of stringent response, inactivation or degradation of quinolones as well as apparently unrelated or forgotten chromosomal mutations. These mechanisms have been largely overlooked, either because of the use of classical approaches to antibiotic resistance determination or due to the low increase in final minimum inhibitory concentration levels. This article is devoted to a review of a series of these mechanisms.
]]>Life doi: 10.3390/life14030382
Authors: Pabulo Henrique Rampelotto
It is with great enthusiasm that we embark on a retrospective journey to the landmark work “Extremophiles and Extreme Environments” (1 in Appendix A), published 10 years ago as part of its Special Issue (2 in Appendix A) [...]
]]>Life doi: 10.3390/life14030381
Authors: Zhaoyao Li Wenxian Chen Zilong Qiu Yuwan Li Jindai Fan Keke Wu Xiaowen Li Mingqiu Zhao Hongxing Ding Shuangqi Fan Jinding Chen
In the original publication [...]
]]>Life doi: 10.3390/life14030380
Authors: Simona Brasoveanu Ligia Balulescu Dorin Grigoraș Dragos Erdelean Flavius Olaru Răzvan Bardan Oana Balint Mădălin-Marius Margan Alexandru Alexandru Ivan Cristiana-Smaranda Laurențiu Pirtea
Objective: This study aims to provide an in-depth analysis of patient preferences and clinical outcomes associated with two prominent surgical techniques for treating Stress Urinary Incontinence (SUI): the modified laparoscopic Burch colposuspension and the transobturator tape (TOT) procedure. Material and Methods: A prospective cohort study was conducted on 145 patients who recieved surgical treatment for SUI, of which 71 patients (49%) underwent the modified laparoscopic Burch procedure, while 74 patients (51%) received the TOT procedure. Data on clinical characteristics, treatment success rates, and postoperative outcomes were collected and analyzed to understand patient preferences and real-world clinical effectiveness. Results: This study revealed notable differences in patient demographics and clinical characteristics between the two groups. At the 2-year follow-up, a success rate of 100% was reported in the modified laparoscopic Burch group and 86.48% in the TOT group. A total of 99 patients (68.28%) were considered cured postoperatively, with 47 (66.20%) in the modified laparoscopic Burch group and 52 (70.27%) in the TOT group (p = 0.598). A significant difference was found in the incidence of dyspareunia, with six cases (8.10%) reported in the TOT group, compared to none reported in the modified laparoscopic Burch group (p = 0.028). The median operation time was significantly shorter in the TOT group, namely 15 min, compared to the modified laparoscopic Burch group, which had a median equal to 27 min (p < 0.001). Despite these differences, patient preference for either surgical technique was observed, along with similar success rates and varied postoperative outcomes. Conclusions: The findings provide a comprehensive overview of patient preferences and factual clinical outcomes for the two surgical techniques in SUI treatment. This study contributes to understanding the factors influencing patient choice and offers valuable insights into the real-world application of these techniques, enhancing patient-centered care in SUI management.
]]>Life doi: 10.3390/life14030379
Authors: Nityashree Kyathegowdanadoddi Lakshmanagowda Niju Sagar Rachitha Puttasiddaiah Kandi Sridhar Vinay Basavegowda Raghavendra Maharshi Bhaswant
The Ayurvedic medical system uses fruits of the Benincasa hispida plant to treat mental diseases, including schizophrenia. The goal of the current study was to assess the aqueous extract of B. hispida fruit’s ability to relieve stress and anxiety induced in zebrafish models using neuropharmacological evaluation, which included determining behavioral parameters in tests such as the T-maze, open tank test (OTT), and light–dark preference test (LDPT). After measuring the zebrafish survival rate for 96 h, the LC50 was found to be 5 µg. AChE (acetylcholinesterase) inhibitory activity and the status of antioxidant enzymes (SOD, CAT, and LDH) were also used to evaluate the toxicity. Furthermore, the administration of the aqueous extract of B. hispida fruit increased the frequency of entry and duration of time spent in the bright section, suggesting a noteworthy reduction in levels of stress and anxiety. Additionally, the antistress and antianxiety activity was confirmed by the docking studies’ mechanism of action, which involves the AChE receptor binding stability of the homogalactaconan molecule found in the aqueous extract of B. hispida fruit. Overall, the findings of this study demonstrated that the aqueous extract of B. hispida fruit is a viable therapeutic molecule for the creation of novel drugs and the treatment of stress since it has the therapeutic advantage of reversing the negative effects of stress and anxiety.
]]>Life doi: 10.3390/life14030378
Authors: Giada Sambugaro Elena Brambilla Giulia Costanzo Vera Bonato Andrea Giovanni Ledda Stefano Del Giacco Riccardo Scarpa Marcello Rattazzi Elisabetta Favero Francesco Cinetto Davide Firinu
This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient’s vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals (p = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity (p = 0.45) and duration of symptoms (p = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms (p = 0.038), dyspnea (p = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections.
]]>Life doi: 10.3390/life14030377
Authors: Hans-Oliver Rennekampff Mayer Tenenhaus Isabelle Rennekampff Ziyad Alharbi
The ability to heal one’s wounds is perhaps one of the most fundamental and critical of physiologic processes. This coordinated and closely regulated sequential biological process involves a variety of migratory and resident cells. The activation, modulation, balance, and control of these functions depend upon soluble mediators that activate cells and modulate their diverse functions. Recent advances have identified mechanotransduction as functionally integral in many different cell types and physiologic processes. The mechanically sensitive ion channel Pieoz1 is expressed on platelets, neutrophils, macrophages, endothelial cells, keratinocytes, and fibroblasts, all of which are principally involved in wound healing. On a cellular level, there have been great advances in our understanding of the functional role of Piezo1 mechanotransduction in cutaneous wounding. The blocking of Piezo1 has recently been shown to reduce scarring in vivo and yet, thus far, a comprehensive understanding of the roles that Piezo1 plays in in vivo wound healing remains lacking. Recognizing the ever-present and critical importance of optimal and reparative wound healing, and with the availability of new physical mechanomodulating devices, the time is ripe for gaining deeper insights into optimizing wound healing. In this review, we describe the current knowledge of Piezo1 related to wound healing.
]]>Life doi: 10.3390/life14030376
Authors: Pavol Pobeha Imrich Mucska Robert Vysehradsky Marta Hajkova Ivana Paranicova Pavol Joppa
Non-invasive positive pressure ventilation (NIPPV) is increasingly used as a treatment method for patients with respiratory failure. The first recommendations for the use of NIPPV in Slovakia were developed by the Slovak Society of Pulmonology and Phthisiology in 2007 and were partially revised in 2015. New scientific evidence prompted the present update, which is based on widely accepted international guidelines and was adapted to address local needs. Important features of the present update include a classification of acute indications for NIPPV into three categories based on the level of supporting evidence, namely 1. definite indications for in-hospital use of NIPPV; 2. possible indications for in-hospital use of NIPPV; and 3. disorders and states in which in-hospital use of NIPPV is not recommended. The current update also reflects the importance of comorbid sleep-related breathing disorders and other chronic respiratory conditions, as well as the use and limitations of continuous positive airway pressure therapy. Since oxygen therapy is often administered along with NIPPV, guidance on the safe use of oxygen in NIPPV-treated patients has also been included. Also, the present update extends the range of its users, addressing the needs of specialists in pediatric respiratory medicine as a novelty.
]]>Life doi: 10.3390/life14030375
Authors: Camille Jacques Flora Marchand Mathias Chatelais Adrien Brulefert Mathieu Riffault Ilaria Floris
As one of the major cytokines implicated in the orchestration of immune responses, interleukin 6 (IL-6) can either act as a pro- or an anti-inflammatory factor, depending on the micro-environment. In micro-immunotherapy (MI) medicines, IL-6 is employed at low doses (LD) and ultra-low doses (ULD), expressed in centesimal Hahnemannian (CH), and used alone or in combination with other immune regulators to modulate patients’ immune responses. The present study focused on assessing the in vitro immune-modulatory effects of two IL-6-containing MI products: (i) the unitary IL-6 (4 CH) and (ii) the complex MI-medicine (MIM) 2LALERG®, which includes IL-6 (17 CH) in association with other actives in its formulation. Our results showed that IL-6 (4 CH) activated granulocytes under basal conditions, and natural killer cells in the presence of an anti-CD3 signal, as assessed by their CD69 expression. In addition, IL-6 (4 CH) balanced the macrophages’ differentiation toward a M2a profile. On the other hand, the tested 2LALERG® capsule inhibited the histamine degranulation of rats’ peritoneal mast cells and reduced the release of IL-6 itself in inflamed human macrophages. Altogether, these data provide novel pieces of evidence on the double-edged potential of the LD and ULD of IL-6 in immune responses modulation, when employed in MI.
]]>Life doi: 10.3390/life14030374
Authors: György Paragh Péter Zilahi László Róbert Kolozsvári Hajnalka Lőrincz Péter Fülöp Mariann Harangi
Cardiovascular disease is the leading cause of mortality worldwide. Despite the availability of effective low-density lipoprotein cholesterol (LDL-C) lowering agents, an increased cardiovascular risk is still observed in individuals with therapeutic LDL-C levels. One of these cardiovascular risk factors is elevated plasma lipoprotein(a) (Lp(a)) concentration, which maintains chronic inflammation through the increased presence of oxidized phospholipids on its surface. In addition, due to its 90 percent homology with the fibrinolytic proenzyme plasminogen, Lp(a) exhibits atherothrombotic effects. These may also contribute to the increased cardiovascular risk in individuals with high Lp(a) levels that previous epidemiological studies have shown to exist independently of LDL-C and other lipid parameters. In this review, the authors overview the novel therapeutic options to achieve effective Lp(a) lowering treatment, which may help to define tailored personalized medicine and reduce the residual cardiovascular risk in high-risk patients. Agents that increase LDL receptor expression, including statins, proprotein convertase subtilisin kexin type 9 inhibitors, and LDL production inhibitors, are also discussed. Other treatment options, e.g., cholesterolester transfer protein inhibitors, nicotinic acid derivatives, thyroid hormone mimetics, lipoprotein apheresis, as well as apolipoprotein(a) reducing antisense oligonucleotides and small interfering RNAs, are also evaluated.
]]>Life doi: 10.3390/life14030373
Authors: Sarah Biganski Oleksii Obshta Ivanna Kozii Roman Koziy Michael W. Zabrodski Midhun S. Jose Jenna M. Thebeau Marina C. B. Silva Muhammad F. Raza Fatima Masood Sarah C. Wood Elemir Simko
(1) Background: Microsporidiosis (nosemosis) is an intestinal disorder of adult honey bees caused by the microsporidian pathogens Vairimorpha apis and Vairimorpha ceranae. In Canada, fumagillin is an approved antibiotic used to treat this disease. However, the recommended dosage is based on efficacy studies for V. apis, the native pathogen in European honey bees. Since the detection of V. ceranae in Apis mellifera, V. ceranae became more prevalent in managed European honey bees and seems to have replaced V. apis due to yet unknown reasons. (2) Methods: This colony study investigated the efficacy of fumagillin administered in the fall to colonies infected with both V. apis and V. ceranae and its effects on the Vairimorpha species’ prevalence overwinter. Spore loads in control and fumagillin-treated colonies were analysed by microscopy; Vairimorpha species prevalence was determined molecularly and infection and treatment effects on colony productivity were assessed. (3) Results: Fall fumagillin treatment was associated with a temporary reduction in spore load, but there was no difference in spore loads between treated and control colonies the following spring. Interestingly, fumagillin-treated colonies had a significantly greater prevalence of V. ceranae relative to V. apis the following spring, suggesting fumagillin is less effective in controlling V. ceranae.
]]>Life doi: 10.3390/life14030372
Authors: Hakim Manghwar Wajid Zaman
In the complex field of plant science, knowledge of the many difficulties that plants encounter from both living and non-living stresses is essential for maintaining biodiversity and managing natural resources in a sustainable manner, in addition to guaranteeing global food security [...]
]]>Life doi: 10.3390/life14030371
Authors: Csilla Mišľanová Martina Valachovičová Zuzana Slezáková
Microplastics are small plastic pieces with sizes less than 5 mm. They are becoming a global concern due to the potential risk to human health. The potential risks of microplastics may be greater for infants because they do not have sufficiently developed metabolizing enzymes, have less ability to remove microplastics, and have highly sensitive target organs. Infants should be breastfed for the first six months of life. Breast milk is considered to be the most complete and suitable source of nutrition. However, if breastfeeding during this period is not possible, it is necessary to use formulas designed for infant initial feeding. Infants may be exposed to higher levels of MPs through infant foods or plastic products. The aim of this study is to describe the possible sources of exposure to microplastics such as the human placenta, plastic feeding bottles, and toys as well as the presence of released microplastics in infant feces, breast milk, and infant formulas. There is still not enough data available for this study area. Therefore, it is necessary to pay increased attention to minimizing the negative effects of microplastics on human health.
]]>Life doi: 10.3390/life14030370
Authors: Ahmed M. A. Mousa Ahmed M. A.-G. Ali Abdelrahman E. A. Omar Khadiga Alharbi Diaa Abd El-Moneim Elsayed Mansour Rasha S. A. Elmorsy
Aerobic rice cultivation represents an innovative approach to reduce water consumption and enhance water use efficiency compared to traditional transplanting methods. Simultaneously, cultivating drought-tolerant rice genotypes becomes crucial to ensure their sustainable production under abrupt climate fluctuations. Hence, this study aimed to explore the physiological, agronomic, and grain quality responses of ten diverse rice genotypes to various irrigation levels under aerobic cultivation conditions. A field experiment was performed for two summer seasons of 2019 and 2020 in an arid Mediterranean climate. The irrigation regimes were well watered (13,998 m3/ha), mild drought (10,446 m3/ha), moderate drought (7125 m3/ha), and severe drought (5657 m3/ha). The results revealed considerable variations among rice genotypes under tested irrigation regimes in all physiological, agronomic, and quality traits. According to drought response indices, rice genotypes were classified into three groups (A–C), varying from tolerant to sensitive genotypes. The identified drought-tolerant genotypes (Giza-179, Hybrid-1, Giza-178, and Line-9399) recorded higher yields and crop water productivity with reduced water usage compared to drought-sensitive genotypes. Thus, these genotypes are highly recommended for cultivation in water-scarce environments. Furthermore, their characteristics could be valuable in breeding programs to improve drought tolerance in rice, particularly under aerobic cultivation conditions. The PCA biplot, heatmap, and hierarchical clustering highlighted specific physiological parameters such as relative water content, chlorophyll content, proline content, peroxidase content, and catalase content exhibited robust associations with yield traits under water deficit conditions. These parameters offer valuable insights and could serve as rapid indicators for assessing drought tolerance in rice breeding programs in arid environments.
]]>Life doi: 10.3390/life14030369
Authors: Robert John Aitken
Over the past half a century many countries have witnessed a rapid fall in total fertility rates, particularly in the world’s most advanced economies including the industrial powerhouses of Eastern Asia and Europe. Such nations have now passed through the first and second demographic transitions and are currently exhibiting fertility rates well below the replacement threshold of 2.1, with no sign of recovery. This paper examines the factors responsible for driving these demographic transitions and considers their impact on both fertility and fecundity (our fundamental capacity to reproduce). I argue that because the first demographic transition was extremely rapid and largely driven by socioeconomic factors, it has had no lasting impact on the genetic/epigenetic underpinnings of human fecundity. However, the second demographic transition will be different. A series of conditions associated with low fertility societies, including relaxed selection pressure for high-fertility genotypes, the indiscriminate use of assisted reproductive technologies to treat human infertility, and environmental contamination with reproductive toxicants, may impact our genetic constitution in ways that compromise the future fecundity of our species. Since any fundamental change in the genetic foundations of human reproduction will be difficult to reverse, we should actively pursue methods to monitor human fecundity, as sub-replacement fertility levels become established across the globe.
]]>Life doi: 10.3390/life14030368
Authors: Mihai Petrescu Georgică Târtea Ion Udriștoiu Felicia Militaru Alexandra-Roxana Petrescu Ana-Maria Ciurea Ana-Maria Petrescu Cosmin Obleagă Cristin Constantin Vere
(1) Background: The aim of our study was to assess the involvement of the sympathetic nervous system in the progression of patients with gastric carcinoma by analyzing the sympathetic neuronal fibers and beta 2 adrenoreceptors. (2) Methods: We performed a retrospective study in which we analyzed the clinical, biological, and histological data from a total of 104 patients diagnosed with stomach cancer. (3) Results: After analyzing the immunoreactivity of beta 2 adrenoreceptors, we observed increased values in patients with tumors larger than 5 cm in diameter (p = 0.0371), with a deeper degree of tumor invasion T3–4 (p = 0.0159), invasion in more than two lymph nodes (p = 0.0462), or a TNM stage III–IV. Regarding the survival analysis, better survival rates (65%) were observed for patients with a low value of beta 2 adrenoreceptors (B2A−), compared to B2A (+) patients, in which survival at 3 years of follow-up was only 43%. In addition, the analysis of intra-tumoral sympathetic fibers showed a better survival rate (83%) for patients with a low value of density compared to patients with increased density, in whom the survival rate was only 24%. (4) Conclusions: The findings of this study indicate that patients with stomach cancer have a more unfavorable prognosis when they have a higher density of sympathetic nerve fibers and an increased expression of beta 2 adrenergic receptors inside the tumor.
]]>Life doi: 10.3390/life14030367
Authors: Jakob Fehlhofer Jutta Ries Florian Tobias Nickel Veit Rothhammer Stefan Schwab Marco Kesting Mayte Buchbender
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of unknown etiology that affects the central nervous system and can lead to neurological impairment. Our aim was to determine whether MS patients also show inflammatory changes in the oral cavity more frequently than healthy individuals. For this purpose, we examined plaque samples for various mediators and their correlation with clinical findings. A study group (MS) and a control group were examined and compared. The plaque samples were analyzed for the expression of interleukins (IL-2, -6, -10), matrix metalloproteinases (MMP-7, MMP-9), and a surface antigen CD90 by quantitative real-time PCR. The clinical parameters examined were the Mombelli plaque index; bleeding on probing (BOP) index; periodontal pocket depth; and decayed, missing, and filled tooth (DMFT) index. The expression of MMP9 was significantly (p = 0.035) higher in the control group. The expression of IL-2 was increased four-fold in the MS group; however, this difference was not statistically significant. The mean PD (p < 0.001) and BOP index (p = 0.029) values were increased in the study group. The clinical parameters of the BOP index and PD were significantly amplified in the MS patients. However, no causal relationship between the investigated inflammatory mediators and the clinical findings could be established in this case series.
]]>Life doi: 10.3390/life14030366
Authors: Qiu Zhou Yuan Gao Yin Li Huili Xie Xiaoxi Liu Yanhong Yong Youquan Li Zhichao Yu Xingbin Ma Xianghong Ju
Although numerous studies have shown that the hypothalamic–pituitary–adrenal axis plays a vital role in the response to environmental stress by mediating the production of a series of hormones, the mechanism underlying these effects has not been elucidated. This study used proteomics techniques to investigate the differentially expressed proteins (DEPs) in the pituitary glands of pigs and to elucidate the potential changes in the immune–neuroendocrine system under heat stress (HS). In total, 2517 peptides corresponding to 205 proteins were detected. A comparison of the expression patterns between HSs and healthy controls revealed 56 DEPs, of which 31 were upregulated and 25 were downregulated. Ingenuity pathway analysis (IPA) was used to reveal the subcellular characteristics, functional pathways, regulatory networks, and upstream regulators of the identified proteins. The results showed that these differentially expressed proteins were involved in intercellular communication, interactions, apoptosis, nervous system development, functions, abnormalities and other functions, and in the regulatory network. Moreover, the upstream regulators of the differentially expressed proteins were mainly transcriptional regulators, hormones, and cytokines. Thus, the functional network and pathway analyses could provide insights into the complexity and dynamics of HS–host interactions and may accelerate our understanding of the mechanisms underlying HS.
]]>Life doi: 10.3390/life14030365
Authors: Petras Prakas Naglis Gudiškis Neringa Kitrytė Dovilė Laisvūnė Bagdonaitė Laima Baltrūnaitė
The genus Sarcocystis is an abundant group of Apicomplexa parasites found in mammals, birds, and reptiles. These parasites are characterised by the formation of sarcocysts in the muscles of intermediate hosts and the development of sporocysts in the intestines of definitive hosts. The identification of Sarcocystis spp. is usually carried out in carcasses of animals, while there is a lack of studies on the detection of Sarcocystis species in blood samples. In the current study, blood samples of 214 yellow-necked mice (Apodemus flavicollis) and 143 bank voles (Clethrionomys glareolus) from Lithuania were examined for Sarcocystis. The molecular identification of Sarcocystis was carried out using nested PCR of cox1 and 28S rRNA and subsequent sequencing. Sarcocystis spp. were statistically (p < 0.01) more frequently detected in the bank vole (6.3%) than in yellow-necked mice (0.9%). The analysed parasites were observed in four different habitats, such as mature deciduous forest, bog, natural meadow, and arable land. Three species, Sarcocystis funereus, Sarcocystis myodes, and Sarcocystis cf. glareoli were confirmed in the bank vole, whereas only Sarcocystis myodes were found in yellow-necked mice. The obtained results are important in the development of molecular identification of Sarcocystis parasites in live animals.
]]>Life doi: 10.3390/life14030364
Authors: Roland Wohlgemuth
The architecture, organization, and functioning of biocatalytic reaction networks, which are coded in the cell-specific genome and which work together in the small space of biological cells, are a fascinating feature of life evolved over more than 3 billion years. Knowledge about the diversity of biocatalytic functions and metabolic pathways sustaining life on our planet is highly important, especially as the currently occurring loss of biodiversity is considered a planetary boundary that is at high risk, and knowledge about the life of current biological organisms should be gained before they become extinct. In addition to the well-known enzymatic reactions involved in biochemical pathways, the enzyme universe offers numerous opportunities for discovering novel functions and pathways. Maintaining thousands of molecules and reactions functioning properly within biological cells, which may be exposed to various kinds of external hazards, environmental stress, enzymatic side reactions, or non-enzymatic chemical reactions, is key for keeping cellular life healthy. This review aims to outline advances in assigning enzyme functions to protein sequences and the discovery of novel biocatalytic functions and pathways.
]]>Life doi: 10.3390/life14030363
Authors: Maximilian T. Antush Onesmo B. Balemba Sarah A. Hendricks Morgan Flynn Rayme Geidl Chantal A. Vella
Human gut microbiome richness, diversity, and composition are associated with physical activity and impaired glycemic control; however, the associations with sedentary behavior and screen time are not as well-established. This study evaluated associations of sedentary behavior and screen time with the alpha diversity and composition of the human gut microbiome in adults with and without impaired glycemic control. Sedentary behavior and screen time data were collected via survey from 47 adults (38% with impaired glycemic control). Microbiome composition and alpha diversity were determined in fecal microbial DNA. Sedentary behavior was negatively associated with the number of observed operational taxonomic units (OTUs), Chao 1 Index, and Fisher’s Alpha Index. These associations were slightly attenuated but remained significant when controlling for covariates. Screen time was negatively associated with the number of observed OTUs, Shannon Index, and Fisher’s Alpha Index; however, only the association with observed OTUs was independent of all covariates. Our findings suggest sedentary behavior and screen time may be significant influencers of compositional changes in human gut microbiota. This may be a potential mechanism linking sedentary behavior and screen time to an increased risk of type 2 diabetes.
]]>Life doi: 10.3390/life14030362
Authors: Dimitrios Külzer Stefan Kalt Peter Walla
Trust and distrust are constructs that have provoked and undergone lots of discussion in the fields of sociology and psychology. However, to our knowledge, there is little agreement about how these constructs should be treated in the future. The present study tries to help in this discussion by re-analyzing prior neurophysiological data highlighting differences between trust and distrust by connecting these data with two distinct personality dimensions. Thus, the objective was to analyze the connection between neurophysiological trust/distrust processing and distinct HEXACO personality dimensions. Differences were found in the event-related potentials (ERPs) calculated for visual presentations of political institution words and brand names, which were evaluated with respect to trust and distrust by button presses. Two time points (330 ms and 780 ms) showed brain activity differences between trust and distrust related to the two word categories at frontal electrode locations. For this study, these findings were taken and connected to HEXACO-60 personality inventory results collected from prior participants. Statistical analysis revealed a significant interaction between the ERPs and two HEXACO personality dimensions concerning trusted brands at the later time point (780 ms) at the right frontal electrode location F8. This result is taken as neurophysiological evidence that parameter values of the personality traits honesty–humility and agreeableness have an influence on brain functions related to trusted brands.
]]>Life doi: 10.3390/life14030361
Authors: Navpreet K. Hehar DeGaulle I. Chigbu
Vernal keratoconjunctivitis (VKC) is a complex and multifactorial disease process that employs Th2 cell-mediated immunologic processes, which involves the overexpression of interleukin 4 (IL-4), IL-5, IL-9, IL-13, and IL-31, and the activation of mast cells that release IL-5 and CCL-11, recruiting eosinophils to the site of inflammation. The disease primarily affects young males and is more common in regions with warm climates. VKC is characterized by persistent and recurrent conjunctival inflammation that can adversely affect the patient’s quality of life, and, when inadequately treated, may lead to a host of ocular complications, such as corneal shield ulcers and scarring. The major distinct forms of VKC include limbal or palpebral, which may occur in combination. The clinicopathological features of VKC include the presence of pseudogerontoxon, limbal gelatinous hyperplasia, and perilimbal hyperpigmentation. Topical immunomodulators are effective anti-steroidal options for controlling severe and chronic cases of VKC. This review will provide a brief overview of topical immunomodulators, including cyclosporin and tacrolimus, and will highlight the clinical manifestations, pathological mechanisms, and fibroproliferative changes in the conjunctiva that can result from recurrent disease.
]]>Life doi: 10.3390/life14030360
Authors: Sanja Medenica Dusan Zivanovic Domenico Milardi Carmine Bruno Ljubica Batkoska Emanuela Traini Alfredo Pontecorvi
Hyperandrogenism is a condition in which the levels of androgen hormones in the blood are significantly increased and could be of an adrenal or ovarian origin. The adrenal androgens, normally secreted by the zona reticularis, are steroid hormones with weak androgen activity. The causes of hyperandrogenism are diverse and could be endogenous and exogenous. Androgen excess affecting different tissues and organs results in clinical features such as acne, hirsutism, virilization, and reproductive dysfunction such as oligomenorrhoea/amenorrhoea. Although androgen excess is rarely associated with adrenal tumours, it is important as it could be predictive of malignancy. A careful evaluation of the androgen pattern, also in patients with clear signs of hyperandrogenism, could be useful. Laboratory evaluation should focus on measuring total testosterone levels, followed by the estimation of other androgens such as dehydroepiandrosterone and androstenedione, and using visualisation procedures in the further management. The treatment of adrenal hyperandrogenism is eminently surgical, in consideration of the frequent malignant origin. The aim of this review is to elaborate and summarize the prevalence and clinical management of hyperandrogenism of an adrenal origin by describing the physiological mechanisms of adrenal androgen steroidogenesis, the clinical manifestations of hyperandrogenism with a special reference to hyperandrogenism in adrenal adenomas and carcinomas, and the diagnostic methods that will lead us to establishing the correct diagnosis and different treatment options to manage this condition according to the clinical presentation of the patient.
]]>Life doi: 10.3390/life14030359
Authors: Zhiyuan Xu David Schlesinger Robert Andrew Drainville David Moore Patcharin Pramoonjago Jason Sheehan Frederic Padilla
The radiosensitization potential of focused ultrasound (FUS)-induced mild hyperthermia was assessed in an allogenic subcutaneous C6 glioma tumor model in rats. Mild hyperthermia at 42 °C was induced in tumors using a single-element 350 kHz FUS transducer. Radiation was delivered with a small animal radiation research platform using a single-beam irradiation technique. The combined treatment involved 20 min of FUS hyperthermia immediately before radiation. Tumor growth changes were observed one week post-treatment. A radiation dose of 2 Gy alone showed limited tumor control (30% reduction). However, when combined with FUS hyperthermia, there was a significant reduction in tumor growth compared to other treatments (tumor volumes: control—1174 ± 554 mm3, FUS-HT—1483 ± 702 mm3, 2 Gy—609 ± 300 mm3, FUS-HT + 2 Gy—259 ± 186 mm3; ANOVA p < 0.00001). Immunohistological analysis suggested increased DNA damage as a short-term mechanism for tumor control in the combined treatment. In conclusion, FUS-induced mild hyperthermia can enhance the effectiveness of radiation in a glioma tumor model, potentially improving the outcome of standard radiation treatments for better tumor control.
]]>Life doi: 10.3390/life14030358
Authors: Michela Palese Gabriella Ferretti Giuseppe Perruolo Sara Serafini Rossana Sirabella Vincenzo Marrone Martina De Rosa Laura Sarno Ida Strina Carmela Matrone Maurizio Guida
Semaphorin 3A (SEMA3A) plays a crucial role in the development, differentiation, and plasticity of specific types of neurons that secrete Gonadotropin-Releasing Hormone (GnRH) and regulates the acquisition and maintenance of reproductive competence in humans and mice. Its insufficient expression has been linked to reproductive disorders in humans, which are characterized by reduced or failed sexual competence. Various mutations, polymorphisms, and alternatively spliced variants of SEMA3A have been associated with infertility. One of the common causes of infertility in women of reproductive age is diminished ovarian reserve (DOR), characterized by a reduced ovarian follicular pool. Despite its clinical significance, there are no universally accepted diagnostic criteria or therapeutic interventions for DOR. In this study, we analyzed the SEMA3A plasma levels in 77 women and investigated their potential role in influencing fertility in patients with DOR. The results revealed that the SEMA3A levels were significantly higher in patients with DOR than in healthy volunteers. Furthermore, the SEMA3A levels were increased in patients who underwent fertility treatment and had positive Beta-Human Chorionic Gonadotropin (βHCG) values (β+) after controlled ovarian stimulation (COS) compared to those who had negative βHCG values (β−). These findings may serve as the basis for future investigations into the diagnosis of infertility and emphasize new possibilities for the SEMA3A-related treatment of sexual hormonal dysfunction that leads to infertility.
]]>Life doi: 10.3390/life14030357
Authors: Anton Y. Skopin Lubov N. Glushankova Konstantin O. Gusev Elena V. Kaznacheyeva
The incidence and development of cancer are highly dependent on pathological disturbances in calcium homeostasis of the cell. One of the major pathways for calcium entry is store-operated calcium entry (SOCE), which functions in virtually all cell types. Changes in the expression level of the main proteins organizing SOCE are observed during the development of various cancer types, particularly breast cancer (BC). This leads to unique SOCE with characteristics individual for each type of BC and requires particular therapeutic approaches. In this study, we tested the sensitivity of SOCE in various BC cells to selective ORAI channel inhibitors and the less selective compounds Leflunomide and Teriflunomide, approved by the FDA for clinical use. We also analyzed the vulnerability of SOCE to the influence of factors typical of the tumor microenvironment: hypoxia and acidification. We have observed that the SOCE inhibitors Leflunomide and Teriflunomide suppress SOCE in the triple-negative BC cell line MDA-MB-231, but not in the luminal A BC cell line MCF-7. MDA-MB-231 cells also demonstrate higher pH dependence of SOCE compared to MCF-7 cells. In addition, the oxygen scavenger sodium dithionide also affects SOCE, stimulating it in MDA-MB-231 cells but inhibiting in MCF-7 cells. Overall, our data highlight the importance of considering the different sensitivities of various BC cell types to inhibitors and to microenvironmental factors such as hypoxia and acidification when developing targeted drugs.
]]>Life doi: 10.3390/life14030356
Authors: Takahiro Miura Naoyuki Okochi Masaki Matsuo Ken-ichiro Yabu Atsushi Katagiri Keiichi Yasu Masatsugu Sakajiri Tohru Ifukube
The ability of individuals with visual impairment to recognize an obstacle by hearing is called “obstacle sense”. This ability is facilitated while they are moving, though the exact reason remains unknown. This study aims to clarify which acoustical factors may contribute to obstacle sense, especially obstacle distance perception. First, we conducted a comparative experiment regarding obstacle distance localization by individuals who are blind (N = 5, five men with blindness aged 22–42 (average: 29.8)) while they were standing and walking. The results indicate that the localized distance was more accurate while walking than while standing. Subsequently, the head rotation angle while walking and acoustic characteristics with respect to obstacle distance and head rotation angle were investigated. The peaks of the absolute head rotation angle during walking ranged from 2.78° to 11.11° (average: 6.55°, S.D.: 2.05°). Regarding acoustic characteristics, acoustic coloration occurred, and spectral interaural differences and interaural intensity differences were observed in the blind participants (N = 4, four men including two blind and two control sighted persons aged 25–38 (average: 30.8)). To determine which acoustic factors contribute, we examined the threshold of changes for interaural differences in time (ITD) and intensity (IID) (N = 11, seven men and four women with blindness aged 21–35 (average: 27.4)), as well as coloration (ICD) (N = 6, seven men and a woman with blindness aged 21–38 (average: 29.9))—depending on the head rotation. Notably, ITD and IID thresholds were 86.2 μs and 1.28 dB; the corresponding head rotation angles were 23.5° and 9.17°, respectively. The angle of the ICD threshold was 6.30° on average. Consequently, IID might be a contributing factor and ICD can be utilized as the cue facilitating the obstacle distance perception while walking.
]]>Life doi: 10.3390/life14030355
Authors: Jun Ho Hwang Chang Kyu Park Seok Bin Kang Man Kyu Choi Won Hee Lee
This study aimed to implement a deep learning-based super-resolution (SR) technique that can assist in the diagnosis and surgery of trigeminal neuralgia (TN) using magnetic resonance imaging (MRI). Experimental methods applied SR to MRI data examined using five techniques, including T2-weighted imaging (T2WI), T1-weighted imaging (T1WI), contrast-enhancement T1WI (CE-T1WI), T2WI turbo spin–echo series volume isotropic turbo spin–echo acquisition (VISTA), and proton density (PD), in patients diagnosed with TN. The image quality was evaluated using the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). High-quality reconstructed MRI images were assessed using the Leksell coordinate system in gamma knife radiosurgery (GKRS). The results showed that the PSNR and SSIM values achieved by SR were higher than those obtained by image postprocessing techniques, and the coordinates of the images reconstructed in the gamma plan showed no differences from those of the original images. Consequently, SR demonstrated remarkable effects in improving the image quality without discrepancies in the coordinate system, confirming its potential as a useful tool for the diagnosis and surgery of TN.
]]>Life doi: 10.3390/life14030354
Authors: Minerva Codruta Badescu Oana Viola Badulescu Liliana Gheorghe Lăcrămioara Ionela Butnariu Anca Ouatu Diana Popescu Oana Nicoleta Buliga-Finiș Eusebiu Vlad Gorduza Manuela Ciocoiu Ciprian Rezus
Hemophiliacs can develop cardiovascular diseases, including valvulopathies of various etiologies and severities. Some require surgical treatment. Performing cardiac surgery in hemophiliacs is a challenge because they maintain an increased risk of bleeding throughout their lives. Our review shows that with a multidisciplinary team and careful planning, cardiac surgery can be safely performed in these patients. Valve repair and bioprosthetic valves should be preferred over mechanical valves to avoid life-long anticoagulation. In patients who cannot receive a bioprosthetic valve, the use of the On-X mechanical valve might be considered because it requires less intensive anticoagulation after 3 months of treatment. Antithrombotic treatment is feasible in hemophiliacs only if the coagulation factor level is kept constantly above a specific trough limit. Our review is valuable because, for the first time, the available data on the modern surgical treatment of valvular disease in hemophiliacs have been synthesized and systematized.
]]>Life doi: 10.3390/life14030353
Authors: Darrell O. Ricke Nora Smith
Background: Vasculitis diseases include Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), Multisystem Inflammatory Syndrome (MIS), Henoch–Schönlein purpura (HS), or IgA vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than in adults. These diseases have been extensively studied, but understanding of the disease etiology remains to be established. Objective: Many studies have failed to demonstrate an association between vasculitis diseases and vaccination; this study examines possible associations. Methods: Herein, the Vaccine Adverse Event Reporting System (VAERS) database is retrospectively examined for associations between vasculitis diseases and immunizations. Results: For some vaccines, the number of rare cases of KD, MIS, and HS are higher than the background rates. These rare cases are predicted to occur in individuals with (1) genetic risk factors with (2) antibody titer levels above the primary immune response level. Herein, the model of humoral immune response antibodies bound to antigens (pathogen or vaccine) creating immune complexes is proposed. These immune complexes are proposed to bind Fc receptors on immune cells and platelets, resulting in cell activation and the release of inflammatory molecules including histamine and serotonin. Immune complexes and inflammatory molecules including serotonin and histamine likely trigger vasculitis. Elevated serotonin and possibly histamine drive initial vasoconstrictions, disrupting blood flow. Increased blood flow pressure from cardiac capillary vasoconstrictions is predicted to trigger coronary artery aneurysms (CAA) or lesions (CAL) in some patients. For KDSS and MIS patients, these cardiac capillary vasoconstrictions are predicted to result in ischemia followed by ventricular dysfunction. Ongoing ischemia can result in long-term cardiac damage. Cases associated with pathogens are likely to have persistent infections triggering disease onset. Conclusion: The proposed model of immune complexes driving disease initial disease etiology by Fc receptor activation of immune cells and platelets, resulting in elevated histamine and serotonin levels, is testable and is consistent with disease symptoms and current treatments.
]]>Life doi: 10.3390/life14030351
Authors: Manuella Pereira Cerqueira Leite Rayane Dias Paulo José Leite Shayenne Olsson Freitas Silva Hélcio Reinaldo Gil-Santana Roger Pimentel Barbosa Cecilia Ferreira de Mello Jeronimo Alencar
Although tropical forests are home to most of the global diversity, they suffer from the most significant knowledge gaps concerning their fauna. Despite its high biodiversity, Brazil is facing an alarming destruction of habitats, with species becoming extinct before they can be discovered or described via science. Therefore, there is an urgent need to expand wildlife inventories, including entomofauna surveys. The present study aimed to analyze the bionomic aspects and the influence of abiotic factors on mosquito fauna whose immature phases develop in two bamboo species, Guadua tagoara and Bambusa vulgaris, in Tijuca National Park, Rio de Janeiro, Brazil. Immatures were collected in 10 artificially drilled bamboo plants, in five stalk internodes per plant, at two sampling points, from March 2022 to March 2023, during 23 collections. A total of 1845 immatures were obtained, 72.14% at sampling point 1 and 27.86% at sampling point 2. Of this, 1162 individuals reached adulthood, belonging to the following species: Culex iridescens, Culex neglectus, Haemagogus leucocelaenus, Orthopodomyia albicosta, Sabethes identicus, Sabethes melanonymphe, Sabethes purpureus, Toxorhynchites bambusicola, Toxorhynchites sp., Trichoprosopon compressum, Trichoprosopon pallidiventer, Wyeomyia arthrostigma, Wyeomyia codiocampa, Wyeomyia lutzi, Wyeomyia oblita, Wyeomyia personata, Wyeomyia serrata, and Wyeomyia sp. The Tijuca National Park is a tourist spot and receives a large number of visitors. Thus, humans can become an accessible food source for mosquitoes in this area, making the species survey critical since important arbovirus vectors have been recorded in Rio de Janeiro.
]]>Life doi: 10.3390/life14030352
Authors: George G. Mitroi Elena Leocadia Pleșea George F. Mitroi Mihaela Roxana Mitroi Carmen Daniela Neagoe Simona Laura Ianoși
Atopic dermatitis (AD) is a persistent inflammatory skin condition that impacts individuals of various age groups, including both children and adults. Its pathophysiology involves allergens penetrating a disrupted epidermal barrier, triggering the dermal cells to produce pro-inflammatory cytokines and eliciting a T-cell-mediated immune response. Notably, interleukins (ILs), particularly interleukin 4 (IL-4) and interleukin 13 (IL-13), play a key role in AD pathogenesis. Therapies directed at inflammatory mechanisms, including Dupilumab, have demonstrated notable effectiveness in enhancing skin lesions, alleviating subjective symptoms, and improving the overall quality of life for individuals with AD. Despite therapeutic advances, assessing AD severity remains challenging. The commonly used tools, such as the SCORAD and DLQI scores, rely on subjective patient responses. Paraclinically, the search for universal biomarkers continues, with efforts to identify reliable indicators reflecting disease severity and treatment response. Various biomarkers, including Th2-related chemokines and cytokines, have been explored, but none have gained universal recognition for routine clinical use. This study aims to investigate the dynamics of the plasma levels of IL-4 and IL-13 during Dupilumab treatment and establish correlations between these ILs and disease severity, as measured using the SCORAD and DLQI scores. The ultimate endpoint is to determine whether IL-4 and IL-13 can serve as reliable biomarkers, assessing their correlation with patient-reported feelings and disease activity and potentially influencing their inclusion or exclusion as diagnostic elements in routine clinical practice.
]]>Life doi: 10.3390/life14030348
Authors: Daniela Păcurar Alexandru Dinulescu Gheorghiță Jugulete Alexandru-Sorin Păsărică Irina Dijmărescu
Hepatitis B virus (HBV) is a frequent cause of chronic hepatitis worldwide, with an estimated 5.6 million children under 5 years being infected. In Romania, there are no available epidemiology reports on large cohorts in children. We aimed to assess the profile of pediatric chronic HBV infection in southern Romania. We conducted an observational retrospective study on 506 HBV-infected children. Based on alaninaminotransferase (ALT), HBV serology and viremia, we identified four states of the disease. We correlated age, gender, household HBV infection, coinfection with other viruses and laboratory parameters. Most patients were in a positive HBV envelope antigen (HBeAg) immune-active state (65.4%). Age at diagnosis was significantly lower for those with household infection (p < 0.05). ALT values were not significantly different between positive or negative HBeAg patients in the immune-active state (p = 0.780). ALT values were higher in patients with hepatitis D virus (HDV)-associated infection (p < 0.001). Children with a household HBV infection had a high viraemia more frequently when compared to those with no infected relative (79.3% vs. 67.4%) (p < 0.001), but the ALT values were not significantly different (p = 0.21). Most of the patients are in an immune-active state (high ALT, high viremia). The percentages of HBV- and HDV-associated infections are high, but lower than the reported prevalence in Romania in the general population.
]]>Life doi: 10.3390/life14030350
Authors: DeGaulle I. Chigbu Nicholas J. Karbach Sampson L. Abu Navpreet K. Hehar
Allergic conjunctivitis is one of the common immune hypersensitivity disorders that affect the ocular system. The clinical manifestations of this condition exhibit variability contingent upon environmental factors, seasonal dynamics, and genetic predisposition. While our comprehension of the pathophysiological engagement of immune and nonimmune cells in the conjunctiva has progressed, the same cannot be asserted for the cytokines mediating this inflammatory cascade. In this review, we proffer a comprehensive description of interleukins 4 (IL-4), IL-5, IL-6, IL-9, IL-13, IL-25, IL-31, and IL-33, as well as thymic stromal lymphopoietin (TSLP), elucidating their pathophysiological roles in mediating the allergic immune responses on the ocular surface. Delving into the nuanced functions of these cytokines holds promise for the exploration of innovative therapeutic modalities aimed at managing allergic conjunctivitis.
]]>Life doi: 10.3390/life14030349
Authors: Ljiljana Žmak Selma Bošnjak Iva Pem Novosel Tajana Juzbašić Tatjana Vilibić-Čavlek Irena Tabain Tihana Miškić Ivana Lohman Janković Inoslav Brkić Ana Gverić Grginić
Bacillus anthracis is a well-known zoonotic pathogen that can cause disease in both animals and humans. Moreover, it has a high bioterrorism potential as its lethal spores are resistant to inactivation, are easy to produce in large quantities, and are easily spread over large areas. Anthrax cases occur in different parts of the world, including most European countries. Specific areas of Croatia are long known as anthrax districts, but with sporadically reported cases over the years. Here, we present a major outbreak of animal and human anthrax in the region of Lonjsko Polje in Croatia, a region not known to have anthrax cases in the past. The outbreak started in July 2022 and lasted several months, but most human and animal cases were reported in the first month. During the outbreak, there were 17 reported human cases of cutaneous anthrax and 29 laboratory-confirmed animal cases. However, due to issues in reporting in animals and the late finding of the carcasses, which made laboratory diagnostics challenging, the actual number of animal cases was probably significantly higher.
]]>Life doi: 10.3390/life14030347
Authors: Federica Di Spirito Annunziata Raimondo Maria Pia Di Palo Stefano Martina Mario Fordellone Donato Rosa Massimo Amato Serena Lembo
Psoriasis is a widespread chronic inflammatory skin disease, that negatively affects physical and emotional well-being and quality of life, as shown by the generally low Dermatology Life Quality Index (DLQI). Psoriasis is burdened by associated comorbidities and some patients manifest concurrent oral lesions, although the existence of oral psoriasis remains controversial. Psoriasis-specific and nonspecific oral lesions and Oral Health-Related Quality of Life (OHRQoL), self-assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire, were retrospectively reviewed in adult untreated psoriasis patients with ≥15 teeth, who were non-smokers and had no dental or periodontal infections. Sample (age, gender, comorbidities) and descriptive variables (Body Surface Area-BSA, Psoriasis Area and Severity Index-PASI, Dermatology Life Quality Index-DLQI, severity of psoriasis, distribution of lesions and predominant involvement, years since diagnosis) were correlated with DLQI and OHIP-14 and compared by baseline DLQI and OHRQoL classes. Charts from 90 participants were included. No oral lesions were detected, and excellent/good OHRQoL was found in 94% of the participants. DLQI scores displayed positive significant associations with PASI and BSA, while OHIP-14 with hypertension and IMID, and age. PASI and BSA were significantly higher in participants with DLQI > 10 and also differed significantly among OHQRoL ranks, as well as mucosal involvement and comorbidities. Specifically, among subjects revealing an Excellent OHQRoL, 92.6% were non-IMID, 75% non-hypertensive, 89.7% non-diabetic subjects, 86.8% of non CVD-subjects.
]]>Life doi: 10.3390/life14030346
Authors: Juraj Javor Vladimíra Ďurmanová Kristína Klučková Zuzana Párnická Dominika Radošinská Stanislav Šutovský Barbora Vašečková Veronika Režnáková Mária Králová Karin Gmitterová Štefan Zorad Ivana Shawkatová
Adiponectin, a hormone secreted by adipose tissue, plays a complex role in regulating metabolic homeostasis and has also garnered attention for its potential involvement in the pathogenesis of late-onset Alzheimer’s disease (LOAD). The objective of this study was to investigate the association of ADIPOQ variants with plasma adiponectin levels and LOAD risk in subjects from the Slovak Caucasian population. For this purpose, 385 LOAD patients and 533 controls without cognitive impairment were recruited and genotyped for a total of eighteen ADIPOQ single nucleotide polymorphisms (SNPs). Both single-locus and haplotype-based logistic regression analyses were employed to assess the association of SNPs with LOAD risk, while linear regression analysis was used to explore their influence on adiponectin levels in LOAD patients. ADIPOQ variants rs822395 and rs2036373 in intron 1 were found to significantly elevate total adiponectin levels after accounting for several potential confounders. Additional SNPs in the 5′ region and intron 1 exhibited a non-significant trend of association with adiponectin. However, none of the ADIPOQ SNPs showed an association with LOAD risk, neither in the whole-group analysis nor in subgroup analyses after stratification for sex or the APOE ε4 allele, a well-established LOAD risk factor. In summary, while adiponectin has emerged as a potential contributor to the development of LOAD, this study did not unveil any significant involvement of its gene variants in susceptibility to the disease.
]]>Life doi: 10.3390/life14030345
Authors: Malin Glindvad Ahlström Rie Dybboe Bjerre Magnus Glindvad Ahlström Lone Skov Jeanne Duus Johansen
Introduction: It is an international standard to recommend patients with atopic dermatitis (AD) to use moisturizers; however, little is known about their effect on lipids in the stratum corneum (SC). Methods: In this randomized clinical experiment of 30 Caucasian participants (15 with AD and 15 healthy controls), the superficial SC lipid profile was assessed through tape stripping non-lesional skin following treatment thrice daily for seven days with a moisturizer, and subsequently compared with untreated skin. Results: No discernible disparity in superficial SC lipid quantity was evident between the AD group and the control group. However, the SC lipid composition diverged significantly, with the AD group exhibiting diminished levels of long-chain EO CERs (p = 0.024) and elevated levels of short-chain C34 CERs (p = 0.025) compared to healthy skin. Moisturizer application significantly reduced the total SC lipids and all lipid subgroups in both groups. Within the AD group, a non-significant inclination towards an augmentation in EO CERs (p = 0.053) and reduction in C34 CERs (p = 0.073) was observed. Conclusion: The recent identification of distinctions in SC lipid composition between AD and healthy skin was substantiated by our findings. Topical moisturizer application, despite reducing overall total lipids, indicated a potential tendency towards a healthier lipid constitution in AD skin.
]]>Life doi: 10.3390/life14030344
Authors: Dimitrios Stefanoudakis Evaggelia Karopoulou Alkis Matsas Georgia Anna Katsampoula Ermioni Tsarna Eleni Stamoula Panagiotis Christopoulos
Gynecological cancers pose a significant burden on women’s health worldwide, necessitating innovative treatment approaches. Immunotherapy has emerged as a promising strategy, harnessing the body’s immune system to combat cancer. This review aims to provide a comprehensive overview of the current landscape and future directions of immunotherapy in cervical and endometrial cancer. Methods: A thorough literature search was conducted to identify relevant studies and clinical trials. The main methods and treatments employed in immunotherapy for cervical and endometrial cancer, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapies, are briefly described. Results: Immune checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies, have shown remarkable clinical efficacy in certain gynecological malignancies, particularly in advanced or recurrent cases. Additionally, ongoing research on cancer vaccines and adoptive cell therapies holds promise for personalized and targeted treatment options.
]]>Life doi: 10.3390/life14030343
Authors: Matteo Di Maso Serena Delbue Maurizio Sampietro Monica Ferraroni Annalisa Modenese Maria Dolci Federico Ambrogi Pasquale Ferrante
We evaluated the association between biomarkers and COVID-19 mortality. Baseline characteristics of 403 COVID-19 patients included sex and age; biomarkers, measured throughout the follow-up, included lymphocytes, neutrophils, ferritin, C-reactive protein, glucose, and LDH. Hazard ratios (HRs) and corresponding 95% credible intervals (CIs) were estimated through joint models (JMs) using a Bayesian approach. We fitted univariable (a single biomarker) and multivariable (all biomarkers) JMs. In univariable analyses, all biomarkers were significantly associated with COVID-19 mortality. In multivariable analysis, HRs were 1.78 (95% CI: 1.13–2.87) with a doubling of neutrophils levels, 1.49 (95% CI: 1.19–1.95) with a doubling of C-reactive protein levels, 2.66 (95% CI: 1.45–4.95) for an increase of 100 mg/dL of glucose, and 1.31 (95% CI: 1.12–1.55) for an increase of 100 U/L of LDH. No evidence of association was observed for lymphocytes and ferritin in multivariable analysis. Men had a higher COVID-19 mortality risk than women (HR = 1.75; 95% CI: 1.07–2.80) and age showed the strongest effect with a rapid increase from 60 years. These findings using JM confirm the usefulness of biomarkers in assessing COVID-19 severity and mortality. Monitoring trend patterns of such biomarkers can provide additional help in tailoring the appropriate care pathway.
]]>Life doi: 10.3390/life14030342
Authors: Cristina Stasi Stefano Brillanti
Globally, liver cancer is the third most frequent etiology of cancer death, with the rates of occurrence of both new cases and mortality estimated to increase. Given the availability of multiple treatments, interdisciplinary management of the patient is crucial. Moreover, the diagnostic assessment of patients with severe liver fibrosis is essential for the staging of HCC and liver cirrhosis and early diagnosis of HCC. In this context, non-invasive evaluation plays a critical role in identifying prognostic factors of clinical application for the surveillance of the occurrence or recurrence of HCC. The new frontiers of transient elastography have become a useful tool to assess the risk of HCC occurrence and recurrence. There has been a major increase in studies investigating the cutoff liver stiffness value that best predicts the need for monitoring for the onset of HCC. Therefore, this review discusses the new advances that have occurred in the last four years on HCC, highlighting the new frontiers of non-invasive evaluation of HCC subjects, with particular attention regarding the clinical application of liver stiffness assessment for de novo HCC and predicting recurrence in patients with chronic HCV achieving sustained virological response after treatment with direct antiviral agents.
]]>Life doi: 10.3390/life14030341
Authors: Michael G. Weller
Homochirality is an obvious feature of life on Earth. On the other hand, extraterrestrial samples contain largely racemic compounds. The same is true for any common organic synthesis. Therefore, it has been a perplexing puzzle for decades how these racemates could have formed enantiomerically enriched fractions as a basis for the origin of homochiral life forms. Numerous hypotheses have been put forward as to how preferentially homochiral molecules could have formed and accumulated on Earth. In this article, it is shown that homochirality of the abiotic organic pool at the time of formation of the first self-replicating molecules is not necessary and not even probable. It is proposed to abandon the notion of a molecular ensemble and to focus on the level of individual molecules. Although the formation of the first self-replicating, most likely homochiral molecule, is a seemingly improbable event, on a closer look, it is almost inevitable that some homochiral molecules have formed simply on a statistical basis. In this case, the non-selective leap to homochirality would be one of the first steps in chemical evolution directly out of a racemic “ocean”. Moreover, most studies focus on the chirality of the primordial monomers with respect to an asymmetric carbon atom. However, any polymer with a minimal size that allows folding to a secondary structure would spontaneously lead to asymmetric higher structures (conformations). Most of the functions of these polymers would be influenced by this inherently asymmetric folding. Furthermore, a concept of physical compartmentalization based on rock nanopores in analogy to nanocavities of digital immunoassays is introduced to suggest that complex cell walls or membranes were also not required for the first steps of chemical evolution. To summarize, simple and universal mechanisms may have led to homochiral self-replicating systems in the context of chemical evolution. A homochiral monomer pool is deemed unnecessary and probably never existed on primordial Earth.
]]>Life doi: 10.3390/life14030340
Authors: Xue Wang Quanzhi Ji Xing Zheng Jun Zhang Rongshen Wang Xinyu Wang Wenjun Peng Jun Guo Yazhou Zhao
The glands of bees are responsible for generating and secreting various biologically active substances that significantly impact bee physiological health and adaptability. This study aimed to investigate the effects of adding citric acid (CA) to bee feed on gland development and royal jelly quality. By formulating feed with varying proportions of CA, evaluation was undertaken of pollen feeding by honeybees under laboratory conditions, along with the impact of CA on the development of major glands, to determine suitable addition proportions. Further optimization of the CA proportion involved feeding colonies and evaluating royal jelly production and quality. The results indicated that feed containing 0.75% CA significantly extended the lifespan of bees and increased their pollen consumption. Gland development in bees showed a positive correlation with CA addition within the range of 0.25% to 0.75%, especially at 0.50% and 0.75%, which notably accelerated the development of mandibular, hypopharyngeal, and cephalic salivary glands, with active proliferation and differentiation of glandular cells and maintenance of normal gland size and morphology. CA added to feed stimulated vigorous secretion of wax glands in worker bees, resulting in prolific wax construction. Colonies consuming feed containing 0.50% CA produced royal jelly with significantly reduced moisture and total sugar content and increased levels of 10-HDA, total phenolic acids, total proteins, and acidity. These findings demonstrate that CA consumption significantly prolongs bee lifespan, increases consumption, promotes gland development, and enhances royal jelly quality. This research provides theoretical guidance for beekeeping practices and feed development, contributing to the sustainable advancement of apiculture.
]]>Life doi: 10.3390/life14030339
Authors: Ju-Hyun Lee Dong-Soon Im
In traditional Korean medicines, Magnolia officinalis is commonly included for the remedy of atopic dermatitis, and magnolol is a major constituent of Magnolia officinalis. Its pharmacological effects include anti-inflammatory, hepatoprotective, and antioxidant effects. Using BALB/c mice repeatedly exposed to 1-chloro-2,4-dinitrobenzene (DNCB), magnolol was evaluated in atopic dermatitis-like lesions. Administration of magnolol (10 mg/kg, intraperitoneal injection) markedly relieved the skin lesion severity including cracking, edema, erythema, and excoriation, and significantly inhibited the increase in IgE levels in the peripheral blood. A DNCB-induced increase in mast cell accumulation in atopic dermatitis skin lesions was reversed by magnolol administration, as well as a rise in expression levels of pro-inflammatory Th2/Th17/Th1 cytokines’ (IL-4, IL-13, IL-17A, IFN-γ, IL-12A, TARC, IL-8, and IL-6) mRNAs in the lymph nodes and skin (n = 5 per group). In lymph nodes, magnolol reversed DNCB’s increase in CD4+RORγt+ Th17 cell fraction and decrease in CD4+FoxP3+ regulatory T cell fraction. The results also showed that magnolol suppressed T cell differentiation into Th17 and Th2 cells, but not Th1 cells. Magnolol suppresses atopic dermatitis-like responses in the lymph nodes and skin, suggesting that it may be feasible to use it as a treatment for atopic dermatitis through its suppression of Th2/Th17 differentiation.
]]>Life doi: 10.3390/life14030338
Authors: Mathilde Bernard Louis-Romée Le Nail Gonzague de Pinieux Ramy Samargandi
Angioleiomyomas are uncommon, noncancerous, smooth muscle tumors that primarily arise from blood vessels. Previous studies have yielded limited data due to the lack of interdisciplinary approaches or restricted patient pools. This study aims to provide a comprehensive analysis of angioleiomyomas, including the demographic, clinical, radiological, and histopathological features, with a large number of patients. Conducted as a retrospective investigation at a single center from January 2005 to June 2023, this study involved 142 patients. Relevant information was extracted from electronic medical records, covering clinical, radiological, histological, and demographic details. Angioleiomyomas mostly occurred at age 59 (1–87), predominately affect females (53%) and commonly arise in subcutaneous tissue (85%) and the lower limbs (76%). MRI findings revealed characteristic signals, with a high prevalence of the solid histologic type (65%), often displaying a reticular sign. Smooth muscle Actin was universally present (n = 95/95), while Desmin and Caldesmon showed positive expression in 83% (n = 71/85) and 98% (n = 92/94) of cases, respectively. This study presents an updated and comprehensive analysis of angioleiomyomas. Typically appearing as well-defined nodules in the extremities, these tumors can be effectively diagnosed using MRI, though histopathological analysis is generally essential for confirmation. Treatment primarily involves straightforward excision, with notable low complication and recurrence rates.
]]>Life doi: 10.3390/life14030337
Authors: Zhe Xu Min Zhang Zhuo Ning Ze He Fenge Zhang
Natural source zone depletion (NSZD) is the main process of LNAPL (Light Non-Aqueous Phase Liquid) removal under natural conditions. The NSZD rates assessed ranged from 0.55 to 11.55 kg·m−2·a−1 (kilograms per square meter per year) in previous studies. However, most of these data were obtained from sandy sites, with few clayey sites. To gain knowledge of NSZD in clayey soil sites, the study assessed the NSZD of a petroleum hydrocarbon-contaminated clayey soil site in China, combining the concentration gradient method with metagenomic sequencing technology. The results show that the abundance of methane-producing key enzyme mcrA gene in the source zone was more abundant than in background areas, which suggests that there was methanogenesis, the key process of NSZD. The concentration gradients of oxygen and carbon dioxide existed only in shallow soil (<0.7 m), which suggests that there was a thin methane oxidation zone in the shallow zone. The calculated NSZD rates range from 0.23 to 1.15 kg·m−2·a−1, which fall within the moderate range compared to previous NSZD sites. This study expands the knowledge of NSZD in clayey soil and enriches the attenuation rate data for contaminated sites, which is of significant importance in managing petroleum contaminants.
]]>Life doi: 10.3390/life14030336
Authors: Ailton S. S. Júnior Felipe J. Aidar Luiz A. S. Silva Thais de B. Silva Sara F. M. de Almeida Daiane C. S. Teles Waldecy de L. Junior Dulce M. Schimieguel Daniel A. de Souza Ana C. S. Nascimento Enilton A. Camargo Jymmys L. dos Santos Ana M. de O. e Silva Rogéria de S. Nunes Lysandro P. Borges Ana A. M. Lira
(1) Background: Species of the genus Cymbopogon and its essential oil are known for their antioxidant and hypoglycemic effects. This study aimed to investigate the impact of the essential oil of Cymbopogon flexuosus (EOCF), and its major component, citral, on glycemic, lipid, antioxidant parameters, and oxidative stress in a type 1 diabetes (DM1) rat model. (2) Methods: Initially, EOCF was analyzed by Gas chromatography-mass spectrometry (GC-MS) and the antioxidant activity of EOCF and citral was evaluated. Next, male Wistar rats (3 months old, 200–250 g) induced with DM1 using Streptozotocin (STZ) were divided into four groups: negative control supplemented with an 80% Tween solution, two groups of animals supplemented with EOCF (32 mg/kg and 64 mg/kg) and with citral (32 mg/kg), and treated for 14 days. Measurements of blood glucose levels and body weight were taken; after euthanasia, biochemical markers, including lipid profile, uric acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were evaluated. (3) Results: The predominant compounds in EOCF were α-citral (53.21%) and neral (19.42%), constituting 72.63% citral. EOCF showed good antioxidant activity, significantly greater than citral. EOCF supplementation demonstrated a mitigating effect on glycemic, lipid, and hepatic abnormalities induced by DM1. (4) Conclusions: EOCF emerges as a promising therapeutic option for the management of DM1.
]]>Life doi: 10.3390/life14030335
Authors: Paulina Anna Wilanowska Piotr Rzymski Łukasz Kaczmarek
Perchlorate salts, including magnesium perchlorate, are highly toxic compounds that occur on Mars at levels far surpassing those on Earth and pose a significant challenge to the survival of life on this planet. Tardigrades are commonly known for their extraordinary resistance to extreme environmental conditions and are considered model organisms for space and astrobiological research. However, their long-term tolerance to perchlorate salts has not been the subject of any previous studies. Therefore, the present study aimed to assess whether the tardigrade species Paramacrobiotus experimentalis can survive and grow in an environment contaminated with high levels of magnesium perchlorates (0.25–1.0%, 1.5–6.0 mM ClO4− ions). The survival rate of tardigrades decreased with an increase in the concentration of the perchlorate solutions and varied from 83.3% (0.10% concentration) to 20.8% (0.25% concentration) over the course of 56 days of exposure. Tardigrades exposed to 0.15–0.25% magnesium perchlorate revealed significantly decreased body length. Our study indicates that tardigrades can survive and grow in relatively high concentrations of magnesium perchlorates, largely exceeding perchlorate levels observed naturally on Earth, indicating their potential use in Martian experiments.
]]>Life doi: 10.3390/life14030334
Authors: Michela Buonocore Davide De Biase Domenico Sorrentino Antonio Giordano Orlando Paciello Anna Maria D’Ursi
Coronaviruses are highly transmissible and pathogenic viruses for humans and animals. The vast quantity of information collected about SARS-CoV-2 during the pandemic helped to unveil details of the mechanisms behind the infection, which are still largely elusive. Recent research demonstrated that different class I/II human leukocyte antigen (HLA) alleles might define an individual susceptibility to SARS-CoV-2 spreading, contributing to the differences in the distribution of the infection through different populations; additional studies suggested that the homolog of the HLA in cats, the feline leukocyte antigen (FLA), plays a pivotal role in the transmission of viruses. With these premises, this study aimed to exploit a bioinformatic approach for the prediction of the transmissibility potential of two distinct feline coronaviruses (FCoVs) in domestic cats (feline enteric coronavirus (FeCV) and feline infectious peritonitis virus (FIPV)) using SARS-CoV-2 as the reference model. We performed an epitope mapping of nonapeptides deriving from SARS-CoV-2, FeCV, and FIPV glycoproteins and predicted their affinities for different alleles included in the three main loci in class I FLAs (E, H, and K). The predicted complexes with the most promising affinities were then subjected to molecular docking and molecular dynamics simulations to provide insights into the stability and binding energies in the cleft. Results showed the FLA proteins encoded by alleles in the FLA-I H (H*00501 and H*00401) and E (E*01001 and E*00701) loci are largely responsive to several epitopes deriving from replicase and spike proteins of the analyzed coronaviruses. The analysis of the most affine epitope sequences resulting from the prediction can stimulate the development of anti-FCoV immunomodulatory strategies based on peptide drugs.
]]>Life doi: 10.3390/life14030333
Authors: Maria Olinic Florin-Leontin Lazar Horea-Laurentiu Onea Calin Homorodean Mihai Ober Dan Tataru Mihail Spinu Alexandru Achim Dan-Mircea Olinic
Atherosclerosis in a progressive disease that is systemic in nature, and hence the simultaneous presentation of coronary artery disease (CAD) and peripheral artery disease (PAD) is not uncommon. As clinically manifested PAD is associated with worse cardiovascular outcomes, the timely identification of subclinical atherosclerosis seems of utmost importance. Ultrasonography (US) is an ideal imaging modality for assessing PAD that is easy to use, accurate, widely available and avoids unnecessary exposure to radiation. Several US parameters have been proposed in the assessment of PAD, with varying prognostic usefulness, depending on disease location. The aim of this review is to summarize the most important evidence available on the association between US-detected atherosclerosis in different vascular sites and the presence and severity of CAD, as well as the impact of the early detection of PAD on the outcomes of patients presenting with CAD.
]]>Life doi: 10.3390/life14030332
Authors: Jae Wan Yoo Geun-Young Park Hae-Yeon Park Yeun Jie Yoo Mi-Jeong Yoon SeungYup Song Kyung Hyun Park Hooman Lee Sangui Choi Sun Im Seong Hoon Lim
Background: We aimed to develop a consensus on the need for and priorities of exercise to treat preexisting sarcopenia with hemiplegic stroke. Methods: A modified three-round Delphi study was conducted. The panelists responded to the questionnaire on a 7-point Likert scale. Responses were returned with descriptive statistics in the next round. Consensus was defined as >75% agreement (score of 5–7) with a median > 5. The percentage of strong agreement (score of 6–7) and Kendall’s coefficient of concordance were calculated to demonstrate a more refined interpretation of the consensus. Results: Fifteen panelists contributed to all rounds. The need for exercise was demonstrated. The consensus was reached on 53 of 58 items in the first round and all items in the second and final rounds. The percentage of strong agreement was high for all but eight items. Conclusions: This study is the first Delphi study to investigate the need for and priorities of exercise for treating preexisting sarcopenia in stroke hemiplegia. We present a standard recommendation including 57 priorities and a strong recommendation including 49 priorities. The eight items that were excluded reflected factors that are less important to hemiplegic patients with poor balance, cognitive decline, or mental vulnerability.
]]>Life doi: 10.3390/life14030331
Authors: Thomas M. H. Hope Sasha Ondobaka Haya Akkad Davide Nardo Katerina Pappa Cathy J. Price Alexander P. Leff Jennifer T. Crinion
Anomia, or difficulty naming common objects, is the most common, acquired impairment of language. Effective therapeutic interventions for anomia typically involve massed practice at high doses. This requires significant investment from patients and therapists. Aphasia researchers have increasingly looked to neurostimulation to accelerate these treatment effects, but the evidence behind this intervention is sparse and inconsistent. Here, we hypothesised that group-level neurostimulation effects might belie a more systematic structure at the individual level. We sought to test the hypothesis by attempting to predict the immediate (online), individual-level behavioural effects of anodal and sham neurostimulation in 36 chronic patients with anomia, performing naming and size judgement tasks. Using clinical, (pre-stimulation) behavioural and MRI data, as well as Partial Least Squares regression, we attempted to predict neurostimulation effects on accuracies and reaction times of both tasks. Model performance was assessed via cross-validation. Predictive performances were compared to that of a null model, which predicted the mean neurostimulation effects for all patients. Models derived from pre-stimulation data consistently outperformed the null model when predicting neurostimulation effects on both tasks’ performance. Notably, we could predict behavioural declines just as well as improvements. In conclusion, inter-patient variation in online responses to neurostimulation is, to some extent, systematic and predictable. Since declines in performance were just as predictable as improvements, the behavioural effects of neurostimulation in patients with anomia are unlikely to be driven by placebo effects. However, the online effect of the intervention appears to be as likely to interfere with task performance as to improve it.
]]>Life doi: 10.3390/life14030330
Authors: Christian Schach Daniel Lavall Nicola Voßhage Thomas Körtl Christine Meindl Ekrem Ücer Okka Hamer Lars S. Maier Rolf Wachter Samuel Sossalla
Background: Arrhythmia-induced cardiomyopathy (AIC) is characterized by the reversibility of left ventricular (LV) systolic dysfunction (LVSD) after rhythm restoration. This study is a cardiac magnetic resonance tomography substudy of our AIC trial with the purpose to investigate whether left ventricular fibrosis affects the time to recovery (TTR) in patients with AIC. Method: Patients with newly diagnosed and otherwise unexplainable LVSD and tachyarrhythmia were prospectively recruited. LV ejection fraction (LVEF) was measured by echocardiography at baseline and 2, 4, and 6 months after rhythm control, and stress markers were assessed. After initial rhythm control, LV fibrosis was assessed through late gadolinium enhancement (LGE). Patients were diagnosed with AIC if their LVEF improved by ≥15% (or ≥10% when LVEF reached ≥50%). Non-responders served as controls (non-AIC). Results: The LGE analysis included 39 patients, 31 of whom recovered (AIC). LV end-systolic diameters decreased and LVEF increased during follow-up. LV LGE content correlated positively with TTR (r = 0.63, p = 0.003), with less LGE favoring faster recovery, and negatively with ΔLVEF (i.e., LVEF at month 2 compared to baseline) as a marker of fast recovery (r = −0.55, p = 0.012), suggesting that LV fibrosis affects the speed of recovery. Conclusion: LV fibrosis correlated positively with the time to recovery in patients with AIC. This correlation may help in the estimation of the recovery period and in the optimization of diagnostic and therapeutic strategies for patients with AIC.
]]>Life doi: 10.3390/life14030329
Authors: Chiahui Yen Ethan P. Valentine Ming-Chang Chiang
This review explores the pivotal role of attention in everyday life, emphasizing the significance of studying attention-related brain functions. We delve into the development of methodologies for investigating attention and highlight the crucial role of brain neuroimaging and transcranial magnetic stimulation (TMS) in advancing attention research. Attention optimization theory is introduced to elucidate the neural basis of attention, identifying key brain regions and neural circuits involved in attention processes. The theory further explores neuroplasticity, shedding light on how the brain dynamically adapts and changes to optimize attention. A comprehensive overview of TMS is provided, elucidating the principles and applications of this technique in affecting brain activity through magnetic field stimulation. The application of TMS in attention research is discussed, outlining how it can be employed to regulate attention networks. The clinical applications of TMS are explored in attention-deficit/hyperactivity disorder (ADHD) and depression. TMS emerges as an effective clinical treatment for ADHD, showcasing its potential in addressing attention-related disorders. Additionally, the paper emphasizes the efficacy of TMS technology as a method for regulating depression, further underlining the versatility and therapeutic potential of TMS in clinical settings. In conclusion, this review underscores the interdisciplinary approach to attention research, integrating neuroimaging, neuroplasticity, and TMS. The presented findings contribute to our understanding of attention mechanisms and highlight the promising clinical applications of TMS in addressing attention-related disorders. This synthesis of theoretical and practical insights aims to propel further advancements in attention research and its therapeutic applications.
]]>Life doi: 10.3390/life14030328
Authors: Yanni Cai Giulia Pascoletti Peter Zioupos Basil Budair Elisabetta M. Zanetti Trevor J. Ringrose Sarah Junaid
Introduction: Flatfoot is a condition commonly seen in children; however, there is general disagreement over its incidence, characterization and correction. Painful flatfoot accompanied with musculoskeletal and soft tissue problems requires surgery to avoid arthritis in adulthood, the most common surgical approach being two osteotomies to the calcaneus and medial cuneiform bones of the foot. Objectives: This study focuses on the parametrization of these two bones to understand their bone morphology differences in a population sample among 23 normal subjects. Population differences could help in understanding whether bone shape may be an important factor in aiding surgical planning and outcomes. Methods: A total of 45 sets of CT scans of these subjects were used to generate surface meshes of the two bones and converted to be iso-topological meshes, simplifying the application of Generalized Procrustes Analysis and Principal Component Analysis, allowing the main sources of variation between the subjects to be quantified. Results: For the calcaneus, 16 Principal Components (PCs) and, for the medial cuneiform, 12 PCs were sufficient to describe 90% of the dataset variability. The quantitative and qualitative analyses confirm that for the calcaneus PC1 describes the Achilles attachment location and PC2 largely describes the anterior part of the bone. For the medial cuneiform, PC1 describes the medial part of the bone, while PC2 mainly describes the superior part. Conclusion: Most importantly, the PCs did not seem to describe the osteotomy sites for both bones, suggesting low population variability at the bone cutting points. Further studies are needed to evaluate how shape variability impacts surgical outcomes. Future implications could include better surgical planning and may pave the way for complex robotic surgeries to become a reality.
]]>Life doi: 10.3390/life14030326
Authors: Linlin Wang Li Zeng Hailun Jiang Zhuorong Li Rui Liu
We have updated the email addresses of Li Zeng and Hailun Jiang as the two authors’ previous email addresses are no longer in use [...]
]]>Life doi: 10.3390/life14030327
Authors: Angelo Onorato Eugenia Guida Ambra Colopi Susanna Dolci Paola Grimaldi
Germ cell tumors (GCTs) are relatively rare tumors. However, they are the most diagnosed malignancies occurring in the testis among men aged between 15 and 40 years. Despite high aneuploidy and a paucity of somatic mutations, several genomic and transcriptomic assays have identified a few significantly mutated somatic genes, primarily KIT and K-RAS. The receptor Tyrosine Kinase (RTK) pathway and the downstream related Mitogen-Activated Protein Kinase (MAPK) cascades are crucial signal transduction pathways that preside over various cellular processes, including proliferation, differentiation, apoptosis, and responses to stressors. They are well described in solid malignancies, where many of the involved factors are used as prognostic molecular markers or targets for precision therapy. This narrative review focused, in the first part, on PGCs’ survival/proliferation and differentiation and on the genetic and epigenetic factors involved in the pathogenesis of testicular germ cell tumors (TGCTs) and, in the second part, on the most recent investigations about the KIT-RAS pathway in TGCTs and in other cancers, highlighting the efforts that are being made to identify targetable markers for precision medicine approaches.
]]>Life doi: 10.3390/life14030325
Authors: Jose R. Conejo-Garcia Carmen M. Anadon Luis U. Lopez-Bailon Ricardo A. Chaurio
Immuno-oncology has traditionally focused on conventional MHC-restricted αβ T cells. Yet, unconventional γδ T cells, which kill tumor cells in an MHC-unrestricted manner, display characteristics of effector activity and stemness without exhaustion and are nearly universally observed in human gynecologic malignancies, correlating with improved outcomes. These cells do not have a clear counterpart in mice but are also found in the healthy female reproductive tract. Interventions that modulate their in vivo activity, or cellular therapies utilizing γδ T cells as an allogeneic, “off-the-shelf” platform (e.g., for chimeric antigen receptor expression) hold significant potential against challenging tumors like ovarian cancer, which has been stubbornly resistant to the immune checkpoint inhibitors that change the landscape of other human tumors. Here, we discuss recent discoveries on the specific populations of γδ T cells that infiltrate human gynecologic cancers, their anti-tumor activity, and the prospect of redirecting their effector function against tumor cells to develop a new generation of immunotherapies that extends beyond the traditional αβ T cell-centric view of the field.
]]>Life doi: 10.3390/life14030324
Authors: Roman Zelentsov Liliya Poskotinova Alexandra Moiseeva Alexander V. Kudryavtsev
The diagnostic value of the computer accommodation method remains insufficiently studied. Accommodative and refractive error is a common problem, accounting for 23% of the world’s population. The aim of the study was to investigate the objective parameters of accommodative insufficiency in young people with and without myopia. A cross-sectional study was carried out using a random sample of 116 of university students at the age of 21–23 years. Normal ranges for accommodation parameters in non-myopic participants were defined by 10th and 90th percentile values. The normal ranges were from −0.17 to −0.38 conventional units (c.u.) for accommodative response coefficient (ARC), from 0.08 to 0.41 c.u. for deviation of ARC (σARC), from 0.0 to 0.43 c.u. for accommodogram growth coefficient (AGC), from 54.26 to 58.55 microfluctuations per minute (mcf/min) for coefficient of microfluctuations (CMF), and from 2.58 to 5.26 c.u. for deviation of CMF (σCMF). Signs of computer visual syndrome were observed in 40.9% of non-myopic participants, eye strain in 11.9%, accommodation cramp in 4.5%, and absence or little accommodative response in 3.6%. Therefore, computer accommodation assessment allowed the detection of young people with an increased risk of myopia among those without this ophthalmic pathology.
]]>Life doi: 10.3390/life14030323
Authors: José Alfredo Aguayo-Guerrero Lucía Angélica Méndez-García Helena Solleiro-Villavicencio Rebeca Viurcos-Sanabria Galileo Escobedo
Sucralose is a food additive initially used to mitigate glycemic peaks and calorie intake in patients with diabetes and obesity. Although sucralose has been considered safe for human consumption, the World Health Organization (WHO) issued a global alert in 2023 concerning the potential health implications of this artificial sweetener. This review aims to comprehensively explore the effects of sucralose intake on human health by understanding sucralose absorption, metabolism, and excretion. We also outline the role of the sweet taste 1 receptor 3 (T1R3) in mediating sucralose-dependent signaling pathways that regulate satiety, incretin release, and insulin response. Finally, we discuss the impact of sucralose on microbiome dysbiosis, inflammatory response origin, liver damage, and toxicity. Gaining a deeper understanding of the manifold effects of sucralose on human physiology will help promote further studies to ensure its consumption is deemed safe for a broader population, including children, adolescents, and pregnant women.
]]>Life doi: 10.3390/life14030322
Authors: Nan Hu Yingdong Li Meizhang Wang Haoyu Ji Xian Zhang Baolong San Hongyue Shi
Many amphibian behaviors and physiological functions adapt to daily environmental changes through variations in circadian rhythms. However, these adaptations have yet to be reported in Dybowski’s frog (Rana dybowskii). We aimed to elucidate the dynamic changes in the behavior and gut microbiota of R. dybowskii within a 24 h cycle during their migration to hibernation sites. Thus, we monitored their behavior at 4 h intervals and collected samples for microbiome analysis. We found that the juvenile frogs arrived at hibernation sites earlier than the adults. Among the adults, the male frogs arrived earlier. The richness and diversity of the gut microbiota in the adult R. dybowskii were lowest at 14:00. At 6:00, the differences between the males and females were most significant. At 18:00, there was an increase in the activity of Bacteroides, Coprobacillus, Ruminococcus, and Dorea in the intestinal tracts of the male frogs, whereas in the intestinal tract of the female frogs, there was an increase in the activity of Pseudoramibacter_Eubacterium, Desulfovibrio, Anaerotruncus, and PW3. This indicated diurnal rhythmic variations in the gut microbiota and significant sex-based differences in the microbial activity at different time points. Our findings contribute to the understanding of the circadian rhythm of R. dybowskii and provide crucial insights into improving breeding strategies.
]]>Life doi: 10.3390/life14030320
Authors: Lysandro Pinto Borges Pamela Chaves de Jesus Jessiane Bispo de Souza Deise Maria Rego Rodrigues Silva Pedro Henrique Macedo Moura Ronaldy Santana Santos Marina dos Santos Barreto Adriana Gibara Guimarães Lucas Alves da Mota Santana Dennyson Leandro Mathias da Fonseca Ikaro Daniel de Carvalho Barreto Breno de Mello Silva Carla Raquel Pereira Oliveira Karla Freire Rezende Naira Horta Melo Elenalda Ferreira dos Santos Carmem Lúcia Matias de Queiroz Lucia Helena Modesto Xavier Otávio Cabral-Marques Eloia Emanuelly Dias Silva
Background: Diabetes Mellitus (DM) is an important chronic disease that occurs worldwide. Aims: This study aims to investigate how the use of the FreeStyle® Libre system in Unified Health System (SUS) patients impacts diabetes parameters in patients who receive education on proper insulin administration and the use of the continuous monitoring device, as well as how this affects patients without any concomitant multidisciplinary support in Sergipe, Brazil. Methods: We conducted a prospective randomized study in a diabetes clinic in Sergipe, Brazil, using the flash method FreeStyle® Libre (Abbott). The participants were divided into two groups: one receiving diabetes education on CGM (continuous glucose monitoring), while the other did not. Before the intervention, the patient’s treatment motivation and quality of life were assessed using a questionnaire, and baseline levels of glycated hemoglobin were measured using high-performance liquid chromatography (HPLC) and the point of care AlereTM Afinion with boronate fixation. We compared first- and second-phase data with respect to glycated hemoglobin, mean interstitial blood glucose, time on and above target for hypoglycemic and hyperglycemic events, and mean hypoglycemic duration. Results: In group A, which received the diabetes education intervention, there was a significant reduction in average HbA1c levels from 8.6% to 7.9% after 3 months (p = 0.001). However, there was no significant difference in average glycemic values. Time above target decreased significantly from 50.62% to 29.43% (p = 0.0001), while time below target decreased from 22.90% to 20.21% (p = 0.002). There was no significant change in the number of hypoglycemic events, but the duration of hypoglycemia decreased significantly from 130.35 min to 121.18 min after 3 months (p = 0.0001). In Group B, there was no significant difference in mean HbA1c levels before (7.07%) and after (7.28%) sensor installation. This group maintained lower HbA1c levels compared to the other group. Average blood glucose levels also remained similar before (148.37 mg/dL) and after (154.65 mg/dL) the intervention. Although the time above the target glucose level increased significantly from 35.94% to 48.17%, the time at target decreased from 50.40% to 37.97%. No significant changes were observed in the time below target, the number of hypoglycemic events, or the duration of hypoglycemia. Conclusions: Our findings indicate that utilizing continuous glucose monitoring technology can enhance glycemic control, particularly in motivated, educated, low-income patients dependent on the SUS. To achieve positive results with FreeStyle Libre, it is imperative to allocate resources for multidisciplinary support.
]]>Life doi: 10.3390/life14030321
Authors: Jakub Caputa Maciej Wielgosz Daria Łukasik Paweł Russek Jakub Grzeszczyk Michał Karwatowski Szymon Mazurek Rafał Frączek Anna Śmiech Ernest Jamro Sebastian Koryciak Agnieszka Dąbrowska-Boruch Marcin Pietroń Kazimierz Wiatr
The primary objective of this research was to enhance the quality of semantic segmentation in cytology images by incorporating super-resolution (SR) architectures. An additional contribution was the development of a novel dataset aimed at improving imaging quality in the presence of inaccurate focus. Our experimental results demonstrate that the integration of SR techniques into the segmentation pipeline can lead to a significant improvement of up to 25% in the mean average precision (mAP) metric. These findings suggest that leveraging SR architectures holds great promise for advancing the state-of-the-art in cytology image analysis.
]]>Life doi: 10.3390/life14030319
Authors: Astrid De Wolf Elise Nauwynck Jesse Vanbesien Willem Staels Jean De Schepper Inge Gies
Childhood obesity, affecting 29% of 7–9-year-olds across 33 European countries, is a significant public health challenge. Its persistence into adulthood poses grave health risks influenced by genetic, environmental, and socio-economic factors. Belgium introduced a new care pathway in December 2023, based on the Edmonton Obesity Staging System for Pediatrics (EOSS-P), addressing four health domains and staging obesity severity. This pathway operates across three levels: primary care physicians, Paediatric Multidisciplinary Obesity Management Centres (PMOCs), and Centers of Expertise for Paediatric Obesity Management (CEPOs). Each stage of EOSS-P demands tailored interventions. Early stages involve dietary interventions, physical activity promotion, and behavior modifications. As obesity severity progresses, treatments intensify, encompassing psychological support, anti-obesity medications, and, in some cases, bariatric surgery. Throughout these stages, the involvement of multidisciplinary teams is crucial, emphasizing family-based approaches and continuous monitoring. This article provides detailed guidelines for healthcare professionals, delineating interventions and recommendations tailored to each EOSS-P stage. It emphasizes a holistic approach that extends beyond BMI-based diagnosis, promoting personalized care and prompt escalations between care levels, thereby ensuring optimal management of childhood obesity. This comprehensive framework aims to address the complexities of childhood obesity, emphasizing the importance of timely and targeted interventions for better health outcomes.
]]>Life doi: 10.3390/life14030318
Authors: Christian Smolle Judith C. J. Holzer-Geissler Patrick Mandal Jessica Schwaller Gert Petje Johannes Rois Lars-Peter Kamolz Werner Girsch
The vascularized fibula transfer is a well-established technique for extremity reconstruction, but operative planning and patient selection remains crucial. Although recently developed techniques for bone reconstruction, such as bone segment transfer, are becoming increasingly popular, bone defects may still require vascularized bone grafts under certain circumstances. In this study, 41 cases, 28 (68%) men and 13 (32%) women (median age: 40 years), were retrospectively analyzed. Therapy-specific data (flap vascularity [free vs. pedicled] size in cm and configuration [single- vs. double-barrel], mode of fixation [internal/external]) and potential risk factors were ascertained. Indications for reconstruction were osteomyelitis at host site (n = 23, 55%), pseudarthrosis (n = 8, 20%), congenital deformity (n = 6, 15%), traumatic defect, and giant cell tumor of the bone (n = 2, 5% each). Complete healing occurred in 34 (83%) patients after a median time of 6 months. Confounders for prolonged healing were female gender (p = 0.002), reconstruction in the lower limb (p = 0.011), smoking (p = 0.049), and the use of an external fixator (p = 0.009). Six (15%) patients required secondary limb amputation due to reconstruction failure, and one patient had persistent pseudarthrosis at last follow-up. The only risk factor for amputation assessed via logistic regression analysis was preexisting PAOD (peripheral artery occlusive disease; p = 0.008) The free fibula is a reliable tool for extremity reconstruction in various cases, but time to full osseous integration may exceed six months. Patients should be encouraged to cease smoking as it is a modifiable risk factor.
]]>Life doi: 10.3390/life14030317
Authors: Malgorzata Buksinska Piotr Henryk Skarzynski Danuta Raj-Koziak Elzbieta Gos Malgorzata Talarek
(1) Background: One of the possible symptoms of COVID-19 is a sudden loss of smell and taste. The main aim of the study was to evaluate the severity of post-COVID-19 olfactory dysfunction (OD). A secondary aim was to assess the relationship between OD and gustatory (taste) dysfunction (GD). Margins: 2.5 cm (1 inch) at top, bottom, right, and left. (2) Methods: The study group consisted of 81 subjects (16 men and 65 women) aged between 12 and 73 years. All of the patients presented to a center for subjective OD associated with COVID-19. They were tested with a Sniffin’ Sticks test (SST) for OD and a Taste Strip test (TS) for GD. (3) Anosmia was present in 18 participants (22%), hyposmia in 52 (64%), and normosmia in 11 (14%). Some 36% of the patients reported imaginary smells (phantosmia), but it did not correlate with olfactory sensitivity. Comparing the different parts of the SST showed that subjects scored lowest on the threshold part of the test. The results of the discrimination and identification parts of the test were better, implying that if the stimulus is intense enough, incorrect discrimination and identification of odors is less frequent. A sweet taste was the easiest to recognize (78% could do so), while the most difficult to recognize was salty (68%). There were weak and statistically non-significant correlations between olfactory and taste dysfunction. (4) Conclusions: The results suggest that post-COVID-19 olfactory dysfunction was more peripheral than central. Testing patients for the severity of post-COVID-19 OD may help clinicians treat the condition. Because there is no fully effective treatment, research on post-COVID-19 OD is needed.
]]>Life doi: 10.3390/life14030316
Authors: Azer Rizikalo Mirko Maglica Nela Kelam Ilija Perutina Marin Ogorevc Anita Racetin Natalija Filipović Yu Katsuyama Zdenka Zovko Josip Mišković Katarina Vukojević
The purpose of this study was to evaluate the effects of Dab1 gene silencing on the immunoexpression of light chain 3 beta (Lc3b), glucose regulating protein 78 (Grp78), heat shock cognate 71 (Hsc70), mammalian target of rapamycin (mTOR) and lysosomal-associated membrane protein 2A (Lamp2a) in the lung tissue of developing yotari (Dab1−/−) and wild-type (wt) mice. The lung epithelium and mesenchyme of the embryos at gestational days E13.5 and E15.5 were examined using immunofluorescence and semi-quantitative methods. In the pulmonary mesenchyme and epithelium, Grp78 and Lc3b of moderate fluorescence reactivity was demonstrated in wt mice for both evaluated time points, while yotari mice exhibited only epithelial reactivity for the same markers. Mild punctate expression of Hsc70 was observed for both genotypes. A significant difference was present when analyzing mTOR expression, where wt mice showed strong perinuclear staining in the epithelium. According to our data, Dab1 gene silencing may result in autophagy abnormalities, which could then cause respiratory system pathologies via defective lung cell degradation by lysosome-dependent cell elimination.
]]>Life doi: 10.3390/life14030315
Authors: Grigorios Tsigkas Maria Bozika Kassiani-Maria Nastouli Anastasios Apostolos Michaela Routoula Athanasia-Maria Georga Anastasia Latta Angeliki Papageorgiou Michail I. Papafaklis Georgios Leventopoulos Grigoris V. Karamasis Periklis Davlouros
SARS-CoV-2 is responsible for the global coronavirus disease 2019 (COVID-19) pandemic. While the cardiovascular effects of COVID-19 have been thoroughly described, there are limited published studies in the literature establishing a connection between spontaneous coronary artery dissection (SCAD) and COVID-19. Cardiovascular manifestations include, among others, myocarditis, acute myocardial infraction, and thrombosis. In general, SCAD is an uncommon and underdiagnosed cause of acute myocardial infarction (AMI), particularly in younger women and in patients with underlying fibromuscular dysplasia (FMD). Many patients with SCAD often report significant emotional stress, especially in relation with job loss, during the week preceding their cardiac event. Moreover, the COVID-19 pandemic has led to societal stress and increased unemployment, factors that have been associated with cardiovascular morbidity. SCAD emerges as a rare manifestation of coronary artery disease, which a few recent case reports link to COVID-19. The aim of this article is to summarize the relevant data on the pathophysiology of COVID-19 and SCAD along with a review of the reported cases on acute coronary syndrome (ACS) following SARS-CoV2 infection and, thus, to provide insights about the relationship between COVID-19 and SCAD.
]]>Life doi: 10.3390/life14030314
Authors: Wonseok Cho Chang Gyun Kim Eun A Jang Kyu Nam Kim
Subciliary incision is a common approach for facial fracture surgery; however, it has a higher incidence of lower lid ectropion, which can be particularly challenging for beginning surgeons to manage. This study reports the usage of lateral tarsoplasty combined with a full-thickness skin graft (FTSG) to correct severe ectropion following the subciliary approach for infra-orbital rim fractures. We retrospectively reviewed all facial fracture cases involving infra-orbital rim fractures through a subciliary approach treated in our department between March 2021 and May 2023. Electronic medical records and clinical digital photographs of patients who met the inclusion criteria were reviewed. After reviewing 196 cases that used the subciliary approach, we found 6 patients (3.06%; 4 males and 2 females; mean age, 68.5 ± 4.89 years) with postoperative severe ectropion managed using lateral tarsoplasty and FTSG. The mean ectropion development and correction times after facial fracture surgery were 0.78 ± 0.24 and 0.91 ± 0.37 months, respectively. At the 12-month follow-up, all patients showed favorable outcomes, and the position of their lower eyelids was well maintained without ectropion recurrence. Based on these successful outcomes, lateral tarsoplasty combined with FTSG is proposed to be an effective and straightforward method for managing lower eyelid ectropion caused by facial fracture surgery.
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Authors: Ayoola T. Brimmo Ayoub Glia Juan S. Barajas-Gamboa Carlos Abril John Rodríguez Matthew Kroh Mohammad A. Qasaimeh
In operating theaters, ventilation systems are designed to protect the patient from airborne contamination for minimizing risks of surgical site infections (SSIs). Ventilation systems often produce an airflow pattern that continuously pushes air out of the area surrounding the operating table, and hence reduces the resident time of airborne pathogen-carrying particles at the patient’s location. As a result, patient-released airborne particles due to the use of powered tools, such as surgical smoke and insufflated CO2, typically circulate within the room. This circulation exposes the surgical team to airborne infection—especially when operating on a patient with infectious diseases, including COVID-19. This study examined the flow pattern of functional ventilation configurations in view of developing ventilation-based strategies to protect both the patient and the surgical team from aerosolized infections. A favorable design that minimized particle circulation was deduced using experimentally validated numerical models. The parameters adapted to quantify circulation of airborne particles were particles’ half-life and elevation. The results show that the footprint of the outlet ducts and resulting flow pattern are important parameters for minimizing particle circulation. Overall, this study presents a modular framework for optimizing the ventilation systems that permits a switch in operation configuration to suit different operating procedures.
]]>Life doi: 10.3390/life14030312
Authors: Venelin Hubenov Iva Varbacheva Lyudmila Kabaivanova
Anaerobic co-digestion of waste wheat straw and horse manure in two steps was revealed as a promising option for renewable energy production in the form of hydrogen and methane. Addition of waste cooking oils, disposal of which could cause damage to health or the environment, as a third substrate for digestion, is suggested as an approach not only to help handle the increasing volume of food waste worldwide but also to improve process performance. In the present study, waste cooking oil, in a concentration of 5%, appeared to be a positive modulator of anaerobic digestion with the production of hydrogen and did not lead to inhibition of the hydrolysis phase. The overall efficiency of the two-stage anaerobic digestion of the mixture, which contains mainly lignocellulose waste, is positively dependent on thermochemical pretreatment with the alkali reagent (Ca(OH)2), but elevated temperature (55 °C) and cooking oil addition revealed the opportunity to omit the pre-treatment step. Nevertheless, the overall energy production was lower due to the methane production step. However, the addition of waste cooking oils to the process in which lig-nocellulose is not pretreated (V3) led to an increase in the methane production and energy yield compared to V1. The anaerobic digestion of lignocellulosic waste is a complex process and comprises successive degradation pathways and syntrophic microbial associations’ activities, so the division in two reactors ensured suitable conditions for the microorganisms residing in each of them. In this study, along with the production of hydrogen and methane and the separation of the hydrolysis and methanogenesis stages, utilization of agriculture- and kitchen-generated wastes was realized in the context of waste-to-energy sustainable production methods.
]]>Life doi: 10.3390/life14030311
Authors: Shaik Ismail Mohammed Thangameeran Po-Kai Wang Hock-Kean Liew Cheng-Yoong Pang
The intricate relationship between alcohol consumption and intracerebral hemorrhage (ICH) presents a nuanced field of study, especially concerning the dose-dependent impact on secondary brain injury (SBI). Recognizing the established risks associated with heavy drinking, this review delves deeper into the less understood territories of low to moderate alcohol consumption. By systematically analyzing recent studies, we uncover critical insights into how varying alcohol intake levels modulate ICH risk through mechanisms such as microglial activation, oxidative stress, and the protective potential of polyphenols. This analysis extends beyond the hypertensive effects of heavy alcohol use to explore the complex molecular pathophysiology involved in alcohol-related ICH. Our findings indicate that while heavy alcohol use unequivocally exacerbates ICH risk, moderate consumption and its associated polyphenols may offer neuroprotective effects against SBI, albeit within a finely balanced threshold. This review highlights the significant gaps in current understanding and underscores the urgent need for targeted research to elucidate these complex interactions. Through this comprehensive examination, we aim to inform more nuanced public health policies and intervention strategies, taking into account the diverse effects of alcohol consumption on ICH risk.
]]>Life doi: 10.3390/life14030310
Authors: Jia-Yuan Zhang Szu-Kai Fu Hsia-Ling Tai Kuo-Wei Tseng Chia-Yu Tang Chia-Hsien Yu Chang-Chi Lai
(1) Background: Years of research have identified ischemic preconditioning (IPC) as a crucial endogenous protective mechanism against myocardial ischemia–reperfusion injury, enhancing the myocardial cell’s tolerance to subsequent ischemic damage. High-intensity interval training (HIIT) is promoted by athletes because it reduces exercise duration and improves metabolic response and cardiopulmonary function. Our objective was to evaluate and compare whether HIIT and IPC could reduce myocardial ischemia and reperfusion injury in rats. (2) Methods: Male Sprague-Dawley rats were divided into four groups: sham surgery, coronary artery occlusion (CAO), high-intensity interval training (HIIT), and ischemic preconditioning (IPC). The CAO, HIIT, and IPC groups experienced 40 min of coronary artery occlusion followed by 3 h of reperfusion to induce myocardial ischemia–reperfusion injury. Subsequently, the rats were sacrificed, and blood samples along with cardiac tissues were examined. The HIIT group received 4 weeks of training before surgery, and the IPC group underwent preconditioning before the ischemia–reperfusion procedure. (3) Results: The HIIT and IPC interventions significantly reduced the extent of the myocardial infarction size and the levels of serum troponin I and lactate dehydrogenase. Through these two interventions, serum pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, were significantly decreased, while the anti-inflammatory cytokine IL-10 was increased. Furthermore, the expression of pro-apoptotic proteins PTEN, caspase-3, TNF-α, and Bax in the myocardium was reduced, and the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) was increased, ultimately reducing cellular apoptosis in the myocardium. In conclusion, both HIIT and IPC demonstrated effective strategies with potential for mitigating myocardial ischemia–reperfusion injury for the heart.
]]>Life doi: 10.3390/life14030309
Authors: Scott Auerbach Beana Puka Upendarrao Golla Ilyas Chachoua
Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs’ emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.
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Authors: Antonio Desai Dana Shiffer Mauro Giordano Alice Giotta Lucifero Elena Generali Francesco Reggiani Marta Calatroni Gabriele Savioli Sabino Luzzi Antonio Voza
Background: Traumatic brain injury (TBI) in the elderly is a noteworthy pathology due to the exponential increase in population age, and the effects of antiplatelet and anticoagulation on patients’ outcomes are still a matter of dispute. The aim of the present study was to evaluate the impact of various antithrombotic agents on patients with mild TBI, focusing on the risk of intracranial bleeding (ICH) and length of hospitalization (LOS). Methods: A retrospective analysis was conducted, including patients with a diagnosis of TBI admitted to the Emergency Department between 2021 and 2022. Patients were classified according to the concurrent antithrombotic therapy as aspirin (ASA), antiplatelets, direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH). The primary outcome was the ICH occurrence, while the secondary outcome was the LOS. The statistical analysis was performed via logistic regression models in R and STATA 13.1 software. Fisher’s exact test was used for the statistical significance. Results: 267 patients with mild TBI were included; 148 were not on antithrombotic agents, 43 were on aspirin, 33 on DOACs, 5 on LMWH, 22 on antiplatelets, and 16 on VKA. Out of the total, 9 patients experienced ICH, none of which were on DOACs, LMWH, or VKA, but 4—out of 65—were on antiplatelets, and 5—out of 148—were not on antithrombotic therapies. Patients not on antithrombotic therapy had the shortest LOS at 0.46 days, while those on VKA had the longest LOS at 1.19 days; similar trends were observed for patients on DOAC and LMWH. Conclusions: The results reveal that TBI patients on anticoagulants/antiplatelets had longer hospital stays compared with those on aspirin alone. Notably, VKA was the strongest predictor for an extended LOS. Regarding ICH, patients taking only aspirin were twice as likely to experience bleeding compared with those on anticoagulants/antiplatelets. However, to achieve statistically significant evidence, further research with a larger cohort of patients is needed.
]]>Life doi: 10.3390/life14030307
Authors: Leonard Jung Gilbert Georg Klamminger Bert Bier Elke Eltze
Over the last century, the narrative of cervical cancer history has become intricately tied to virus research, particularly the human papillomavirus (HPV) since the 1970s. The unequivocal proof of HPV’s causal role in cervical cancer has placed its detection at the heart of early screening programs across numerous countries. From a historical perspective, sexually transmitted genital warts have been already documented in ancient Latin literature; the remarkable symptoms and clinical descriptions of progressed cervical cancer can be traced back to Hippocrates and classical Greece. However, in the new era of medicine, it was not until the diagnostic–pathological accomplishments of Aurel Babeş and George Nicolas Papanicolaou, as well as the surgical accomplishments of Ernst Wertheim and Joe Vincent Meigs, that the prognosis and prevention of cervical carcinoma were significantly improved. Future developments will likely include extended primary prevention efforts consisting of better global access to vaccination programs as well as adapted methods for screening for precursor lesions, like the use of self-sampling HPV-tests. Furthermore, they may also advantageously involve additional novel diagnostic methods that could allow for both an unbiased approach to tissue diagnostics and the use of artificial-intelligence-based tools to support decision making.
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Authors: Liliana Mititelu-Tartau Maria Bogdan Liliana Lăcrămioara Pavel Ciprian Rezus Cezar Ilie Foia Nicoleta Dima Irina Luciana Gurzu Ana-Maria Pelin Beatrice Rozalina Buca
Compelling evidence indicates that nitric oxide (NO) exerts a significant influence on the central nervous system, participates in the modulation of neurotransmitter release, contributes to the regulation of cognitive functions, and plays a crucial role in modulating various aspects of neural activity. We aimed to explore the influence of two NO donors, molsidomine (MSD) and V-pyrro/NO, on the innate spontaneous psychomotor abilities and short-term memory in rats. Using an actimeter test, the locomotor activity, stress-sensitive behavior, and anxiety level were investigated. The influence on the animal`s cognitive functions was evaluated usingthe Y-maze test to assess the spontaneous alternation percentage, number of arms visited, number of alternations, and the preference index. Four distinct groups of five white male Wistar rats were exposed to the intraperitoneal treatments as follows: Control batch—0.3 mL/100 g of body weight saline solution, Mg batch—200 mg/kbwof magnesium chloride, MSD batch—1 mg/kbw of molsidomine, and V-pyrro/NO batch—5 mg/kbwof V-pyrro/NO. The intraperitoneal administration of MSD resulted in a significant reduction in spontaneous behavior and exploratory skills but was less pronounced than the positive control drug, magnesium chloride. Conversely, treatment with V-pyrro/NO led to only a slight decrease in horizontal movements during the actimeter test. MSD administration, but not V-pyrro/NO, notably increased the rate of spontaneous alternation in the Y-maze test. Additionally, the use of MSD resulted in an increase in the blood level of brain-derived neurotrophic factor and the intensification of the antioxidant enzymes, superoxide dismutase, and glutathione peroxidase activity. In our experimental setup, we demonstrated that MSD exposure led to a decrease in spontaneous behavior, showed anxiolytic effects and antioxidant activity, and improved spatial memory acquisition in rats.
]]>Life doi: 10.3390/life14030305
Authors: Emilia Lazarou Christos Koutsianas Panagiotis Theofilis George Lazaros Dimitrios Vassilopoulos Charalambos Vlachopoulos Costas Tsioufis Massimo Imazio Antonio Brucato Dimitris Tousoulis
Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients.
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