Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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19 pages, 4721 KiB  
Review
The Global Decline in Human Fertility: The Post-Transition Trap Hypothesis
by Robert John Aitken
Life 2024, 14(3), 369; https://doi.org/10.3390/life14030369 - 11 Mar 2024
Viewed by 1995
Abstract
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 [...] Read more.
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. Full article
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17 pages, 722 KiB  
Article
Adiponectin Gene Polymorphisms: A Case–Control Study on Their Role in Late-Onset Alzheimer’s Disease Risk
by Juraj Javor, Vladimíra Ďurmanová, Kristína Klučková, Zuzana Párnická, Dominika Radošinská, Stanislav Šutovský, Barbora Vašečková, Veronika Režnáková, Mária Králová, Karin Gmitterová, Štefan Zorad and Ivana Shawkatová
Life 2024, 14(3), 346; https://doi.org/10.3390/life14030346 - 7 Mar 2024
Viewed by 953
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Alzheimer's Disease: From Pathogenesis to Therapy)
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11 pages, 545 KiB  
Article
Prospects for Using Computer Accommodography to Predict Myopia Development in Young Adults
by Roman Zelentsov, Liliya Poskotinova, Alexandra Moiseeva and Alexander V. Kudryavtsev
Life 2024, 14(3), 324; https://doi.org/10.3390/life14030324 - 29 Feb 2024
Viewed by 881
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Section Epidemiology)
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17 pages, 1108 KiB  
Review
Interleukin-1 Blockers: A Paradigm Shift in the Treatment of Recurrent Pericarditis
by Emilia Lazarou, Christos Koutsianas, Panagiotis Theofilis, George Lazaros, Dimitrios Vassilopoulos, Charalambos Vlachopoulos, Costas Tsioufis, Massimo Imazio, Antonio Brucato and Dimitris Tousoulis
Life 2024, 14(3), 305; https://doi.org/10.3390/life14030305 - 26 Feb 2024
Viewed by 1169
Abstract
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, [...] Read more.
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. Full article
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10 pages, 413 KiB  
Article
Increased Upper Extremity Muscle Mass in Ambulatory Children with Cerebral Palsy
by Taeyoung Song, Jaewon Kim and Dae-Hyun Jang
Life 2024, 14(3), 303; https://doi.org/10.3390/life14030303 - 26 Feb 2024
Viewed by 770
Abstract
Aim: To compare muscle mass in the upper and lower extremities between ambulatory children with cerebral palsy (CP) and typically developing (TD) children. Materials and Methods: A total of 21 children aged 2 to 12 years with CP and a Gross Motor Function [...] Read more.
Aim: To compare muscle mass in the upper and lower extremities between ambulatory children with cerebral palsy (CP) and typically developing (TD) children. Materials and Methods: A total of 21 children aged 2 to 12 years with CP and a Gross Motor Function Classification System (GMFCS) level of I, II, or III were matched with 21 TD children for age, sex, and body mass index. The lean body mass (LBM) of each extremity was calculated from whole-body dual-energy X-ray absorptiometry. Results: The LBM of the upper extremities was greater in children with CP compared to TD children, and the difference was significant in the GMFCS level II group (1340.6 g vs. 1004.2 g, p = 0.027). There was no significant difference in the LBM of the lower extremities between the CP and TD groups (p = 0.190). The ratio of lower extremity LBM to total extremity LBM was lower in children with CP, while the ratio of upper extremity LBM to total extremity LBM was higher in children with CP (73.2% vs. 78.5% [p < 0.001] and 26.7% vs. 21.5% [p < 0.001], respectively). Conclusions: Ambulatory children with CP, especially in the GMFCS level II group, exhibit greater muscle mass in the upper extremities compared to TD children. Full article
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37 pages, 2103 KiB  
Review
Integrating Artificial Intelligence for Drug Discovery in the Context of Revolutionizing Drug Delivery
by Anita Ioana Visan and Irina Negut
Life 2024, 14(2), 233; https://doi.org/10.3390/life14020233 - 7 Feb 2024
Cited by 4 | Viewed by 5983
Abstract
Drug development is expensive, time-consuming, and has a high failure rate. In recent years, artificial intelligence (AI) has emerged as a transformative tool in drug discovery, offering innovative solutions to complex challenges in the pharmaceutical industry. This manuscript covers the multifaceted role of [...] Read more.
Drug development is expensive, time-consuming, and has a high failure rate. In recent years, artificial intelligence (AI) has emerged as a transformative tool in drug discovery, offering innovative solutions to complex challenges in the pharmaceutical industry. This manuscript covers the multifaceted role of AI in drug discovery, encompassing AI-assisted drug delivery design, the discovery of new drugs, and the development of novel AI techniques. We explore various AI methodologies, including machine learning and deep learning, and their applications in target identification, virtual screening, and drug design. This paper also discusses the historical development of AI in medicine, emphasizing its profound impact on healthcare. Furthermore, it addresses AI’s role in the repositioning of existing drugs and the identification of drug combinations, underscoring its potential in revolutionizing drug delivery systems. The manuscript provides a comprehensive overview of the AI programs and platforms currently used in drug discovery, illustrating the technological advancements and future directions of this field. This study not only presents the current state of AI in drug discovery but also anticipates its future trajectory, highlighting the challenges and opportunities that lie ahead. Full article
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11 pages, 461 KiB  
Article
How Much Does SARS-CoV-2 Infection during Pregnancy Affect the Neonatal Brain, Heart, and Kidney? A Parallel between COVID-19, Vaccination, and Normal Pregnancy
by Daniela Eugenia Popescu, Ana Maria Cristina Jura, Dana Știube, Adrian Ciulpan, Florina Stoica, Simona Ioana Șipoș, Cosmin Cîtu, Florin Gorun and Mărioara Boia
Life 2024, 14(2), 224; https://doi.org/10.3390/life14020224 - 5 Feb 2024
Viewed by 1088
Abstract
During the last decades, a growing number of studies have shown that infections during pregnancy have an important impact on both pregnant women and their fetuses. Our goal was to include newborns from pregnancies with SARS-CoV-2 infection and to investigate the extension of [...] Read more.
During the last decades, a growing number of studies have shown that infections during pregnancy have an important impact on both pregnant women and their fetuses. Our goal was to include newborns from pregnancies with SARS-CoV-2 infection and to investigate the extension of neonatal complications using cardiac, abdominal, and cerebral ultrasonography; hearing testing; and indirect ophthalmoscopy. Likewise, neonates whose mothers were vaccinated against COVID-19 during pregnancy and those from pathology-free pregnancies were examined. A total of 458 mother–newborn dyads were included over a period of 10 months and divided into three groups: the COVID-19 group, vaccine group, and control group. Although six cardiac malformations were found in the COVID-19 group, no correlation was made compared to the vaccine and control group (p = 0.07). Grade 1 intraventricular hemorrhage and hypoxic ischemic encephalopathy were the most prevalent among neonates from mothers with SARS-CoV-2 infection (p = 0.002 and p < 0.001, respectively). The kidney anomaly found to be most frequent in this group was grade 1 unilateral hydronephrosis (p < 0.001). COVID-19 disease during the gestational period had no effect on the auditory or visual function. Our findings highlight the importance of implementing proper infection control practices for future mothers, and by continuing to investigate this topic, we can gather valuable insights that will improve neonatal health in this context. Full article
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21 pages, 1149 KiB  
Review
Mitochondria in Alzheimer’s Disease Pathogenesis
by Allison B. Reiss, Shelly Gulkarov, Benna Jacob, Ankita Srivastava, Aaron Pinkhasov, Irving H. Gomolin, Mark M. Stecker, Thomas Wisniewski and Joshua De Leon
Life 2024, 14(2), 196; https://doi.org/10.3390/life14020196 - 30 Jan 2024
Cited by 1 | Viewed by 3344
Abstract
Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in [...] Read more.
Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in the brain of extracellular plaques of amyloid-β and intracellular tangles of phosphorylated tau. The importance of mitochondrial dysfunction in AD pathogenesis, while previously underrecognized, is now more and more appreciated. Mitochondria are an essential organelle involved in cellular bioenergetics and signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, mitochondrial trafficking, mitochondrial fission, and mitochondrial fusion are dysregulated in the AD brain. Excess fission and fragmentation yield mitochondria with low energy production. Reduced glucose metabolism is also observed in the AD brain with a hypometabolic state, particularly in the temporo-parietal brain regions. This review addresses the multiple ways in which abnormal mitochondrial structure and function contribute to AD. Disruption of the electron transport chain and ATP production are particularly neurotoxic because brain cells have disproportionately high energy demands. In addition, oxidative stress, which is extremely damaging to nerve cells, rises dramatically with mitochondrial dyshomeostasis. Restoring mitochondrial health may be a viable approach to AD treatment. Full article
(This article belongs to the Special Issue Mitochondria: Biological Targets for Fighting Disease)
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15 pages, 1517 KiB  
Article
Chemical Analysis and Biological Activities of Extracts Isolated from Symbiotic L. japonicus Plants
by Foteini D. Kalousi, Michail Tsakos, Christina N. Nikolaou, Achilleas Georgantopoulos, Anna-Maria G. Psarra and Daniela Tsikou
Life 2024, 14(2), 189; https://doi.org/10.3390/life14020189 - 27 Jan 2024
Viewed by 1026
Abstract
Plants produce a wide variety of secondary metabolites, including compounds with biological activities that could be used for the treatment of human diseases. In the present study, we examined the putative production of bioactive molecules in the legume plant Lotus japonicus, which engages [...] Read more.
Plants produce a wide variety of secondary metabolites, including compounds with biological activities that could be used for the treatment of human diseases. In the present study, we examined the putative production of bioactive molecules in the legume plant Lotus japonicus, which engages into symbiotic relationships with beneficial soil microorganisms. To monitor the production of secondary metabolites when the plant develops beneficial symbiotic relationships, we performed single and double inoculations with arbuscular mycorrhizal fungi (AMF) and nitrogen-fixing Rhizobium bacteria. Plant extracts from non-inoculated and inoculated plants were chemically characterized and tested for anti-proliferative, apoptotic, and anti-inflammatory effects on human HEK-293 cells. Both shoot and root extracts from non-inoculated and inoculated plants significantly reduced the HEK-293 cell viability; however, a stronger effect was observed when the root extracts were tested. Shoot and root extracts from Rhizobium-inoculated plants and shoot extracts from AMF-inoculated plants showed apoptotic effects on human cells. Moreover, both shoot and root extracts from AMF-inoculated plants significantly reduced TNFα-induced NF-κB transcriptional activity, denoting anti-inflammatory activity. These results suggest that symbiotic L. japonicus plants are enriched with metabolites that have interesting biological activities and could be further explored for putative future use in the pharmaceutical sector. Full article
(This article belongs to the Special Issue Plants as a Promising Biofactory for Bioactive Compounds: 2nd Edition)
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11 pages, 825 KiB  
Article
The Association between Abstinence Period and Semen Parameters in Humans: Results in Normal Samples and Different Sperm Pathology
by Min Xie, Silvan Hämmerli and Brigitte Leeners
Life 2024, 14(2), 188; https://doi.org/10.3390/life14020188 - 27 Jan 2024
Viewed by 2804
Abstract
Background: The impact of sexual abstinence on sperm quality, particularly in pathological cases, is a subject of debate. We investigated the link between abstinence duration and semen quality in both normal and pathological samples. Methods: We analyzed semen samples from 4423 men undergoing [...] Read more.
Background: The impact of sexual abstinence on sperm quality, particularly in pathological cases, is a subject of debate. We investigated the link between abstinence duration and semen quality in both normal and pathological samples. Methods: We analyzed semen samples from 4423 men undergoing fertility evaluation, comprising 1256 samples from healthy individuals and 3167 from those with conditions such as oligozoospermia, asthenozoospermia, teratozoospermia, or a combination of these factors, namely oligoasthenoteratozoospermia (OAT). Parameters including sperm concentration, the percentage of progressively motile spermatozoa, total motile sperm count, and the percentage of spermatozoa with normal morphology were assessed at various abstinence durations (each day, 0–2, 3–7, and >7 days). Results: Extended abstinence correlated with higher sperm concentration overall (p < 0.001), except in oligozoospermia. Longer abstinence reduced progressive motility in normal (p < 0.001) and teratozoospermic samples (p < 0.001). Shorter abstinence was linked to higher morphologically normal sperm in normal samples (p = 0.03), while longer abstinence did so in oligoasthenoteratozoospermic samples (p = 0.013). Conclusion: The findings suggest that a prolonged abstinence time is linked to higher sperm concentration, while optimal sperm motility is observed after shorter abstinence periods. However, results regarding morphology remain inconclusive. Recommendations on abstinence duration should be tailored based on the specific parameter requiring the most significant improvement. Full article
(This article belongs to the Special Issue Novel Therapeutics for Male Infertility)
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10 pages, 5435 KiB  
Article
Gut Microbiota Is Not Essential for Survival and Development in Blattella germanica, but Affects Uric Acid Storage
by Rebeca Domínguez-Santos, Joaquín Baixeras, Andrés Moya, Amparo Latorre, Rosario Gil and Carlos García-Ferris
Life 2024, 14(1), 153; https://doi.org/10.3390/life14010153 - 21 Jan 2024
Viewed by 1205
Abstract
Cockroaches harbor two coexisting symbiotic systems: the obligate endosymbiont Blattabacterium cuenotii, and a complex gut microbiota. Blattabacterium is the only bacterium present in the eggs, as the gut microbiota is acquired by horizontal transmission after hatching, mostly through coprophagy. Blattella germanica, [...] Read more.
Cockroaches harbor two coexisting symbiotic systems: the obligate endosymbiont Blattabacterium cuenotii, and a complex gut microbiota. Blattabacterium is the only bacterium present in the eggs, as the gut microbiota is acquired by horizontal transmission after hatching, mostly through coprophagy. Blattella germanica, a cosmopolitan omnivorous cockroach living in intimate association with humans, is an appropriate model system for studying whether the gut microbiota is essential for the cockroach’s survival, development, or welfare. We obtained a germ-free cockroach population (i.e., containing normal amounts of the endosymbiont, but free of microbes on the insects’ surface and digestive tract). Non-significant differences with the controls were detected in most fitness parameters analyzed, except for a slight shortening in the hatching time of the second generation and a reduction in female weight at 10 days after adult ecdysis. The latter is accompanied by a decrease in uric acid reserves. This starvation-like phenotype of germ-free B. germanica suggests that the microbiota is not essential in this species for survival and development throughout its complete life cycle, but it could participate in complementation of host nutrition by helping with food digestion and nutrient absorption. Full article
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0 pages, 1342 KiB  
Review
Cutaneous Hyalohyphomycosis and Its Atypical Clinical Presentations in Immunosuppressed Patients
by Nikola Ferara, Sanja Špoljar, Liborija Lugović-Mihić, Ana Gverić Grginić, Violeta Rezo Vranješ, Iva Bešlić, Judita Perović and Tihana Regović Džombeta
Life 2024, 14(1), 154; https://doi.org/10.3390/life14010154 - 21 Jan 2024
Viewed by 1372
Abstract
There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become [...] Read more.
There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become emerging pathogens. One of them is Purpureocillium lilacinum, a ubiquitous filamentous fungus commonly found in the environment, especially in the air and soil. P. lilacinum belongs to a bigger group of hyaline fungi that cause hyalohyphomycosis, a fungal infection caused by fungi with colorless hyphae. Although this is a heterogeneous group of fungi, there are similarities regarding their ubiquity, ways of transmission, affected patients, and difficulties in diagnostics and treatment. In hyalohyphomycosis, the skin is one of the most affected organs, which is why the involvement of dermatologists is crucial for the initial assessment, since the timely recognition and early diagnosis of this condition can prevent life-threatening infections and death. In this review, we covered cutaneous hyalohyphomycosis caused by P. lilacinum and other fungi in the same group, including Fusarium, Penicilium, Scedosporium, Scopulariopsis, Acremonium, and Trichoderma genera. Full article
(This article belongs to the Section Microbiology)
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13 pages, 1239 KiB  
Review
Connectome-Based Neurosurgery in Primary Intra-Axial Neoplasms: Beyond the Traditional Modular Conception of Brain Architecture for the Preservation of Major Neurological Domains and Higher-Order Cognitive Functions
by Marcello Magnani, Arianna Rustici, Matteo Zoli, Constantin Tuleasca, Bipin Chaurasia, Enrico Franceschi, Caterina Tonon, Raffaele Lodi and Alfredo Conti
Life 2024, 14(1), 136; https://doi.org/10.3390/life14010136 - 18 Jan 2024
Cited by 1 | Viewed by 1192
Abstract
Despite the therapeutical advancements in the surgical treatment of primary intra-axial neoplasms, which determined both a significative improvement in OS and QoL and a reduction in the incidence of surgery-induced major neurological deficits, nowadays patients continue to manifest subtle post-operative neurocognitive impairments, preventing [...] Read more.
Despite the therapeutical advancements in the surgical treatment of primary intra-axial neoplasms, which determined both a significative improvement in OS and QoL and a reduction in the incidence of surgery-induced major neurological deficits, nowadays patients continue to manifest subtle post-operative neurocognitive impairments, preventing them from a full reintegration back into social life and into the workforce. The birth of connectomics paved the way for a profound reappraisal of the traditional conception of brain architecture, in favour of a model based on large-scale structural and functional interactions of a complex mosaic of cortical areas organized in a fluid network interconnected by subcortical bundles. Thanks to these advancements, neurosurgery is facing a new era of connectome-based resections, in which the core principle is still represented by the achievement of an ideal onco-functional balance, but with a closer eye on whole-brain circuitry, which constitutes the foundations of both major neurological functions, to be intended as motricity; language and visuospatial function; and higher-order cognitive functions such as cognition, conation, emotion and adaptive behaviour. Indeed, the achievement of an ideal balance between the radicality of tumoral resection and the preservation, as far as possible, of the integrity of local and global brain networks stands as a mandatory goal to be fulfilled to allow patients to resume their previous life and to make neurosurgery tailored and gentler to their individual needs. Full article
(This article belongs to the Section Medical Research)
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16 pages, 1845 KiB  
Review
Breast Reconstruction following Mastectomy for Breast Cancer or Prophylactic Mastectomy: Therapeutic Options and Results
by Laurentiu Simion, Ina Petrescu, Elena Chitoran, Vlad Rotaru, Ciprian Cirimbei, Sinziana-Octavia Ionescu, Daniela-Cristina Stefan, Dan Luca, Dana Lucia Stanculeanu, Adelina Silvana Gheorghe, Horia Doran and Ioana Mihaela Dogaru
Life 2024, 14(1), 138; https://doi.org/10.3390/life14010138 - 18 Jan 2024
Cited by 1 | Viewed by 1686
Abstract
(1) Importance of problem: Breast cancer accounted for 685,000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor besides gender and age group. During the last four decades, we have seen a 40% reduction in [...] Read more.
(1) Importance of problem: Breast cancer accounted for 685,000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor besides gender and age group. During the last four decades, we have seen a 40% reduction in age-standardized breast cancer mortality and have also witnessed a reduction in the medium age at diagnosis, which in turn means that the number of mastectomies performed for younger women increased, raising the need for adequate breast reconstructive surgery. Advances in oncological treatment have made it possible to limit the extent of what represents radical surgery for breast cancer, yet in the past decade, we have seen a marked trend toward mastectomies in breast-conserving surgery-eligible patients. Prophylactic mastectomies have also registered an upward trend. This trend together with new uses for breast reconstruction like chest feminization in transgender patients has increased the need for breast reconstruction surgery. (2) Purpose: The purpose of this study is to analyze the types of reconstructive procedures, their indications, their limitations, their functional results, and their safety profiles when used during the integrated treatment plan of the oncologic patient. (3) Methods: We conducted an extensive literature review of the main reconstructive techniques, especially the autologous procedures; summarized the findings; and presented a few cases from our own experience for exemplification of the usage of breast reconstruction in oncologic patients. (4) Conclusions: Breast reconstruction has become a necessary step in the treatment of most breast cancers, and many reconstructive techniques are now routinely practiced. Microsurgical techniques are considered the “gold standard”, but they are not accessible to all services, from a technical or financial point of view, so pediculated flaps remain the safe and reliable option, along with alloplastic procedures, to improve the quality of life of these patients. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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13 pages, 1125 KiB  
Review
Primary Role of the Kidney in Pathogenesis of Hypertension
by Gheun-Ho Kim
Life 2024, 14(1), 119; https://doi.org/10.3390/life14010119 - 14 Jan 2024
Viewed by 2510
Abstract
Previous transplantation studies and the concept of ‘nephron underdosing’ support the idea that the kidney plays a crucial role in the development of essential hypertension. This suggests that there are genetic factors in the kidney that can either elevate or decrease blood pressure. [...] Read more.
Previous transplantation studies and the concept of ‘nephron underdosing’ support the idea that the kidney plays a crucial role in the development of essential hypertension. This suggests that there are genetic factors in the kidney that can either elevate or decrease blood pressure. The kidney normally maintains arterial pressure within a narrow range by employing the mechanism of pressure-natriuresis. Hypertension is induced when the pressure-natriuresis mechanism fails due to both subtle and overt kidney abnormalities. The inheritance of hypertension is believed to be polygenic, and essential hypertension may result from a combination of genetic variants that code for renal tubular sodium transporters or proteins involved in regulatory pathways. The renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) are the major regulators of renal sodium reabsorption. Hyperactivity of either the RAAS or SNS leads to a rightward shift in the pressure-natriuresis curve. In other words, hypertension is induced when the activity of RAAS and SNS is not suppressed despite increased salt intake. Sodium overload, caused by increased intake and/or reduced renal excretion, not only leads to an expansion of plasma volume but also to an increase in systemic vascular resistance. Endothelial dysfunction is caused by an increased intracellular Na+ concentration, which inhibits endothelial nitric oxide (NO) synthase and reduces NO production. The stiffness of vascular smooth muscle cells is increased by the accumulation of intracellular Na+ and subsequent elevation of cytoplasmic Ca++ concentration. In contrast to the hemodynamic effects of osmotically active Na+, osmotically inactive Na+ stimulates immune cells and produces proinflammatory cytokines, which contribute to hypertension. When this occurs in the gut, the microbiota may become imbalanced, leading to intestinal inflammation and systemic hypertension. In conclusion, the primary cause of hypertension is sodium overload resulting from kidney dysregulation. Full article
(This article belongs to the Special Issue Pulmonary Hypertension: From Bench to Bedside: 2nd Edition)
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16 pages, 374 KiB  
Review
The Most Recent Insights into the Roots of Gastric Cancer
by Lorena Elena Meliț, Cristina Oana Mărginean and Reka Borka Balas
Life 2024, 14(1), 95; https://doi.org/10.3390/life14010095 - 8 Jan 2024
Cited by 1 | Viewed by 1365
Abstract
Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to [...] Read more.
Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to know if the most early premalignant transformation occurs in children or later since, this would enable the development of effective anti-tumorigenesis strategies. The interplay between H. pylori virulence factors, the host’s responses modified by this infection, and the gastric microecology are complex and eventually lead to the development of gastric cancer in susceptible individuals. Several biomarkers were identified as major contributors of this long-lasting process, such as pepsinogens, gastrin 17, lipid-, glucose- and iron-metabolism parameters, immunity players, aberrant bacterial DNA methylation, H. pylori virulence factors, and hallmarks of gastric dysbiosis. Several of these biomarkers were also identified in children with H. pylori infection, independently of the presence of premalignant lesions, which were also proven to be present in a subgroup of H. pylori-infected children, especially those carrying extremely virulent strains. Therefore, the most incipient premalignant gastric changes might indeed occur early during childhood, opening a promising research gate for further studies to delineate the border between infection and cancer. Full article
(This article belongs to the Special Issue Helicobacter pylori)
10 pages, 2218 KiB  
Communication
Biological Activities of Molecules Derived from Olea europaea L. Tested In Vitro
by Giulia Marrone, Silvia Urciuoli, Eleonora Candi, Roberta Bernini, Gianluca Vanni, Claudia Masci, Cristina Guerriero, Mara Mancini, Antonino De Lorenzo, Pamela Vignolini and Annalisa Noce
Life 2024, 14(1), 49; https://doi.org/10.3390/life14010049 - 28 Dec 2023
Cited by 3 | Viewed by 1044
Abstract
Background: Extra virgin olive oil is a typical food of the Mediterranean area, obtained by pressing Olea europaea L. fruits. Its polyphenols have been studied for their antioxidant function and protective action against cancer and chronic kidney disease. In this in vitro study, [...] Read more.
Background: Extra virgin olive oil is a typical food of the Mediterranean area, obtained by pressing Olea europaea L. fruits. Its polyphenols have been studied for their antioxidant function and protective action against cancer and chronic kidney disease. In this in vitro study, we tested titrated extracts from Olea europaea L. on a human embryonic kidney 293 (HEK-293E) cell line, regarding their pro-apoptotic and antiproliferative capacities, using “ IncuCyte® S3 Live-Cell Analysis System”. Materials and Methods: We selected Olea europaea L. active compounds like hydroxytyrosol (HT) and oleuropein (OLE). These extracts were tested at different concentrations and characterized by HPLC-DAD-MS for the content in secondary active metabolites. The real-time observation of cell behavior was performed by IncuCyte, which can quantitatively analyze the cell proliferation and death. Results: This study showed that all the tested extracts can significantly inhibit cellular growth at 50 µM but the reduced proliferation is not related to an increase in cellular apoptosis. Instead, the same analysis performed by using extracts at 100 µM reveals that they can inhibit cellular growth, further inducing cellular apoptosis. Conclusions: The results on the HEK-293E cells confirmed the antiproliferative and proapoptotic actions of active compounds from an Olea europaea L. matrix in this cell line. Full article
(This article belongs to the Section Pharmaceutical Science)
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27 pages, 447 KiB  
Review
Traditional Therapeutics and Potential Epidrugs for CVD: Why Not Both?
by Lauren Rae Gladwell, Chidinma Ahiarah, Shireen Rasheed, Shaikh Mizanoor Rahman and Mahua Choudhury
Life 2024, 14(1), 23; https://doi.org/10.3390/life14010023 - 22 Dec 2023
Cited by 1 | Viewed by 1900
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide. In addition to the high mortality rate, people suffering from CVD often endure difficulties with physical activities and productivity that significantly affect their quality of life. The high prevalence of debilitating risk factors [...] Read more.
Cardiovascular disease (CVD) is the leading cause of death worldwide. In addition to the high mortality rate, people suffering from CVD often endure difficulties with physical activities and productivity that significantly affect their quality of life. The high prevalence of debilitating risk factors such as obesity, type 2 diabetes mellitus, smoking, hypertension, and hyperlipidemia only predicts a bleak future. Current traditional CVD interventions offer temporary respite; however, they compound the severe economic strain of health-related expenditures. Furthermore, these therapeutics can be prescribed indefinitely. Recent advances in the field of epigenetics have generated new treatment options by confronting CVD at an epigenetic level. This involves modulating gene expression by altering the organization of our genome rather than altering the DNA sequence itself. Epigenetic changes are heritable, reversible, and influenced by environmental factors such as medications. As CVD is physiologically and pathologically diverse in nature, epigenetic interventions can offer a ray of hope to replace or be combined with traditional therapeutics to provide the prospect of addressing more than just the symptoms of CVD. This review discusses various risk factors contributing to CVD, perspectives of current traditional medications in practice, and a focus on potential epigenetic therapeutics to be used as alternatives. Full article
(This article belongs to the Section Pharmaceutical Science)
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11 pages, 771 KiB  
Review
Advances in Identifying the Mechanisms by Which Microorganisms Improve Barley Salt Tolerance
by Zhiwei Chen, Zhenzhu Guo, Longhua Zhou, Hongwei Xu, Chenghong Liu and Xin Yan
Life 2024, 14(1), 6; https://doi.org/10.3390/life14010006 - 19 Dec 2023
Viewed by 1003
Abstract
As the global human population continues to increase, the use of saline–alkali land for food production is an important consideration for food security. In addition to breeding or cultivating salt-tolerant crop varieties, microorganisms are increasingly being evaluated for their ability to improve plant [...] Read more.
As the global human population continues to increase, the use of saline–alkali land for food production is an important consideration for food security. In addition to breeding or cultivating salt-tolerant crop varieties, microorganisms are increasingly being evaluated for their ability to improve plant salt tolerance. Barley is one of the most important and salt-tolerant cereal crops and is a model system for investigating the roles of microorganisms in improving plant salt tolerance. However, a comprehensive review of the mechanisms by which microorganisms improve barley salt tolerance remains lacking. In this review, the mechanisms of barley salt tolerance improvement by microorganisms are summarized, along with a discussion of existing problems in current research and areas of future research directions. In particular, with the development of sequencing technology and the great reduction of prices, the use of omics can not only comprehensively evaluate the role of microorganisms but also evaluate the impact of the microbiome on plants, which will provide us with many opportunities and challenges in this research area. Full article
(This article belongs to the Special Issue Cereals: Stress Resistance and Breeding)
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15 pages, 1974 KiB  
Article
Combined Soil Microorganism Amendments and Foliar Micronutrient Nanofertilization Increased the Production of Allium cepa L. through Aquaporin Gene Regulation
by José A. Berna-Sicilia, Mercy Quizhpe-Romero, María Hurtado-Navarro, José A. Pascual, Micaela Carvajal and Gloria Bárzana
Life 2024, 14(1), 4; https://doi.org/10.3390/life14010004 - 19 Dec 2023
Viewed by 899
Abstract
The aim of this study was to investigate the impact of changes in aquaporin expression on the growth of onion (Allium cepa L.) plants when subjected to dual applications of microorganism-based soil amendments and foliar nanoencapsulated mineral nutrients. Multiple physiological parameters related [...] Read more.
The aim of this study was to investigate the impact of changes in aquaporin expression on the growth of onion (Allium cepa L.) plants when subjected to dual applications of microorganism-based soil amendments and foliar nanoencapsulated mineral nutrients. Multiple physiological parameters related to water, gas exchange, and nutrient content in leaf, root, and bulb tissues were determined. Additionally, the gene expression of aquaporins, specifically PIP1, PIP2 (aquaporin subfamily plasma membrane intrinsic protein), and TIP2 (aquaporin subfamily tonoplast intrinsic protein), was analyzed. The findings revealed that the foliar application of nutrients in a nanoencapsulated form significantly enhanced nutrient penetration, mobilization, and overall plant growth to a greater extent than free-form fertilizers. Amendments with microorganisms alone did not promote growth but influenced the production of secondary metabolites in the bulbs. The combination of microorganisms and nanoencapsulated mineral nutrients demonstrated synergistic effects, increasing dry matter, mineral content, and aquaporin gene expression. This suggests that aquaporins play a pivotal role in the transport of nutrients from leaves to storage organs, resulting in the overexpression of PIP2 aquaporins in bulbs, improved water uptake, and enhanced cell growth. Therefore, the combined treatment with microorganisms and nanoencapsulated mineral nutrients may be an optimal approach for enhancing onion productivity by regulating aquaporins under field conditions. Full article
(This article belongs to the Special Issue Effect of Biostimulants in the Soil-Plant-Microbe System)
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13 pages, 501 KiB  
Review
Dermatophyte Infections Worldwide: Increase in Incidence and Associated Antifungal Resistance
by Caroline Kruithoff, Ahmed Gamal, Thomas S. McCormick and Mahmoud A. Ghannoum
Life 2024, 14(1), 1; https://doi.org/10.3390/life14010001 - 19 Dec 2023
Cited by 4 | Viewed by 3488
Abstract
The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can [...] Read more.
The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections. Full article
(This article belongs to the Special Issue Fungal Disease Epidemiology: Current State and Future Prospects)
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0 pages, 676 KiB  
Article
Ocular Motility Patterns in Intellectual Disability: Insights from the Developmental Eye Movement Test
by Elvira Orduna-Hospital, Diego Hernández-Aranda and Ana Sanchez-Cano
Life 2023, 13(12), 2360; https://doi.org/10.3390/life13122360 - 18 Dec 2023
Viewed by 783
Abstract
Purpose: To measure the ocular motility parameters of the Developmental Eye Movement (DEM) test objectively, with an eye tracker in subjects with intellectual disability (ID). Methods: The DEM test was performed on 45 subjects with ID, while their eye movements were recorded with [...] Read more.
Purpose: To measure the ocular motility parameters of the Developmental Eye Movement (DEM) test objectively, with an eye tracker in subjects with intellectual disability (ID). Methods: The DEM test was performed on 45 subjects with ID, while their eye movements were recorded with an eye tracker. Some objective parameters of ocular motility were obtained through each subtest (A, B, and C) of the full DEM test. Results: There was a significant positive correlation between the saccadic speed (cc: 0.537; p = 0.001) and length (cc: 0.368; p = 0.030) of both eyes for the same subject. People with a higher percentage of ID exhibited a greater number of fixations, saccades, and errors, and took longer to perform the DEM test than those with a lower ID percentage, who had greater numbers of these parameters than subjects without ID. Subjects without ID exhibited faster saccades, with a higher amplitude, than subjects with ID. Conclusions: The eye tracker quantifies ocular motility parameters involved in the DEM test in subjects with ID. Both eyes’ movements in subjects with ID were conjugated, exhibiting saccades of the same length and speed. All parameters were different in subjects with ID compared to those in subjects without ID, so normative tables specifically for subjects with ID are necessary. Full article
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18 pages, 8612 KiB  
Review
The Cavernous Nerve Injury Rat Model: A Pictorial Essay on Post-Radical Prostatectomy Erectile Dysfunction Research
by Silviu Constantin Latcu, Dorin Novacescu, Victor-Bogdan Buciu, Cristina-Stefania Dumitru, Raluca Amalia Ceausu, Marius Raica, Talida Georgiana Cut, Razvan Ilina, Daniel Claudiu Malita, Cristi Tarta and Alin Adrian Cumpanas
Life 2023, 13(12), 2337; https://doi.org/10.3390/life13122337 - 13 Dec 2023
Cited by 1 | Viewed by 1627
Abstract
Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to [...] Read more.
Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to translate efficiently into clinical practice, with post-RP ED therapeutic management remaining cumbersome and enigmatic. This disparity highlights the need for further standardization and optimization of the elaborate surgical preparation protocols and multifaceted reporting parameters involved in reliable CN injury rat model experimentation. Even so, despite its technical complexity, this animal model remains instrumental in exploring the functional implications of RP, i.e., surgical lesions of the neurovascular bundles (NVBs). Herein, besides cavernous nerve (CN) dissection, injury, and electrostimulation, multiple pressure measurements, i.e., mean arterial pressure (MAP) and intra-cavernosal pressure (ICP), must also be achieved. A transverse cervical incision allows for carotid artery cannulation and MAP measurements. Conversely, ICP measurements entail circumcising the penis, exposing the ischiocavernous muscle, and inserting a needle into the corporal body. Finally, using an abdominal incision, the prostate is revealed, and the major pelvic ganglia (MPG) and CNs are dissected bilaterally. Specific surgical techniques are used to induce CN injuries. Herein, we provide a narrative and illustrative overview regarding these complex experimental procedures and their particular requirements, reflecting on current evidence and future research perspectives. Full article
(This article belongs to the Special Issue Prostate Cancer: 3rd Edition)
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22 pages, 911 KiB  
Article
Pilot Lipidomics Study of Copepods: Investigation of Potential Lipid-Based Biomarkers for the Early Detection and Quantification of the Biological Effects of Climate Change on the Oceanic Food Chain
by Paul L. Wood, Michael D. Wood and Stan C. Kunigelis
Life 2023, 13(12), 2335; https://doi.org/10.3390/life13122335 - 13 Dec 2023
Cited by 1 | Viewed by 1073
Abstract
Maintenance of the health of our oceans is critical for the survival of the oceanic food chain upon which humanity is dependent. Zooplanktonic copepods are among the most numerous multicellular organisms on earth. As the base of the primary consumer food web, they [...] Read more.
Maintenance of the health of our oceans is critical for the survival of the oceanic food chain upon which humanity is dependent. Zooplanktonic copepods are among the most numerous multicellular organisms on earth. As the base of the primary consumer food web, they constitute a major biomass in oceans, being an important food source for fish and functioning in the carbon cycle. The potential impact of climate change on copepod populations is an area of intense study. Omics technologies offer the potential to detect early metabolic alterations induced by the stresses of climate change. One such omics approach is lipidomics, which can accurately quantify changes in lipid pools serving structural, signal transduction, and energy roles. We utilized high-resolution mass spectrometry (≤2 ppm mass error) to characterize the lipidome of three different species of copepods in an effort to identify lipid-based biomarkers of copepod health and viability which are more sensitive than observational tools. With the establishment of such a lipid database, we will have an analytical platform useful for prospectively monitoring the lipidome of copepods in a planned long-term five-year ecological study of climate change on this oceanic sentinel species. The copepods examined in this pilot study included a North Atlantic species (Calanus finmarchicus) and two species from the Gulf of Mexico, one a filter feeder (Acartia tonsa) and one a hunter (Labidocerca aestiva). Our findings clearly indicate that the lipidomes of copepod species can vary greatly, supporting the need to obtain a broad snapshot of each unique lipidome in a long-term multigeneration prospective study of climate change. This is critical, since there may well be species-specific responses to the stressors of climate change and co-stressors such as pollution. While lipid nomenclature and biochemistry are extremely complex, it is not essential for all readers interested in climate change to understand all of the various lipid classes presented in this study. The clear message from this research is that we can monitor key copepod lipid families with high accuracy, and therefore potentially monitor lipid families that respond to environmental perturbations evoked by climate change. Full article
(This article belongs to the Special Issue Feature Paper in Physiology and Pathology)
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16 pages, 1624 KiB  
Systematic Review
Why Does Your Uterus Become Malignant? The Impact of the Microbiome on Endometrial Carcinogenesis
by Katarzyna Morańska, Monika Englert-Golon, Magdalena Durda-Masny, Stefan Sajdak, Marlena Grabowska and Anita Szwed
Life 2023, 13(12), 2269; https://doi.org/10.3390/life13122269 - 28 Nov 2023
Viewed by 1499
Abstract
The aim of this review was to describe the uterine microbiome composition that has been analyzed so far and describe potential pathways in the carcinogenesis of the endometrium. The microbiome in the uterine environment is involved in apoptosis and proliferation during the menstruation [...] Read more.
The aim of this review was to describe the uterine microbiome composition that has been analyzed so far and describe potential pathways in the carcinogenesis of the endometrium. The microbiome in the uterine environment is involved in apoptosis and proliferation during the menstruation cycle, pregnancy maintenance, and immune system support. However, bacteria in the uterus could stimulate inflammation, which when chronic results in malignancy. An altered gut microbiota initiates an inflammatory response through microorganism-associated molecular patterns, which leads to intensified steroidogenesis in the ovaries and cancers. Moreover, intestinal bacteria secreting the enzyme β-glucuronidase may increase the level of circulating estrogen and, as a result, be influential in gynecological cancers. Both the uterine and the gut microbiota play a pivotal role in immune modulation, which is why there is a demand for further investigation from both the diagnostic and the therapeutic perspectives. Full article
(This article belongs to the Collection Feature Papers in Microbiology)
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28 pages, 1858 KiB  
Review
Point-of-Care Testing for Hepatitis Viruses: A Growing Need
by Matthew D. Pauly and Lilia Ganova-Raeva
Life 2023, 13(12), 2271; https://doi.org/10.3390/life13122271 - 28 Nov 2023
Cited by 1 | Viewed by 2375
Abstract
Viral hepatitis, caused by hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV), is a major global public health problem. These viruses cause millions of infections each year, and chronic infections [...] Read more.
Viral hepatitis, caused by hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV), is a major global public health problem. These viruses cause millions of infections each year, and chronic infections with HBV, HCV, or HDV can lead to severe liver complications; however, they are underdiagnosed. Achieving the World Health Organization’s viral hepatitis elimination goals by 2030 will require access to simpler, faster, and less expensive diagnostics. The development and implementation of point-of-care (POC) testing methods that can be performed outside of a laboratory for the diagnosis of viral hepatitis infections is a promising approach to facilitate and expedite WHO’s elimination targets. While a few markers of viral hepatitis are already available in POC formats, tests for additional markers or using novel technologies need to be developed and validated for clinical use. Potential methods and uses for the POC testing of antibodies, antigens, and nucleic acids that relate to the diagnosis, monitoring, or surveillance of viral hepatitis infections are discussed here. Unmet needs and areas where additional research is needed are also described. Full article
(This article belongs to the Section Epidemiology)
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18 pages, 342 KiB  
Review
Gut Microbiota, Inflammation, and Probiotic Supplementation in Fetal Growth Restriction—A Comprehensive Review of Human and Animal Studies
by Naser A. Alsharairi and Li Li
Life 2023, 13(12), 2239; https://doi.org/10.3390/life13122239 - 21 Nov 2023
Cited by 1 | Viewed by 1693
Abstract
Fetal growth restriction (FGR) is a pathological state that represents a fetus’s inability to achieve adequate growth during pregnancy. Several maternal, placental, and fetal factors are likely associated with FGR etiology. FGR is linked to severe fetal and neonatal complications, as well as [...] Read more.
Fetal growth restriction (FGR) is a pathological state that represents a fetus’s inability to achieve adequate growth during pregnancy. Several maternal, placental, and fetal factors are likely associated with FGR etiology. FGR is linked to severe fetal and neonatal complications, as well as adverse health consequences in adulthood. Numerous randomized controlled trials (RCTs) have demonstrated improved growth in FGR fetuses with promising treatment strategies such as maternal micronutrient, amino acid, and nitric oxide supplementation. Elevated inflammation in pregnant women diagnosed with FGR has been associated with an imbalance between pro- and anti-inflammatory cytokines. Gut microbiota dysbiosis may result in increased FGR-related inflammation. Probiotic treatment may relieve FGR-induced inflammation and improve fetal growth. The aim of this review is to provide an overview of the gut microbiota and inflammatory profiles associated with FGR and explore the potential of probiotics in treating FGR. Full article
(This article belongs to the Special Issue From Stem Cells to Embryos, Congenital Anomalies and Epidemiology)
15 pages, 897 KiB  
Review
Celebrating Versatility: Febuxostat’s Multifaceted Therapeutic Application
by Krasimir Iliev Kraev, Mariela Gencheva Geneva-Popova, Bozhidar Krasimirov Hristov, Petar Angelov Uchikov, Stanislava Dimitrova Popova-Belova, Maria Ilieva Kraeva, Yordanka Mincheva Basheva-Kraeva, Nina Staneva Stoyanova and Vesela Todorova Mitkova-Hristova
Life 2023, 13(11), 2199; https://doi.org/10.3390/life13112199 - 11 Nov 2023
Viewed by 1818
Abstract
Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat’s mechanism of action, its effectiveness in gout management, its cardiovascular safety [...] Read more.
Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat’s mechanism of action, its effectiveness in gout management, its cardiovascular safety profile, renal and hepatic effects, musculoskeletal applications, safety considerations, and emerging research prospects. Febuxostat’s primary mechanism involves selective inhibition of xanthine oxidase, resulting in reduced uric acid production. Its pharmacokinetics require personalized dosing strategies based on individual characteristics. In gout management, febuxostat offers a compelling alternative, effectively lowering uric acid levels, relieving symptoms, and supporting long-term control, especially for patients intolerant to allopurinol. Recent studies have demonstrated its cardiovascular safety, and it exhibits minimal hepatotoxicity, making it suitable for those with liver comorbidities. Febuxostat’s potential nephroprotective effects and kidney stone prevention properties are noteworthy, particularly for gout patients with renal concerns. Beyond gout, its anti-inflammatory properties hint at applications in musculoskeletal conditions and a broader spectrum of clinical contexts, including metabolic syndrome. Emerging research explores febuxostat’s roles in cardiovascular health, neurological disorders, rheumatoid arthritis, and cancer therapy, driven by its anti-inflammatory and antioxidative properties. Future directions include personalized medicine, combination therapies, mechanistic insights, and ongoing long-term safety monitoring, collectively illuminating the promising landscape of febuxostat’s multifaceted therapeutic potential. Full article
(This article belongs to the Section Medical Research)
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13 pages, 4288 KiB  
Article
Recurrent Somatic Copy Number Alterations and Their Association with Oncogene Expression Levels in High-Grade Ovarian Serous Carcinoma
by Hillary P. Esplen, Richard K. Yang, Awdhesh Kalia, Zhenya Tang, Guilin Tang, L. Jeffrey Medeiros and Gokce A. Toruner
Life 2023, 13(11), 2192; https://doi.org/10.3390/life13112192 - 10 Nov 2023
Cited by 1 | Viewed by 1535
Abstract
Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome [...] Read more.
Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly correlated for 274 genes; 24 genes were classified as a Tier 1 gene in the Cancer Gene Census in the Catalogue of Somatic Mutations in Cancer (CGC-COSMIC). Of these, 11 Tier 1 genes had highly correlated SCNA and mRNA expression levels: TBL1XR1, PIK3CA, UBR5, EIF3E, RAD21, EXT1, RECQL4, KRAS, PRKACA, BRD4, and TPM4. There was no association between gene amplification and disease stage or PFS. EIF3E, RAD21, and EXT1 were more frequently amplified in younger patients, specifically those under the age of 55 years. Patients with tumors carrying PRKACA, BRD4, or TPM4 amplification were associated with a significantly shorter OS. RECQL4 amplification was more frequent in younger patients, and tumors with this amplification were associated with a significantly better OS. Full article
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19 pages, 689 KiB  
Review
The Therapeutic Potential of Amphetamine-like Psychostimulants
by Bruno Pires, Luana M. Rosendo, Ana Teresa Brinca, Ana Y. Simão, Mário Barroso, Tiago Rosado and Eugenia Gallardo
Life 2023, 13(11), 2180; https://doi.org/10.3390/life13112180 - 8 Nov 2023
Cited by 1 | Viewed by 2590
Abstract
This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), [...] Read more.
This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), drug dependence, post-traumatic stress disorder (PTSD), and obesity. Lisdexamphetamine dimesylate has shown promise in effectively treating ADHD symptoms in both children and adults. Additionally, it has been explored as a potential treatment for drug dependency and withdrawal, demonstrating encouraging results. Mixed amphetamine salts have also exhibited efficacy in reducing ADHD symptoms in adults. Future research should explore their potential use in treating bipolar disorder and cocaine dependence, considering the associated risks and benefits. MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth. Furthermore, it has shown promise in managing anxiety related to life-threatening illnesses. Dextroamphetamine and phentermine have demonstrated efficacy in treating cocaine and opioid dependence, ADHD, and obesity. However, careful consideration and monitoring by medical professionals are essential due to the potential risks and benefits associated with them. In conclusion, amphetamine-type stimulants present a promising avenue for therapeutic interventions in various psychiatric conditions. Nevertheless, further research is necessary to comprehensively understand their mechanisms of action, dosage requirements, and long-term effects in different patient populations. Full article
(This article belongs to the Special Issue The Implication of Psychoactive Substance Consumption)
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14 pages, 3234 KiB  
Article
Therapeutic Potential of P110 Peptide: New Insights into Treatment of Alzheimer’s Disease
by Ankita Srivastava, Maryann Johnson, Heather A. Renna, Katie M. Sheehan, Saba Ahmed, Thomas Palaia, Aaron Pinkhasov, Irving H. Gomolin, Joshua De Leon and Allison B. Reiss
Life 2023, 13(11), 2156; https://doi.org/10.3390/life13112156 - 2 Nov 2023
Cited by 1 | Viewed by 1731
Abstract
Mitochondrial degeneration in various neurodegenerative diseases, specifically in Alzheimer’s disease, involves excessive mitochondrial fission and reduced fusion, leading to cell damage. P110 is a seven-amino acid peptide that restores mitochondrial dynamics by acting as an inhibitor of mitochondrial fission. However, the role of [...] Read more.
Mitochondrial degeneration in various neurodegenerative diseases, specifically in Alzheimer’s disease, involves excessive mitochondrial fission and reduced fusion, leading to cell damage. P110 is a seven-amino acid peptide that restores mitochondrial dynamics by acting as an inhibitor of mitochondrial fission. However, the role of P110 as a neuroprotective agent in AD remains unclear. Therefore, we performed cell culture studies to evaluate the neuroprotective effect of P110 on amyloid-β accumulation and mitochondrial functioning. Human SH-SY5Y neuronal cells were incubated with 1 µM and 10 µM of P110, and Real-Time PCR and Western blot analysis were done to quantify the expression of genes pertaining to AD and neuronal health. Exposure of SH-SY5Y cells to P110 significantly increased APP mRNA levels at 1 µM, while BACE1 mRNA levels were increased at both 1 µM and 10 µM. However, protein levels of both APP and BACE1 were significantly reduced at 10 µM of P110. Further, P110 treatment significantly increased ADAM10 and Klotho protein levels at 10 µM. In addition, P110 exposure significantly increased active mitochondria and reduced ROS in live SH-SY5Y cells at both 1 µM and 10 µM concentrations. Taken together, our results indicate that P110 might be useful in attenuating amyloid-β generation and improving neuronal health by maintaining mitochondrial function in neurons. Full article
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16 pages, 1659 KiB  
Article
Enhanced Microvascular Adaptation to Acute Physical Stress and Reduced Oxidative Stress in Male Athletes Who Consumed Chicken Eggs Enriched with n-3 Polyunsaturated Fatty Acids and Antioxidants—Randomized Clinical Trial
by Luka Kolar, Petar Šušnjara, Marko Stupin, Ana Stupin, Ivana Jukić, Zrinka Mihaljević, Nikolina Kolobarić, Iva Bebek, Diana Nejašmić, Marija Lovrić and Ines Drenjančević
Life 2023, 13(11), 2140; https://doi.org/10.3390/life13112140 - 31 Oct 2023
Cited by 1 | Viewed by 1382
Abstract
This randomized interventional study aimed to determine the effects of n-3 polyunsaturated fatty acids, selenium, vitamin E, and lutein supplementation in the form of enriched chicken egg consumption on microvascular endothelium-dependent vasodilation, oxidative stress, and microvascular response to an acute strenuous training session [...] Read more.
This randomized interventional study aimed to determine the effects of n-3 polyunsaturated fatty acids, selenium, vitamin E, and lutein supplementation in the form of enriched chicken egg consumption on microvascular endothelium-dependent vasodilation, oxidative stress, and microvascular response to an acute strenuous training session (ASTS) in competitive athletes. Thirty-one male athletes were assigned to a control (n = 17) or a Nutri4 group (n = 14) who consumed three regular or enriched chicken eggs per day, respectively, for 3 weeks. Significantly enhanced endothelium-dependent responses to vascular occlusion (PORH) and iontophoresis of acetylcholine (AChID) were observed in the Nutri4 group but not in the control group after egg consumption. Formation of peroxynitrite and hydrogen peroxide in peripheral blood mononuclear cells, as well as serum concentration of 8-iso prostaglandin F2α, decreased in the Nutri4 group while remaining unchanged in controls. PORH and AChID were reduced post-ASTS compared with pre-ASTS, both before and after the diets, in both groups. However, the range of PORH responsiveness to ASTS (ΔPORH) increased after consumption of enriched eggs. These results suggest that consumption of enriched chicken eggs has a beneficial effect on microvascular endothelium-dependent vasodilation and the reduction of oxidative stress levels in competitive athletes. Also, microvascular adaptation to the ASTS was improved after consumption of Nutri4 eggs. Full article
(This article belongs to the Special Issue New Insights into Cardiovascular and Exercise Physiology)
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20 pages, 2495 KiB  
Article
Microbial Ecosystems in Movile Cave: An Environment of Extreme Life
by Joost W. Aerts, Serban M. Sarbu, Traian Brad, Pascale Ehrenfreund and Hans V. Westerhoff
Life 2023, 13(11), 2120; https://doi.org/10.3390/life13112120 - 26 Oct 2023
Viewed by 1335
Abstract
Movile Cave, situated in Romania close to the Black Sea, constitutes a distinct and challenging environment for life. Its partially submerged ecosystem depends on chemolithotrophic processes for its energetics, which are fed by a continuous hypogenic inflow of mesothermal waters rich in reduced [...] Read more.
Movile Cave, situated in Romania close to the Black Sea, constitutes a distinct and challenging environment for life. Its partially submerged ecosystem depends on chemolithotrophic processes for its energetics, which are fed by a continuous hypogenic inflow of mesothermal waters rich in reduced chemicals such as hydrogen sulfide and methane. We sampled a variety of cave sublocations over the course of three years. Furthermore, in a microcosm experiment, minerals were incubated in the cave waters for one year. Both endemic cave samples and extracts from the minerals were subjected to 16S rRNA amplicon sequencing. The sequence data show specific community profiles in the different subenvironments, indicating that specialized prokaryotic communities inhabit the different zones in the cave. Already after one year, the different incubated minerals had been colonized by specific microbial communities, indicating that microbes in Movile Cave can adapt in a relatively short timescale to environmental opportunities in terms of energy and nutrients. Life can thrive, diversify and adapt in remote and isolated subterranean environments such as Movile Cave. Full article
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19 pages, 22552 KiB  
Review
Pityriasis Versicolor—A Narrative Review on the Diagnosis and Management
by Nina Łabędź, Cristian Navarrete-Dechent, Honorata Kubisiak-Rzepczyk, Monika Bowszyc-Dmochowska, Anna Pogorzelska-Antkowiak and Paweł Pietkiewicz
Life 2023, 13(10), 2097; https://doi.org/10.3390/life13102097 - 22 Oct 2023
Cited by 2 | Viewed by 4938
Abstract
This narrative review presents a comprehensive overview of the diagnosis and management of pityriasis versicolor (PV), a common superficial fungal infection caused by the yeast Malassezia. PV is characterised by scaly hypopigmented or hyperpigmented patches, primarily affecting the upper trunk, neck, and upper [...] Read more.
This narrative review presents a comprehensive overview of the diagnosis and management of pityriasis versicolor (PV), a common superficial fungal infection caused by the yeast Malassezia. PV is characterised by scaly hypopigmented or hyperpigmented patches, primarily affecting the upper trunk, neck, and upper arms. Regarding commensal interactions, Malassezia utilises nutrient sources without affecting the human host. In cases of pathogenicity, Malassezia can directly harm the host via virulence factors or toxins, or indirectly by triggering damaging host responses. The diagnosis typically relies on recognising characteristic clinical features. Due to the wide variability in its clinical presentation, recognising the differential diagnosis is critical. In this paper, we discuss the clinical differentials, with their dermatoscopic presentation, but also describe a range of helpful diagnostic techniques (microscopy, conventional and ultraviolet-induced fluorescence dermatoscopy, and confocal microscopy). Topical therapies are the primary treatment for PV, encompassing non-specific antifungal agents like sulphur with salicylic acid, selenium sulphide 2.5%, and zinc pyrithione. Additionally, specific topical antifungal medications with either fungicidal or fungistatic properties may also be incorporated into the topical treatment regimen, such as imidazoles, allylamines, and ciclopirox olamine. Systemic therapies might occasionally be used. Patient education and the promotion of good personal hygiene are pivotal to reduce the risk of recurrence. In recurrent cases, particularly during warmer and more humid periods, prolonged prophylaxis with topical agents should be considered. Full article
(This article belongs to the Special Issue Applications of Dermatoscopy in Skin Diseases)
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15 pages, 1706 KiB  
Review
Liver Transplantation in People Living with HIV: Still an Experimental Procedure or Standard of Care?
by Erica Nicola Lynch and Francesco Paolo Russo
Life 2023, 13(10), 1975; https://doi.org/10.3390/life13101975 - 27 Sep 2023
Viewed by 1484
Abstract
Liver transplantation (LT) is the only curative treatment for various liver diseases, including acute liver failure, end-stage liver disease, and selected unresectable liver malignancies. Combination antiretroviral therapy has improved outcomes for people living with HIV (PLWH), transforming the status of acquired immune deficiency [...] Read more.
Liver transplantation (LT) is the only curative treatment for various liver diseases, including acute liver failure, end-stage liver disease, and selected unresectable liver malignancies. Combination antiretroviral therapy has improved outcomes for people living with HIV (PLWH), transforming the status of acquired immune deficiency syndrome from a fatal disease to a chronic and manageable condition. These powerful antiviral therapies have not only increased the number of HIV+ enlisted patients by improving their survival but also made the use of HIV+ organs a viable option. In this review, we summarise current knowledge on the peculiarities of liver transplantation in PLWH. In particular, we focus on the indications, contraindications, specific considerations for treatment, and outcomes of LT in PLWH. Finally, we present available preliminary data on the use of HIV+ liver allografts. Full article
(This article belongs to the Special Issue New Scenarios in Liver Transplantation)
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13 pages, 765 KiB  
Article
Occupational Exposure during Pregnancy and Effects on Newborns: A Nested Case-Control Study
by Gabriele Donzelli, Beatriz Marcos-Puig, Isabel Peraita-Costa, Juan Llopis-Morales and María Morales-Suarez-Varela
Life 2023, 13(10), 1962; https://doi.org/10.3390/life13101962 - 26 Sep 2023
Viewed by 1192
Abstract
Background: The protection of pregnant workers should be based on evidence regarding the risks to reproductive health from exposure to specific work environments and conditions. The objective of this study was to identify the effects on mothers and newborns resulting from environmental exposure [...] Read more.
Background: The protection of pregnant workers should be based on evidence regarding the risks to reproductive health from exposure to specific work environments and conditions. The objective of this study was to identify the effects on mothers and newborns resulting from environmental exposure to various occupational risks. Methods: The study cohort was composed of 399 women admitted to the Obstetrics/Postpartum ward at Hospital La Fe in Valencia, Spain. Face-to-face interviews were conducted to establish associations between workplace exposure during pregnancy and its effects on maternal and newborn health. Sex, anthropometric characteristics, and blood gas analysis in arterial and venous umbilical cord blood at delivery were collected. Results: A total of 138 women were exposed to biological and/or chemical risks, 122 to physical risks, and 139 at no risk of exposure. In the group with chemical and/or biological risks, the frequency of women who resorted to in vitro fertilization to achieve the studied pregnancy is less than half of the group exposed to physical risks, with statistically significant differences (p = 0.047). The mean values for the arterial analysis in both exposure groups were within average values, with similar pH values between them, but the mean values of PCO2 and PO2 were lower in the group of neonates of mothers exposed to physical risks, with a significant difference for arterial PO2 (p = 0.027). Conclusion: Our analysis contributes evidence for planning and prioritizing preventive actions to protect women’s reproductive health. The results suggest the continuation of a future project that would consider more factors and potentially increase the sample size. Full article
(This article belongs to the Section Epidemiology)
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22 pages, 3698 KiB  
Systematic Review
The Role of Bifidobacterium in COVID-19: A Systematic Review
by Clarissa Reginato Taufer and Pabulo Henrique Rampelotto
Life 2023, 13(9), 1847; https://doi.org/10.3390/life13091847 - 31 Aug 2023
Cited by 2 | Viewed by 2971
Abstract
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, mainly causes respiratory and intestinal symptoms and changes in the microbiota of patients. We performed a systematic search in major databases using “Bifidobacterium” and “COVID-19” or “SARS-CoV-2” as key terms to assess the [...] Read more.
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, mainly causes respiratory and intestinal symptoms and changes in the microbiota of patients. We performed a systematic search in major databases using “Bifidobacterium” and “COVID-19” or “SARS-CoV-2” as key terms to assess the relationship of the genus to COVID-19. After the selection steps, 25 articles were analyzed. Of these, eighteen were observational, and seven were interventional articles that evaluated the use of Bifidobacterium alone or in mix as probiotics for additional treatment of patients with COVID-19. All stages and severities were contemplated, including post-COVID-19 patients. Overall, Bifidobacterium was associated with both protective effects and reduced abundance in relation to the disease. The genus has been found to be abundant in some cases and linked to disease severity. The studies evaluating the use of Bifidobacterium as probiotics have demonstrated the potential of this genus in reducing symptoms, improving pulmonary function, reducing inflammatory markers, alleviating gastrointestinal symptoms, and even contributing to better control of mortality. In summary, Bifidobacterium may offer protection against COVID-19 through its ability to modulate the immune response, reduce inflammation, compete with pathogenic microbes, and maintain gut barrier function. The findings provide valuable insights into the relationship between the disease and the genus Bifidobacterium, highlighting the potential of microbiota modulation in the treatment of COVID-19. Full article
(This article belongs to the Collection Feature Papers in Microbiology)
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12 pages, 4743 KiB  
Article
Novel Compounds Derived from DFPM Induce Root Growth Arrest through the Specific VICTR Alleles of Arabidopsis Accessions
by Seojung Kim, Miri Cho and Tae-Houn Kim
Life 2023, 13(9), 1797; https://doi.org/10.3390/life13091797 - 23 Aug 2023
Viewed by 892
Abstract
The small compound [5-(3,4-dichlorophenyl) furan-2-yl]-piperidine-1-ylmethanethione (DFPM) inhibits ABA responses by activating effector-triggered immune signal transduction in Arabidopsis. In addition to the known function of DFPM as an antagonist of ABA signaling, DFPM causes accession-specific root growth arrest in Arabidopsis Columbia-0 via the TIR-NLR [...] Read more.
The small compound [5-(3,4-dichlorophenyl) furan-2-yl]-piperidine-1-ylmethanethione (DFPM) inhibits ABA responses by activating effector-triggered immune signal transduction in Arabidopsis. In addition to the known function of DFPM as an antagonist of ABA signaling, DFPM causes accession-specific root growth arrest in Arabidopsis Columbia-0 via the TIR-NLR protein VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response) in an EDS1/PAD4/RAR1/SGT1B-dependent manner. Although DFPM could control the specific steps of various cellular responses, the functional residues for the activity of DFPM or the existence of a stronger version of DFPM modification have not been characterized thoroughly. This study analyzed twenty-two DFPM derivatives during root growth arrest, inhibition of ABA signaling, and induction of biotic signal transduction to determine critical residues that confer the specific activity of DFPM. Furthermore, this study identified two more Arabidopsis accessions that generate significant root growth arrest in response to DFPM derivatives dependent on multiple amino acid polymorphisms in the coding region of VICTR. The isolation of novel compounds, such as DFPM-5, and specific amino acid polymorphisms critical for the compound-induced responses will help determine the detailed regulatory mechanism for how DFPM regulates abiotic and biotic stress signaling interactions. Full article
(This article belongs to the Special Issue Abiotic Stress in Plants_Life)
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22 pages, 1361 KiB  
Review
Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality
by Anna Gagliardi, Gzona Bajraktari-Sylejmani, Elisabetta Barocelli, Johanna Weiss and Juan Pablo Rigalli
Life 2023, 13(8), 1745; https://doi.org/10.3390/life13081745 - 14 Aug 2023
Cited by 1 | Viewed by 1515
Abstract
Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. [...] Read more.
Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. Determining the expression of these proteins in the liver, intestine, and kidney requires the collection of biopsy specimens. Instead, the isolation of extracellular vesicles (EVs), which are nanovesicles released by most cells and present in biological fluids, could deliver this information in a less invasive way. In this article, we review the use of EVs as surrogates for the expression and activity of DMEs, uptake, and efflux transporters. Preliminary evidence has been provided for a correlation between the expression of some enzymes and transporters in EVs and the tissue of origin. In some cases, data obtained in EVs reflect the induction of phase I-DMEs in the tissues. Further studies are required to elucidate to what extent the regulation of other DMEs and transporters in the tissues reflects in the EV cargo. If an association between tissues and their EVs is firmly established, EVs may represent a significant advancement toward precision therapy based on the biotransformation and excretion capacity of each individual. Full article
(This article belongs to the Special Issue New Insights into Extracellular Vesicles in Health and Disease)
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12 pages, 2023 KiB  
Article
Evaluation of Rapid Multiplex Reverse Transcription-Quantitative Polymerase Chain Reaction Assays for SARS-CoV-2 Detection in Individual and Pooled Samples
by Young-Hyun Baek, Min-Young Park, Ho-Jae Lim, Dong-Jae Youm, Youngshin You, Seojin Ahn, Jung-Eun Park, Min-Jin Kim, Sun-Hwa Lee, Yong-Hak Sohn and Yong-Jin Yang
Life 2023, 13(8), 1717; https://doi.org/10.3390/life13081717 - 10 Aug 2023
Viewed by 1073
Abstract
Although coronavirus disease 2019 (COVID-19) is no longer a Public Health Emergency of International Concern (PHEIC), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a vast impact to date. Hence, continuous management is required, given the uncertainty caused by the potential [...] Read more.
Although coronavirus disease 2019 (COVID-19) is no longer a Public Health Emergency of International Concern (PHEIC), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a vast impact to date. Hence, continuous management is required, given the uncertainty caused by the potential evolution of SARS-CoV-2. Reverse transcription-quantitative PCR (RT-qPCR) diagnosis has been fundamental in overcoming this issue. In this study, the performances of two rapid RT-qPCR assays (Real-Q Direct SARS-CoV-2 Detection Kit and Allplex™ SARS-CoV-2 fast PCR Assay) with short PCR times were comparatively evaluated using a STANDARD M nCoV Real-Time Detection Kit (STANDARD M, conventional RT-qPCR assay). All kits showed a limit of detection values (102–103 copies/reaction). The evaluation showed that the two rapid assay tests had ≥97.89% sensitivity and ≥99.51% specificity (κ = 0.98) for individual samples and ≥97.32% sensitivity and ≥97.67% specificity for pooled samples compared to STANDARD M. These results indicate that the two rapid RT-qPCR kits, which showed significant time reduction in performance, are as effective as a conventional RT-qPCR assay. They are likely to increase not only the number of tests that can be performed but also the efficiency of sustainable management of COVID-19 in the long term. Full article
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14 pages, 2314 KiB  
Article
Unexpected Adverse Events of Immune Checkpoint Inhibitors
by Walid Shalata, Alexander Yakobson, Aharon Y. Cohen, Iris Goldstein, Omar Abu Saleh, Yulia Dudnik and Keren Rouvinov
Life 2023, 13(8), 1657; https://doi.org/10.3390/life13081657 - 29 Jul 2023
Cited by 6 | Viewed by 1533
Abstract
The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events [...] Read more.
The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter’s syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis. Full article
(This article belongs to the Special Issue Drug Interactions in Cancer Therapy)
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43 pages, 1636 KiB  
Review
The Cytotoxic Properties of Extreme Fungi’s Bioactive Components—An Updated Metabolic and Omics Overview
by Attila Kiss, Farhad Hariri Akbari, Andrey Marchev, Viktor Papp and Iman Mirmazloum
Life 2023, 13(8), 1623; https://doi.org/10.3390/life13081623 - 25 Jul 2023
Cited by 1 | Viewed by 1904
Abstract
Fungi are the most diverse living organisms on planet Earth, where their ubiquitous presence in various ecosystems offers vast potential for the research and discovery of new, naturally occurring medicinal products. Concerning human health, cancer remains one of the leading causes of mortality. [...] Read more.
Fungi are the most diverse living organisms on planet Earth, where their ubiquitous presence in various ecosystems offers vast potential for the research and discovery of new, naturally occurring medicinal products. Concerning human health, cancer remains one of the leading causes of mortality. While extensive research is being conducted on treatments and their efficacy in various stages of cancer, finding cytotoxic drugs that target tumor cells with no/less toxicity toward normal tissue is a significant challenge. In addition, traditional cancer treatments continue to suffer from chemical resistance. Fortunately, the cytotoxic properties of several natural products derived from various microorganisms, including fungi, are now well-established. The current review aims to extract and consolidate the findings of various scientific studies that identified fungi-derived bioactive metabolites with antitumor (anticancer) properties. The antitumor secondary metabolites identified from extremophilic and extremotolerant fungi are grouped according to their biological activity and type. It became evident that the significance of these compounds, with their medicinal properties and their potential application in cancer treatment, is tremendous. Furthermore, the utilization of omics tools, analysis, and genome mining technology to identify the novel metabolites for targeted treatments is discussed. Through this review, we tried to accentuate the invaluable importance of fungi grown in extreme environments and the necessity of innovative research in discovering naturally occurring bioactive compounds for the development of novel cancer treatments. Full article
(This article belongs to the Collection Bacterial Infections, Treatment and Antibiotic Resistance)
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13 pages, 1707 KiB  
Review
Cerebral Vasomotor Reactivity in COVID-19: A Narrative Review
by Zahra Ghotbi, Mehrdad Estakhr, Melika Hosseini and Reza Bavarsad Shahripour
Life 2023, 13(7), 1614; https://doi.org/10.3390/life13071614 - 24 Jul 2023
Cited by 2 | Viewed by 2274
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the respiratory system but can also lead to neurological complications. Among COVID-19 patients, the endothelium is considered the Achilles heel. A variety of endothelial dysfunctions may result from SARS-CoV-2 infection and subsequent endotheliitis, such [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the respiratory system but can also lead to neurological complications. Among COVID-19 patients, the endothelium is considered the Achilles heel. A variety of endothelial dysfunctions may result from SARS-CoV-2 infection and subsequent endotheliitis, such as altered vascular tone, oxidative stress, and cytokine storms. The cerebral hemodynamic impairment that is caused is associated with a higher probability of severe disease and poor outcomes in patients with COVID-19. This review summarizes the most relevant literature on the role of vasomotor reactivity (VMR) in COVID-19 patients. An overview of the research articles is presented. Most of the studies have supported the hypothesis that endothelial dysfunction and cerebral VMR impairment occur in COVID-19 patients. Researchers believe these alterations may be due to direct viral invasion of the brain or indirect effects, such as inflammation and cytokines. Recently, researchers have concluded that viruses such as the Human Herpes Virus 8 and the Hantavirus predominantly affect endothelial cells and, therefore, affect cerebral hemodynamics. Especially in COVID-19 patients, impaired VMR is associated with a higher risk of severe disease and poor outcomes. Using VMR, one can gain valuable insight into a patient’s disease progression and make more informed decisions regarding appropriate treatment options. A new pandemic may develop with the COVID-19 virus or other viruses, making it essential that healthcare providers and researchers remain focused on developing new strategies for improving survival in such patients, particularly those with cerebrovascular risk factors. Full article
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14 pages, 1436 KiB  
Review
Current Nuclear Engineering Strategies in the Green Microalga Chlamydomonas reinhardtii
by Federico Perozeni and Thomas Baier
Life 2023, 13(7), 1566; https://doi.org/10.3390/life13071566 - 15 Jul 2023
Cited by 6 | Viewed by 2097
Abstract
The green model microalga Chlamydomonas reinhardtii recently emerged as a sustainable production chassis for the efficient biosynthesis of recombinant proteins and high-value metabolites. Its capacity for scalable, rapid and light-driven growth in minimal salt solutions, its simplicity for genetic manipulation and its “Generally [...] Read more.
The green model microalga Chlamydomonas reinhardtii recently emerged as a sustainable production chassis for the efficient biosynthesis of recombinant proteins and high-value metabolites. Its capacity for scalable, rapid and light-driven growth in minimal salt solutions, its simplicity for genetic manipulation and its “Generally Recognized As Safe” (GRAS) status are key features for its application in industrial biotechnology. Although nuclear transformation has typically resulted in limited transgene expression levels, recent developments now allow the design of powerful and innovative bioproduction concepts. In this review, we summarize the main obstacles to genetic engineering in C. reinhardtii and describe all essential aspects in sequence adaption and vector design to enable sufficient transgene expression from the nuclear genome. Several biotechnological examples of successful engineering serve as blueprints for the future establishment of C. reinhardtii as a green cell factory. Full article
(This article belongs to the Special Issue Algae Biotechnology: Green Chemistry for High-Value Products)
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17 pages, 1612 KiB  
Article
Variation of Circulating Brain-Derived Neurotrophic Factor (BDNF) in Depression: Relationships with Inflammatory Indices, Metabolic Status and Patients’ Clinical Features
by Valentina Falaschi, Lionella Palego, Donatella Marazziti, Laura Betti, Laura Musetti, Alessandra Maglio, Valerio Dell’Oste, Simona Sagona, Antonio Felicioli, Barbara Carpita, Alberto Brogi, Federico Mucci, Enrico Massimetti, Liliana Dell’Osso and Gino Giannaccini
Life 2023, 13(7), 1555; https://doi.org/10.3390/life13071555 - 13 Jul 2023
Cited by 5 | Viewed by 1595
Abstract
This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the [...] Read more.
This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs. Full article
(This article belongs to the Section Pharmaceutical Science)
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7 pages, 348 KiB  
Case Report
A Case of Delirious Mania Treated with Electroconvulsive Therapy
by Beniamino Tripodi, Manuel Glauco Carbone, Irene Matarese, Lorenzo Lattanzi and Pierpaolo Medda
Life 2023, 13(7), 1544; https://doi.org/10.3390/life13071544 - 12 Jul 2023
Cited by 2 | Viewed by 1348
Abstract
(1) Background: Delirious mania is a neuropsychiatric condition characterized by the rapid onset of delirium, psychosis, and mania. Due to the presence of catatonic signs and symptoms, some authors considered this syndrome to be a specific excited catatonia subtype. Usually, delirious mania is [...] Read more.
(1) Background: Delirious mania is a neuropsychiatric condition characterized by the rapid onset of delirium, psychosis, and mania. Due to the presence of catatonic signs and symptoms, some authors considered this syndrome to be a specific excited catatonia subtype. Usually, delirious mania is responsive to intravenous benzodiazepines (BZDs) or to electroconvulsive therapy (ECT). (2) Methods: In the present study, we describe the case of a 64-year-old woman with a diagnosis of recurrent major depressive disorder. We assessed the severity of the clinical picture and the response to ECT treatment with the Bush–Francis Catatonia Rating Scale (BFCRS). (3) Results: After eleven sessions of ECT, the patient presented a reduced BFCRS total score, with a resolution of the autonomic abnormalities (temperature, respiratory, and heart rate). (4) Conclusions: These data demonstrate how important it is to diagnose this syndrome as soon as possible to set up an effective therapy, avoiding the use of antipsychotic drugs and preventing potentially fatal complications. The initial administration of BZDs IV and the subsequent ECT application, associated with intensive care of life-threatening general medical conditions, guaranteed us a good level of efficacy in obtaining a complete resolution of the clinical picture. Full article
(This article belongs to the Special Issue What Is New in Psychiatry and Psychopharmacology?)
11 pages, 260 KiB  
Review
Pathophysiology of Acute Coronary Syndromes—Diagnostic and Treatment Considerations
by Panagiotis Theofilis, Evangelos Oikonomou, Christos Chasikidis, Konstantinos Tsioufis and Dimitris Tousoulis
Life 2023, 13(7), 1543; https://doi.org/10.3390/life13071543 - 12 Jul 2023
Cited by 4 | Viewed by 4276
Abstract
Coronary artery disease and acute coronary syndromes are accountable for significant morbidity and mortality, despite the preventive measures and technological advancements in their management. Thus, it is mandatory to further explore the pathophysiology in order to provide tailored and more effective therapies, since [...] Read more.
Coronary artery disease and acute coronary syndromes are accountable for significant morbidity and mortality, despite the preventive measures and technological advancements in their management. Thus, it is mandatory to further explore the pathophysiology in order to provide tailored and more effective therapies, since acute coronary syndrome pathogenesis is more varied than previously assumed. It consists of plaque rupture, plaque erosion, and calcified nodules. The advancement of vascular imaging tools has been critical in this regard, redefining the epidemiology of each mechanism. When it comes to acute coronary syndrome management, the presence of ruptured plaques almost always necessitates emergent reperfusion, whereas the presence of plaque erosions may indicate the possibility of conservative management with potent antiplatelet and anti-atherosclerotic medications. Calcified nodules, on the other hand, are an uncommon phenomenon that has largely gone unexplored in terms of the best management plan. Future studies should further establish the importance of detecting the underlying mechanism and the role of various treatment plans in each of these distinct entities. Full article
(This article belongs to the Section Medical Research)
23 pages, 4607 KiB  
Article
Novel Hydrogenated Derivatives of Chemically Modified Curcumin CMC2.24 Are Potent Inhibitors of Melanogenesis in an In Vitro Model: Influence of Degree of Hydrogenation
by Shilpi Goenka
Life 2023, 13(6), 1373; https://doi.org/10.3390/life13061373 - 12 Jun 2023
Cited by 3 | Viewed by 1583
Abstract
Chemically modified curcumin, CMC2.24, is a promising therapeutic that has shown efficacy in ameliorating excessive pigmentation in our previous studies. However, its inherent disadvantages of color, stability, solubility, and cytotoxicity to melanocytes and keratinocytes at concentrations > 4 µg/mL posed challenges in its [...] Read more.
Chemically modified curcumin, CMC2.24, is a promising therapeutic that has shown efficacy in ameliorating excessive pigmentation in our previous studies. However, its inherent disadvantages of color, stability, solubility, and cytotoxicity to melanocytes and keratinocytes at concentrations > 4 µg/mL posed challenges in its use in cosmetic formulations. To overcome these limitations, chemical reduction by hydrogenation of CMC2.24 (compound 1) was developed to yield products at different time points of hydrogenation (1 h, 2 h, 4 h, and 24 h) referred to as partially (2, 3, 4) or fully hydrogenated (5) products, and the effects of the degree of hydrogenation on melanogenesis in vitro were explored. Compound 1 and products 25 were evaluated using mushroom tyrosinase activity assays with two substrates (L-tyrosine and L-DOPA), then cellular assays using B16F10 mouse melanoma cells, MNT-1 human melanoma cells, and physiological normal human melanocytes (HEMn-DP cells). The cytotoxicity, melanin contents, cellular tyrosinase activities, and cellular oxidative stress were evaluated. Moreover, the recovery of melanin contents in HEMn-DP cells was also studied. Our results provide novel insights into the role of the degree of hydrogenation of compound 1 on the biological effects of melanogenesis, which were dependent on cell type. To the best of our knowledge, this is the first study to show that in HEMn-DP cells, the anti-melanogenic efficacy of the yellow-colored CMC2.24 is retained as early as 1 h after its hydrogenation; this efficacy is enhanced with longer durations of hydrogenation, with a robust efficacy achieved for the 24 h hydrogenated product 5 at the lowest concentration of 4 µg/mL. A similar potency could be achieved for product 4 at higher concentrations, although interestingly, both differ only by a minor amount of dihydro-CMC2.24. Our results indicate promise for using products 4 & 5 as a skin-lightener in cosmetic formulations with the advantages of lack of color combined with a potency much greater than that of the parent compound 1 at lower concentrations and reversibility of the effects on melanocytes. This, along with the easy synthesis and scale-up of the hydrogenation method for CMC2.24 and the documented higher solubility, stability, and bioavailability of tetrahydrocurcumin, provides further impetus to incorporating these derivatives in cosmetic formulations. The results of this study can help to extend the therapeutic window of the lead compound CMC2.24 by providing options for selecting partially or fully hydrogenated derivatives for cosmetic applications where a trade-off between color and efficacy is needed. Thus, the degree of hydrogenation can be tuned for desired biological effects. Further studies are warranted to evaluate the efficacy of products 4 & 5 at suppressing pigmentation in 3D skin-tissue equivalents and in vivo models. Full article
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20 pages, 1847 KiB  
Article
Effect of Adherence to the Mediterranean Diet on Maternal Iron Related Biochemical Parameters during Pregnancy and Gestational Weight Gain
by María Morales-Suárez-Varela, Isabel Peraita-Costa, Alfredo Perales-Marín, Beatriz Marcos Puig, Juan Llopis-Morales and Yolanda Picó
Life 2023, 13(5), 1138; https://doi.org/10.3390/life13051138 - 8 May 2023
Cited by 2 | Viewed by 1792
Abstract
Gestation is a crucial life stage for both women and offspring, and outcomes are affected by many environmental factors, including diet. The Mediterranean dietary pattern (MD) is considered a healthy eating pattern that can provide the nutritional requirements of pregnancy. Meanwhile, iron deficiency [...] Read more.
Gestation is a crucial life stage for both women and offspring, and outcomes are affected by many environmental factors, including diet. The Mediterranean dietary pattern (MD) is considered a healthy eating pattern that can provide the nutritional requirements of pregnancy. Meanwhile, iron deficiency anemia is one of the most frequent complications related to pregnancy. This study aimed to evaluate how the level of adherence to the MD influences maternal gestational weight gain and specific iron-related maternal biochemical parameters during the pregnancy. Accordingly, an observational, population-based study using data from pregnant women conducted over the entire course of their pregnancy was carried out. Adherence to the MD was assessed once using the MEDAS score questionnaire. Of the 506 women studied, 116 (22.9%) were classified as demonstrating a high adherence, 277 (54.7%) a medium adherence, and 113 (22.3%) a low adherence to the MD. No differences were observed in gestational weight gain among the MD adherence groups but the adequacy of weight gain did vary among the groups, with the proportions of inadequate (insufficient or excessive) weight gain presenting the most notable differences. Total anemia prevalence was 5.3%, 15.6%, and 12.3%, respectively, during the first, second, and third trimesters. For iron-related biochemical parameters, no differences are observed among the adherence groups during pregnancy. With high adherence to the MD as the reference group, the crude odds of iron deficiency diagnosis are significant in the first trimester for both the medium [OR = 2.99 (1.55–5.75)] and low [OR = 4.39 (2.15–8.96)] adherence groups, with deficient adherence to the Mediterranean dietary pattern being responsible for 66.5% (35.5–82.6) and 77.2% (53.5–88.8) of the risk of iron deficiency diagnosis for medium and low adherence, respectively. However, adjusted odds ratios were not significant, possibly due to the small sample size. Our data suggest that MD adherence could be related to gestational weight gain adequacy and that optimal adherence could reduce iron deficiency and/or anemia during pregnancy in the studied population. Full article
(This article belongs to the Special Issue Nutrition and Dietary Pattern Associated with Diseases)
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16 pages, 2623 KiB  
Article
Detection of Enterotoxigenic Escherichia coli and Clostridia in the Aetiology of Neonatal Piglet Diarrhoea: Important Factors for Their Prevention
by Nikolaos Tsekouras, Eleftherios Meletis, Polychronis Kostoulas, Georgia Labronikou, Zoi Athanasakopoulou, Georgios Christodoulopoulos, Charalambos Billinis and Vasileios G. Papatsiros
Life 2023, 13(5), 1092; https://doi.org/10.3390/life13051092 - 27 Apr 2023
Cited by 4 | Viewed by 1891
Abstract
This study aimed to research the involvement of enterotoxigenic E. coli (ETEC) and C. difficile or C. perfringens type C in the aetiology of neonatal piglet diarrhoea in Greece and to identify preventive factors for them. A total of 78 pooled faecal samples [...] Read more.
This study aimed to research the involvement of enterotoxigenic E. coli (ETEC) and C. difficile or C. perfringens type C in the aetiology of neonatal piglet diarrhoea in Greece and to identify preventive factors for them. A total of 78 pooled faecal samples were collected randomly from 234 suckling piglets (1–4 days of age) with diarrhoea from 26 pig farms (3 piglets × 3 litters × 26 farms = 234 piglets = 78 faecal pool samples). The collected samples were initially screened for the presence of E. coli and C. difficile or C. perfringens via cultivation on MacConkey and anaerobic blood agar, respectively. Subsequently, the samples were pooled on ELUTE cards. From samples tested, 69.23% of those in the farms were ETEC F4-positive, 30.77% were ETEC F5-positive, 61.54% ETEC were F6-positive, 42.31% were ETEC F4- and E. coli enterotoxin LT-positive, 19.23% were ETEC F5- and LT-positive, 42.31% were ETEC F6- and LT-positive, while LT was found in 57.69% of those in the farms. C. difficile was involved in many cases and identified as an emerging neonatal diarrhoea etiological agent. Specifically, Toxin A of C. difficile was found in 84.62% and Toxin B in 88.46% of those in the farms. Antibiotic administration to sows in combination with probiotics or acidifiers was revealed to reduce the detection of antigens of ETEC and the enterotoxin LT of E. coli. Full article
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