This study aimed to investigate the potential of Cord Blood Stem Cell-derived exosome vesicles (CBSC-EVs) in regulating cancer growth and preventing cellular damage. The study aimed to examine the effects of CBSC-EVs on CHL1 cancer cells and healthy fibroblasts. The study results reveal that CBSC-EVs have an anti-cancer/antioxidant effect on CHL1 cancer cells without inducing any toxic effects on healthy lymphocytes. Further analysis of CBSC-EVs revealed the presence of seven miRNAs (noncoding RNA molecules), including three from the Let 7 family, two from the Let 5 family, and two novel miRNAs. The function of the novel miRNAs was the main focus of the study. To assess the efficacy of CBSC-EVs, CHL1 cells (a type of malignant melanoma cell line) and human fibroblasts were grouped into different treatments. One group of those cell lines were treated with CBSC-EVs, and in the second group, the cells were transfected with either miRNA inhibitor Novel 1 (miRNA IN1) plus CBSC-EVs or miRNA inhibitor Novel 2 (miRNA IN2) and CBSC-EVs to knock down those novel miRNAs in the CBSC-EVs. Therefore, by comparing these groups, the function of novel miRNAs is more understandable. In this study, the Comet assay was employed to evaluate cancer cells' DNA damage and CCK8 to measure cell viability. The findings revealed that CBSC-EVs caused an increase in DNA damage in CHL1 cells compared to cells without treatment (p

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

Background: The prevalence of falls among the older population underscores the imperative of comprehending human adaptations to gait perturbations. Dual-belt treadmills offer a controlled setting for such investigations. The purpose of this study was to examine the effect of acceleration of one belt of the treadmill during three different phases of the gait cycle on kinematic and kinetic parameters and relate these changes to unperturbed gait. Methods: Twenty-one healthy young females walked on a treadmill in a virtual environment, in which five unexpected perturbations were applied to the left belt at the Initial Contact (IC), Mid Stance (MS), and Pre-Swing (PS) phase of the gait cycle. Data from the undisturbed gait and the first disturbance of each trial were extracted for analysis. Results: All perturbations significantly affected the gait pattern, mainly by decreasing the knee extension angle. The perturbation in the IC phase had the most significant effect, resulting in a 248.48% increase in knee flexion torque. The perturbation in the MS phase mainly affected plantar flexion torque, increasing it by 118.18%, while perturbation in the PS phase primarily increased the hip extension torque by 73.02%. Conclusions: The presence of perturbations in the IC and PC phases caused the most aggressive and significant changes in gait parameters.

Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. Previously, we developed a sublingual vaccine formulated with the SARS-CoV-2 receptor binding domain antigen and Poly(I:C) adjuvant in nonhuman primates, cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvant and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccineproduced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines—IFN-alpha, IFN-gamma, and IL-17—in the blood, nor upregulated the gene expression of proinflammatory cytokines—IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B—in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with Poly(I:C) adjuvant is safe and creates a balanced state of enhancing and suppressing the immune-related response.

Uterine pathologies pose a challenge to women’s health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the Microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.

Intelligence is a human construct to represent the ability to achieve goals. Given this wide berth, intelligence has been defined countless times, studied in a variety of ways and represented using numerous measures. Understanding intelligence ultimately requires theory and quantification, both of which have proved elusive. I develop a framework – the Theory of Intelligences (TIS) – that applies across all systems from physics, to biology, humans and AI. TIS likens intelligence to a calculus, differentiating, correlating and integrating information. Intelligence operates at many levels and scales and TIS distils these into a parsimonious macroscopic framework centered on solving, planning and their optimization to accomplish goals. Notably, intelligence can be expressed in informational units or in units relative to goal difficulty, the latter defined as complexity relative to system (individual or benchmarked) ability. I present general equations for intelligence and its components, and a simple expression for the evolution of intelligence traits. The measures developed here could serve to gauge different facets of intelligence for any step-wise transformation of information. I argue that proxies such as environment, technology, society and collectives are essential to a general theory of intelligence and to possible evolutionary transitions in intelligence, particularly in humans. I conclude with testable predictions of TIS and offer several speculations.

The clinical features of increasing muscle weakening are shared by a diverse set of illnesses known as muscular dystrophies. In early childhood, males with Duchenne muscular dystrophy (DMD) exhibit proximal muscle weakening and calf enlargement, making it the most frequent X-linked disease of muscular dystrophy in children. Development of motor skills is typically delayed, and wheelchair confinement eventually leads to early death from heart or lung problems. In terms of function, ambulation, quality of life, and life expectancy, treatment approaches like corticosteroid therapy and intermittent positive pressure breathing have improved. This is a case report of a 6-year-old kid who had early ambulatory stage Duchenne Muscular Dystrophy and complained to the neuro-physiotherapy department about frequent falls, walking difficulties, and dyspnea when walking. Other grievances included being unable to get off the ground and having trouble ascending stairs. He had physiotherapy and dynamic neuromuscular stabilization for his complaints. The main goals of treatment were educating the family, respiratory training, preventing ankle plantar flexors, maintaining strength, balance and gait training.

Astaxanthin (ATX) is a carotenoid nutraceutical with a poor bioavailability due to its high lipophilicity. We tested a new tailored nano-droplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX, manufactured by Lyotropic Delivery Systems (LDS)), for its capacity to improve ATX pharmacokinetic profile and anti-oxidant efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to compare the pharmacokinetic profile of ATX and LDS-ATX and protein carbonylation and lipid peroxidation assays to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage. Our results show that only LPS-induced oxidative damage was corrected by ATX and LDS-ATX. While in the liver and muscle LDS-ATX was more efficacious than ATX in attenuating oxidative damage to both proteins and lipids, only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. These results strongly suggest improvement of ATX bioavailability and efficacy by the LDS-ATX nano-formulation.

The maintenance of traditional agricultural practices in protected small islands is closely linked to the preservation of the land, the protection of natural resources, and the conservation of local traditions. For this purpose, the Tuscan Archipelago National Park promoted the census of ancient horticultural varieties preserved by some farmers on the island of Elba. The survey revealed a deep-rooted historical, cultural, social, and economic link between this germplasm and the island’s territory. A scientific characterization of the landrace under ethnobotanical, morphological, and genetic aspects was carried out. Among these local varieties, two landraces of the Brassica species and three landraces of the Phaseolus species were identified and analyzed in this study. To ascertain their distinguishability and uniqueness, similar varieties were also identified based on morpho-physiological characteristics or territorial proximity and compared with the Elban landraces. Morpho-phenological data were collected, and molecular analyses were carried out using Simple Sequence Repeats (SSR) markers. Ten different SSR loci were considered for the Phaseolus species and nine for the Brassica species. The Tuscan Archipelago landraces showed a high level of internal variability but were clearly distinct from each other and from the analyzed varieties, as shown by AMOVA (Analysis of Molecular Variance). Their distinctness was further highlighted by the UPGMA dendrogram obtained from the genetic distance matrix. The same results were confirmed by Principal Coordinate Analysis (PCoA). This study confirms the peculiarity of the Elban landraces, their biodiversity is a heritage to be safeguarded, which can also be used in future breeding programs. These ancient Elban landraces were allocated to local farmers (most were young farmers) to protect them from extinction and to promote more resilient varieties cultivation compared to commercial hybrids widely spread in the area. Local farmhouses also play a strategic role in safeguarding the germplasm and dissemination of sustainable agricultural practices. There is high demand for ancient Elban landraces, this has led to the development of a new local economy balanced between agricultural tradition and innovation.

Mast cells are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, mast cells act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. Mast cells originate from bone marrow progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating in heterogeneous tissue-specific subsets. Even though mast cell activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of mast cell biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand mast cell origin and differentiation as well as the phenotype and functions within different tissues, including the gut. This review recapitulates how single cell transcriptomic studies provided insight into mast cell development as well as into the functional role of intestinal MC subsets in health and disease.

The study of the human microbiome has been a hot topic during the last decades and more recently the skin microbiome has aroused great interest as well. So that, scientists have turned their attention to the role of the skin microbiome in skin health, and its relationship with different disorders as atopic dermatitis, psoriasis, acne, and rosacea, among others. Numerous studies and investigations have been performed to study the role of pre and probiotics as nutraceuticals in the treatment of skin diseases, with growing evidence along the last ten years. This review gathers information on the use of “nutribiotics” in skin care health, focus on the main dermatological diseases and other skin conditions. Clinical studies show that nutribiotics could be a new tool to improve skin health and pre, pro, syn, post and para-probiotics seem to be beneficial on several skin disorders, as well as repairing the skin barrier, or promoting wound healing. In conclusion, skin microbiome has emerged as a new field with high potential to develop disruptive solutions to manage skin health and disease. Future advances in this field may facilitate the treatment of skin dysbiosis being nutribiotics a suitable method for skin care.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Dietary intake and alcohol consumption might be influenced by genetic variations in taste receptor genes. The objectives of this study were to examine the relationship between polymorphisms in bitter taste receptor genes TAS2R13 (rs1015443) and TAS2R38 (rs1726866, rs10246939, and rs713598) as well as alcohol consumption and body fat percentage in college students. Four hundred and two students with a mean age of 20.2 years participated in this study. An NIH Diet History Questionnaire (DHQ II) was used to collect data on their dietary intake, while AUDIT survey was used to determine their level of alcohol consumption. Bitter taste receptor gene polymorphisms were assessed by TaqMan allelic discrimination assays. Despite significant associations between TAS2R13 (rs101544) and certain aspects of alcohol consumption, including the frequency of alcohol intake, no indeed significant associations were found between TAS2R13 (rs1015443) and alcohol consumption after accounting for confounding variables in the regression model. Neither association was found regarding percent of body fat. In contrast, ethnicity and gender significantly influenced percent of body fat (p < 0.001), while no significant association was observed between TAS2R13 (rs1015443) and percent of body fat. Likewise, TAS2R38 (rs1726866, rs10246939 and rs713598) demonstrated no significant association with alcohol consumption and percent of body fat. These results were controlled for confounding factors, such as ethnicity and gender. Body fat percentage and alcohol consumption may be influenced by ethnicity, gender and age rather than SNPs of TAS2R13 and TAS2R38 genes. Assessing the taste genes’ interactions with diet and body composition might be useful in identifying human disease risk.

Artificial intelligence (AI) refers to computer algorithms that replicate the cognitive function of humans. Machine learning is widely applicable using structured and unstructured data, while deep learning is derived from the neural networks of the human brain that process and interpret information. During the last decades, AI has been introduced in several aspects of healthcare. In this review, we aim to present the current application of AI in the neonatal intensive care unit. AI-based models have been applied to neurocritical care, including automated seizure detection algorithms and electroencephalogram-based hypoxic-ischemic encephalopathy severity grading systems. Moreover, AI models evaluating magnetic resonance imaging contributed to the progress of the evaluation of the neonatal developing brain and the understanding of how prenatal events affect both structural and functional network topologies. Furthermore, AI algorithms have been applied to predict the development of bronchopulmonary dysplasia and assess the extubation readiness of preterm neonates. Automated models have been also used for the detection of retinopathy of prematurity and the need for treatment. Among others, AI algorithms have been utilized for the detection of sepsis, the need for patent ductus arteriosus treatmnet, the evaluation of jaundice, and the detection of gastrointestinal morbidities. Finally, AI prediction models have been constructed for the evaluation of the neurodevelopmental outcome and the overall mortality of neonates. Although the application of AI in neonatology is encouraging, further research in AI models is warranted in the future including retraining clinical trials, validating the outcomes, and addressing serious ethics issues.

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces "enhanced exosomes," a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HTRA1, PAM, RSU1, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified altered expression of various miRNAs, such as miR-106a-5p, miR-130b-5p, and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women's reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders.

Exposure to ionizing radiation, accidental or intentional, may lead to delayed effects of acute radiation exposure (DEARE) that manifest as injury to organ systems including kidney, heart, and brain. This study examines the role of activated protein C (APC), a known mitigator of radiation-induced early toxicity, in long-term plasma metabolite and lipid panels that may be associated with DEARE. Male and female cohorts of C57BL/6N wild-type and APCHi transgenic mice were exposed to 9.5 Gy γ-rays with their hind-legs shielded to allow long-term survival that is necessary to monitor DEARE, and plasma was collected at 6 months for LC-MS based metabolomics and lipidomics. We observed significant dyslipidemia, indicative of inflammatory phenotype, upon radiation exposure. Additionally, observance of several other metabolic dysregulations was suggestive of gut damage, perturbations in TCA and urea cycles, and arginine metabolism. We also observed gender and genotype modulated metabolic perturbations post radiation exposure. The APCHi mice showed near normal abundance for several lipids. Moreover, restoration of plasma levels of some metabolites including amino acids, citric acid, and hypoxanthine in APCHi mice are indicative of APC-mediated protection from radiation injuries. With the help of these findings the role of APC in plasma molecular events after acute -radiation exposure in a gender-specific manner can be established for the first time.

Abstract: Lipidic carriers employed for the entrapment, encapsulation and precise targeting the bioactive compounds offer significant advantages to the biomedical, pharmaceutical, nutraceutical and cosmeceutical industries. These lipid and phospholipid-based vesicles can improve the solubility, permeation, pharmacokinetics, pharmacodynamics and bioavailability of the encapsulated material. As a matter of fact, nano-sized phospholipid vesicles have attained the highest success rate in commercialization among the available drug encapsulation technologies. Nevertheless, developing industrially acceptable products still remains a challenge. Among the main disadvantages of conventional lipidic carriers are their instability in the biological environments, and their sensitivity to changes in the pH, temperature and enzymes. To overcome these problems, the new generation of phospho/lipid-based carrier systems was developed using ingredients from microorganisms living in extremely harsh environments (i.e., archeaeobacteria). The present entry aims to review unique features of archaeolipids and recent developments in their application for the encapsulation of genetic material as well as their role and function as adjuvants and vaccine candidates.

Background and objectives: sickle cell disease is the most common hemoglobinopathy in the world. It is considered to be a real public health problem. Sickle cell patients are subjected to several factors causing inflammation such as iron metabolism. The study aimed to look for inflammation in children with sickle cell disease in Cameroon, identify the factors associated with inflammation, and raise the consequences for the patient including the iron profile and the profile of the hemogram. Materials and methods: We conducted an analytical cross-sectional study for 03 months. The sickle cell disease patients coming and/or followed at the Hematology Department of the Regional Hospital of Bafoussam and the Central Hospital of Yaoundé have been recruited. The exploration of inflammation was made by determining CRP, IL6, and ferritin concentrations. The hematological parameters and iron profile were evaluated using standard methods. Statistical analysis of the data was performed; Univariate and multivariate logistic regression analyses allowed to identification of factors associated with inflammation in patients, using the statistical tool R version 4.1.1.. The proportions were compared with the chi-square test when the expected numbers were greater than 5 and the Fisher test when not. Results: The frequency of inflammation in the population was 42.3%. Hyperferritinemia was significantly greater (p<0.001) in patients with inflammation compared to the non-inflammatory patients (96.8% and 76.7% respectively). Patients with inflammation showed a significant elevation of iron parameters (p<0.05). In addition, ferritin and IL6 elevation were associated with inflammation during sickle cell disease respectively (Or = 4.96; 95% CI [1.15-36.42]; p=0.056) and (Or =6.23; 95% CI [1.43-45.96]; p=0.030). Conclusions: The elevated iron in plasma is an effect of inflammation in sickle cell patients. Hence the need of controlling inflammation and iron in the latter is necessary.

(1) The purpose of this study was to compare the percentages of quarterly change for each of the variables analysed (height, weight, body fat percentage and muscle mass) as a function of the quarter in a sample of adolescent football players. (2) The sample consisted of young male football players of different categories belonging to a high-performance football academy, (more than 5 years in football and have spent 1 full year at the academy). (3) Two-way repeated measures ANOVA revealed for the anthropometric variable, P_value

Stress has been identified as a prominent contributor to the development and advancement of bowel cancer, however its specific involvement is intricate and diverse. This abstract tries to offer a concise summary of the correlation between stress and bowel cancer, consolidating significant discoveries from several research fields. The investigation commences by studying the molecular pathways by which chronic stress impacts the development of colon cancer. Chronic stress causes disruption in the functioning of neuroendocrine, immunological, and inflammatory pathways, leading to the development of a microenvironment within the gastrointestinal system that promotes the growth of tumours. Furthermore, changes in the composition of gut microbiota, variations in epigenetics, and alterations in immune function caused by stress also have a role in increasing the risk and advancing the advancement of cancer. Psychological aspects, including how one perceives stress, the tactics they use to cope with it, and the level of psychosocial support they receive, are crucial in determining a person's susceptibility to bowel cancer and impacting the effectiveness of treatment. Stress management therapies, such as cognitive-behavioral therapy and mindfulness-based stress reduction, have demonstrated potential in enhancing patient well-being and promoting adherence to treatment. Moreover, epidemiological studies and clinical trials offer vital knowledge regarding the correlation between stress and the risk, prognosis, and treatment results of bowel cancer. Although the evidence is inconclusive, it is essential to continue researching the intricate relationship between stress and bowel cancer. This will help us understand the connection better and create specific strategies to reduce its impact on patient outcomes.

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1&gt;49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p&lt;0.05). In addition, patients diagnosed with adenocarcinoma, PDL1&lt;49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p&lt;0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

It is the aim of this article to introduce a concise notation that is be able to capture the most important dimensions of sexuality and thus facilitate discussions. Moreover, the major three dimensions - sex, gender, and sexual orientation - lead to a straightforward classification which motivates the quest for stringent explanatory models, some of which are also discussed.

The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection, and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley Rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and were killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis and evaluation of biological effects was performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function and cancer and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples are needed for validation.

Intestinal parasitic infections pose a significant public health challenge in Northern Nigeria, with prevalence rates ranging from 20% to 70%. Traditional diagnostic methods, primarily microscopic examination of stool samples, face limitations such as low sensitivity and high costs. This research addresses these challenges by proposing an Artificial Intelligence (AI)-based platform for the identification and counting of intestinal parasites. A total of 651 samples were collected from the 7 Northern State of Nigeria along with questionnaire collecting data on demographic, socio-economic, hygiene habits and environmental factors. Leveraging the You Only Look Once (YOLO) V8 model, trained on a dataset of 360 pre-processed and 467 annotated images, the AI model demonstrated promising performance metrics. Information-Theory-Based approaches including (CIFE, CMIM, DISR and ICAP) were used on various machine learning models (Naïve Bayes, Random Forest, Support Vector Machine and Decision Tree) to analyse the risk factors associated with the parasitic disease. The precision-recall curve, average precision, mean average precision, and F1 score indicated reliable detection and classification across various parasite classes. The accuracy (97%) and AUC (99%) scores shows that CIFE with Random Forest has the best performance indicating the significant risk factors associated with the parasitic diseases. The model exhibited a well-balanced trade-off between precision and recall, showcasing its potential as a cost-effective and accessible tool for improving the diagnosis and treatment of intestinal parasitic infections in resource-limited settings.

The Herpotrichiellaceae family is an important group of dematiaceous filamentous fungi, associated with a variety of pathogenic fungal species causing Chromoblastomycosis (CBM) and Phaeohyphomycosis (PHM), both with polymorphic clinical manifestations and worldwide incidence. Currently, the identification of this family and determination of the causative agent is challenging due to the subjectivity of morphological identification methods, necessitating the use of molecular techniques to complement diagnosis. In this context, genetic sequencing of the Internal Transcribed Spacer (ITS) has become the norm due to a lack of alternative molecular tools for identifying these agents. Therefore, this study aimed to develop PCR-Multiplex methodologies to address this gap. Sequences from the ITS and Large subunit (LSU) of ribosomal DNA were used, and after manual curation and in vitro analyses, primers were synthesized for the identification of the aforementioned targets. The primers were optimized and validated in vitro, resulting in two PCR-Multiplex methodologies: one for identifying the Herpotrichiellaceae family and the bantiana clade, and another for determining the species Fonsecaea pedrosoi and Fonsecaea monophora. Ultimately, the assays developed in this study aim to complement other identification approaches for these agents, reducing the need for sequencing, improving the management of these infections, and enhancing the accuracy of epidemiological information.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

Studies of Phytophthora impacts in forests generally focus on individual species without recogni-tion that Phytophthora occur in multispecies communities. We investigated community structure of Phytophthora species in the rhizosphere of Agathis australis (kauri) in Te Wao Nui o Tiriwa / Waitākere Ranges, New Zealand, in the context of kauri dieback disease expression. Soil sampling and tree health monitoring was conducted on 767 randomly selected mature kauri trees. Phy-tophthora species were detected using both soil baiting and DNA metabarcoding of eDNA. Four species were detected with soil baiting (P. agathidicida, P. cinnamomi, P. multivora, and P. pseudo-cryptogea) and an additional three species with metabarcoding (P. kernoviae, P. cactorum/P. aleatoria and an unknown clade 7 species). Phytophthora cinnamomi was the most abundant species and was distributed throughout the forest. Both P. multivora and P. agathidicida were limited to forest edges, suggesting more recent arrivals. P. agathidicida presence was strongly correlated with declining canopy health, confirming its role as the main river of kauri dieback. The limited distribution of P. agathidicida and infrequent detections (11.0% samples) suggests that that this species is spreading as an introduced invasive pathogen and provide hope that with strategic management uninfected areas of the forest can be protected. The frequent detections of P.cinnamomi and P. multivora, from symptomatic trees in the absence of P. agathidicida suggest more research is needed to understand their roles in kauri forest health.

Introduction: Bovine tuberculosis is a zoonotic disease of considerable impact, especially in livestock countries, which can cause human disease. Despite its importance, Colombia is a country in which few studies analyse its behaviour, and none develop maps using geographic information systems to characterise it. Objective: To describe the temporal-spatial distribution of bovine tuberculosis in Colombia between 2001 and 2019. Methods: Retrospective cross-sectional descriptive study, based on reports by the Colombian Agricultural Institute, of tuberculosis surveillance in cattle on farms in Colombia from 2001 to 2019. The data were converted into databases in Microsoft Access 365®, and multiple epidemiological maps were generated with the Kosmo RC1®3.0 software coupled to shape files of all the country's departments. Results: During the study period, 5,273 tuberculosis cases in bovines were identified in the different departments of Colombia (mean 278 cases/year). Regarding its temporal distribution, the number of cases varied from a maximum of 903 cases (17.12% of the total) in 2015 to a minimum of 0 between 2001 and 2004 and between 2017 and 2019 (between 2005 and 2016, the minimum was 46 cases, 0.87%). Conclusions: GIS is an essential tool for understanding the temporospatial behaviour of zoonotic diseases in Colombia, as is the case of bovine tuberculosis, with its potential implications for Human and One Health.

New biomedical technologies are examined in depth and the legal and ethical challenges they pose. Key issues such as gene editing, the application of artificial intelligence in the medical field, and the protection of biological information data are analyzed. At the same time, we also found that technological advances in the development of the enormous potential of biomedicine, but also raises a series of ethical and legal issues. To this end, the paper proposes a series of effective response strategies aimed at providing guidance to policy makers, researchers, and healthcare professionals to ensure the rational and safe application of new technologies. Solutions to these challenges are elaborated. When it comes to gene editing, the article stresses the responsibility of scientists not only to push the boundaries of technology, but also to ensure that edited genes are in the public interest and respect individual rights. To this end, strict regulatory mechanisms should be put in place to ensure that gene editing is carried out only in certain and ethical circumstances. Although AI technology has brought many conveniences to the medical field, it also involves data privacy protection, the transparency of the AI decision-making process, and the impact of AI on traditional medical models. Therefore, it is necessary to formulate corresponding regulations to regulate its application, ensure the fairness and transparency of AI decision-making, and promote its integration and development with traditional medicine. The importance of the protection of biometric data was also emphasized. In biomedical research, a large number of personal biological information data, such as genome and proteome, are often involved. This data should be effectively protected to prevent data leakage and misuse. To this end, it is necessary to strengthen data security measures and establish standards and norms for data sharing and utilization to ensure the rational use and protection of data.

Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7,738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method. We further applied Cochran’s Q statistical analysis, MR-Egger intercept, and MR-PRESSO for heterogeneity and pleiotropy assessment, alongside a Bonferroni correction ((P

Analysis of complex DNA mixtures is limited by the selected genetic markers characterized and assay technology. Small panels of short tandem repeats (STRs) are the current standards in most countries. Extension of STRs with hundreds of single nucleotide polymorphisms (SNPs) is now commercially available. The current set of extension SNPs focus on phenotypic and biogeographic ancestry informative SNPs. Larger panels with thousands of SNPs have been developed that can identify up to 10 contributors to forensic DNA samples. Herein, multiple sets of SNPs were selected with the focus of increasing the upper limit of detectable contributors. Larger SNP panel sets with lower minor allele frequency (MAF) alleles can detect large numbers of contributors to in silico mixtures of randomly selected profiles from the 1,000 Genomes project. These results provide a path to enable characterization of complex DNA mixtures that are currently impossible to analyse.

Forage fish are crucial to human nutrition, especially in developing countries. However, in these countries, most forage fish catches are used to make aquafeeds for aquaculture, which leaves only a small quantity for direct human consumption. This practice increases fish prices in local markets and undermines people's nutrition. Overfishing forage fish for industrial purposes harms the ecosystem, reduces the catch of larger fish, and marginalizes local fishermen. Although previous discussions have touched qualitatively on the ethics and injustice of this practice, this article provides quantitative scales to measure the impact of the practice on the finances and forage fish consumption of low-income consumers using reasonable assumptions and literature values. Increasing the annual supply of forage fish by 25% to the 5 million MT of fresh fish markets globally could save consumers several billion US dollars annually. Families could consume a higher percentage of nutritious fish for less money. Furthermore, leaving forage fish in the sea could benefit wildlife and increase the capture of larger fish, such as mackerel, which are in demand in local markets and fished by local fishermen. The unintentional and involuntary contributions of low-income societies to enable the growth of high-value fish and shrimp for affluent societies seem unjust and warrant further investigation.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

Prokaryotic genomes are dynamic tapestries that are strongly influenced by mobile genetic elements (MGEs), including transposons (Tn’s), plasmids, and bacteriophages. Of these, miniature inverted-repeat transposable elements (MITEs) are undoubtedly the least studied MGEs in bacteria and archaea. This review explores the diversity and distribution of MITEs in prokaryotes and describes what is known about their functional roles in the host and involvement in genomic plasticity and evolution.

French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there are few data available on the description of parasites circulating in this area, especially on protozoan belonging to the phy-lum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on Oxford Nanopore Technologies sequencing platform using the 18S gene of fourteen Apicomplexa-positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify as Apicom-plexa-positive 10 samples out of 14 and reveal the presence of co-carriages. The same samples were also sequenced with Illumina platform, for validation purposes. On samples identified as Apicomplexa-positive by both platforms, a strong positive correlation at up to genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detec-tion, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.

In horses, quantitative assessment of gait parameters, as the use of inertial measurement units system (IMUs), might help in the decision-making process. However, it requires financial investment, is time-consuming, and lacks accuracy if displaced. An innovative Artificial Intelligence marker-less Motion Tracking System (AI-MTS) may overcome these limitations in the field. Our aim was to compare the level of agreement and accuracy between both systems and visual clinical assessment. Twenty horses underwent locomotion analysis by visual assessment, IMUs and AI- MTS systems, in the following conditions: straight hard (SH), straight soft (SS), left and right circle hard (LCH, RCH) and soft (LCS, RCS). A greater number of horses were considered sound by clinical examination, compared to those identified as symmetric by the two gait analysis systems. More limbs were considered asymmetric by the AI-MTS compared to IMUs, suggesting its greater sensitivity. The greatest agreement between the two systems was found for the difference between two minima in vertical head position in SH, while the lowest for the difference between two minima in vertical pelvis position in SS, reflecting the difficulties in assessing asymmetry of hindlimbs. Some degree of asymmetry may be clinically relevant, suggesting its regular use in training horses.

Metabolites are at the end of the gene-transcript-protein-metabolism cascade. As such, metabo-lomics is the omic approach that offers the most direct correlation with phenotype. This allows that, where genomics, transcriptomics and proteomics fail to explain a trait, metabolomics might give an answer. Complex phenotypes, which are determined by the influence of multiple small effect alleles, are an example of these situations. Consequently, the interest in metabolomics has increased ex-ponentially in the last years. As a newer discipline, the metabolomics bioinformatics analysis pipe-lines are not as standardized as in the other omic approaches. In this review we synthesized the different steps that need to be carried out to obtain biological insight from the annotated metabolite abundance raw data. These steps were grouped in three different modules: preprocessing, statistical analyses and metabolic pathway enrichment. We included within each one of them the different state-of-the art procedures and tools that can be used depending on the characteristics of the study, providing details about the characteristics of each method has, as well as the issues the reader might encounter. Finally, we introduce genome scale metabolic modeling as a tool for obtaining pseu-do-metabolomic data in situations where its acquisition is difficult, being possible to analyze the resulting data with the modules of the described workflow.

New onset diabetes mellitus after transplantation (NODAT) is a common complication following solid organ transplantation, with varying incidence rates due to discrepancies in defining NODAT and follow-up duration, alongside modifiable and non-modifiable risk factors. NODAT adversely affects patient survival and graft longevity, warranting early detection, especially in countries experiencing a rise in kidney transplant cases, emphasizing the need for understanding diagnostic criteria, risk factors, pathogenic mechanisms, and post-transplant outcomes.

Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations, characterized by distinct interactomes – namely protein assemblies - under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly and disease.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures whit bulging calvaria, hypoplasia or aplasia of clavicles permitting abnormal opposition of the shoulders, wide public symphysis, short middle phalanx of the fifth fingers and vertebral, craniofacial and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The responsible gene of CCD is the runt-related transcription factor 2 gene (RUNX2). We characterize the clinical, genetic and bioinformatic results of four CCD cases. Two Mexican familial with 6 affected members, 9 asymptomatic individuals, and two sporadic cases with CCD, as well as 100 healthy controls. Genomic DNA analyses of the RUNX2 gene was performed for Sanger sequencing. Bioinformatics tools, used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652del; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability, and structural alterations in RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. In addition, one patient presented clinical data not previously reported that could represent an expanded phenotype of sever expression.

Machine Learning classifiers are used to classify a very wide dataset containing gene ex-pression microarray data of patients with five types of cancer (breast cancer, kidney cancer, Colon cancer, lung cancer and prostate cancer). Since the dataset was very wide with a large number of columns, the code yielded stack overflow errors, and we resorted to Principal Components Analysis (PCA) for dimensionality reduction, and principal component scores of the raw data for classification. PCA was run using a fast algorithm which is able to compute PC scores for very large datasets. High classification accuracies are obtained using just the first two principal component scores. Machine Learning (ML) classifiers Linear Discriminant Analysis (LDA) & Random Forest (RF) methods were utilized where the latter provided with higher accuracy than the former. The results of this article should be helpful to researchers who are dealing with large number of genes in microarray data.

We present the full case pictorial assay including preoperative imaging as well as the surgical correction of the uterine anomaly and associated complication of a very rare case of occult unicornuate right uterus with rudimentary non-communicating functioning left horn and its natural evolution following an initially incomplete surgical treatment.

The advent of CRISPR/Cas9 technology has revolutionized genome editing, enabling the attainment of once-unimaginable goals. CRISPR/Cas's groundbreaking attributes lie in its simplicity, versatility, universality, and its independence from customized DNA-protein systems, erasing the need for specialized expertise and broadening its scope of applications. Beyond its editing prowess, the discovery of novel Cas-based systems has spawned an array of additional biotechnological tools, empowering both fundamental and applied research. Researchers have harnessed CRISPR/Cas for gene regulation, deepening insights into gene expression and epigenetic changes. Precisely targeting DNA or RNA sequences, CRISPR/Cas effectively identifies and counters pathogens. Furthermore, it aids in genome imaging and sequencing, revealing genome spatial organization and chromatin dynamics. The non-editing applications of CRISPR/Cas exhibit tremendous potential across diverse domains, including diagnostics, biotechnology, and fundamental research. This article reviews and critically evaluates the primary CRISPR/Cas-based tools developed for plants and animals, underlining their transformative impact.

Using the h-index to assess individual researchers is not only unethical and unfair but also inaccurate and misleading. This index fails to offer a reliable measure of a researcher's impact based on their citation scores. Beyond statistical and conceptual considerations, authorship practices, especially in the case of multi-authored publications, give rise to significant problems that often go unnoticed. While some modifications of the h-index have been proposed to mitigate these weaknesses, the fundamental deficiencies persist. Most of these flaws have been effectively addressed by the c-score, a composite citation index. The c-score excludes self-citations, normalizes the number of citations by considering the number of authors in each paper, and takes into account first, single, and last authorship. This approach provides a more realistic measure of the impact of each individual researcher based on raw citations.

Food allergy (FA) affects approximately 6–8% of children worldwide causing a significant impact on the quality of life of children and their families. In the years, the possible role of weaning in the development of FA has been studied. According to recent studies, the role of weaning in its development is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collected the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food.

The major arboviruses belong mainly to the families Bunyaviridae, Togaviridae, and Flaviviridae amongst which chikungunya virus and dengue virus have emerged as a global public health problem. The main objective of the study was to develop a specific, sensitive, and cost-effective molecular multiplex RT-PCR and RT-qPCR assay for the rapid and simultaneous detection of CHIKV and the four serotypes of DENV for arbovirus surveillance. Specific primers of all virus were designed, one step multiplex RT-PCR (mRT-PCR) and RT-qPCR (mRT-qPCR) was developed using reference strains of CHIKV and DENV serotypes. The specificity of the test for all the viruses was confirmed by sequencing. The standard curves showed a high correlation coefficient, R2= 0.99, for DENV-2 and DENV-3; R2= 0.98, for DENV-4 and CHIKV; R2= 0.93, for DENV-1. The limits of detection were calculated to be 10-2 copies/µL for all viruses. The specificity and sensitivity of the newly developed mRT-PCR and mRT-qPCR were validated using positive serum samples collected in India and Burkina Faso. The sensitivity of mRT-PCR and mRT-qPCR are 91%, and 100% respectively. The specificity of both assays was 100% specific. mRT-PCR and mRT-qPCR assays are low cost and a combination of both will be a useful tool for arbovirus surveillance.

The goal of this study was to characterize the initial growth trajectory of Epicrates assisi, 1 Epicrates cenchria, and Epicrates crassus snakes raised in captivity. An exponential model with 2 parameters for birth weight (A) and growth rate (k) was fitted for each animal. There was a significant 3 difference A and k among the three species, the means (standard error) for A and k parameters were 4 31 (0.3) g and 0.0027 (0.00006) for E. assisi, 27.6 (0.6) g and 0.0046 (0.00013) for E. cenchria and 25.9 5 (1.4) g and 0.0033 (0.00027) for E. crassus. We showed a significative variability between species for 6 initial growth trajectory. In addition, we also demonstrated the existence of variability within species, 7 which can be used to change the growth trajectory of snakes, being a tool for selection and genetic 8 improvement.9

Phytoplankton guilds are commonly characterised by dominance effects, while the main contribution to biological diversity is given by rare species. Here, we analysed the influence of rare species on taxonomic and functional diversity, described by taxa richness and composition, cell size and size abundance relationships in phytoplankton guilds. We explore these relationships at global and regional scales by analysing phytoplankton guilds from five biogeographical regions: Northern Atlantic Ocean (Scotland), South-Western Atlantic Ocean (Brazil), South-Western Pacific Ocean (Australia), Indo-Pacific Ocean (Maldives) and Mediterranean Sea (Greece and Turkey). We have comparatively analysed the phytoplankton taxonomic diversity of the whole dataset and with the datasets obtained by progressively subtracting taxa occurring in the last 1%, 5%, 10% and 25% of both numerical abundance and overall biomass. Globally 306 taxa were identified across five ecoregions with only 27 taxa accounting for the 75% of overall numerical abundance and biomass; almost the 50% of taxa were lost on every step. The removal of 1% most rare taxa significantly affected the phytoplankton size-abundance relationships and body-size structure, strongly impacting on small taxa. The progressive removal of additional rare taxa did not further affect phytoplankton size-abundance relationships and size structure.

Apex predators were extirpated from the UK hundreds of years ago. Practitioners have recently advocated for reintroductions of predators in the UK given their role as keystone species. For a reintroduction to take place, a survey of public desirability needs to be conducted. We aimed to understand the perspectives of people across the United Kingdom on the reintroduction of Eurasian lynxes, grey wolves, and brown bears. We collected data via questionnaires from 78 key stakeholders, such as farmers, general public, nature conservationists, and those in environmental sectors, with these areas being seen as the most affected by these reintroductions. It was organizations which front these stakeholder groups which mainly distributed the survey, as well as social media groups. We ran a path analysis, which highlighted that there was a negative correlation between respondents viewing the species as a danger towards livestock and humans, and the respondent seeing it being good to have that species in their region. Overall, participants who stated that rewilding their region was a priority also stated that it would be good to have Eurasian lynx in their region. That said, 70% of farmers strongly disagreed with the reintroduction of Eurasian lynx. These findings showed that much of the United Kingdom would welcome the reintroduction of Eurasian lynx, but both farmers and the public would fear the loss of livestock that may come along with these species. Support can be gained through education and knowledge, a necessary step needed especially targeting farmers before any reintroduction plans can be made.

Abstract: Intra-abdominal abscesses (IAA) may commonly arise following complicated gastrointestinal tract infections and, on occasion, from infections within the urinary system. Many of these IAA are initiated as a consequence of post-surgical complications. These abscesses have a substantial risk of morbidity and mortality. As a result, it is crucial to diagnose and treat them promptly to minimise these adverse outcomes. Therefore, radiological modalities play a vital role in diagnosing, localising, and detecting associated complications of IAA, as sometimes other investigations could be less reliable and non-specific. Radiological modalities are pivotal in achieving an accurate diagnosis, localising the abscesses, and identifying associated complications. This is especially important since alternative investigative methods may be misleading in certain situations. Radiological techniques such as ultrasound scans (USS), contrast-enhanced computed tomography (CECT), and even magnetic resonance imaging (MRI) are immensely helpful in diagnosing these conditions. These imaging tools guide clinicians in determining the most appropriate patient management strategies. In this article, we compile a case series involving tubo-ovarian abscess, appendicular abscess, diverticular abscess and infected walled-off pancreatic necrosis, paying particular attention to radiological features in the diagnosis. Furthermore, we reviewed the existing literature to delineate characteristic radiological features related to the cases we discussed.

1. Background Septic shock is a rare and serious infectious disease. Patients surviving the early phase are at high risk of multiple amputations of limbs. They are potential sources of serious disability. 2. Methods The objective was to describe the functional prognosis and quality of life of the four-limb amputee patients following septic shock. This is a descriptive, retrospective and mono-centric study. The patients included between 2010 and 2019 had septic shock after 18 years, responsible for amputation of the four limbs. We studied the mean age of septic shock, the causative organisms, the infectious door enter, the different levels of amputation, the fitting process, the resumption of walking, the Functional Independence Measure (FIM) and the SF-12 Quality of Life Questionnaire. 3. Results We suceed to include 15 patients.. 53.3% women and 46.7% men with an average age of 46.1 years. 80% presented bilateral trans-tibial amputations, all were able to return walking even over short distances, within an average of 8.4 months. 40% did not require a technical walking aid, 33.3% had no walking perimeter limitation. 47% had a higher mental and social quality of life score than the general population. The younger the patients, the better their physical quality of life. After two years of follow-up, the younger the patients, the better their functional autonomy. Patients with better functional autonomy had a better physical quality of life. 4. Conclusion The number of amputations due to spetic shock is likely to increase in the years to come throughout the world. Our study prove that quadri-amputee patient can regain a fully acceptable functional and quality of life being monitored in a specialized health center with multidisciplinary health professional to help him.

Sleep disorders are a frequent problem in pediatrics. The prevalence is variable (from 15 to 50%) although the majority of papers coincide in that 1 every 3 kids can experiment some kind of sleep disorder. Underlying medical problems usually manifest by difficulty to fall asleep or stay asleep. The diagnosis and resolution of the medical problems with the specific treatment should be the prime concern, before starting with the treatment of the sleep behavioral problem

Fresh-cut apple is commonly known as minimally processed agriculture products because of their convenience and ease of consumption. However, during storage, the quality of the apple rapidly changes after the cutting process due to enzymatic and non-enzymatic processes. This study aimed to monitor the quality changes of fresh-cut apples at various temperatures and different types of products in the application of a cold chain system during distribution and storage. The results showed that the total viable count in fresh-cut apples initially differed between apple only and mixed products (apple, orange, and tomato) during storage (p &lt; 0.05). Moreover, there are no significant differences (p &gt; 0.05) in physicochemicals except firmness, titratable acidity, and pH, which are highly correlated to microbial growth (total viable count and total coliform number). Furthermore, the optimal temperature for extending the shelf-life of fresh-cut apples was at 4°C.

Knowing that biomolecules, such as β-amyrin and α-amyrin, have some pharmacological effects, the aim of this study was directed towards exploring the protective effect of a Tomato Peel and Seed Extract (TPSE) for its soothing function but also for its capacity to modulate the adrenal axis, involved in stress response. Ex vivo tests were carried out on skin explants to evaluate the effectiveness of TPSE formulated at 0.5% on Calcitonin Gene-Related Peptide (CGRP) and IL-10 release, Kappa Opioid Receptor (KOR) and Caspase 14 expression. An in vivo study combined a clinical evaluation of skin homogeneity, psychological parameter as well as analysis of salivary cortisol and dehydroepiandrosterone concentrations. All measurements were carried out at the beginning and after 28 days of applying a TPSE face cream. TPSE regulated not only the release of CGRP and Il-10, reflecting an anti-neurogenic and anti-inflammatory properties, but also modulated KORs. Twenty height days of TPSE application induced a significant decrease in intensity and extent erythrosis, a lower output of salivary cortisol and a significant increase in pleasant emotions when compared to placebo. These results provide encouragement to continue exploring the impact of cosmetic ingredient on psychophysiological parameters to improve skin health and well-being.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and is associated with various gastrointestinal disorders. H. pylori is a pervasive pathogen, infecting nearly 50% of the world's population, and presents a substantial concern due to its link with gastric cancer, ranking as the third most common cause of global cancer-related mortality. This review article provides an updated and comprehensive overview of the current understanding of H. pylori infection, focusing on its pathogenesis, diagnosis, and treatment strategies. The intricate mechanisms underlying its pathogenesis, including virulence factors and host interactions, are discussed in detail. Diagnostic methods, ranging from traditional techniques to advanced molecular approaches, are explored, highlighting their strengths and limitations. The evolving landscape of treatment strategies, including antibiotic regimens and emerging therapeutic approaches, is thoroughly examined. Through a critical synthesis of recent research findings, this article offers valuable insights into the contemporary knowledge of Helicobacter pylori infection, guiding both clinicians and researchers toward effective management and future directions in combating this global health challenge.

Fungi belong to the species with the highest biodiversity and high potential for use in biotechnology and industry. Therefore, their long-term quality conservation is very important and it is necessary to continuously develop new methods and improve existing methods. Currently, cryopreservation appears to be the best available technique for the preservation of fungi. This study summarises the latest trends and advances in fungal cryopreservation over the last 7 years, i.e. findings from scientific publications from 2017 to 2023 dealing with cryopreservation of both basidiomycetes and non-basidiomycete fungi. The work analyzed the studied organisms and the cryopreservation method used, focused on the use of new procedures and modifications of existing methods; summarized the conditions for successful cryopreservation, such as cryopreservation time and temperature, as well as the substrate and cryoprotectant used.

The Swiss Personalized Health Network has developed a national framework for enabling the semantic representation of health data within a Knowledge Graph. This framework has been implemented in all Swiss university hospitals, promoting seamless sharing and integration of clinical routine data with other health-related data, including omics and clinical research data. While research projects often have flexibility in selecting terminologies and specific versions, historical clinical routine data are typically coded for billing or administrative purposes using predefined terminologies in various (sometimes even unknown) versions over time. Some of these terminologies do not adhere to best practices for ontology design, presenting significant challenges to the retrospective re-use of such coded data for research. Common issues with these terminologies include the lack of machine-readable traceability across versions and non-adherence to FAIR principles. Terms from older versions frequently disappear in newer ones, making it challenging to distinguish outdated from invalid terms. Additionally, 'semantic drift' occurs, where the meaning of terms changes across versions. To address these challenges, we have implemented FAIR and historized versions of ATC, CHOP, and ICD-10-GM. We represent each version in RDF using versioned URIs and track meaning changes between versions in a machine-readable way using OWL and RDFS. The integration of these historized terminologies into our quality control framework, based on SHACLs, enables comprehensive data quality control in hospitals and empowers researchers to effectively utilize this data. Our work aims to bridge the gap between health data coded in different terminology versions, ensuring a consistent and reliable semantic representation.

In the field of modeling social systems, the use of agent-based models (AM) has become a powerful tool for understanding processes occurring in society, in particular, for studying the spread of infections among the population. The agent model is based on a synthetic population consisting of agents, their interactions and sometimes the territory in which the interaction occurs. The choice of an appropriate method for creating such artificial populations and the selection of parameters becomes a key issue affecting the realism of the model and its ability to reflect real-world scenarios. This article delves into the interplay between agent-based modeling, synthetic population construction, and parameter selection, offering our insight into the complex process of modeling infectious disease dynamics. The review concludes with an exploration of extending the Covasim model [1] to experiments in computational epidemiology. Covasim, a dynamic transmission modeling tool, is known for its ability to adapt to different scenarios and offers predictive information critical for managing epidemiological situations. The Covasim model could include improvements to better simulate real-world epidemic conditions, including a revised transmission strategy to account for accumulation through daily contacts. In addition, we propose to add a module for intercity travel and a visualization package that will significantly expand the functionality of Covasim. These improvements make Covasim a more versatile and efficient tool for modeling and analyzing epidemic processes.

This paper presents a concise exploration of the synthetic biology currently to artificially 1 create life, juxtaposed against natural life’s emergence over Earth’s 4.5-billion-year history. It explores 2 the complexities of life’s origins, sustaining factors, and the consequences of synthetic life creation, 3 addressing key scientific milestones such as the Urey-Miller experiment and Jacques Monod’s pro- 4 posals. The narrative navigates through the roles of energy, Maxwell’s demons, bifurcations, and 5 genetic information in the emergence and evolution of complex biological systems. Despite significant 6 strides in genetic engineering, the challenge of creating life from scratch persists, necessitating a deep 7 understanding of diverse scientific disciplines. While synthetic biology holds promise for medicine 8 and biotechnology, the creation of truly autonomous synthetic life forms raises ethical concerns. The 9 paper also stresses the imperative for careful ethical evaluation of the societal and environmental 10 implications arising from these advancements.

Deeper understanding of biological processes, disease mechanisms, and prospective therapeutic targets can be attained by Gene Expression Network Analysis (GENA), which offers a potent framework for revealing the intricate regulatory mechanisms controlling gene expression. GENA is a computational method used to understand the intricate interactions and relationships between the genes in a biological system. It entails using network theory, statistical analysis, and gene expression data to pinpoint functional modules, regulatory linkages, and important genes or pathways involved in a particular biological process or illness. This chapter broadly outlines the principles and practice of GENA, to an novice reader and outlines a simple method of performing a GENA using online Rice gene expression datasets available in various websites.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

The COVID-19 pandemic has created unique challenges for people with comorbidities, including hereditary diseases and cancer cancers. Several studies have reported a link between the presence of disease-causing genetic variants and the outcome of the COVID-19 infection. In this study, we used clinical exome sequencing in a cohort of 840 COVID-19 patients to identify pathogenic and likely pathogenic genetic variants present in these individuals. While we did not identify any statistically significant differences in the overall burden of pathogenic variants between different patient groups, we discovered three known pathogenic alleles associated with hereditary cancer syndromes, including a frameshift mutation in MSH6 and two missense mutations in TP53. The patients carrying these mutations presented with different severity of the disease and outcome. Thus, a 58-year old male subject with an MSH6 mutation developed a severe form of COVID-19 that resulted in death, even though the patient had few pre-existing conditions and no evidence of malignant tumors. On the other hand, two female subjects carrying pathogenic TP53 variants successfully recovered from the disease despite suffering from various forms of cancer. Our results highlight the importance of personalized approaches to the diagnosis, management and treatment of COVID-19 in patients with specific genetic mutations. Further studies are needed to elucidate the complex relationship between these mutations and COVID-19.

Considering bitemark evidence, forensic dentists must give testimony that could have catastrophic consequences. A bitemark is often the only physical evidence on a body, and odontologists' testimony should be powerful and simple to understand. Given that perpetrators may be executed or imprisoned for life, a defective bitemark analysis is comparable to dentists' most crucial clinical decisions regarding diagnosis. Bias affects human bitemark analysis, and forensic dentists must examine its invisible impacts to avoid making mistakes. The aim of this study was to explore the potential of different types of bias in bitemark analysis and methods during analysis by conducting a scoping review. The majority of the 14 articles that were taken into consideration were published in 2019. USA, UK, Australia, New Zealand, and the Netherlands published the most articles. 36% of the publications addressed contextual bias, while 57% acknowledged cognitive bias. Preventive measures have been recommended to address bias in bitemark analysis. These consist of limiting the availability of unrelated data during the research, employing several comparison samples for a more impartial assessment, and repeating the analysis while being blind to past findings. These preventative measures reduce cognitive and contextual bias and improve bitemark analysis in forensic investigations.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating acquisition of a rapid supply of ATP for proliferation in AML. Therefore, targeting of mesothelin presents a potentially promising approach for mitigating the progression of AML through inhibition of glycolysis and mitochondrial respiration in myeloid cells.

The principal goal of this current study was to isolate a new potential probiotic strain to prepare contamination-free probiotic dahi in a dosage form with desired shelf life. To achieve our target, firstly, probiotic dahi was prepared by a probiotic strain, Lactobacillus acidophilus JB2CON (OM909067) (identified by 16S sequencing) isolated from natural dahi in Dhaka, Bangladesh. The isolate showed five probiotic features by in vitro test and had an antagonistic effect against five different pathogens. More interestingly, it inhibited Escherichia coli (diameter of zone of inhibition = 15.75±0.35) the most. In the time-kill analysis method, E. coli was killed totally within 5.50 hours of fermentation. Finally, the time duration of 14 days was an ideal shelf life, because the probiotic count increased but a slight change in pH did not affect the taste (sourness/acidity) of dahi. The most significant impact of this research is that the probiotic dahi of our experiment might be used as a cheap option for preventing pathogenic Escherichia coli-related foodborne diseases worldwide, especially in underdeveloped countries like Bangladesh.

Autoimmune hepatitis (AIH) is a chronic, relapsing and remitting, immune mediated liver disease which progresses to cirrhosis if left untreated. A significant number of patients may present with acute hepatitis or acute liver failure, which are often misdiagnosed as toxic liver injury. AIH shows a preponderance for young women but may be seen in children and elderly. Diagnosis requires integration of clinical, biochemical and serologic parameters along with supportive liver histology and exclusion of other causes of liver disease. Liver biopsy is a pre-requisite for diagnosis of AIH, to assess severity and stage of disease, exclude other entities and recognize any concurrent morbidities. No single biomarker or histologic feature is pathognomonic for AIH. The diagnostic and histologic criteria have undergone several modifications since the Original Scoring system proposed by the International Autoimmune Hepatitis Group (IAIHG) in 1993. Recently, IAIHG has proposed consensus recommendations for histologic criteria, relevant for both acute and chronic AIH. This review article will describe the evolving diagnostic criteria for AIH with their limitations and utility, with an emphasis on the role of liver histology in diagnosis and management of AIH.

Background: This study aimed to investigate how external perturbations caused by the treadmill belt's acceleration (Acc) and deceleration (Dec) during the Initial Contact (Initial), Mid Stance (Mid) and Pre-Swing (ToeOff) phase affect gait regularity in young adults. Methods: Twenty-one healthy young females walked on a treadmill in a virtual environment (Grail, Motek), where four unexpected perturbations were applied to the left belt at Initial, Mid, and ToeOff. Sample Entropy (SampEn) was calculated for the center of mass (CoM) displacements, for six perturbation scenarios in three directions: anterior-posterior (AP), medial-lateral (ML), and vertical (vert), with SampEn vector lengths (m) ranging from 2 to 10. Results: The CoM displacement exhibited its highest regularity (low SampEn values) in the AP and vert-directions during Dec_ToeOff, across all m values. Similarly, this pattern was observed in the ML-direction, but exclusively for m = 2 and 4. The least regular CoM trajectories (high SampEn values) were for Dec_Mid in the AP-direction, across all m values. This trend persisted in the ML-direction, only for m = 2 and 4. However, the most irregular CoM displacements in the ML-direction occurred during Dec_ToeOff for the remaining m values. Vertical CoM displacements exhibited the highest irregularities during Dec_Initial for m ≥ 4. Conclusions: Evaluating the regularity of CoM displacements using SampEn can be a useful tool for assessing how gait perturbations are handled.

Machine learning, including deep learning, reinforcement learning, and generative artificial intelligence are revolutionising every area of our lives when data is made available. With the help of these methods, we can decipher information from larger datasets while addressing the complex nature of biological systems in a more efficient way. Although machine learning methods have been introduced to human genetic epidemiological research as early as 2004, those were never used to their full capacity. In this review, we outline some of the main applications of machine learning to assigning human genetic loci to health outcomes. We summarise widely used methods and discuss their advantages and challenges. We also identify several tools, such as Combi, GenNet and GMSTool, specifically designed to integrate these methods for hypothesis-free analysis of genetic variation data. We elaborate on the additional value and limitations of these tools from a geneticist’s perspective. Finally, we discuss the fast-moving field of foundation models and large multi-modal omics biobank initiatives.

The study of angiosperm flora, endemic plants in the literature, and investigations of ‘POWO Build a checklist’ were used to compile an updated list of Bangladesh's endemic plants. According to the study, at least 49 (1.24%) of Bangladesh's 3,956 plant species are endemic to the country including 5 varieties, belonging to 41 genera in 26 families. Magnoliopsida account for thirty of them, Liliopsida for the remaining sixteen, and Pteridohpytes for the final three. The four families Zingiberaceae (9 taxa), Araceae (6 taxa), Rubiaceae (4 taxa), and Euphorbiaceae (3 taxa), include the most endemic taxa. The five most numerous endemic taxa belong to the Curcuma genus. The endemic flora, which is mostly found in the districts of Chattogram, Moulvibazar, and Rangamati, consists of 13 tree species, 4 shrubs, 5 climbers, and 27 herbaceous plant species.

Many bacteria have the ability to survive in challenging environments; however, they cannot grow on standard culture media, a phenomenon known as the Viable but Non-Culturable (VBNC) state. Bacteria commonly go into the VBNC state under nutrient-poor environments or under stressful conditions. This review explores the concept of the VBNC state, providing insights into the beneficial bacteria known to employ this strategy. The investigation covers different chemical and physical factors that can induce the latency state, cell features, and gene expression observed in cells in the VBNC state. The revision also covered the significance and applications of beneficial bacteria, methods for evaluating bacterial viability, the ability of bacteria to persist in environments associated with higher organisms, and the factors that facilitate the return to the culturable state. Knowledge about beneficial bacteria capable of entering the VBNC state remains limited, however, beneficial bacteria in this state could face adverse environmental conditions, and return to culturable state when conditions become suitable and continue to exert their beneficial effects. Likewise, this unique feature positions them as potential candidates for healthcare applications, such as the use of probiotic bacteria to enhance human health, applications in industrial microbiology for the production of prebiotics, functional foods, and in the beer and wine industry. Moreover, their use in formulations to increase crop yield and for bacterial bioremediation offers an alternative pathway to harness their beneficial attributes.

Phα1β a spider peptide, purified from the venom of Phoneutria nigriventer inhibits high voltage calcium channels and is antagonist of TRPA1 receptor two important pain transduction path-ways. In the last 15 years, we have showed, in preclinical tests with Phα1β native and recombi-nant in rodent models of pain the potential of Phα1β to become a new analgesic drug. Evaluation of new drug on human ERG channel is requirement of the regulatory agencies. For the hERG channel inhibition assay it was used the commercial kit FLIPR® Potassium Assay. It was tested the effect of Phα1β and as positive control dofetilide, a well characterized hERG block-er. Phα1β 56, 225, 450 and 900 pMol caused at a higher concentration a very weak inhibition of the hERG channel activity of about 13.47 % with channel inhibition at 50%, IC50 > 900 pMol. Dofetilide (0.0001 - 10 µM), a known hERG inhibitor, caused a well-known, concentra-tion-dependent inhibition of the hERG channel with a mean IC50 of 0.1642 µM (0.1189 – 0.2282 µM. For the cytotoxicity assay, Phα1β concentrations of 56, 225, 450 and 900 pMol incubated for 24 h with HEK293-hERG cells did not alter the viability of the HEK293-hERG cells. It is con-cluded that Phα1β even at high concentrations does not interfere with hERG channels.

The goal of the current study was to discover a novel potential probiotic strain of Lactobacillus spp. with anti-Escherichia coli activity from locally produced yogurt in Tongi, Gazipur, Bangladesh, compare its antagonistic activity with a commercial probiotic mixture of several strains, and approve a novel method for confirming the viability and relative abundance of the microbial community in a probiotic mixer. We carried out 16S sequencing, 16S metagenomics, Transmission Electron Microscopy (TEM) analysis, and other in vitro laboratory experiments to reach this objective. The strain TY-11 was identified as Lactobacillus delbrueckii subsp. indicus (16S sequence accession number OQ652026). It was gram-positive, anaerobic, lactose fermenting, and round-ended rod that typically measured 0.7 to 1.3 µm by 2.2 to 9 µm. In addition to having seven probiotic characteristics, it also showed an antagonistic impact on six different pathogens, but what's more noteworthy is that E. coli was the pathogen it inhibited most strongly (inhibition zone diameter was 18.88±0.18 mm). The most important and ground-breaking finding of this work was determining the probiotic features of a new probiotic strain, TY-11, whose antibacterial activity was virtually as effective as that of the probiotic combination with three different strains. Furthermore, the results of 16S high throughput sequencing and the conventional plate count method demonstrated a strong correlation (0.999) at the genus level, indicating that the use of both of these approaches in combination may be a practical way to assess the relative abundance of the microbial community and their viability in commercially available probiotic blends.

Pregnancy at advanced maternal age is considered a risk factor for adverse maternal, fetal, and neonatal outcomes. Here we investigated whether maternal age could be associated with differences in the blood levels of newborn screening (NBS) markers for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP). Population-level NBS data from screen-negative singleton infants were examined, which included blood metabolic markers and covariates such as gestational age, birth weight, age at blood collection, infant sex, parent-reported ethnicity, and maternal age at delivery. Marker levels were compared between maternal age groups (age range: 15-44 years) using effect size analyses, which controlled for group size differences and potential confounding from other covariates. Our results showed that 13% of the markers had maternal age-related differences including newborn metabolites with either increased (C14, C16, C18, C18:1, C3DC) or decreased (C5OH) levels at advanced maternal age group (≥35 years, absolute Cohen’s d ≥ 0.2). The increased C3DC levels in this group correlated with a higher false-positive rate in newborn screening for malonic acidemia (p-value < 0.001), while no significant difference in screening performance was seen for other markers. Maternal age at delivery is associated with inborn metabolic differences and should be considered together with other clinical variables in genetic disease screening.

Sulforaphane, the native but unstable form of SFX-01, is an antioxidant that activates NRF2 and inhibits NF-KB pathways to achieve its actions. Resolving the mechanism(s) by which SFX-01 serves to control the various osteoclastogenic stages may expose pathways that could be explored for therapeutic use. Here we seek to identify the stage of osteoclastogenesis targeted by SFX-01 and explore whether, like SFN, it exerts its actions via the NRF2 and NF-KB pathways. Osteoclasts generated from the bone marrow (BM) of mice were cultured with SFX-01 at different timepoints to examine each phase of osteoclastogenesis separately. This showed that SFX-01 exerted actions throughout the process of osteoclastogenesis, but had its largest effects in the early osteoclast precursor differentiation stage. Thus, treatment with SFX-01 for the duration of culture, for the initial 3 days differentiation or for as little as the first 24 hours was sufficient for effective inhibition. This aligned with data suggesting that SFX-01 reduced DC-STAMP levels, osteoclast nuclear number and modified cytoskeletal architecture. Pharmacological regulation of NRF2 pathways, via selective inhibitors/activators, supported anti-osteoclastogenic roles for an SFX-01-mediated by NRF2 activation, as well as a need for tight NF-KB pathway regulation in osteoclast formation/function.

Constraint-based metabolic modeling approaches have enhanced our knowledge and understanding of the metabolism of prokaryotes and eukaryotes. This approach highly depends on the reconstruction process of genome-scale metabolic models (Mmodels). M-models can guide effective experimental design and yield new insights into the function and control of biological systems. Despite the recent advances in the automated generation of draft metabolic network reconstructions, the manual curation of these networks remains a labor-intensive and challenging task. Thus, these ten quick tips for the manual curation process are essential for optimizing high-quality metabolic model generation in less time. This collection of tips describes in great detail the resources and methods to ensure successful reconstruction. Furthermore, it increases the scope of other protocols of metabolic modeling by including resources to reconstruct eukaryotic organisms. Thus, all tips are applicable to a wide range of eukaryotic organisms. We believe this manuscript will interest a broad audience and researchers from different disciplines, spanning from microbiology and systems biology to biotechnology.

Trypanosoma cruzi, the protozoan causative of Chagas disease (ChD), exhibits striking genetic and phenotypic intraspecific diversity, along with ecoepidemiological complexity. Human-pathogen interactions lead to distinct clinical presentations of ChD. In 2009, an international consensus classified T. cruzi strains into six discrete typing units (DTUs), TcI to TcVI, later including TcBat, and proposed reproducible genotyping schemes for DTU identification. This article aims to review the impact of classifying T. cruzi strains into DTUs on our understanding of biological, ecoepidemio-logical, and pathogenic aspects of T. cruzi. We will explore the likely origin of DTUs and the intrinsic characteristics of each group of strains concerning genome organization, genomics, and suscepti-bility to drugs used in ChD treatment. We will also provide an overview of the association of DTUs with mammalian reservoirs, and summarize the geographic distribution, and the clinical implica-tions, of prevalent specific DTUs in ChD patients. Throughout this review, we will emphasize the crucial roles of both parasite and human genetics in defining ChD pathogenesis and chemotherapy outcome.

Normally, people lose between 50 and 100 hairs a day and generate new ones from the stem cells of hair follicles, but in people suffering from baldness, the condition called alopecia or androgenetic alopecia, the stem cells remain inactive and are unable to regenerate new hair. The stages of hair growth have been studied to better understand how hair grows and what might be done to prevent or treat premature hair loss. Anagen is referred to as the active phase of hair growth in which the hair shaft is produced by the hair follicle, whereas during catagen and telogen phases the lower part of hair follicle regresses until its growth stops. Although 9% of hair follicles remain in telogen at any one time, a variety of factors including growth factors and cytokines promote the transition from telogen to anagen and the subsequent stimulation of hair growth. In this work, we discuss a new possible treatment, AMPLEX PLUS that could help significantly slow hair loss and encourage new hair growth.

Estimating age at death is essential to establish a biological profile from human skeletal remains in both forensic and archeological settings. Imaging studies of skeletal age changes in adults have described metamorphosis of trabecular bone structure and bone loss in the proximal femur , as well as changes in morphology during different stages of life. This study aims to assess the utility of a digital representation of conventional X-ray films of the proximal femur for the estimation of age at death in a sample of 91 adult individuals (47 females and 44 males) of the Coimbra Identified Skeletal Collection. The proposed approach showed a root mean squared error (RMSE) of 17.32 years (and mean absolute error of 13.47 years) for females and an RMSE of 14.06 years (mean absolute error of 11.08 years) for males. The main advantage of this approach is the consistency in the feature detection and extraction, as X-ray images projected on the femora space will always produce the same set features to be analyzed for age estimation while more traditional methods rely heavily on operator experience which can lead to inconsistent age estimates among experts.

Despite recent advancements, therapies remain ineffective against advanced oral squamous cell carcinoma (OSCC), resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Yet, the exact mechanisms driving CAP-induced cancer cell death are not fully understood. This study revealed a significant reduction in the viability of OSCC cell lines, inactivation of AKT and ERK, and the downregulation of the miR-21, miR-31, miR-134, miR-146a and miR-211 expression followed the CAP treatment. Pretreatment with ZVAD, 3-MA, and Fer-1 synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways by CAP. Activation of AKT and ERK, alongside combined treatments using death inhibitors and miRNA mimics, counteracted the cell mortality associated with CAP. CAP-induced downregulation of miR-21, miR-31, miR-187 and miR-211 expression was rescued by AKT and ERK activation. Additionally, CAP treatments notably inhibited the growth of SAS cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study indicates that CAP jet treatment diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

This review resumes published data on fungal diversity in and within monuments (e.g., religious and secular monuments, museums, and statues), covering a multidisciplinary investigation into the complex interactions between fungi and cultural heritage structures. Fungi represent remarkable adversaries to monuments, potentially compromising their structural integrity and aesthetic value. Based on a bibliographic search of manuscripts published, the knowledge of fungal communities colonizing monuments was comprehensively assessed. This work first describes the diverse fungal species implicated in the degradation of monument materials (e.g., stone, metal, and glass). It elucidates the factors governing fungal colonization and proliferation in and within these structures (e.g., environmental conditions, construction materials, and human interventions). Finally, the efficacy of preservation and restoration techniques to mitigate fungal threats and safeguard our cultural heritage is also discussed. This synthesis highlights the pivotal role of mycological research in heritage conservation, and a platform for future studies to address critical knowledge gaps is provided. Understanding fungal diversity in and within monuments is critical to preserving these invaluable cultural treasures, as it informs targeted conservation strategies and ensures their longevity in the face of fungal challenges.

Mucormycosis is known to be a rare opportunistic infection caused by Syncephalastrum species, which are Mucorales fungi of the Zygomycetes class. These moulds are rarely involved in clinical diseases and are generally seen as contaminants in the clinical laboratory. However, in recent years, case reports of human infections due to Syncephalastrum have increased, especially in immunocompromised hosts. In this study, we describe two new Syncephalastrum species, which were isolated from human nails and sputum samples from two different patients. We used several methods of genomic and phenotypic characterisation. The phenotypic analysis, relied on morphological features, analysed both by optical and scanning electron microscopy. We used Matrix Assisted Laser Desorption Ionization-Time of Flight mass spectrometry, energy-dispersive X-ray spectroscopy, and BiologTM technology to characterise the proteomic, chemical mapping, and carbon source assimilation profiles, respectively. The genomic analysis relied on multilocus sequence analysis of the rRNA internal transcribed spacers and D1/D2 large-subunit domains, and fragments of the translation elongation factor 1-alpha, and the β-tubulin genes. The two novel species in the genus Syncephalastrum, namely S. massiliense PMMF0073 and S. timoneanum PMMF0107, have a similar morphology to S. racemosum, but each display distinct phenotypic and genotypic features. The polyphasic approach, combining the results of complementary phenotypic and genomic assays, was instrumental in describing and characterising these two new Syncephalastrum species.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

The Supersymmetry Genetic code (SSyGC) table is based on five physicochemical symmetries: 1) double mirror symmetry on the principle of the horizontal and vertical mirror symmetry axis between all bases (purines [A, G) and pyrimidines (U, C)], and 2) of bases in form of codons 3) direct – complement like codon/anticodon symmetry in the sixteen alternating boxes of the genetic code columns, 4) A+T rich and C+G rich alternate codons in the same row between both columns of the genetic code, 5) the same position between divided and undivided codon boxes in relation to horizontal mirror symmetry axes. The SSyGC table has a unique physicochemical purine – pyrimidine symmetry net which is as the core symmetry common for all, more than thirty different nuclear and mitochondrial genetic codes. This net is present in the SSyGC table of all RNA and DNA living species. None of these symmetries is present in the Standard Genetic Code (SGC) table which is constructed on the alphabetic horizontal and vertical U-C-A-G order of bases. Here we show that the free energy value of each codon incorporated as fundamentally mapping the “energy code” in the SSyGC table is compatible with mirror symmetry. On the other hand, in the SGC table the same free energy values of codons are dispersed and a mirror symmetry between them is not recognizable. At the same time the mirror symmetry of the SSyGC table and the DNA quadruplets together with our classification of codons/trinucleotides are perfectly imbedded in the mirror symmetry energy mapping of codons/trinucleotides and point out in favor of maintaining the integrity of the genetic code and DNA genome. We also argue that physicochemical symmetries of the SSyGC table in the manner of the purine – pyrimidine symmetry net, the quadruplet symmetry of DNA molecule and the free energy of codons have remined unchanged during all of evolution. The unchangeable and universal symmetry properties of the genetic code, DNA molecule and energy code are decreasing disorder between codons/trinucleotides and shed a new light on evolution. Diversity in all living species on Earth is broad, but the symmetries of the Supersymmetry Genetic Code as the code of life and the DNA quadruplets related to the” energy code” are unique, unchangeable and have the power of natural laws.

This study assessed the acute effects of oral methylliberine (DynamineTM) supplementation on cognitive function and indices of well-being. This was a double-blind, randomized, within-subject crossover trial. 25 healthy men and women (33.5±10.7yr, 172.7±8.6cm, 73.3±11.0kg) underwent pretesting before ingesting methylliberine (100mg) or placebo (PLA) for 3 days. On the fourth day participants were tested before their 4th dose (baseline) and every hour post-ingestion for 3 hours. After a one-week washout period, participants repeated testing with the alternate investigational product. The testing battery consisted of vitals, Stroop test and Trail Making Test-B, and visual analog scales that assessed various indices of well-being. Mixed factorial ANOVA with repeated measures were used to assess all variables. There were significant (p≤0.050) interactions in concentration, motivation, and mood. Methylliberine improved concentration 1- and 3-hours, motivation 3 hours, and mood 1-, 2-, and 3 hours (p≤0.050). Methylliberine improved energy, sustained energy, and mood in all participants to a greater extent than PLA at 1-hour and 3-hours relative to baseline (p≤0.050). PLA improved motivation at 1- and 2-hours and mood at 2-hours (p≤0.050). Methylliberine improved concentration, well-being, and the ability to tolerate stress to a greater extent than PLA at 3-hours relative to baseline (p≤0.050). Women observed elevations in sustained energy 1- and 3-hours (p≤0.050) in methylliberine vs. PLA. Methylliberine had negligible influence on cognitive function, vitals (p>0.050), and no adverse events were reported. Methylliberine significantly improved subjective feelings of energy, concentration, motivation, and mood, but not cognitive function. PLA improved motivation and mood at hours 1 and 2, while methylliberine sustained benefits for longer. Methylliberine also improved concentration, well-being, and the ability to tolerate stress to a greater degree than PLA while having no detrimental effects on vital signs. Methylliberine also seems to have a positive impact on sustained energy in women.

A drinking strategy aiming to replace a given percentage of the sweat losses incurred during exercise should result in reproducible fluid intake volume and, hence, fluid balance from one exercise session to the other performed under similar scenarios. Whether this may also be the case with ad libitum drinking during exercise is unclear. We characterized the repeatability of ad libitum fluid intake during repeated 1 h exercise sessions and examine its effect over time on fluid balance and selected physiological functions and perceptual sensations. Twelve (3 women) healthy individuals participated in this study. At weekly intervals, they completed 4, 2 x 30 min walking/jogging exercise bouts (55% VO2max, 40°C, 20-30% relative humidity) interspersed by a 3 min recovery period. During exercise, participants replaced water (20°C) ad libitum. There were no significant differences among the 4 exercise sessions for absolute fluid intake volume (~ 1000 mL · h-1), percent body mass loss (~ 0.4%), sweat rate (~ 1300 mL · h-1) and percent of sweat loss replaced by fluid intake (~ 80%). Heart rate, rectal temperature and perceived thirst and heat stress did not differ significantly between the first and fourth exercise session. Perceived exertion was significantly lower during the fourth vs. the first exercise session, but the difference was trivial, &lt; 1 arbitrary unit. In conclusion, ad libitum fluid intake during 4 successive identical 1 h walking/jogging sessions conducted in the heat will result in similar fluid intake volumes and perturbations in fluid balance, heart rate, rectal temperature and perceived thirst, heat stress and exertion.

The present study was conducted to explore the floristic composition, life form, and leaf size spectrum of vegetation, seasonality, and habitat condition of the Sultan Khail valley, Hindu Kush range, Pakistan. Regular trips were arranged during 2017–2019 to collect plant specimens and prepare a checklist of the flora of the area. The life form and leaf size spectrum of vegetation were determined. The plant species were also classified based on their habitat. The area is home to 332 species belonging to 234 genera and 96 families. Asteraceae (32 species) was the dominant family in the area, followed by Rosaceae (28 species) and Lamiaceae (21 species). Therophytes were found to be dominant in the area, followed by phanerophytes, while microphylls were the dominant leaf size class, followed by nanophylls. Seasonal variation in life forms showed that the spring, autumn, and winter seasons' flora was dominated by phanerophytes, while therophytes were dominant in the summer season. Seasonal variation in leaf size spectra showed that microphylls were dominant in the spring and summer, while in the autumn and winter seasons, nanophylls were dominant. The highest numbers of species were found in dry places, followed by forests. The flora of the study area is diverse. The habitat condition of the area is dry. The area's phytoclimate is thero-phanerophytic. The flora of the area is subjected to severe anthropogenic stress and needs proper conservation.

The sharing of genome sequences in online data repositories, allows for large scale analyses of specific genes or gene families. This can result in the detection of novel gene subtypes as well as development of improved detection methods. Here we used publicly available WGS data to detect a novel Stx subtype, Stx2n in two clinical E. coli strains isolated in the USA. During this process, additional Stx2 subtypes were detected; six Stx2j one Stx2m strain and one Stx2o, all were analyzed for variability from the originally described subtypes [1,2]. Complete genome sequences were assembled from short or long read sequencing and analyzed for serotype, and ST types. The stx2n and Stx2o WGS were further analyzed for virulence genes pro-phage analysis and phage insertion sites. Nucleotide and amino acid maximum parsimony trees showed expected clustering of the previously described subtypes and a clear separation of the novel Stx2n subtype. WGS data was used to design OMNI PCR primers for the detection of all known Stx1 (283 bp amplicon), Stx2 (400 bp amplicon), eae (222bp amplicon) and Stx2f (438 bp amplicon) subtypes. These primers were tested in three different laboratories, using standard reference strains. Analysis of complete genome sequence showed variability in serogroup, virulence genes, ST type, and Stx2 pro-pages showed variability in size, gene composition, and phage insertion sites. The isolates with Stx2n and Stx2o in this study demonstrated toxicity for Vero cells. The Stx2n strain were induced when grown with sub-inhibitory concentrations of Cip, and toxicity was detected. Taken together, these data highlight the need to reinforce genomic surveillance to identify the emergence of potential new Stx2 or Stx1 variants. The importance of this surveillance has a paramount impact in public health. Per our description in this study, we suggest that 2017C-4317 be designated as the Stx2n type-strain.

Background: Ultrasonography (US) represents the gold standard imaging method for the assessment of testicular lesions (TL). The gray-scale (GSUS) and color-Doppler (CDUS) ultrasound examination allow sonographers to investigate size, margins, echotexture and vascular features of TL, with the effort to differentiate benign from malignant lesions. Recently, the use of contrast-enhanced US (CEUS) and sonoelastography (SE) led to further improvements in the differential diagnosis of TL. Although GSUS and CDUS are often sufficient to suggest the benign or malignant nature of TL, CEUS can be decisive in the differential diagnosis of unclear findings, while SE can help to strengthen the diagnosis. The contemporary combination of GSUS, CDUS, CEUS and SE led to a new diagnostic paradigm named multiparametric US (mp-US), able to provide a more detailed characterization of TL than the single techniques alone. This narrative and pictorial review is aimed to describe the mp-US appearance of several TL. Methods: An extensive Medline search was performed identifying studies in the English language focusing on mp-US evaluation of TL. Results: a practical mp-US “identity card” and iconographic characterization of several benign and malignant TL is provided herein. Conclusions: the mp-US characterization of TL reported herein can be useful in daily clinical practice.

Proprioception is an essential part of human movement and body awareness. It is the body's perception of its own spatial understanding, which helps us to accurately move our limbs and maintain balance. Purpose: This study aims to provide a comprehensive overview of the current state of knowledge and analyse bibliometric data about proprioception in gymnastics and acrobatics. Methodology: This article consisted of two phases: 1) a bibliometric review (based Web of Science) and 2) a systematic review (Web of Science, PubMed, and Scopus) of literature. "Gymnast*", "propriocep*", were utilized as search terms to find and choose published data. From a total of 164 studies, 30 were included for data extraction (n participants= 1432 of different age, sports, physical activities, and physical condition. Heterogeneity of studies design and assessment make it difficult to interpret the outcomes and the effect of proprioceptive interventions and comparations between samples. Proprioception is difficult to define in gymnastics considering the evidence references and the physiological considerations. Also, assessment tools used do not necessary evaluate proprioception globally considering the senses involved in gymnastics. Gymnastics training enhances joint awareness and force sense, improving proprioception and reducing injury risk. Proprioceptive exercises should be incorporated into gymnastics programs to enhance stability and precision in movements.

Three tiny bones compose the human ossicular chain: malleus, incus and stapes. Also known as auditory ossicles, they are united by joints in the middle ear cavity of the petrous part of the temporal bone. Completely developed 2 years after birth, the ossicular chain is involved in the physiological process of hearing, by which sound waves from the environment are converted into electrochemical impulses. In the last 500 years, most studies have focussed on the morphogenesis, morphological variability and clinical pathology of the ossicular chain, whilst only a few studies have added relevant knowledge to anthropology and forensic science. The auditory ossicles and the enclosing petrous bone are some of the hardest in the human skeleton. This reflects in a relative resistance to fire. In the post mortem period and in favourable circumstances, the auditory ossicles can fossilize and survive for millions of years. Post mortem loss in skeletal or decomposed remains can be ascribed to their destruction or physical displacement, by either macro-micro-faunal action and/or any other natural or artificial disturbance. Physical displacement is closely connected to the depositional environment of the skeletal remains, such as burial, entombment (sarcophagus, coffin, vault…), submersion or exposure to natural elements. Auditory ossicles can be recovered in situ, or very close to their anatomical location, when the skeletal material has been involved in an archaeological excavation. In the case of accessible or disturbed remains, scavengers may remove the tiny ossicles, and/or they can slip out of the middle ear cavity following skull movements. Entombment offers an effective protection against the displacement of the auditory ossicles, whereas aquatic submersion and aquatic movement almost invariably displace them. The preservation of the human auditory ossicles should be critically considered in the comprehensive context of any forensic investigation on human remains, since it can assist the reconstruction of their taphonomic history. Taphonomic histories of remains can add crucial information to forensic investigations (e.g., the Post Mortem Interval, PMI). The aim of this study, limited by scarce relevant literature, is to discuss the potential role of the ossicular chain, detected by post mortem imaging techniques, as a taphonomical indicator in decomposing and/or skeletonized bodies.

Our previous study found that intravesical perfusion metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel for-mulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong in-hibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and expression of tumour biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPK/mTOR signalling pathway compared with metformin alone. These findings highlighted the potential of this novel formulation as an efficient candidate for managing BC via intravesical ad-ministration.

Clopidogrel is one of the most prescribed antiplatelet drugs for cardiovascular diseases prevention. Clopidogrel is a prodrug metabolised by CYP2C19 in active metabolites with anti-aggregant effect. Pharmacogenetic variants such as CYP2C19*2 variant can alter the anti-aggregant effect of clopidogrel leading to a higher risk of cardiovascular disease relapse. The aim of this study was to evaluate the prescription characteristics of CYP2C19 pharmacogenetics in patients on clopidogrel treatment, based on a specific query in a clinical data warehouse. We evaluated the demographics of patients, prescribers, medical indications, CYP2C19 pharmacogenetic tests and therapeutic changes. Neurologists were the main prescribers of CYP2C19 pharmacogenetic tests associated with clopidogrel treatment in a context of suspicion of stroke relapse. Pharmacogenetic tests were mainly prescribed a posteriori to clopidogrel prescription. Clopidogrel pharmacogenetic resistance was associated with the prescription of lysine acetylsalicylate in substitution of clopidogrel. Clear clinical practice guidelines are needed to position CYP2C19 pharmacogenetic testing for patients on clopidogrel treatment.

Pacing strategy refers to the distribution of effort and speed throughout the race to achieve optimal performance. The study aims to understand whether the choice of pacing strategy in swimming depends on the length of competitions and how sex, age, and performance level influence this strategy. Participants were the finalists of the 800-meter and 1500-meter freestyle events at the elite and junior world championships in 2022-2023. Race outcomes and pacing parameters were compared between the two distances and across different groups of swimmers. Swimmers in both distances did not break world records. Pacing strategy generally followed a U-shape with significant differences in the frequency and duration of speed changes between the two distances. The 800-meter exhibited more frequent changes in acceleration while the 1500-meter events generally followed a more consistent time series pattern. There were differences in pacing strategies between males and females and between junior and elite swimmers. Swimmers closer to world records showed more consistent pacing patterns compared to those farther from records. The study suggests that pacing strategies are influenced by race distance, sex, age, and performance level. The research highlights the complex interplay between physiological and psychological factors that shape a swimmer's decision-making during a race.

Consumption of high amounts of ethanol is a risk factor for development of cardiovascular diseases such as arterial hypertension. The hypertensive state induced by ethanol is a complex multi-factorial event, and oxidative stress is a pathophysiological hallmark of vascular dysfunction associated with ethanol consumption. Increasing levels of reactive oxygen species (ROS) in the vasculature triggers important processes underlying vascular injury, including accumulation of intracellular Ca2+ ions, reduced bioavailability of nitric oxide (NO), activation of mitogen-activated protein kinases (MAPKs), endothelial dysfunction, and loss of the anticontractile effect of perivascular adipose tissue (PVAT). The enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a central role in vascular ROS generation in response to ethanol. Activation of the renin-angiotensin-aldosterone system (RAAS) is an upstream mechanism which contributes to NADPH oxidase stimulation, overproduction of ROS and vascular dysfunction. This review discusses the mechanisms of vascular dysfunction induced by ethanol, detailing the contribution of ROS to these processes. Data examining the association between neuroendocrine changes and vascular oxidative stress induced by ethanol are also reviewed and discussed. These issues are of paramount interest to public health as ethanol contributes to blood pressure elevation in the general population, and it is linked to cardiovascular conditions and diseases.

Intestinal microbiota attracts daily attention of a growing number of study which have attempted to link gut dysbiosIs with a variety of disease states: irritable bowel syndrome (IBS), inflamed bowel disease (IBD), Crohn's disease (CD), leaky gut syndrome (LGS), food intolerance, diabetes, metabolic syndrome, cancer, etc.. In our study we analyzed how intestinal dysbiosis may be related to chronic fatigue syndrome (CFS) and depression through the exchange of information through the gut-brain axis (GBA). We studied 33 subjects, 13 males and 20 females, who reported CFS or/and depression: we investigated their salivary cortisol levels, blood serotonin, omega 3/6 ratio, intestinal dysbiosis (calculated on the urinary levels of indoxyl sulfate and skatole), and we looked for the presence of Candida a. or mycetes in the stool; the data accumulated with this research show a correlation between the presence of Candida a./miceti, indoxyl sulfate urine values beyond the physiological and low serotonin levels. In addition, data analysis showed that the EPA/DHA values also show pro-inflammatory levels in case of dysbiosis and low serotonina levels. The relationship, however, with cortisol levels requires further research although this study showed a statistically significant positive correlation between these values, measured at specific times, and serotonin levels. Aims its connections with We investigated the relationship between stress (evaluated through the measurement of salivary cortisol levels) and gastrointestinal efficiency measured as a function of intestinal fermentative and putrefactive dysbiosis, evaluating the levels of urinary indoxyl sulfate in the first case (a possible correlation with the presence of Candida spp or Mycetes in the subjects feces was investigated), urinary skatole levels in the second one, in patients with chronic fatigue syndrome (SFC) and depression. In these patients we also have studied omega 3/6 ratio, and finally we have analized the impact that the alteration of these parameters can have on the serotonin levels. This research attemps to highlight the contact points, in some cases not so obvious, among these topics, contact points that, although they give us interesting indications, show the need to be further deepened by analyzing a larger amount of data.

New antibiotics are unquestionably needed in the fight to the emergence and spread of multidrug-resistant bacteria. So far, antibiotics targeting bacterial central metabolism have been poorly investigated. By determining the minimal inhibitory concentration (MIC) of desmethylphosphinothricin (Glu-γ-PH), an analogue of glutamate with a phosphinic moiety re-placing the γ-carboxyl group, we previously showed its promising antibacterial activity on Escherichia coli. Herein we synthetized and determined the growth inhibition exerted on E. coli by an L-Leu dipeptide derivative of Glu-γ-PH (L-Leu-D,L-Glu-γ-PH). Furthermore, we compared the growth inhibition obtained with this dipeptide with that exerted by the free amino acid, i.e. Glu-γ-PH, and by their phosphonic and non-desmethylated analogues. All tested compounds were more effective when assayed in chemically defined minimal medium. The dipeptide L-Leu-D,L-Glu-γ-PH had a significantly improved antibacterial activity (2 μg/mL), at a concentra-tion between the non-desmethytaled (0.1 μg/mL) and the phosphonic (80 μg/mL) analogues. Also in Bacillus subtilis the dipeptide L-Leu-D,L-Glu-γ-PH displayed an activity comparable to that of the antibiotic amoxicillin. This work highlights the antibacterial relevance of the phosphinic pharmacophore and proposes new avenues to the development of novel antimicrobial drugs containing the phosphinic moiety.

The hepatic sinusoids are lined by thin endothelium containing transcellular pores dubbed fenestra. These fenestrations are completely open channels connecting the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. The fenestrations are in the size range 0.05-0.35µm in diameter and cover between 5-15% of the sinusoidal endothelial surface area depending on their location along the sinusoids. Motivation/Research Question: So far, the narrowness of the sinusoids prevented the direct measurement of hemodynamic features such as sinusoidal pressure and flow velocity. A better understanding of these parameters might help in better understanding the physiology of the hepatic niche and possible implications in liver diseases. Few simulations of liver blood flow focus on the level of the individual sinusoid, fewer still include the transcellular pores (fenestrations) of the sinusoidal endothelium, and none have included i) a porosity gradient along the sinusoid wall modelled with through-all pores rather than a porus medium, ii) the presence of the Space of Disse, iii) lymphatic drainage. Model: Computed fluid dynamic (CFD) simulations performed using a numerical model with relevant anatomical characteristics (length, diameter, porous size and porosity). Boundary conditions included physiological/pathological values of inlet/outlet pressure and lymphatic outflow from the portal region of the SoD. Results: The pressure and flow velocity of the sinusoidal lumen was entirely dependent on the shape, i.e. constant versus divergent radius and not dependent on porosity in the sinusoidal wall. The velocity through the space of Disse (SoD) was affected by the addition of lymphatic drainage and increases in porosity in the pericentral area of the model. Variations in porosity also affected flow velocity through the fenestrations. Conclusions: The flow velocity in the SoD was modified by differences in porosity, while the flow velocity in the lumen of the sinusoids was unaffected, even by the absence of fenestrations. The overall shape of the vessel is the singular most important factor in the pressure flow behavior of the sinusoidal lumen. The flow rate over the hepatocytes is the flow rate through the SoD, and is modestly affected by the distribution of porosity along the sinusoid, and by the addition of a lymphatic drainage, this parameter would be of interest for modelling blood exchange with the hepatic parenchyma, especially if accounting for zonation.

Primary central nervous system and brain tumors are one of the global burdens that are continuously increasing in cases and requiring more treatment options. Surgery has been the leading treatment option for tumors, however, the localization of the tumor and its infiltrating nature make this option challenging. DNA microarray expression profiles of different CNS tumors provide insight into potential biomarkers for identifying different tumor types and subtypes. Here, we utilized the differentially expressed genes common in four expression profiles, GSE66354, GSE68848, GSE74195, and GSE43290 to reconstruct the gene co-expression network. In this study, we were able to identify preserved cluster genes, hub genes, co-regulating transcription factors, miRNA families, and candidate repurposed drugs. Fourteen identified hub genes, which were, CACNA1A, DNM1, GABRA1, GRIA2, MAPT, SLC17A7, SNAP25, SNAP91, STXBP1, SYT1, COL1A1, COL6A2, FBN2, and FN1 appeared to play a role in tumor progression and may serve as drug targets. We also reported the DEGs in each tumor type, which were ATRT, EPN, PA, MED, PNET, MEN, ACM, ODG, and GBM. Five identified miRNA families, which were, let-7 family, mir-124 family, mir-1 family, mir-103 family, and mir-27 family described in the literature to have tumor-suppressing characteristics. Drug-gene and drug-transcription factor network revealed 32 candidate repurposed drugs and 13 were validated through connectivity map analysis. Here, two main repurposed drugs fit the regulatory requirement for gene interaction, these were, quercetin and vorinostat. Future validation in experimental studies may utilize the future use of the candidate repurposed drugs. Our study provides insights into drug repurposing prospects and understanding tumor expressions.

Effective management of retinoblastoma (RB), the most prevalent childhood eye cancer, depends on reliable monitoring and diagnosis. A promising candidate in this context is the secreted trefoil family factor peptide 1 (TFF1), recently discovered as a promising new biomarker in patients with a more advanced subtype of retinoblastoma. The present study investigated TFF1 expression within aqueous humor (AH) of enucleated eyes and compared TFF1 levels in AH and corresponding blood serum samples from RB patients undergoing intravitreal chemotherapy (IVC). TFF1 was consistently detectable in AH, confirming its potential as a biomarker. Crucially, our data confirmed that TFF1 secreting cells within the tumor mass originate from RB tumor cells, not from surrounding stromal cells. IVC therapy responsive patients exhibited remarkably reduced TFF1 levels post-therapy. By contrast, RB patients` blood serum displayed low to undetectable levels of TFF1 even after sample concentration and no therapy-dependent changes were observed. Our findings suggest that compared to blood serum AH represents the more reliable source for TFF1 if used for liquid biopsy RB marker analysis in RB patients. Thus, analysis of TFF1 in AH of RB patients potentially provides a minimal invasive tool for monitoring RB therapy efficacy, suggesting its importance for effective treatment regimens.