Life, Volume 14, Issue 6 (June 2024) – 75 articles

Purpose of review: New daily persistent headache (NDPH) is a primary headache disorder characterized by the sudden onset of continuous pain and its intractability to treatment. It is more prevalent in the pediatric population than the adult population, but remains understudied and underdiagnosed. The purpose of the current article is to provide a current overview of new daily persistent headache in the pediatric and adolescent population, including history, pathophysiology, clinical findings, current and emerging treatment options, and the results of recent studies and meta-analyses. Recent findings: Despite recent studies and meta-analyses showing significant phenotypic overlap between chronic migraine and NDPH in the pediatric population, multiple recent studies have come to conflicting conclusions about the overlap of medication overuse in headache and pediatric NDPH. Recent studies reveal alterations in neuroimaging, particularly in functional connectivity, in patients with NDPH. Patients frequently remain treatment-refractory even to medications that have historically proven helpful in this population; however, new treatment options, including calcitonin gene-related peptide (CGRP) monoclonal antibodies, may be more effective. Summary: NPDH remains a perplexing and difficult-to-manage condition for both children and adults. Despite a higher prevalence in the pediatric population, there are relatively few studies to guide the evaluation and treatment of NDPH in pediatric and adolescent patients. Early treatment, both pharmacological and non-pharmacological, should be employed to reduce disability. Overall, further studies are needed to better understand pathogenesis and to identify more effective therapeutic strategies, both pharmacological and non-pharmacological. Full article

Methamphetamine (METH) exposure increases locomotor sensitization. However, no study has explored the occurrence of cardiovascular sensitization. The present study, carried out in mice, analyzed the following: (i) METH sensitization extending to systolic blood pressure (SBP); (ii) a potential correlation between ambulatory and cardiovascular sensitization; and (iii) morphological alterations within meso-striatal, meso-limbic and pontine catecholamine systems including c-fos expression. Locomotor activity, SBP and occurrence of morphological alterations of catecholaminergic neurons were assessed in C57Bl/6J mice following daily i.p. injections of either saline or METH (1, 2 or 5 mg/kg) for 5 consecutive days and following 6 days of withdrawal. Reiterated exposure to the lower doses of METH (1 mg/kg and 2 mg/kg) produced in mice locomotor sensitization without altering SBP. In contrast, repeated treatment with the highest dose of METH (5 mg/kg) produced sensitization of SBP in the absence of locomotor sensitization. No morphological alterations but increases in c-fos expression within neurons of locus coeruleus and nucleus accumbens were detected. The present data suggest that METH produces plastic changes that extend beyond the motor systems to alter autonomic regulation. This cardiovascular sensitization occurs independently of locomotor sensitization. The persistency of increased blood pressure may underlie specific mechanisms operating in producing hypertension. Full article

The phosphoinositide 3-kinase (PI3K)/Akt pathway is a key signaling cascade responsible for the regulation of cell survival, proliferation, and metabolism in the ovarian microenvironment. The optimal finetuning of this pathway is essential for physiological processes concerning oogenesis, folliculogenesis, oocyte maturation, and embryo development. The dysregulation of PI3K/Akt can impair molecular and structural mechanisms that will lead to follicle atresia, or the inability of embryos to reach later stages of development. Due to its pivotal role in the control of cell proliferation, apoptosis, and survival mechanisms, the dysregulation of this molecular pathway can trigger the onset of pathological conditions. Among these, we will focus on diseases that can harm female fertility, such as polycystic ovary syndrome and premature ovarian failure, or women’s general health, such as ovarian cancer. In this review, we report the functions of the PI3K/Akt pathway in both its physiological and pathological roles, and we address the existing application of inhibitors and activators for the balancing of the molecular cascade in ovarian pathological environments. Full article

Microglia are the primary innate immune cells of the central nervous system and extensively contribute to brain homeostasis. Dysfunctional or excessive activity of microglia may be associated with several neuropsychiatric disorders, including schizophrenia. Therefore, we examined whether aripiprazole and risperidone could influence the expression of the Cd200–Cd200r and Cx3cl1–Cx3cr1 axes, which are crucial for the regulation of microglial activity and interactions of these cells with neurons. Additionally, we evaluated the impact of these drugs on microglial pro- and anti-inflammatory markers (Cd40, Il-1β, Il-6, Cebpb, Cd206, Arg1, Il-10 and Tgf-β) and cytokine release (IL-6, IL-10). The research was executed in organotypic cortical cultures (OCCs) prepared from the offspring of control rats (control OCCs) or those exposed to maternal immune activation (MIA OCCs), which allows for the exploration of schizophrenia-like disturbances in animals. All experiments were performed under basal conditions and after additional stimulation with lipopolysaccharide (LPS), following the “two-hit” hypothesis of schizophrenia. We found that MIA diminished the mRNA level of Cd200r and affected the OCCs’ response to additional LPS exposure in terms of this parameter. LPS downregulated the Cx3cr1 expression and profoundly changed the mRNA levels of pro- and anti-inflammatory microglial markers in both types of OCCs. Risperidone increased Cd200 expression in MIA OCCs, while aripiprazole treatment elevated the gene levels of the Cx3cl1–Cx3cr1 dyad in control OCCs. The antipsychotics limited the LPS-generated increase in the expression of proinflammatory factors (Il-1β and Il-6) and enhanced the mRNA levels of anti-inflammatory components (Cd206 and Tgf-β) of microglial polarization, mostly in the absence of the MIA procedure. Finally, we observed a more pronounced modulating impact of aripiprazole on the expression of pro- and anti-inflammatory cytokines when compared to risperidone in MIA OCCs. In conclusion, our data suggest that MIA might influence microglial activation and crosstalk of microglial cells with neurons, whereas aripiprazole and risperidone could beneficially affect these changes in OCCs. Full article

A number of Phytophthora species have been identified as destructive plant pathogens and invasive species. They have the potential to affect a wide range of host plants and cause diseases in agricultural and forest ecosystems. Two Phytophthora species from rhizosphere soil samples collected from declining Alnus glutinosa in Bulgaria were isolated in the autumn of 2022. They were identified as Phytophthora polonica and Phytophthora hydropathica according to the DNA sequence analysis of the ITS region, as well as their morphological and physiological characteristics. The pathogenicity of both species to common and gray alder was evaluated by the inoculation of detached leaves and cuttings. Experimental data proved that P. polonica and P. hydropathica are able to cause leaf necrosis not only on A. glutinosa from which they were derived, but also on A. incana. No significant deference in the aggressiveness of the studied isolates from both Phytophthora species against the two tested plants was observed. Therefore, P. polonica and P. hydropathica were determined as potential threats for alder ecosystems in the country. This is the first report for the isolation of P. polonica in Bulgaria and represents the most southeastern point of the species distribution in Europe. Full article

Amino acids are one of the most important building blocks of life. During the biochemical process of translation, cells sequentially connect amino acids via amide bonds to synthesize proteins, using the genetic information in messenger RNA (mRNA) as a template. From a prebiotic perspective (i.e., without enzymatic catalysis), joining amino acids to peptides via amide bonds is difficult due to the highly endergonic nature of the condensation reaction. We show here that amides can be formed in reactions catalyzed by the transition metal sulfides from acetylene, carbon monoxide and ammonia under aqueous conditions. Some α- and β-amino acids were also formed under the same conditions, demonstrating an alternative cyanide-free path for the formation of amino acids in prebiotic environments. Experiments performed with stable isotope labeled precursors, like ¹⁵NH₄Cl and ¹³C-acetylene, enabled the accurate mass spectroscopic identification of the products formed from the starting materials and their composition. Reactions catalyzed using the transition metal sulfides seem to offer a promising alternative pathway for the formation of amides and amino acids in prebiotic environments, bypassing the challenges posed by the highly endergonic condensation reaction. These findings shed light on the potential mechanisms by which the building blocks of life could have originated on early Earth. Full article

Objective evaluations of transverse tarsometatarsal (TMT) hypermobility/instability are lacking. This study aims to radiographically explore the relationship between transverse TMT instability and metatarsus adductus (MA) in hallux valgus (HV). This study retrospectively analyzed 207 feet with varying degrees of HV, employing the distance between the first and second metatarsals (M1-2 distance) to assess transverse TMT instability of the first ray. Participants were categorized into MA and non-MA groups. It was found that the M1-2 distance significantly increased with the hallux valgus angle (HVA) and metatarsus adductus angle (MAA), demonstrating significant differences between the MA and non-MA groups. The measurement of M1-2 distance showed high reliability, and its cutoff value was determined to be 4.05 mm. Additionally, the results suggest that the widening of the M1-2 distance may be a predisposing factor for MA in HV patients, highlighting its role in the pathogenesis of this foot condition. These findings highlight the need for a comprehensive assessment of TMT instability on both the axial and sagittal planes for the surgical planning of HV, particularly when complicated by a large MAA. Based on these insights, reoriented first-TMT arthrodesis might be recommended for HV with significant MA to address potential multiplanar instability. Full article

Background: The purpose of this review is to clarify the natural course of benign paroxysmal torticollis (BPT) and update the information on the relationship of this disorder with migraine. BPT belongs to a group of “episodic syndromes that may be associated with migraine” and is diagnosed according to diagnostic criteria of the International Classification of Headache Disorders, 3rd edition. BPT affects infants and young children and is often an underdiagnosed manifestation since it is not recognized in cases with a benign evolution, requiring a careful differential diagnosis. It was first described by Snyder in 1969 as a movement disorder, a cervical dystonia consequent to labyrinthic disorder. Materials and methods: The PubMed and Web of Science databases were consulted from 1968 to 2024, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Results: In total, 113 articles were identified, 86 selected, and 25 considered for the purpose of this review. Clinical studies were considered in relation to evolution, cognitive, and motor development; genetic and not genetic etiology; the relationship with migraine with and without aura; vestibular migraine; hemiplegic migraine; and paroxysmal vertigo. Full article

Cardiovascular disease is the leading cause of morbidity and mortality in patients with rheumatoid arthritis and systemic lupus erythematosus. Traditional cardiovascular risk factors, although present in lupus and rheumatoid arthritis, do not explain such a high burden of early cardiovascular disease in the context of these systemic connective tissue diseases. Over the past few years, our understanding of the pathophysiology of atherosclerosis has changed from it being a lipid-centric to an inflammation-centric process. In this review, we examine the pathogenesis of atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis, the two most common systemic connective tissue diseases, and consider them as emblematic models of the effect of chronic inflammation on the human body. We explore the roles of the inflammasome, cells of the innate and acquired immune system, neutrophils, macrophages, lymphocytes, chemokines and soluble pro-inflammatory cytokines in rheumatoid arthritis and systemic lupus erythematosus, and the roles of certain autoantigens and autoantibodies, such as oxidized low-density lipoprotein and beta2-glycoprotein, which may play a pathogenetic role in atherosclerosis progression. Full article

Background: The coronavirus disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine: the development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to COVID-19 vaccines’ allergic potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyze the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. Methods: The total number of administrated vaccine doses was extracted on 5 October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines were extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. Results: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta, and 3.1 for Valneva. The most prevalent reported reactions were edema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. Conclusions: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria. Full article

Background and Objectives: Maternal–fetal gestational pathology is one of the biggest challenges in the field of health at this moment. The current study is designed to determine the effects of vitamin D on pregnancy, starting with the idea that impairment of vitamin D status is thought to be correlated with impairment of the newborn’s health. Materials and Methods: In this retrospective study, we tried to establish the link between vitamin D deficiency and maternal characteristics and also how it impacted the clinical status of the newborn. We analyzed a group of 260 patients: 130 pregnant women and 130 newborns, in whom vitamin D status was detected using the serum levels of 25-hydroxyvitamin D (25-(OH)D). Results: The results showed that vitamin D deficiency has a high incidence among pregnant women, as was presented in many important international studies. Our study also showed a positive, direct correlation between the mother’s and newborn’s vitamin D status. Conclusions: Taking into consideration that vitamin D deficiency has been correlated with many complications, both in maternal and newborn health, a serum level determination of 25-(OH)D is necessary in the first trimester of pregnancy, and after that, adequate supplementation is necessary in order to prevent any negative effects. Full article

The oriental fruit fly, Bactrocera dorsalis (Hendel), poses a significant threat to the global fruit industry, causing damage to diverse fruits like citrus, mango, and guava. Chemical pesticides have limited effectiveness, and pesticide residues and pesticide resistance are pressing issues. Therefore, it is essential to develop environmentally friendly pest control methods to address this problem. Behavior-modifying chemicals, including male attractants and intersex protein baits, play a critical role in the control of B. dorsalis. The mature host fruit serves as both an oviposition site and food source under natural conditions, making it a potential attraction source for oriental fruit flies. Orange, Citrus sinensis, is a main host of B. dorsalis, and commercial orange juice is a common attractant for the egg laying of B. dorsalis. Although it can both attract and elicit oviposition behaviors in B. dorsalis adults, its active components are still unclear. This study utilized analytical chemistry, behavioral tests, and electrophysiology to identify the active components of commercial orange juice that attract B. dorsalis, with the aim of providing a reference for the development of behavior-modifying chemical-based techniques to control B. dorsalis. Five compounds with a high abundance were identified via a GC-MS, including D-Limonene, butanoic acid ethyl ester, β-myrcene, linalool, and α-terpineol. Behavioral and electrophysiological experiments uncovered that D-Limonene was the active substance that was the main attractant in the mixture of these five substances, evoking a strong electrophysiological response in adult B. dorsalis. D-Limonene strongly attracts adult B. dorsalis only when they are sexually mature, and the attraction is not rhythmic. Olfaction plays a leading role in the attraction of D-Limonene to adult B. dorsalis, and Orco^−/− mediates the perception of D-Limonene by B. dorsalis. Overall, D-Limonene is one of the key attractant compounds for B. dorsalis in the volatile compounds of commercial orange juice, offering possible support for the development of behavior-modifying chemical-based technology to control B. dorsalis in the future. Full article

(1) Background: Achieving inactive disease decreases long-term joint damage in patients with polyarticular juvenile idiopathic arthritis (polyJIA). The aim of our study was to describe average time to treatment and medication changes over time. (2) Methods: Incident polyJIA patients were retrospectively identified in the InGef and WIG2 longitudinal health claims databases. Drug escalation level changes were evaluated longitudinally and cross-sectionally across three years, as follows: no treatment, glucocorticoids (GCs) and/or non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biological disease-modifying antirheumatic drugs (bDMARDs). (3) Results: On average, newly diagnosed polyJIA patients received their first csDMARD prescription after 128 days and their first bDMARD prescription after 327 days. More patients were treated with csDMARDs than with bDMARDs at diagnosis; however, 24% and 12% (InGef and WIG2 databases, respectively) had no JIA treatment. After three years, 45% and 31% were not taking any treatments, while 18% and 36% were prescribed bDMARDs. Among patients initiating bDMARDs, most continued treatment for three years, with some switching to csDMARDs or discontinuing treatment. Patients treated only with csDMARDs took them longer, compared to those additionally taking other DMARDs. Patients treated with bDMARDs took them about twice as long as the csDMARDs they took prior. (4) Conclusion: A substantial number of patients with polyJIA are not treated as intensively as guidelines recommend. Full article

There is limited information regarding the influence of mangrove growth on the morphological evolution of intertidal mudflats. In this study, Tan Phu Dong district, Tien Giang Province, Vietnam, was selected for investigating how mangrove growth influenced the morphological evolution of an intertidal mudflat. The authors analyzed a series of satellite images (from 1995 and 2022), calculated the enhanced vegetation index (EVI), and documented field visits and observations in pursuit of the objective of the study. The findings revealed that fine-grained sediment accumulated as unconsolidated substratum (US) in the first step of the morphological evolution of the intertidal mudflat, with sediment accumulation of 910 ha in 1995. The US provided favorable conditions for mangroves to grow, while mangrove growth helped compact the US into a compact substratum (CS) in addition to promoting continuous sediment accumulation, increased the vegetation cover of the island, and elevated the substrate density of the remaining areas. As a result, the US and CS decreased steadily between 1995 and 2020, from 910 ha in 1995 to 401 ha in 2020 and from 433 ha in 2005 to 111 ha in 2020, respectively. Meanwhile, the low-vegetation area (LVA), medium-vegetation area (MVA), and high vegetation area (HVA) gradually increased between 1995 and 2015, from 0 ha in 1995 to 104 ha in 2015, from 0 ha in 1995 to 96 ha in 2015, and from 0 ha in 1995 to 114 ha in 2015, respectively. However, the LVA decreased slightly between 2015 and 2020 due to significant sand accumulation, which significantly killed the mangrove trees. In contrast, the MVA and HVA steadily increased between 2015 and 2020, from 96 ha in 2015 to 116 ha in 2020 and from 114 ha in 2015 to 221 ha in 2020, respectively. In 2022, there was a steady increase in HVA (298 ha in 2022), although the date of the 2022 satellite retrieval was 28 January 2022. This study recommends that the technical design of the existing coastal protection works should be revised or adapted to take account of sediment accumulation as the first step in the morphological evolution of the examined intertidal mudflat, rather than mangrove growth. Full article

Recent studies have shown that seagrasses could possess potential applications in the treatment of inflammatory disorders. Five seagrass species (Zostera muelleri, Halodule uninervis, Cymodocea rotundata, Syringodium isoetifolium, and Thalassia hemprichii) from the Great Barrier Reef (QLD, Australia) were thus collected, and their preliminary antioxidant and anti-inflammatory activities were evaluated. From the acetone extracts of five seagrass species subjected to 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging antioxidant assay, the extract of Z. muelleri had the highest activity (half minimal concentration of inhibition (IC₅₀) = 138 µg/mL), with the aerial parts (IC₅₀ = 119 µg/mL) possessing significantly higher antioxidant activity than the roots (IC₅₀ ≥ 500 µg/mL). A human peripheral blood mononuclear cells (PBMCs) assay with bacterial lipopolysaccharide (LPS) activation and LEGENDplex cytokine analysis showed that the aerial extract of Z. muelleri significantly reduced the levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 by 29%, 74%, and 90%, respectively, relative to the LPS treatment group. The aerial extract was thus fractionated with methanol (MeOH) and hexane fraction, and purification of the MeOH fraction by HPLC led to the isolation of 4-hydroxybenzoic acid (1), luteolin (2), and apigenin (3) as its major constituents. These compounds have been previously shown to reduce levels of TNF-α, IL-1β, and IL-6 and represent some of the major bioactive components of Z. muelleri aerial parts. This investigation represents the first study of the antioxidant and anti-inflammatory properties of Z. muelleri and the first isolation of small molecules from this species. These results highlight the potential for using seagrasses in treating inflammation and the need for further investigation. Full article

Recreational team sports have received great acceptance lately, in different populations, indicating encouraging results in health-related quality of life. This study examined the efficacy of a 3-month basketball exercise program on selected indices of health (body mass—BM, body fat—BF, blood pressure—BP), functional capacity (flexibility of lower and upper limbs, balance), and physical fitness (maximum strength of lower limbs, trunk and handgrip, aerobic capacity) in middle-aged individuals. Forty middle-aged individuals (males and females; 40–55 years old) were randomly divided into (a) exercise (EG; n = 20) and (b) control groups (CG; n = 20). The EG followed a 3-month modified basketball exercise program (2 times/week; 24 training units), including different basketball drills with and without the ball (dribbling, passing, pivot, stops, etc.), to improve participants’ health and physical fitness. Repeated measures ANOVA showed that the EG significantly increased their flexibility (17.23–74.88%; p < 0.001), static balance (44.76–54.69%; p < 0.001), and strength of lower limbs and trunk (11.67–13.13%; p < 0.001), while reducing BP (7.31–12%; p < 0.001), heart rate and RPE (5.30–34.37%; p < 0.001), and time during time-up-and-go test (−10.91%; p < 0.001). Handgrip strength, BM, and BF did not change following the program in the EG (p > 0.05). In the CG, the above variables remained stable. In conclusion, this program may be used to eliminate the detrimental effects of aging on health, functional capacity, and physical fitness parameters. Full article

The Ebola virus disease (EVD) is an extremely contagious and fatal illness caused by the Ebola virus. Recently, Uganda witnessed an outbreak of EVD, which generated much attention on various social media platforms. To ensure effective communication and implementation of targeted health interventions, it is crucial for stakeholders to comprehend the sentiments expressed in the posts and discussions on these online platforms. In this study, we used deep learning techniques to analyse the sentiments expressed in Ebola-related tweets during the outbreak. We explored the application of three deep learning techniques to classify the sentiments in 8395 tweets as positive, neutral, or negative. The techniques examined included a 6-layer convolutional neural network (CNN), a 6-layer long short-term memory model (LSTM), and an 8-layer Bidirectional Encoder Representations from Transformers (BERT) model. The study found that the BERT model outperformed both the CNN and LSTM-based models across all the evaluation metrics, achieving a remarkable classification accuracy of 95%. These findings confirm the reported effectiveness of Transformer-based architectures in tasks related to natural language processing, such as sentiment analysis. Full article

Introduction: Due to the complex nature of chronic pain, especially in older adults, a biopsychosocial approach is more effective than an isolated approach for its management. Furthermore, when patients are actively engaged in their pain management, they are more likely to be successful than relying totally on others. Objective: To analyze the self-management strategies currently used by older adults with chronic pain. Method: An integrative review was conducted through seven online databases, searching for scientific studies on this topic published in the last 10 years. Results and conclusion: Fifty-eight studies were included in the final sample. Research on chronic pain self-management for older adults has increased in recent years. Although a diversity of chronic physical painful conditions are being investigated, many conditions are still under-investigated. Online and in-person strategies are currently adopted, demonstrating similar results. Positive results are evidenced by strategies including health promotion, mind control, social participation and take-action fields. Major results come from a combination of strategies focusing on biopsychosocial aspects of pain management. Results include not only the reduction of pain itself, but increased self-efficacy, adoption of health behaviors and improvement of functionality, among others, i.e., improved QoL, despite pain. Full article

Patent foramen ovale (PFO) is a remnant of the foetal circulation resulting from incomplete occlusion of the septum primum and septum secundum. Although prevalent in about 25% of the population, it mainly remains asymptomatic. However, its clinical significance in situations such as cryptogenic stroke, migraine, and decompression illness (DCI) has been well described. Recent randomised clinical trials (RCTs) have demonstrated the efficacy of percutaneous PFO closure over pharmacological therapy alone for secondary stroke prevention in carefully selected patients. Notably, these trials have excluded older patients or those with concurrent thrombophilia. Furthermore, the role of closure in other clinical conditions associated with PFO, like decompression sickness (DCS) and migraines, remains under investigation. Our review aims to summarise the existing literature regarding epidemiology, pathophysiological mechanisms, optimal management, and closure indications for these special patient groups. Full article

Breast cancer is the most frequently diagnosed cancer in women worldwide. According to recent studies, alterations in the microbiota and epigenetic modulations are risk factors for this disease. This systematic review aims to determine the possible associations between the intestinal and mammary microbial populations, epigenetic modifications, and breast cancer. To achieve this objective, we conducted a literature search in the PubMed, Web of Science, and Science Direct databases following the PRISMA guidelines. Although no results are yet available in humans, studies in mice suggest a protective effect of maternal dietary interventions with bioactive compounds on the development of breast tumors in offspring. These dietary interventions also modified the gut microbiota, increasing the relative abundance of short-chain fatty acid-producing taxa and preventing mammary carcinogenesis. In addition, short-chain fatty acids produced by the microbiota act as epigenetic modulators. Furthermore, some authors indicate that stress alters the gut microbiota, promoting breast tumor growth through epigenetic and gene expression changes in the breast tumor microenvironment. Taken together, these findings show the ability of epigenetic modifications and alterations of the microbiota associated with environmental factors to modulate the development, aggressiveness, and progression of breast cancer. Full article

Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma—EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the PTEN tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC. Full article

Multiple Sclerosis (MS) is a demyelinating and chronic disease with variable neurological symptoms. There are different scales that score the level of disability, but only few papers have taken into consideration the 5-times sit-to-stand (5STS) test and the 30 s chair stand test (30CST), which are valid and easily obtainable indicators of other neurological diseases. The aim of our research is to verify the validity, reproducibility, and responsiveness of these tests. Patients afflicted with MS were enrolled in the AISM outpatient facility. The inclusion criterion was an EDSS score less than 6.5. We performed the 5STS, 30CST, and timed 25-foot walk (T25-FW) tests and recorded EDSS scores in the first evaluation. Then, we recorded the performance after 5 days (conducted by a second blind operator to ensure test–retest reproducibility), and the last evaluation was made after 12 sessions of physiotherapy. We recruited 38 patients diagnosed with MS. The results show significant data regarding validity, reproducibility, and responsiveness for both scales. The data argue in favor of adding these tests to the relevant clinical assessments. These two tests are simple, reliable, and easy to administer, and the data confirm that they can be included in the evaluation of patients with MS. Full article

Pulmonary metastasectomy has become a well-established procedure for patients with certain types of solid tumors. Patients are usually scheduled for staged lung metastasectomy in case of primary tumor control, the absence of distant non-lung metastases, and when complete resection is achievable. Nodules are removed with precision resection in order to ensure radical resection with minimal margins; this technique permits good oncological results, preserving the surrounding pulmonary parenchyma and causing minimal distortion compared to staplers. When possible, anatomical resections should be avoided since they are not justified by real oncological advantages and, in the majority of cases, sacrifice too much healthy tissue, possibly leading to inoperability in the case of metachronous relapses. Thus, preserving the maximum amount of pulmonary parenchyma is crucial because repeated metastasectomies are possible and frequent, with no theoretical limits to the number of reinterventions. In our multidisciplinary board team, we support the role of pulmonary metastasectomy as a useful curative therapy, with acceptable morbidity and mortality, with indications to be discussed case-by-case. Full article

This paper describes the in situ spores of the Calamospora type, macerated from sixty-one specimens of calamitean cones belonging to sixteen species of genera, such as the Palaeostachya, Macrostachya, Calamostachys, and Huttonia from the Pennsylvanian Czech Republic period, specifically from the Moscovian/Kasimovian ages (i.e., Duckmantian-Stephanian). The in situ spores were compared to twenty dispersed species of Calamospora. The majority of spores were microspores; however, some cones yielded both micro- and megaspores. Morphological variations of the in situ spores, including the diameter, labrum, contact area, ontogenetic stages, and secondary folds of the exine, are described, including their importance for the classification of calamospores. The relationships of Elaterites, Pteroretis, Vestispora, and some monopseudosaccate spores are discussed. All Paleozoic Calamospora-producing parent plants are summarized. Full article

Psoriasis is a chronic inflammatory disease with specific cutaneous and nail lesions. Recent data has emphasized its systemic nature, highlighting metabolic conditions found in patients. Insulin resistance was identified in adult psoriasis, sometimes related to psoriasis severity. Data regarding this relationship in children are limited. Consequently, we tested the association between the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Psoriasis Area and Severity Index (PASI) using a retrospective dataset of 43 children with various types of psoriasis. First, we attempted to replicate the relationship between the HOMA-IR and PASI. Second, we explored potential associations between these variables and others in the dataset. The results illustrated no association between HOMA-IR and PASI (p-value = 0.512). The exploratory findings hinted at a connection between nail pitting and insulin resistance (p-value = 0.038), yet Bonferroni adjustments suggested the risk of a false-positive finding. Noteworthy associations were found between the HOMA-IR and body mass index (BMI) (p-value = 0.001), the PASI and quality of life impairment (p-value = 0.005), and psoriasis severity and type (p-value = 0.001). The null hypothesis that insulin resistance in children is not positively associated with psoriasis severity cannot be rejected. Pilot estimates of variables and covariates of interest are provided for further confirmatory studies assessing this hypothesis. Full article

Rabbit coccidiosis is caused by infection with one or, more commonly, several Eimeria species that parasitize the hepatobiliary ducts or intestinal epithelium of rabbits. Currently, there are eleven internationally recognized species of rabbit coccidia, with the complete mitochondrial (mt) genomes of six species commonly infecting rabbits having been sequenced and annotated. Eimeria kongi was initially discovered in 2011 and prompted a preliminary study on this species. Through traditional morphological analysis, E. kongi was identified as a novel species of rabbit coccidia. To further validate this classification, we sequenced and annotated its mitochondrial genome. The complete mt genome of E. kongi spans 6258 bp and comprises three cytochrome genes (cytb, cox1, cox3), fourteen gene fragments for the large subunit (LSU) rRNA, and nine gene fragments for the small subunit (SSU) rRNA, lacking transfer RNA (tRNA) genes. Moreover, phylogenetic analysis of the mitochondrial genome sequence of E. kongi revealed its clustering with six other species of rabbit coccidia into a monophyletic group. Additionally, E. irresidua and E. flavescens were grouped within the lineage lacking oocyst residuum, consistent with their morphological characteristics. Consistent with multiple molecular phylogenies, in this investigation, E. kongi was further confirmed as a new species of rabbit coccidia. Our research findings are of great significance for the classification of coccidia and for coccidiosis prevention and control in rabbits. Full article

Introduction: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study aimed to investigate changes in microbiome composition associated with CCC and its metabolic signature by integrating taxonomic and functional information with metabolomics data and in vitro experimental results. Methods: From February 2019 to January 2021, this study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), both with and without a diagnosis of CCC. Bile samples were collected via endoscopic nasobiliary drainages (ENBD) and subjected to DNA extraction, PCR amplification of the bacterial 16S rRNA gene V3-V4 region, and data analysis using QIIME2. In vitro Carboxyfluorescein succinimidyl ester (CFSE) proliferation and Annexin V/PI apoptosis assays were performed to investigate the effects of metabolites on CCC cells. Results: A total of 24 patients were included in the study. Bile fluid analysis revealed a significantly higher abundance of Escherichia coli in the CCC group. Alpha diversity analyses exhibited significant differences between the CCC and non-CCC groups, and Nuclear Magnetic Resonance (NMR) spectroscopy metabolic profiling identified 15 metabolites with significant concentration differences; isoleucine showed the most notable difference. In vitro experiments demonstrated that isoleucine suppressed CCC cell proliferation but did not induce apoptosis. Conclusions: This research underlines the significance of biliary dysbiosis and specific bile metabolites, such as isoleucine, in influencing the development and progression of CCC. Full article

Haemophilia presents a significant challenge to the quality of life of affected individuals. Evaluating the health-related quality of life (HRQoL) of people with haemophilia (PwH) provides a valuable mean of assessing their perception of overall care outcomes, while also identifying influential factors across various age and condition severity demographics. This observational retrospective study determined the HRQoL of 100 adult PwH in Northern Greece through comprehensive analysis and interpretation of their HRQoL levels, particularly in domains concerning their physical, emotional, and mental well-being, obtained through the Haem-A-QoL index questionnaire. Disease severity and young age were significantly associated with the administration of prophylactic treatment (84.2% of patients with severe haemophilia and 65.2% of patients aged 18–30). The mean Haem-A-QoL score was 40.11 ± 17.38, with the lowest HRQoL observed in the 46–60 age group (46.16), and the highest in the ≥61 age groups (35.16). Notably, the ‘Sports/Leisure’ and ‘Physical Health’ domains exhibited the highest scores, in contrast to ‘Family Planning’ and ‘Relationships/Sexuality’. Individuals with mild haemophilia recorded the lowest mean score (39.38), while those with a severe condition exhibited the highest (41.23). Age, disease severity, and physical activity emerged as primary determinants significantly affecting HRQoL outcomes. Full article

Background and objectives: The aim of this study was to evaluate the clinical–pathological profile in young patients with thyroid cancer. Materials and methods: We realized a retrospective study on patients with thyroid neoplasms who underwent surgery at the “Pius Brinzeu” County Clinical Emergency Hospital in Timisoara, Romania. A comparative analysis of some parameters between two groups, young patients (<45 years) versus patients ≥45 years, was performed. Results: A total of 211 patients met the study inclusion criteria, mostly females (86.26%) with a female/male ratio of 6.81:1. In patients <45 years old (25.64%), papillary thyroid carcinoma was identified in 51.85% of cases; in 53.85% of cases, the tumor was >1 cm; 13.46% had extrathyroidal extension (p = 0.0430); 21.15% capsule invasion (p = 0.1756); 23.08% lympho-vascular invasion (p = 0.0048); and 13.46% of cases locoregional nodal invasion (p = 0.0092). Conclusions: Thyroid cancer in young people was associated with chronic lymphocytic thyroiditis and tumor progression parameters, identifying more cases of extrathyroidal extension, locoregional nodal invasion, lympho-vascular invasion and perineural invasion in young patients compared to older ones. For a better understanding of this pathology and to improve diagnosis and therapeutic management, more studies are needed for these patients. Full article

Treatment of IgE-mediated food allergy involves avoiding the food causing the allergic reaction. In association, an action plan for allergic reactions is indicated, sometimes including self-injectable adrenaline. In addition to these dietary and medical implications, there are two equally important ones: nutritional and psychosocial. From a nutritional point of view, it is known that children suffering from food allergy have a growth delay in height and weight compared to their non-allergic peers. Specifically, this condition is directly related to the specific food excluded from the diet, the number of foods excluded and the duration of the elimination diet. From a psychosocial point of view, the child often cannot eat the foods other guests eat. Children with food allergy may perceive an aura of parental anxiety around their mealtime and may be afraid that what they eat could have harmful consequences for their health. Furthermore, children’s and their parents’ quality of life appears to be affected. The need to manage the allergy and the nutritional and psychosocial problems positions the pediatric nutritionist and the child neuropsychiatrist as support figures for the pediatric allergist in managing the child with food allergy. Full article