More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

The present study aimed to undertake a detailed investigation of pathological epidemiology and molecular confirmation of Ehrlichia canis among pet dogs in smart city Bhubaneswar, Odisha, a state in eastern India. A total of 178 dogs were screened for Ehrlichiosis on the basis of history, clinical signs, blood, and buffy coat smear examination, resulting in only 56 dogs (31.46%) screening positive. The epidemiological study recorded an increase in incidences among dogs less than one year of age (41%), males (68%), German Shepherds (25%), dogs more than 20 kg body weight (75%), summer months (55%) and dogs housed on pukka houses with exposure to the outside (59%). The majority of the infected dogs had a history of tick infestation (79%) at some point in their life. Clinical signs showed non-typical manifestations like fever, lethargy, diarrhoea, epistaxis, hind limb edema, and corneal opacity. Haematological studies revealed anaemia and thrombocytopenia along with neutrophilia with relative lymphopenia and monocytosis. A decreasing trend was observed in the levels of total protein and albumin with an increase in the levels of globulin, AST, ALT, BUN, and creatinine. The ultrasonography studies revealed hepatosplenomegaly along with hyper-echogenicity in various organs. Pro-teinuria and haematuria were consistent, along with the presence of bile salts in the urine of affected dogs. Molecular confirmation from n-type PCR data using Ehrlichia-specific primers targeting p28 gene (843 bp) was done, and the identified gene sequences submitted to NCBI databases have accession numbers OQ383671-OQ383674 and OP886674-OP886677. Ticks collected from dogs were identified morphologically through microscopy and scanning electron microscopy as Rhipicephalus sanguineus.

This study delves into the dynamic field of medical education research, emphasizing the integration of research training within medical curricula. It seeks to understand the impact of such integration on the competencies of future medical professionals. The primary aim is to systematically categorize and analyze the current trends and future directions in medical education research. This involves assessing the influence of research training on medical students' skills and the methodologies used in such research. Methods: The research employs an extensive bibliographic literature review across multiple databases. It classifies studies into categories like experiential or case studies, editorials, and original research articles. This classification is based on criteria such as geographical location, research objectives, theoretical frameworks, and methodologies. Results: Findings reveal a diverse landscape in medical education research, with a significant emphasis on research training. The research showcases varying methodologies and approaches used globally, highlighting the thematic focus and geographical distribution of these studies. Conclusion: Medical education research is a globally expansive and evolving field. It underscores the importance of continuous investigation, particularly focusing on integrating research elements at curricular levels and exploring innovative educational strategies. The study also points out potential gaps in research, especially in underrepresented regions, indicating directions for future research efforts.

The growing population in Yucatan has led to the expansion of construction in the Mayan jungle for tourist spaces, residential areas, and agriculture. Recently, rabies cases in cats (Felis catus) have increased. This study aimed to perform the antigenic and genetic characterization of the RABV and to try to identify factors contributing to the increased transmission of rabies virus from wildlife to cats in the State of Yucatan. The ArcGIS software was employed to generate maps depicting the geographic locations of rabies outbreaks in cats. A mixed-effects Poisson regression model was applied to investigate the association between cat rabies cases and sociodemographic and ecological variables. A total of nine feline rabies cases occurred, three antigenic variants were detected: RVV1 (n=1); (RVV3) (n=1), and the canine-originated atypical variant (n=7). Rabies cases were spatially distributed at the urban-jungle interface, which may favor contact between cats and wildlife. No statistically significant associations with sociodemographic/ecological variables were observed. Urban areas with low (0-2%) to moderate (2-4%) changes in land cover showed a substantial increase in the probability of feline rabies cases. This study highlights the concerning resurgence of rabies infections in cats, emphasizing the looming threat of its reintroduction in dogs should vaccination rates diminish. The genetic affinity between the atypical variant and the canine virus underscores the urgent need for vigilance in maintaining high vaccination coverage across all susceptible species.

In this work, we analysed human isolates of nontyphoidal Salmonella enterica subsp. enterica (NTS), which were collected from salmonellosis cases in Armenia from 1996 to 2019. This disease became a leading food-borne bacterial infection in the region, with the younger age groups especially affected. The isolates were characterised by serotyping, Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR) typing, and whole genome sequencing (WGS). The main serotypes were S. Typhimurium, S. Enteritidis, and S. Arizonae. ERIC-PCR indicated a high degree of clonality among S. Typhimurium strains, which were also multidrug-resistant and produced extended spectrum beta-lactamases. During the study period, the frequency of S. Typhimurium and S. Arizonae isolations were decreasing, but with the increase of S. Enteritidis and other NTS. A total of 42 NTS isolates were subjected to WGS and explored for virulence-related traits and the corresponding genetic elements. Some virulence and genetic factors were shared by all NTS serotypes, while the main differences were attributed to the serotype-specific diversity of virulence genes, SPIs, virulence plasmids, and phages. The results indicated the variability and dynamics in the epidemiology of salmonellosis and a high virulence potential of human NTS isolates circulating in the region.

Parents play an important role in shaping the eating habits of their children through: appropriate selection of food products, snacking between meals and appropriate exposure to information from television advertisements, the press or the Internet. The level of parents' knowledge about proper nutrition and substances added to food is therefore crucial in promoting appropriate dietary choices in children and adolescents in order to prevent diet-related diseases. Objectives: Assessment of the consumption of snack foods by children and adolescents according to the surveyed parents and analysis of parents' knowledge about additional substances in food. Methods: The study was conducted among 129 parents of students from selected primary schools. The research tool was an original survey questionnaire consisting of 24 questions. Survey interviews were conducted with parents during meetings at schools. Statistical analysis was performed using the Pearson ch2 test, the significance level was set to p<0.05. Results: Parents most often indicated sweets, confectionery products and sweetened drinks (25%) and vegetables or fruit (21%) as the form of snack for their children. 46% of children and adolescents drank sweetened drinks at least once a day. Parents had an average level of knowledge about food additives. Significant correlations were found between the level of knowledge of parents of school-age children about food additives and their level of education. Parents' knowledge and education did not significantly influence the level of snack consumption by their children. Children's eating behavior should be considered unsatisfactory. Conclusions: Research has shown the need for parents to be educated about food additives and to pay more attention to reading food labels so that they can reliably prepare their children to make the right food choices. Measures should be implemented to improve the eating habits of children and adolescents.

Cutaneous melanoma (CM) is a candidate for screening programs, since its prognosis is excellent when diagnosed in an early disease stage. Targeted screening of those at high risk for developing CM, a cost-effective alternative to population-wide screening, requires valid procedures to identify the high-risk group. Self-assessment of the number of nevi has been suggested as a component of such procedures, but its validity has not yet been established. We analyzed the level of agreement between self-assessments and expert assessments of the number of melanocytic nevi in the area between the wrist and the shoulder of both arms based on 4548 study subjects in whom mutually blinded double counting of nevi was performed. Nevus counting followed the IARC protocol. Study subjects received written instructions, photographs, a mirror, and a “nevometer” to support self-assessment of nevi larger than 2 mm. Nevus counts were categorized based on the quintiles of the distribution into five levels defining a nevus score. Cohen’s weighted kappa-coefficient was estimated to measure the level of agreement. In the total sample, agreement between self-assessments and expert-assessments was moderate (raw agreement: 50.29%, weighted κ=0.596). Self-assessed nevus counts were higher than those determined by experts (mean differ-ence: 3.33 nevi). The level of agreement was independent of sociodemographic and cutaneous factors; however, participants’ eye color had a significant impact on the level of agreement. Our findings show that even with comprehensive guidance, only a moderate level of agreement between self-assessed and expert-assessed nevus counts can be achieved. Self-assessed nevus information does not appear to be reliable enough to be used in individual risk assessment to target screening activities.

Papain-like protease PLpro, a domain within a large polyfunctional protein nsp3, plays key roles in the life cycle of SARS-CoV-2, being responsible for the first events of cleavage of a polyprotein into individual proteins (nsp1-4) as well as for the suppression of cellular immunity. Here, we developed a new genetically encoded fluorescent sensor, named PLpro-ERNuc, for detection of PLpro activity in living cells using translocation-based readout. The sensor was designed as follows. A fragment of nsp3 protein was used to direct the sensor on the cytoplasmic surface of endoplasmic reticulum (ER) membrane, thus closely mimicking the natural target of PLpro. The fluorescent part included two bright fluorescent proteins - red mScarlet I and green mNeonGreen, separated by a linker with the PLpro cleavage site. Nuclear localization signal (NLS) was attached to ensure accumulation of mNeonGreen into the nucleus upon cleavage. We tested PLpro-ERNuc in the model of recombinant PLpro expressed in HeLa cells. The sensor demonstrated expected cytoplasmic reticular network in the red and green channels in the absence of protease, and efficient translocation of the green signal into nuclei in the PLpro-expressing cells (14-fold increase of the nucleus/cytoplasm ratio). Then, we used PLpro-ERNuc in the model of Huh7.5 cells infected with SARS-CoV-2 virus, where it showed robust ER-to-nucleus translocation of the green signal in the infected cells 24 h post infection. We believe that PLpro-ERNuc represents a useful tool for screening PLpro inhibitors as well as for monitoring virus spread in a culture.

Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) are a serious healthcare concern that must be treated with appropriate antibiotic therapy. However, antibiotic resistance among UPEC strains is increasing, particularly among individuals with recurrent illness. The proliferation of Extended-Spectrum Beta-Lactamase (ESBL) generating UPEC, as well as the increase of UPEC strains that display resistance to several antimicrobial drugs, adds to the difficulty of managing UTIs. UPEC strain genetic variants have a significant influence in their capacity to resist antimicrobial agents and adapt to changing environments. Understanding the genomic landscape of developing UPEC strains is critical for understanding the genetic basis of their resistance. Furthermore, tracking these genetic strains is critical for identifying patterns of resistance spread, directing infection control efforts, and educating.

There are few longitudinal studies on the association between dietary vitamin C and sleep disorders. The aim of this study was to investigate the association between dietary vitamin C intake and various types of sleep disorders, including sleep apnea and insomnia, as well as recommended dietary intakes. A total of 68,221 participants from the UK Biobank were enrolled in the study. Dietary vitamin C intake was calculated by a 24-hour dietary recall questionnaire. We used Cox regression model to assess the association between dietary vitamin C and sleep disorders and restricted cubic spline models to explore potential nonlinear relationships. Stratified analyses and sensitivity analyses were also performed to further test the results. The results showed that vitamin C intake at the Q4 level (132.88-191.51 mg/d) was significantly protective against sleep disorders with an HR (95% CI) of 0.78 (0.65-0.94), and against sleep apnea with an HR (95% CI) of 0.75 (0.62-0.92). The protective effect remained significant in stratified analyses of men and age ≤60 years, and the results were robust in sensitivity analyses. Adequate dietary vitamin C intake may have a protective effect in preventing sleep disorders.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

1) Background: carbapenem-resistant Acinetobacter baumannii (CRAB) is an opportunistic Gram-negative pathogen that has a significant role in healthcare-associated infections. Unlike several studies on the antibiotic-resistant epidemiology of A. baumanni, virulence molecular epidemiology was less studied. This study aimed to investigate CRAB virulence genes and their ability to form biofilms, and to correlate their biofilm formation ability with both; biofilm-encoding virulence genes and carbapenemase-encoding resistance genes. 2) Methods: 107 CRAB clinical isolates were collected from two hospitals in Jordan between 2018 and 2019 and were screened for virulence genes using PCR. In addition, biofilm formation ability was assessed using the microtiter plate method. 3) Results: the frequencies of the bap, OmpA, surA, PLD, paaE, basD, and traT virulence genes were 99.10%, 98.20%, 98.20%, 95.50%, 89.10%, 86.40%, and 8.20%, respectively. Overall, 86.4% of the tested isolates were biofilm formers with varying degrees; weak (28.2%), moderate (36.4%) and strong (21.8%). A significant relationship was found between the carbapenemase-encoding gene (OXA-23 gene) and biofilm production. 4) Conclusion: to the best of our knowledge, this is the first study in Jordan that inspected CRAB virulence genes and highlighted the importance of improving infection control measures to avoid CRAB outbreaks.

Few studies have examined the dietary protein intake and sources in combination with the longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were included in the analysis. The relative and absolute amounts of dietary protein intake were calculated through a 24-hour dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake is associated with a slower reduction in the total hippocampus volume (THV, β: -0.02524, P<0.05), left hippocampus volume (LHV, β: -0.02435, P<0.01) and right hippocampus volume (RHV, β: -0.02544, P<0.05).Higher intake of animal protein relative to plant protein is linked to a lower atrophy rate in THV (β: -0.01249, P<0.05) and LHV (β: -0.01173, P<0.05) and RHV (β: -0.01193, P<0.05). Individuals with higher intake of seafood exhibit lower longitudinal rate of change in HV compared to those with no consume (THV, β: -0.004514; P<0.05; RHV, β: -0.005527, P<0.05). In subgroup and sensitivity analyses, there was not a significantly alteration. A moderate increase in the intake and proportion of animal protein in the diet, especially from seafood, is associated with a lower longitudinal change rate in hippocampus volume.

Monkeypox virus belongs to the Orthopoxvirus genus, which belongs to the Poxviridae family. The Monkeypox virus is responsible to cause monkeypox, a developing zoonotic disease that has been identified as the most common orthopoxvirus infection in humans in the post-eradication era of smallpox. The virus can be transmitted by a variety of animals, including monkeys and rodents as well as person-to-person. Monkeypox has a clinical presentation that is quite similar to smallpox but mortality is low, in that the febrile prodrome is followed by a period of skin eruption. Monkeypox cases have extended outside the forests of central Africa, where they were first discovered, to other regions of the globe, where they have been imported. This pattern of transmission is most likely related to a global reduction in orthopoxvirus immunity following the discontinuation of smallpox vaccination in 1980, when smallpox was proclaimed eliminated. As a result, monkeypox might become the very common orthopoxvirus infection that affect humans. The emergence of epidemics outside of Africa emphasizes the disease's global significance. Increased monitoring and identification of monkeypox cases are critical tools for gaining a better knowledge of the disease's ever-changing epidemiology.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

Innovation is a crucial issue in healthcare services since it can affect job-related variables such as productivity, satisfaction and burnout. The aim of our study was to examine the impact of innovation support on quiet quitting, innovative behavior and innovation outputs among nurses. We conducted a cross-sectional study in Greece during April 2024. We employed a convenience sample of nurses. We used the following instruments: (a) the Innovation Support Inventory (ISI) to measure innovation support, (b) the Quiet Quitting Scale (QQS) to measure quiet quitting, (c) the Innovative Behavior Inventory (IBI) to measure innovative behavior, and (d) the Innovation Outputs (IO) scale to measure innovation outputs. Our multivariable analysis identified a negative relationship between innovation support and quiet quitting. Moreover, we found that managerial support and cultural support improved several aspects of innovative behavior, such as idea generation, idea search, idea communication, implementation starting activities, involving others, and overcoming obstacles. Additionally, managerial support improved innovation outputs. Our findings suggested the positive impact of innovation support on quiet quitting, innovative behavior and innovation outputs among nurses. Organizations and nurses’ managers should establish an innovative working environment to improve nurses’ passion, motives and productivity.

Recurrent Pregnancy Loss (RPL) affects 1-2% of women, and its triggering factors are unclear. Several studies have shown the vaginal, endometrial, and gut microbiota may play a role in RPL. A decrease in the quantity of Lactobacillus crispatus in local microbiota has been associated with an increase in local (vaginal and endometrial) inflammatory response and immune cell activation that leads to pregnancy loss. The inflammatory response may be triggered by gram-negative bacteria, lipopolysaccharides (LPS), viral infections, mycosis, or atypia (tumor growth). Bacterial structures and metabolites produced by microbiota could be involved in immune cell modulation and may be responsible for immune cell activation and molecular mimicry. Gut microbiota metabolic products may increase the amount of circulating pro-inflammatory lymphocytes, which, in turn, will migrate into vaginal or endometrial tissues. Local proinflammatory Th1 and Th17 subpopulations along with a decrease in Treg and tolerogenic NK cells are accountable for the increase in pregnancy loss. Local microbiota may modulate the local inflammatory response increasing pregnancy success. Analyzing local and gut microbiota may be necessary to characterize some RPL patients. Although oral supplementation of probiotics has not been shown to modify vaginal or endometrial microbiota, the metabolites produced by it may benefit patients. Lactobacillus crispatus transplantation into the vagina may enhance the required immune tolerogenic response to achieve a normal pregnancy. The effect of hormone stimulation and progesterone to maintain early pregnancy on microbiota has not been adequately studied, and more research is needed in this area. Well-designed clinical trials are needed to ascertain the benefit of microbiota modulation in RPL.

Early childhood may be a stressful period for families with a significant impact on parents’ mental health and the child’s healthy development. The goal of the SKKIPPI cohort study was to assess the occurrence and determinants of psychosocial stress and mental health disorders in parents as well as in their offspring in early childhood in three German regions. Based on random samples from three residents' registration offices, parents with infants up to 12 months of age at the time of sampling, were invited to participate in the study. A screening online questionnaire was newly developed, available in four languages, to assess common psy-chosocial stressors and mental health problems of parents with small children. The study enrolled 4,984 mothers and 962 fathers. The most common potential psychosocial stressors at baseline were professional problems (mothers 22%, fathers 33%), lack of social sup-port (20%, 14%), and severe, negative experiences in childhood (22%, 16%). Obses-sive-compulsive thoughts (21%, 16%), depressive (9%, 9%) and anxiety symptoms (11%, 7%) were the most frequently reported mental health problems by both parents. Regulatory prob-lems of the child were reported by between 1.5% and 5.1% of parents. The SKKIPPI study showed that a substantial proportion of parents are burdened by psychoso-cial problems and suffer from mental health problems in the first years after birth. Early pre-ventive and low-threshold support measures should be available in the health and social care system. The newly developed questionnaire can be used to screen in the relevant populations in order to avoid disturbances in the mother-child attachment.

In Pakistan, bats are one of the dominant mammals that play an important role in the ecosystem in terms of pollination, seed dispersal, and control of pest insects. Bats have also played an im-portant role in the emergence and transmission of zoonotic pathogens; however, most current studies focus on viral pathogens, not potential bacterial pathogens. This study was designed to estimate the prevalence and antibiotic profiling of Staphylococcus (S.) aureus in oral and rectal samples from bats captured in northern Pakistan and to determine the factors associated with in-fection. Two hundred individual bats of five species: Pipistrellus javanicus (n = 17), Pipistrellus pipistrellus (n = 10), Rhinopoma microphyllum (n = 48), Rousettus leschenaultii (n = 124), and Scotophilus kuhlii (n = 1) were captured for non-lethal collection of oral and rectal samples to iso-late S. aureus. Bats were sampled from three sites: a natural cave, a man-made castle, and an an-imal shed, in Khyber Pakhtunkhwa and Punjab provinces. Oral (n = 200) and rectal (n = 200) swabs were collected from each individual bat using sterile cotton swabs specifically for use in bacteriological studies. Each isolate of bacteria was identified by using phenotypic tests and con-firmed as S. aureus based on PCR assay. Out of a cumulative four hundred samples, 80 swabs were positive for S. aureus including 47 rectal and 33 oral swabs. Prevalence of S. aureus infection varied significantly among species, with Rousettus leschenaultii exhibiting the highest prevalence (n = 77; 37.90%). In addition to bat species, prevalence varied significantly among habitats but not between sex, age class, or reproductive status. This study confirmed the occurrence of S. aureus in oral and rectal microbiota of bats in Pakistan. Importantly, S. aureus isolates showed resistance to tetracycline, gentamicin, and erythromycin and carried resistant genes such as TetK, TetM, Erma, and aacA-D. In this regard, efforts should be taken to educate the local communities on how to minimize exposure to an antibiotic-resistant bacterial pathogen through contact with bats while simultaneously increasing the awareness of protecting bats as a vital component of our ecosystem.

Background: Cardiomyopathy is commonly observed disease that may occurs due to mutations in either susceptible genes or modifier gene. People with broad age group are affected either attributable to spontaneous or inherited mutations of these genes. Various gene mutations are reported so far but only few of them were studied in detail. Methods: In the current study, we evaluated epidemiological variables like age, sex, familial status, parental consanguinity. We also described specific clinical symptoms associated with the cardiomyopathy condition in Indian population. Results: Our studies on mutation screening of phospholamban gene revealed two transitions (4880 C/T, 4887 T/G) in 5’ flanking region which might cause inherited dilated cardiomyopathy with refractory congestive heart failure are We further deliberated the gene polymorphism of renin angiotensin system gene angiotensin-1-converting enzyme as an associated marker/ modifier in cardiomyopathy patients and their family members. Conclusions: Information on epidemiological, clinical statistics, phospholamban gene mutation analysis and angiotensin-1-converting enzyme gene polymorphism is essential to guide the successful execution for future therapies and benefits us to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia.

Purpose: This study aimed to describe the molecular epidemiology and seasonality of human rhinovirus (HRV) in chronic obstructive pulmonary disease (COPD) and its association with COPD exacerbations in Abu Dhabi, the United Arab Emirates (UAE). Methods: Sputum specimens were collected for analysis from all COPD patients who visited a medical center from November 2021 to October 2022. The real-time quantitative polymerase chain reaction (qPCR) test was used to detect HRV. Results: Of the 78 COPD patients included in the study, 58 (74%) pa-tients presented with one or more exacerbation episodes. The incidence of COPD exacerbation peaked over the winter and substantially decreased during the summer. HRV positivity in pa-tients during exacerbation (E1) was 11/58 (19%) and 15/58 (26%) two weeks after the exacerbation episode (E2). There was no significant difference in the HRV load in these patients. No statistically significant difference was observed in the detection of HRV during exacerbation compared to patients with stable COPD. Conclusion: This is the first study to assess the association between HRV detection by qPCR and COPD exacerbations in the UAE. The high sensitivity of the detec-tion technology helped collect reliable epidemiologic data. Few studies have provided similar Middle East data. This study's pattern of COPD exacerbations and HRV detection parallels that of temperate countries. This information can help with future, more extensive surveillance of res-piratory viruses in the UAE and the Middle East and their association with COPD exacerbations.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole. Letrozole inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. Letrozole resistance is increasingly being observed, which poses a unique problem for patients. We reanalyzed transcriptomic data comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two genes that significantly differed between these patients; with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 as the top transcriptional biomarkers for ER+ treatment resistance. Many of the other significant gene products play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified do not have a characterized role in ER+ breast cancer. Our analysis identified a set of genes that warrant further research to elucidate the molecular mechanism of Letrozole resistance in this patient population, as well as novel high-performing biomarkers. We anticipate that these findings could contribute to improved therapeutic outcomes in human patients.

In 2011-2012, Northern Vietnam suffered its first large scale hand foot and mouth disease (HFMD) epidemic. Two sets of official guidelines were issued during the outbreak to handle the HFMD crisis. The city of Hai Phong was therefore used as a model to analyze the impact of the guidelines release. 9621 HFMD cases were reported in Hai Phong city from April 2011 to December 2012. Three distinct waves of HFMD occurred. Enterovirus A71 and Coxackievirus A16 were successively associated to the epidemics. Two periods, before and after guidelines realease, could be distinguished which were characterized by different patient patterns Time to admission and severity changed notably. Guideline publication help the health system refocusing on the 0.5-3 years age group with highest incidence of the disease. The three waves showed different special distribution but main routes of infection were rivers and local secondary roads most likely through local trade and occupational movements of people.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the province of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. We performed genomic analysis to identify the changes in genetic diversity of SARS-CoV-2 between December 2019 and November 2020, and through molecular surveillance, we monitored the mutations that could be involved in viral fitness. We analyzed 2,213 complete genomes from 6 geographical regions worldwide, which were downloaded from GenBank and GISAID databases. Although SARS-CoV-2 presented low genetic diversity, there has been an increase over time, with the presence of several hotspot mutations throughout its genome. We identified 7 frequent mutations that resulted in non-synonymous substitutions (dN). Two of them, C14408T>P323L and A23403G>D614G, located in the nsp12 and Spike protein, respectively, emerged early in the pandemic and showed a considerable increase in frequency over time. Two other mutations, A1163T>I120F in nsp2 and G22992A>S477N in the Spike protein emerged recently and have spread in Oceania and Europe. Continuous molecular surveillance of SARS-CoV-2 will be necessary to detect and describe the transmission dynamics of new variants of the virus with clinical relevance. This information is important to improve programs to control the virus.

Brucella abortus is a facultative intracellular Gram-negative bacterium that causes chronic persistent infections in humans and livestock. In this study, conventional bio-typing, multiple-locus variable-number tandem repeat analysis (MLVA), and whole-genome sequencing-single-nucleotide polymorphism (WGS-SNP) were used to investigate the molecular epidemiology characteristics of Brucella abortus strains in China and their relationships to world lineages. A total of 100 strains were collected from 1953 to 2013, suggesting that B. abortus circulated in China in the past five decades. Moreover, most strains were mainly distributed in the northwest area. During this period, seven biovars were found, indicating that B. abortus displayed a high diversity of biovars and that the main epidemic areas are in the northern provinces. Strains have high genetic diversity, and bruce07 is the most helpful locus for genotyping of this population. Moreover, 17 MLVA-11 genotypes were found; 13 of them are of known genotypes and four are unassigned genotypes, indicating that B. abortus in this study had several geographic origins. Still, strains from unassigned genotypes may originate from China. Many shared MLVA-16 genotypes were observed in strains from the same provinces in Northern China, which confirmed a brucellosis outbreak within northern regions. WGS-SNP analysis showed that eight Chinese strains formed a ladder-like phylogram (C. Ⅶ) with strains from nine countries, including Uganda, Iraq, Russia, Georgia, Spain, Italy, Egypt, Mongolia, and China; strains were introduced to these countries from a single source. Notably, Chinese strains were closely related to strains from Russia and Mongolia; frequent animal (cattle) trade and exchanges may promote this process. We will provide new and insightful information for strength surveillance and control of B. abortus brucellosis in China.

National heatwave plans are aimed at reducing the avoidable human health consequences due to heatwaves, by providing warnings to and improving communication between relevant stakeholders. The aim of this study was to assess the perceptions of key stakeholders within plans in Belgium and the Netherlands on their responsibilities, the partnerships, and the effectiveness of the local implementation in Brussels and Amsterdam. Key informant interviews were held with stakeholders that had an important role in development of the heatwave plan in these countries, or its implementation in Brussels or Amsterdam. Care organisations, including hospitals and elderly care organisations, had a lack of familiarity with the national heatwave plan in both cities, and prioritised heat the lowest. Some groups of individuals, specifically socially isolated individuals, are not sufficiently addressed by the current national heatwave plans and most local plans. Stakeholders reported that responsibilities were not clearly described and that the national plan does not describe tasks on a local level. We recommend to urgently increase awareness on the impact of heat on health among care organisations. More emphasis needs to be given to the variety of heat risk groups. Stakeholders should be involved in the development of updates of the plans.

LCK, a member of the Scr kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation. However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibition of Lck has been mainly to treat hematologic malignancies with a high rate of success. They may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion. New, more selective inhibitors have been documented, and they have shown inter-esting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs host disease. Drug repurposing and bioinformatics can aid in solving several unsolved is-sues on the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.

With the increasing use of genome sequencing as a surveillance tool for molecular epidemiology of antimicrobial resistance, we are seeing an increased intersection of genomics, microbiology, and clinical epidemiology. Clear nomenclature for AMR gene families and pathogens is critical for communication. For CARD release version 3.0.3 (July 2019), we updated the entire CARD database to reflect the latest pathogen names. In total, we detected 48 name changes or updates, some of which reflect major changes in familiar names.

Background and Objectives: Most of the research of the BRCA1 inactivation is focused on monoallelic germline alterations and loss of heterozygosity in tumour. The aim of this study was to identify characteristic transcriptomic pattern of monoallelic somatic BRCA1 inactivation and estimate its impact to the event-free breast cancer survival prognosis. Materials and Methods: We conducted global transcriptome sequencing of breast cancer tissue samples to identify differentially expressed genes and signalling pathways associated with monoallelic somatic BRCA1 inactivation. The study group involved 36 patient samples categorized based on BRCA1 inactivation status. Subsequently, the differential gene expression and Kaplan-Meier analyses in the groups with and without monoallelic somatic BRCA1 inactivation were performed. Results: Kaplan-Meier analysis showed tendency for longer event-free survival in patients with monoallelic somatic BRCA1 inactivation, suggesting somatic BRCA1 inactivation is favourable prognostic. Differential gene expression analysis followed by the STRING tool enrichment analysis showed significant enrichment of proteins in the extracellular region and extracellular space. Conclusion: In this study we identified transcriptomic profile of differentially expressed genes TPSD1, FABP4, CARTPT and MMP9 as indicative for homologous recombination impaired tumours with tendency for better therapy results.

Intermittent religious fasting increases a risk of hypo- and hyperglycemia in individuals with diabetes, but its impact in those without diabetes is poorly investigated. The study aim was to examine the effects of religious Bahá'í fasting (BF) on glycemic control and variability and compare these effects with time-restricted eating (TRE). In a three-arm randomized controlled trial, 16 subjects without diabetes were assigned to a BF, 16:8 TRE or control group. Continuous glucose monitoring and food intake documentation was conducted before and during the 19 days of intervention, and 24-hour mean glucose, glycemic variability indices, and glucotypes were assessed. BF and TRE groups, but not the control group, markedly reduced the daily eating window while maintaining macronutrient composition. Only the BF group decreased caloric intake (-677.8 ± 357.6 kcal, p=0.013), body weight (-1.92 ± 0.95 kg, p=0.011) and BMI (-0.65 ± 0.28 kg, p=0.006). Higher maximum glucose values were observed during BF in the within-group (+1.41 ± 1.04, p=0.039) and between-group comparison (BF vs. Control: p= 0.010 and TRE vs. BF: p= 0.022). However, there were no alterations of 24-hour mean glucose, intra- and inter-day glycemic variability indices, or glucotypes in any group. Proportions of time above and below range (70-180mg/dl) and HbA1c values remained unchanged. BF and TRE do not exhibit negative effects on glycemic control and variability in subjects without diabetes.

The keratinocyte carcinomas, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment.

Acting as the most abundant and widely distributed volatile secondary metabolites in plants, terpenoids play crucial roles in diverse physiological regulations and metabolic processes. Terpene synthases occupy a decisive proportion in determining the composition and diversity of terpenoids; though their regulatory effects have been extensively investigated across various plant species, limited studies have focused on the upstream transcriptional regulation of terpene synthases. In this study, we unveil linalool as the predominant volatile compound in Freesia hybrida flowers, demonstrating a gradual release pattern during flower blooming. In the context of the transcriptome, a typical MYB transcription factor, FhMYB108, was screened based on digital expression profile correlation analysis and homologous gene comparison. FhMYB108 is capable of regulating the expression of terpene synthase FhTPS1, and both their expression levels exhibit a gradual increase concomitant with flower opening. Moreover, transcriptional regulation and transient expression assays revealed that FhMYB108 exerts a stimulatory effect on the transcription of A. thaliana AtTPS14, while no significant increase in AtTPS14 expression was observed upon stabilization of FhMYB108 in Arabidopsis. Investigate its reason, the highly expressed AtMYC2 in A. thaliana can interact with FhMYB108 to suppress the activation of AtTPS14 by FhMYB108. The present study not only elucidated the regulatory mechanism underlying linalool synthesis, but also discovered the synergistic effect of MYB and bHLH transcription factors in governing the biosynthesis of volatile terpenoids.

Emotional intelligence may help nurses to cope with demanding work environments. Although it is well known that emotional intelligence is positively related to work performance literature on nurses is limited. The aim of our study was to examine the impact of emotional intelligence on work performance in a sample of nurses in Greece. We conducted a cross-sectional study in Greece. We collected data from a convenience sample of nurses during January 2024. We measured emotional intelligence with the Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF), and work performance with the Individual Work Performance Questionnaire (IWPQ). We created multivariable linear regression models adjusted for sex, age, educational level, and work experience. We found that the four streams of emotional intelligence (i.e. well-being, self-control, emotionality, sociability) increases nurses’ work performance. In particular, we found a positive relationship between well-being and task performance and contextual performance. Similarly, there was a positive relationship between self-control and task performance. Additionally, sociability increased task performance and contextual performance. Moreover, emotionality and sociability reduced counterproductive work behavior. Our multivariable models identified a positive impact of emotional intelligence on nurses’ work performance. Nurses managers and healthcare organizations should adopt appropriate interventions to improve nurses’ emotional intelligence.

ABSTRACT Background: To date, the COVID-19 pandemic has been the foremost health concern for humankind in the new millennia. This paper aims to describe the related hospitalizations in Italy during the first two years of the health emergency. Design and methods: This is a retrospective, population-based study of Italian hospitalizations for patients diagnosed with COVID-19 during the 2020-2021 period, extracted from the National Hospital Discharge Registry. The outcome variables considered include hospital admissions, costs, and length of stay, among other hospitalization-level variables. Costs were estimated through the charges associated with the Diagnosis-Related Group and Major Diagnostic Categories coding system, plus an additional cost attributed to COVID-19 admissions. To these charges was added an extra cost defined by the ministry of health. Results: In Italy, there were 357,354 hospitalizations for COVID-19 attributed to 298,856 patients in 2020 and 399,043 hospitalizations for COVID-19 attributed to 333,447 patients in 2021. COVID-19 patients faced a transfer rate thrice that of other patients. Hospitalizations were concentrated predominantly in the northern regions, particularly in the first year. Hospitalization rates varied by age in a sine wave pattern, peaking in the youngest and oldest age groups, with mortality rates escalating with age— tending to remain below 3% for those under 44 but surging to 40% in individuals over 75. The financial impact of COVID-19 hospitalizations was substantial, with total costs reaching €3.97 billion in 2020 and €4.99 billion in 2021. Costs per admission and per day also rose, from €11,112 and €807 in 2020 to €12,503 and €844 in 2021, respectively. Excluding the added financial burden of COVID-19, costs would have been notably lower. Hospitalizations involving continuous invasive mechanical ventilation were particularly costly (about 24.000 euros x admission), reflecting the significant resources required for these treatments. Conclusion: Implementing a protective pad around the entire health system that leverages networks of family doctors and nurses, connected in real time to the entire health system, can be crucial. Such a network, tasked with monitoring the local epidemiological situation, protecting vulnerable individuals also through telehealth visits, and establishing a triage system for infections in the initial phase, may effectively help in managing virus spread and protecting hospitals from unpredictable waves of admission demand. Strengthening primary health care could be a decisive factor for the future and enhance the system's resilience in facing new challenges.

Presynaptic Ca²⁺-influx through voltage-gated Ca²⁺ channels (VGCC) is a key signal for synaptic vesicle release. Synaptic neurexins can partially determine the strength of transmission by regulating VGCCs. However, it is unknown whether neurexins modulate Ca²⁺-influx via all VGCC subtypes similarly. Here, we performed live cell imaging of synaptic boutons from primary hippocampal neurons with a Ca²⁺-indicator. We used the expression of inactive and active Cre recombinase to compare control to conditional knockout neurons lacking either all or selected neurexin variants. We found that reduced total presynaptic Ca²⁺-transients caused by the deletion of all neurexins were primarily due to the reduced contribution of P/Q-type VGCCs. The deletion of neurexin1α alone also reduced the total presynaptic Ca²⁺-influx but increased Ca²⁺-influx via N-type VGCCs. Moreover, we tested whether the decrease of Ca²⁺-influx induced by activation of cannabinoid receptor 1 (CB1-receptor) is modulated by neurexins. Unlike earlier observations emphasizing a role for β-neurexins, we found that the decrease of presynaptic Ca²⁺-transients induced by CB1-receptor activation depended more strongly on the presence of α-neurexins in hippocampal neurons. Together, our results suggest that neurexins have unique roles in the modulation of presynaptic Ca²⁺-influx through VGCC subtypes and that different neurexin variants may affect specific VGCCs.

The COVID-19 pandemic halted progress in global vaccine coverage and disrupted routine childhood vaccination practices worldwide. While there is ample evidence of vaccination declines experienced during the pandemic, it is less clear how low-income countries were affected. We executed a systematic review to synthesize the current literature on impacts to routine childhood vaccinations in low-income countries from January 1, 2020 to February 8, 2023. We collected data using an extraction form on Covidence and assessed the quality of studies included in the review using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Effect estimates for changes in vaccination during the pandemic were reported and summarized. Factors that influenced changes were grouped into descriptive themes. Thirteen studies, encompassing 18 low-income countries and evaluating 15 vaccines at varying doses, were included in the final review. We found that routine childhood vaccinations during the COVID-19 pandemic varied considerably by vaccine type, location, and phase of the pandemic. Nine different themes were identified as factors that influenced changes in vaccination. Documenting past experiences and lessons learned is crucial for informing preparedness efforts in anticipation of future public health emergencies. Failure to effectively address these things in the next public health emergency could result in a recurrence of declining routine childhood vaccinations.

Introduction Sepsis-associated encephalopathy (SAE) is common in sepsis and is linked to high mortality and impaired neurologic outcome. Brain ultrasonography (US), including transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS), is a non-invasive tool for cerebral monitoring and might be useful in sepsis. The aims of this review are: 1) to explore whether brain perfusion is altered in sepsis, 2) to determine the role of brain US in guiding resuscitation, and 3) its ability to predict neurological outcomes in septic patients. Materials and methods This scoping review adhered to the PRISMA-ScR protocol and JBI methodology. A comprehensive literature search was conducted across MEDLINE, Scopus, and Web of Science. The review included studies on adults with sepsis or septic shock in the ICU. Randomised controlled trials, clinical trials, observational studies and systematic reviews were included. All the data related to the review's key questions were extracted and charted independently by two authors. Results 625 articles were screened, and 34 were ultimately included after application of exclusion criteria. 85% of the studies were observational 15% were systematic reviews with or without meta-analysis. The studies primarily focused on cerebral blood flow (CBF) alterations in sepsis, reporting variable results. Findings showed variable cerebral autoregulation (CAR) impairment, with higher incidence in the early stages of sepsis and associations with poor neurological outcomes. However, while alterations in CAR and CBF are common in septic patients, their impact on neurological outcomes and mortality is not clear. Regarding resuscitation, only a paucity of studies were found and no conclusions can be drawn. Conclusions The current body of evidence has a poor grade, but it is possible to say that brain US can identify cerebral perfusions alterations. Its usage during resuscitation is feasible and warrants further investigations. Use of brain US during resuscitation and for prediction of outcome is not currently supported by evidence. Further studies on brain perfusion, acquisition of 2D images of parenchyma (TCCS) and application of a multimodal brain monitoring might be useful in these contexts.

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

Nurses have experienced several psychological and work-related issues during the COVID-19 pandemic including pandemic burnout and job burnout. The aim of the study was to examine the impact of social support and resilience on COVID-19 pandemic burnout and job burnout among nurses. We conducted a cross-sectional study in Greece. Study population included 963 nurses. We measured social support, resilience, COVID-19 pandemic burnout, and job burnout with the Multidimensional Scale of Perceived Social Support, Brief Resilience Scale, COVID-19 burnout scale, and single item burnout measure respectively. Nurses received high levels of social support, while their resilience was moderate. Additionally, nurses experienced moderate levels of COVID-19 burnout and job burnout. Increased social support (adjusted beta = -0.075, 95% CI = -0.125 to -0.024) and increased resilience (adjusted beta = -0.399, 95% CI = -0.491 to -0.308) were associated with reduced COVID-19 pandemic burnout. We found a negative relationship between social support and job burnout (adjusted beta = -0.263, 95% CI = -0.405 to -0.121). A similar negative relationship was found between resilience and job burnout (adjusted beta = -0.529, 95% CI = -0.785 to -0.272). Social support and resilience can act as protective factors against COVID-19 pandemic burnout and job burnout among nurses. Policy makers should develop and implement appropriate strategies to improve nurses’ social support and resilience since they are the backbone of healthcare systems worldwide.

Estimating parameters for multiple datasets can be time consuming, especially when the number of datasets is large. One solution is to sample from multiple datasets simultaneously using Bayesian methods such as adaptive multiple importance sampling (AMIS). Here we use the AMIS approach to fit a von Misses distribution to multiple datasets for wind trajectories derived from a Lagrangian Particle Dispersion Model driven from a 3D meteorological data. The primary objective is to characterise the uncertainties in wind trajectories in a form that can be used as inputs for predictive models of wind-dispersed insect pests and pathogens of agricultural crops for use in evaluating risk and in planning mitigation actions. Our results show that AMIS can significantly improve the efficiency of parameter inference for multiple datasets.

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatic and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many of the ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the diagnostic and prognostic value of these ncORF as well as their carcinogenic role in cancer progression and underestimated potential as therapeutic targets.

Workplace bullying is common among nurses affecting negatively several work-related variables, such as job burnout and job satisfaction. However, no study until now has examined the impact of workplace bullying on quiet quitting among nurses. Thus, our aim was to examine the direct effect of workplace bullying on quiet quitting and to investigate the mediating effect of coping strategies on the relationship between workplace bullying and quiet quitting in nurses. We conducted a cross-sectional study with a convenience sample of 650 nurses in Greece. We collected our data during February 2024. We used the Negative Acts Questionnaire-Revised, the Quiet Quitting Scale and the Brief COPE to measure workplace bullying, quiet quitting and coping strategies, respectively. We found that workplace bullying and negative coping strategies were positive predictors of quiet quitting, while positive coping strategies was a negative predictor of quiet quitting. Our mediation analysis showed that positive and negative coping strategies partially mediated the relationship between workplace bullying and quiet quitting. In particular, positive coping strategies caused competitive mediation, while negative coping strategies caused complimentary mediation. Nurses’ managers and policy makers should improve working conditions by reducing workplace bullying and strengthening positive coping strategies among nurses.

Background: Rabies, a zoonotic disease caused by the lyssavirus genus, is widely distributed and a significant cause of human death in Africa and Asia. This study aimed to investigate human rabies exposure and associated risk factors in Northwest Ethiopia. Methods: The study encompassed four zones, seven districts, and four kebeles from each district. The research team developed a questionnaire for data collection. Results: A total of 642 households were interviewed. The current study rabies exposure was revealed 10.47%. Over 98% of respondents displayed a strong understanding of rabies, with 99.69% correctly identifying rabies as a zoonotic disease. However, 80% of the interviewees were trusted traditional medicine could treat rabies. Only 21.93% of victims were took post exposure prophylaxis. Dogs were the primary affected animals (87.73%), of this 48.70% was bites by own dogs. Metema district had higher risk (p < 0.001) compared to others six districts. Dog ownership (p<0.05) and a higher number of households (p<0.01) were also identified as risk factors for rabies exposure. Conclusion: Residence, low education levels, high household density, free-roaming dogs, and dog ownership as key risk factors for rabies exposure. Public health awareness campaigns are crucial to emphasise the risks associated with animal bites.

The continues evolution of coronaviruses has gained considerable attention prior to the outbreak of COVID 19. Although, COVID-19 is currently not recognized as a global pandemic, the virus's ability to evolve and cause disease outbreaks in both humans and animals necessitates ongoing research into its genetic and structural characteristics. Therefore, understanding the molecular origin, rapid evolution, as were as the immunogenicity of coronaviruses is a critical step towards preparing for and preventing future outbreaks. This study aimed to uncover the genetic diversity and evolutionary relationships among the main viral proteins of SARS-CoV-2 and other related coronaviruses. Amino acid sequences of structural viral proteins spike glycoprotein, nucleocapsid protein, membrane protein, and envelope protein were retrieved from the NCBI database for SARS-CoV-2 and 13 other coronaviruses. Here, we identified that SARS-CoV-2 is closely related to BatCoV RaTG13 and Pangolin-CoV, suggesting their potential role in the emergence of the virus. Additionally, we predicted novel epitopes, glycosylation sites, and cleavage sites, identifying three novel glycosylation sites (NATR, NXSN, and NGTK) and six new CTL epitopes (XSNQVAVLY, NSFTRGVYY, NATRFASVY, STQDLFLPF, NSASFSTFK, and ASFSTFKCY). Our comparative analysis revealed that BatCoV RaTG13 has the closest cleavage site to SARS-CoV-2, with significant similarities also observed with Pangolin-CoV. The study highlighted the unique features of SARS-CoV-2, including its furin cleavage site, which may account for its high infectivity during the pandemic. These findings contribute to the understanding of SARS-CoV-2 evolution and its relationship with other coronaviruses, providing critical insights for the development of broad-spectrum vaccines and antiviral therapies.

The Aspergillus genus comprises fungi that are widely distributed in nature. The Terrei section is particularly important due to its functions in recycling organic matter. Aspergillus hortae is a species from this section that has been isolated from clinical samples, but its role as a pathogenic agent is unclear. In this study, three clinical A. hortae isolates from Colombia, initially identified as A. terreus, were characterised by micro and macro-morphological analysis at 26°C and 37°C. A bioinformatic pipeline was used for molecular typing, which included analysis of whole genome sequences for accurate species identification. Susceptibility assays were also conducted using the microdilution broth method (EUCAST). It was confirmed that this species is intrinsically resistant to Amphotericin B with a minimum inhibitory concentration (MIC) of 2-4 mg/L, and is also thermotolerant. We obtained the in vitro susceptibility profiles for three azole drugs (MIC, 0.25-1 mg/L). The three isolates showed phylogenetic divergence from the reference genome strain. A mutation (M769K) in the MelA ortholog of a hypopigmented isolate, which had the lowest MIC value for AmB (2 mg/L), was identified. This study presents the morphological characterization, molecular typing through whole-genome analysis and identification of susceptibility profiles to azoles and amphotericin B of three clinical isolates of A. hortae from Colombia.

The BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises Brd2, Brd3, Brd4, and Brdt, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-Myc. These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.

Circulating tumor cells (CTCs) are cells released from the primary tumor and intravasate into the blood or lymphatic vessels, where they are transported to distant sites and act as seeds that initiate cancer metastases. Recent advances in CTC research have shown their relevance as prognostic markers for early and metastatic disease detection, predictive biomarkers for relapse, and response to medical intervention or therapy. The rapidly evolving landscape of CTC biology has opened new avenues for understanding cancer progression, metastasis, and treatment response. Additionally, translating these findings into clinical applications holds promise for improving cancer diagnostics, prognosis, and personalized therapeutic strategies. This review discusses the significance of CTCs in cancer research and their associated challenges. We explore recent developments in the detection and characterization of CTCs and their implications in cancer research and clinical practice.

Continuing the investigation already started (See Farcaş, A.-A.; Bende, A. PCCP 2024, 26, 14937), the light absorption and charge-transfer properties of the dopamine (DA), dopamine zwitterion (called as dopamine-semi-quinone or DsQ) and dopamine-o-quinone (DoQ) adsorbed on the graphene nanoparticle surface have been investigated using the ground state and linear-response time-dependent density functional theories, considering the B97X-D3BJ/def2-TZVPP level of theory. In terms of the strength of molecular adsorption on the surface, the DsQ form has 50 % higher binding energy than that for the DA or DoQ cases (-20.24 kcal/mol vs. -30.41 kcal/mol). The results obtained for electronically excited states and UV-Vis absorption spectra show that the photochemical behavior of DsQ is more similar to DA than that observed for DoQ. Of the three systems analyzed, the DsQ-based complex showed the most active CT phenomenon, both in terms of the number of CT-like states and the amount of charge transferred. Of the first thirty electronically excited states computed for the DsQ case, eleven are purely CT-type and nine are mixed CT and localized (or Frenkel) excitations. By varying the adsorption distance between the molecule and the surface vertically, the amount of charge transfer obtained for DA decreases significantly as the distance increases, for DoQ it remains stable, while for DsQ there are states for which little change is observed, while for others there is a significant change. Furthermore, the mechanistic compilation of the electron orbital diagrams of the individual components cannot describe in detail the nature of the excitations inside the complex.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

Diffusion magnetic resonance imaging (dMRI) is an imaging technique that provides information on the microstructural organization of biological tissue. dMRI allows for non-invasive visualization and quantitative assessment of white matter architecture in the brain by characterizing restrictions on the random motion of water molecules. Ultra-high field MRI scanners, such as those operating at 7 Tesla (7T) or higher, can boost signal-to-noise ratio (SNR) to improve dMRI compared with what is attainable at conventional field strengths such as 3T or 1.5T. However, at 7T wavelength effects cause lower transmit magnetic field efficiency in the human brain, mainly in the posterior fossa region, manifesting as signal dropouts in this region. Recently, we reported a simple approach of using a wireless radiofrequency (RF) surface array to improve transmit efficiency and signal sensitivity at 7T. Here we demonstrate the feasibility and effectiveness of using this RF enhancer for in-vivo dMRI at 7T. The use of the RF enhancer can effectively recover signal dropouts in the regions with intrinsically lower SNR such as cerebellum, leading to a better depiction of principal fiber orientations and enhanced visualization of extended tracts to the brainstem and pons enabling more comprehensive delineation of the full white matter architecture.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

From their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses [1]. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3 to 10% of reported cases [2-5]. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches have been taken for the treatment of BRAF mutant cancers. In this review we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.

Reconstructing the Tree of Life remains a central goal in biology. Early methods, relying on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the Tree of Life, two recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in two or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. We identify and discuss specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the Tree of Life.

Oligopeptide transporters (OPTs) are a group of membrane localized proteins that have a broad range of substrate transport capabilities and contribute to numerous biological processes. However, limited information has been reported on OPTs in higher plants. In this study, a comprehensive analysis of the OPT gene family in Medicago truncatula was performed. A total of 26 OPT genes (MtOPT01-MtOPT26) have been identified in the Medicago truncatula genome. Phylogenetic analyses indicated that MtOPTs consisted of two distinct subgroups, 12 MtOPTs belonged to the peptide transport subgroup (PT-OPT) based on their predicted amino acid sequences containing the two highly conserved motifs (NPG and KIPPR) and 14 MtOPTs belonged to yellow stripe subgroup (YS-OPT). The MtOPTs distributed on each of 8 chromosomes in Medicago truncatula. Sequence analysis verified that MtOPTs significant similar to those in other plants. The copy number of MtOPTs was low and the multiply of MtOPTs was simple relatively. Gene structure analysis showed that most of the MtOPTs have various numbers of introns. The multiple of MtOPTs might play different biological roles which were supported by the fact that MtOPTs have a distinct tissue-specific expression pattern. The data obtained in this study will help to better understand the complexity of the MtOPTs gene family and provide new evidence for the function and evolution of the OPT gene family in higher plants.

Lyme disease is a highly prevalent tick-borne infection caused by Borrelia burgdorferi spirochetes in North America and Eurasia. Diagnosis of the early disease remains difficult with the currently approved serological tests in the absence of noticeable tick bite or erythema migrans due to presentation of non-specific symptoms and the absence of antibodies early in infection. Furthermore, it is difficult to distinguish persistence of disease and reinfection in the endemic regions. If not treated early, infection spreads throughout the body and affects most organs with disease manifestations including arthritis, musculoskeletal pain, neuroborreliosis and acrodermatitis chronicum atrophicans. Although most patients recover after antibiotic treatment, ~10-12% of show recurrence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). Various causes of PTLDS are not well-defined; however, the spirochete persisters, antigenic debris, dysregulation of immunological response in individuals or a combination of these factors are proposed to result in continuation of Lyme disease manifestations. Based on these considerations, this review highlights currently employed treatment approaches with antimicrobials and vaccines being tried for prevention of B. burgdorferi infection. We also summarize combinatorial approaches that could be employed to alleviate symptoms to improve the quality of life of the individuals suffering from long Lyme disease.

Huperzine A is an herbal reversible inhibitor of Acetylcholinesterase (AChE). A molecular docking analysis on Huperzine A molecule has been carried out to understand its structure, conformational flexibility, intermolecular interaction and the binding affinity in the active site of AChE enzyme. Further, the charge density distribution of huperzine A molecule (lifted from the active site of AChE) was determined from the high level quantum chemical calculations coupled with charge density analysis. The binding affinity of Huperzine A towards AChE was calculated from the molecular docking; the lowest docked energy is -8.46 kcal/mol. In the active site, huperzine A molecule interacts with acyl binding pocket-Phe330 of AChE, that is, the bicyclo ring group of huperzine A forms an intermolecular interaction with the oxygen atom of main chain of the amino acid residue Phe330 at the distances 3.02 and 3.25 Å respectively. On the other hand, a gas phase study on huperzine A molecule also performed using HF and DFT (B3LYP) methods with the basis set 6-311G**. The molecular structure, conformation, and the charge density distribution of huperzine A molecule in the gas phase have determined using quantum chemical calculations and the charge density analysis. The comparative studies between the gas phase and the active site forms of huperzine A molecule, explicitly reveals the degree of conformational modification and the charge density redistribution of huperzine A when present in the active site. The dipole moment of the molecule in the active site is 6.85 D, which is slightly higher than its gas phase value (5.91 D). The electrostatic potential (ESP) surface of active site molecule clearly shows the strong electronegative and positive ESP regions of the molecule, which are the expected strong reactive locations of the molecule.

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease that infects both human and animals. This is a descriptive study summarizes investigation and response to RVF outbreak, using surveillance data. A RVF outbreak occurred in Berber locality in northern Sudan. We identified 246 cases of RVF including seven deaths among humans, 119 deaths and 82 abortions among Livestock. Our entomological surveillance confirmed the presence of Anopheles arabiensis, An. stephensi, Aedes aegypti, Ae. vexans, Culex pipiens, Cx. Quinquefasciatus, and Cx. theileri in the area during the outbreak. In a comparison with another outbreak of Rift Valley fever in nearby area while ago, a multisectoral One Health response strategy has resulted in strengthening the health system through re-innovating health facilities and centres and training about 200 healthcare and emergency responders. Additionally, it reduced cases and fatalities among humans by 78% and 63%, respectively, and loss in livestock due to deaths and/or abortions by 82%. The added-value of implementing One Health strategy was saving more lives and resources, while strengthening the health system. We recommend the systematic institutionalization of One Health strategy in the country as a core part of the national prevention and control strategy for zoonotic diseases epidemics and pandemics.

Enteroaggregative Escherichia coli (EAEC) is an emerging pathogen frequently associated with acute diarrhea in children and travelers to endemic regions. EAEC was found the most prevalent bacterial diarrheal pathogen from hospitalized Bolivian children less than five years of age with acute diarrhea from 2007 to 2010. Here, we further characterized the epidemiology of EAEC infection, virulence genes, and antimicrobial susceptibility of EAEC isolated from 414 diarrheal and 74 non-diarrheal cases. EAEC isolates were collected and subjected to a PCR-based virulence gene screening of seven virulence genes and a phenotypic resistance test to nine different antimicrobials. Our results showed that atypical EAEC (a-EAEC, AggR-negative) was significantly associated with diarrhea (OR, 1.62, 95% CI, 1.25 to 2.09, P < 0.001) in contrast to typical EAEC (t-EAEC, AggR-positive). EAEC infection was most prevalent among children between 7 - 12 months of age. The number of cases exhibited a biannual cycle with a major peak during the transition from warm to cold season (April – June). Both typical and a-EAEC infections were graded as equally severe; however, t-EAEC harbored more virulence genes. aap, irp2, and pic were the most prevalent genes. Surprisingly, we detected 60% and 52.6% of multidrug resistance (MDR) EAEC among diarrheal and non-diarrheal cases. Resistance to ampicillin, sulfonamides, and tetracyclines was most common, being the corresponding antibiotics, the ones that are frequently used in Bolivia. Our work is the first study that provides comprehensive information on the high heterogenicity of virulence genes in t-EAEC and a- EAEC and the large prevalence of MDR EAEC in Bolivia.

This paper presents the novel development of a shape memory polymer foam based on polymer-polymer nanocomposites. Herein, polylactide (PLA)/biosourced polyamide (PA) foams are fabricated by in-situ fibrillation of polymer blends and subsequent supercritical CO2 foaming technique. In this system, PLA serves as a shape memory polymer to endow this foam with a shape memory effect (SME), and in-situ generated PA nanofibers are employed to reinforce the PLA cell walls and provide an additional permanent phase. Concentration of PA, 5 wt.%, is chosen to form an entangled nanofibrillar network. Foams of PLA/PA nanoblends with the same content of constituents are fabricated to reveal the effect of minor phase morphology on the cell structure and shape memory behavior of polymer foams. Profiting from the reinforcing effect of PA nanofibers, the PLA/PA nanocomposite foam exhibits smaller foam cells, a narrower cell size distribution and a comparable cell concentration than the PLA/PA nanoblend foam. In addition, PA nanofibers, unlike PA nanodroplets, favor the shape fixation ratio and recovery ratio and shorten the shape recovery time.

Background: Obesity remains a widely debated issue, often criticized for the limitations in its identification and classification. This study aims to compare two distinct systems for classifying obesity: Body Mass Index (BMI) and body fat percentage (BFP) as assessed by bioelectrical impedance analysis (BIA). By examining these measures, the study seeks to clarify how different metrics of body composition influence the identification of obesity-related risk factors. Methods: The study enrolled 1255 adults, comprising 471 males and 784 females, with a mean age of 36 ± 11.90 years. Participants exhibited varying degrees of weight status, including optimal weight, overweight, and obesity. Body composition analysis was conducted using the TANITA Body Composition Analyzer BC-418 MA III device (T5896, Tokyo, Japan), evaluating the following parameters: current weight, basal metabolic rate (BMR), adipose tissue (%), muscle mass (%), and hydration status (%). Results: Age and psychological factors like cravings, fatigue, stress, and compulsive eating were significant predictors of obesity in the BMI model but not in the BFP model. Additionally, having a family history of diabetes was protective in the BMI model (OR: 0.33) but increased risk in the BFP model (OR: 1.66). The BMI model demonstrates exceptional predictive ability (AUC=0.998). In contrast, the BFP model, while still performing well, exhibits a lower AUC (0.975), indicating slightly reduced discriminative power compared to the BMI model. Conclusions:BMI classification demonstrates superior predictive accuracy, specificity, and sensitivity. This suggests that BMI remains a more reliable measure for identifying obesity-related risk factors compared to the BFP model.

Some medical professional organizations have advocated for including the menstrual cycle as a vital sign in adolescence, but not in adulthood. However, documenting menstrual cycle patterns is not routine clinical or research practice. Vital signs are used to predict health outcomes, indicate needed treatment, and monitor a clinical course. They can help identify pathologies, affirm wellness, and are responsive to exposures. Here we review the scientific evidence showing how the menstrual cycle meets these criteria and should therefore be treated as a vital sign. Using key words and controlled vocabulary terms, we carried out multiple literature searches, prioritizing the inclusion of systematic reviews, meta-analyses, and clinical practice guidelines. This review describes how the menstrual cycle is a health indicator, can cyclically impact health conditions, and its associations with long-term post-menopausal health outcomes. We review exposures influencing the menstrual cycle, evidence underlying its use to optimize wellness, and available tools for documenting cycles. Supplementary materials include patient handouts on menstrual cycle tracking, and an index of related clinical practice guidelines and reviews by subject. The menstrual cycle is a vital sign from menarche through menopause, an underutilized but powerful tool for understanding gynecological and general health.

Systemic Lupus Erythematosus (lupus) and B-cell lymphoma (lymphoma) are serious diseases. Lupus and lymphoma co-occur at higher-than-expected rates and primarily depend on B-cells for their pathology, implicating shared inflammation-related B-cell molecular mechanisms as a potential cause of co-occurrence. We consequently implemented a novel Immune Imbalance Transcriptomics (IIT) algorithm and applied IIT to lupus, lymphoma, and healthy B-cell RNA-seq data to find shared- and contrasting mechanisms potentially targetable for treatment. We observed 8,562 genes significantly dysregulated in both lupus and lymphoma. Of those genes, we found 5,335 to have a significant immune imbalance, defined as significant dysregulation by both diseases, as determined by IIT. Gene Ontology (GO) term and pathway enrichment of IIT genes yielded immune-related “Neutrophil Degranulation” and “Adaptive Immune System”, validating that the IIT algorithm isolates biologically relevant genes in immunity and inflammation. We found that 389 IIT gene products are drug-targetable with established or repurposed drugs. Among our results, we found 40 known and 349 novel lupus targets, along with 151 known and 238 novel lymphoma targets. Known disease drug targets in our IIT results further validate that IIT isolates genes with disease-relevant mechanisms. We anticipate the IIT algorithm and shared and contrasting gene mechanisms uncovered here will contribute to the development of immune-related therapeutic options for lupus and lymphoma patients.

The immune response is crucial in Pregnancy Loss (RPL), which affects 1-2% of women. In RPL, peripheral blood lymphocytes and local immune cells are activated with a concomitant decrease in the leukocyte tolerogenic response in the uterus and decidua. IL-17 plays an essential role in T cell activation, weakening tolerogenic responses of the T cells. The report aims to analyze the IL-17 genetic polymorphism, circulating IL-17 lymphocyte populations, the reaction upon lymphocyte priming, the amount of cytokine in serum, and the number of T-reg cells in a group of 50 RPL and 50 normal women from the admixed Venezuelan population. No differences were observed in the genetic polymorphisms rs2275913 and rs763780. A significant decrease (P&lt;0.001) was observed in RPL patients compared to controls in the IL-17+ cell populations CD3+, CD8+, CD56+, and CD4CD25 FoxP3, but not in the CD4IL17+ cells. The response upon cell priming was significantly decreased (P&lt;0.001) in all subpopulations of RPL as compared to controls. It is concluded that despite the increase in IL-17A in the serum of patients, the number of circulating IL-17 cells and the lymphocyte response to stimulation was significantly decreased (p&lt;0.001). No differences in the genetic polymorphism compared to controls suggest that biological factors influence IL-17 levels in RPL patients, which must be carefully studied.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it is related to the loss of a suppressing protein called merlin. At the same time, alterations in energy production are visible in cancer cells where increased demand for energy is observed. Fatty acid oxidation could be one of the ways cancer cells obtain energy. This metabolic pathway uses the acylcarnitine shuttle system, which is responsible for the acylation of fatty acids and their transport through mitochondria. Therefore, this study aimed to profile acylcarnitines with short-, medium- and long-acyl chain length in meningiomas to assess their changes in tumors with different NF2 mutation statuses. For the analysis, solid-phase microextraction (SPME) coupled with liquid chromatography high resolution mass spectrometry (LC-HRMS) was used. The presented sampling method enables low invasive and easy collection of the analytes from the studied lesions, which can be crucial for future analysis of potential biomarkers in the surgery room. It was observed that higher levels of these analytes characterized meningiomas with NF2 mutation. Moreover, increased energy consumption and elevated levels of acylcarnitines show that these analytes can be considered as a marker of increased fatty acid oxidation in NF2 mutated cells.

Brucellosis is a zoonoses caused by bacteria of the genus Brucella, which causes economic losses in livestock and threatens public health. A cross-sectional study was conducted to determine the prevalence of Brucella species and risk factors in smallholder dairy cattle in six regions of Tanzania from July 2019 to October 2020. Dairy cattle (n=2048) were sampled from 1371 farms. DNA ex-tracted from blood and vaginal swabs was tested for Brucella using qPCR targeting the IS711 gene and positives were tested for the alkB marker for B. abortus and BMEI1172 marker for B. melitensis. The molecular prevalence was 3.5% (95% CI: 2.8-4.4) with the highest prevalence 8.1% (95%CI: 4.6-13.0) in Njombe region. B. melitensis was the predominant species detected (66.2%). Logistic regression revealed PCR positivity in dairy cattle was higher in the animals with a history of abortion (OR: 3.17, 95%CI: 1.05-9.62) and farms without dogs around (OR: 2.68, 95%CI: 1.12-5.90). Further studies are recommended to understand the source of B. melitensis and the implications to veterinary public health. Livestock keepers should be informed of the risks and biosecurity practices to reduce introduction and control Brucella. Cattle and small ruminant vaccination pro-grams could be implemented to control brucellosis in high-risk populations in the country.

Numerous varieties of Capsicum annuum L. with multiple valuable traits, such as adaptation to biotic and abiotic stress factors, can be found in south-east Romania, well known for vegetable cultivation and an important area of biodiversity conservation. To obtain useful information toward a sustainable agriculture, management and conservation of local pepper varieties, we analyzed the genetic diversity and we did deep molecular characterization using Whole Genome Resequencing (WGS) for variant/mutation detection. The pepper varieties used in the present study were registered by VRDS in the ISTIS catalog between 1974 and 2019 and maintained in conservative selection, however, no studies have been published yet using WGS analysis in order to characterize this specific germplasm. The genome sequences, annotation and alignments provided in this study offer essential resources for genomic research as well as for future breeding efforts using the C. annuum local varieties.

The extensive metabolic diversity of microalgae, coupled with their rapid growth rates and cost-effective production, position these organisms as highly promising resources for a wide range of biotechnological applications. These characteristics allow microalgae to address crucial needs in both the agricultural, medical, and industrial sectors. Microalgae are proving to be val-uable in various fields, including the remediation of diverse wastewater types, the production of biofuels and biofertilizers, and the extraction of various products from their biomass. For decades, the microalga Chlamydomonas has been widely used as a fundamental research model organism in various areas such as photosynthesis, respiration, sulfur and phosphorus metabolism, nitrogen metabolism, and flagella synthesis, among others. However, in recent years, the potential of Chlamydomonas as a biotechnological tool for bioremediation, biofertilization, biomass, and bio-products production has been increasingly recognized. Bioremediation of wastewater using Chlamydomonas presents significant potential for sustainable reduction of contaminants and fa-cilitates resource recovery and valorization of microalgal biomass, offering important economic benefits. Chlamydomonas has also established itself as a platform for the production of a wide va-riety of biotechnologically interesting products, such as different types of biofuels, and high-value-added products. The aim of this review is to achieve a comprehensive understanding of the potential of Chlamydomonas in these aspects, and to explore their interrelationship, which would offer significant environmental and biotechnological advantages.

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing antibodies (bnAbs) that retain prominent effectiveness against emerging variants including Omicron sub-lineages. The molecular characteristics, epitope conservation, and resistance mechanisms of these antibodies are further detailed, aiming to offer suggestion or direction for the development of therapeutic antibodies, and facilitate the vaccine design with broad-spectrum potential.

Background and Objectives: Wilson disease (WD) is a disorder of copper metabolism caused by genetic muta-tions in the ATP7B gene which lead to the accumulation of copper in the body. The aim of the present study is to investigate the severity of WD in patients in Romania. Materials and Methods: This study was conducted us-ing an online questionnaire consisting of 32 questions in a group of patients suffering from Wilson disease. Results: The study included 67 people aged 7 to 56 with WD. The most common symptoms of the participants were hepatic and neurological in 22 cases (32.8%). The most common neurological symptom in the assessed cases was muscle stiffness (49.5%), followed by tremor (45%), and speech disorders (40.5%). The Kay-ser-Fleischer ring was present in 50.7% of the participants. The most commonly used drug treatment in the participants was D-penicillamine (77.61%). Conclusions: The severity of WD is based on many aspects, the most important being early diagnosis and access to treatment throughout the year. The prognosis is favorable with early diagnosis and treatment, but it is crucial to diagnose individuals before they develop major symp-toms. Therefore, advances in WD screening can lead to an earlier diagnosis and better results.

In bacteria, enzymes usually comprise of enzymatic domains only. In eukaryotes/mammals, and here particularly in context of signal transduction, proteins with enzymatic functions contain additional modules promoting interactions with cooperating signaling proteins. Often such protein-protein interaction domains, such as SH2- and SH3-domains, help to localize the enzymatic function (e.g. kinase, phosphatase) to another protein, cellular compartment, or membrane nanodomain. In such cases, the interaction domain(s) serve(s) the enzymatic function. However, there are molecular situations in which an interaction domain fulfills its task completely independent of the protein´s enzymatic function and in this review, we call such function the adapter function of an enzyme. Though many stories can be told, we will concentrate on several proteins playing crucial roles in cells of the immune system, such as BTK, PI3K, and SHIP1, as well as in cancer cells, such as proteins of the RAS/ERK MAPK pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors, thereby highlighting the need to develop pharmacological approaches, such as PROTACs, that eliminate the entire protein. We also review how genetic kock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins.

Silencing of the fragile X mental retardation 1 (FMR1) gene and consequently lack of synthesis of FMR protein (FMRP) are associated with fragile X syndrome, which is one of the most prevalent inherited intellectual disabilities. FMRP is a multifunctional protein involved in many cellular functions in nearly all subcellular compartments under normal conditions and under conditions of cellular stress in both neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.

In Cameroon, Aedes mosquitoes transmit various arboviruses, posing significant health risks. We aimed to characterize the Aedes virome in southwestern Cameroon and identify potential core viruses which might be associated with vector competence. A total of 398 Aedes mosquitoes were collected from four locations (Bafoussam, Buea, Edea and Yaounde). Aedes albopictus dominated all sites except for Bafoussam where Aedes africanus prevailed. Metagenomic analyses of mosquitoes grouped per species into 54 pools revealed notable differences in eukaryotic viromes between Ae. africanus and Ae. albopictus, with the former exhibiting greater richness and diversity. Thirty-seven eukaryotic virus species from 16 families were identified, including six novel viruses with near complete genome sequences. Seven viruses were further quantified in individual mosquitoes via qRT-PCR. Although none of them could be identified as core viruses, Guangzhou sobemo-like virus and Bafoussam mosquito solemovirus virus were highly prevalent regionally in Ae. albopictus and Ae. africanus, respectively. This study highlights the diverse eukaryotic virome of Aedes species in southwestern Cameroon. Despite their shared Genus, Aedes species exhibit limited viral sharing, with varying viral abundance and prevalence across locations. Ae. africanus, an understudied vector, harbors a rich and diverse virome, suggesting potential implications for arbovirus vector competence.

Wastewater-Based Epidemiology (WBE) is currently used to monitor not only the spread of the pandemic virus SARS-CoV-2 but also for other viruses in endemic conditions, particularly in the absence of syndromic surveillance. Continuous monitoring of sewage requires high costs and significant time investment, highlighting the need for standardized methods and structured monitoring strategies. In this context, we conducted weekly wastewater monitoring in northwestern Italy, targeting Human Adenovirus (HAdV), Norovirus Genogroup II (NoVggII), Enterovirus (EV), and SARS-CoV-2. Samples collected at the entrance of treatment plants were concentrated using PEG/NaCl precipitation and viral nucleic acids were extracted and detected by real-time (RT-)qPCR. NoVggII resulted the most identified target (84.4%), followed by HAdV, SARS-CoV-2, and EV. Only HAdV and EV exhibited seasonal peaks in spring and summer. SARS-CoV-2 results compared with data previously collected in the same study area (February 2021 to September 2021) revealed a shift from an epidemic to a pandemic status, likely due to the evolution of variants. In conclusion, WBE, using standardized methods and an efficient monitoring strategy, proves valuable for virus surveillance in pandemic and epidemic scenarios, enabling the identification of temporal-local distribution patterns that are useful for making informed public health decision.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Plant growth-promoting rhizobacteria (PGPR) are beneficial bacteria that play a crucial role in sustainable agriculture by enhancing plant growth through various mechanisms. This review examines the contributions of PGPR in improving nutrient availability, producing phytohormones, providing biocontrol against pathogens, and enhancing abiotic stress tolerance. By reducing the necessity for chemical fertilizers and pesticides, PGPR mitigate environmental impacts, enhance soil health, and support long-term agricultural productivity. However, challenges such as inconsistent performance across various soils, regulatory barriers, and limited farmer awareness hinder their widespread adoption. Recent advancements in nano-encapsulation technology, genetic engineering, and bioinformatics present promising solutions for overcoming these obstacles and enhancing PGPR efficacy. The incorporation of PGPR into biofertilizers, biopesticides, and integrated pest management (IPM) strategies offers a sustainable resolution to global agricultural challenges. This review addresses the current state of PGPR research, applications, and future directions for optimizing their use in promoting sustainable agriculture.

Viral contamination in the aquaculture industry is a significant challenge that requires further research. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a role in regulating various biological processes, including immunity. However, most studies have focused on model organisms, and little is known about non-coding RNAs in the immune response to viral hemorrhagic septicemia (VHS) in rainbow trout. In this study, we investigated the listing of non-coding RNAs (ncRNAs) in rainbow trout challenged with VHS virus. We explored their potential role in defense-like responses based on transcriptomic analysis of the virus-treated and control groups. As a result of this research, 4207 lncRNAs were identified, of which 182 lncRNAs were differentially expressed between treated and untreated samples. Among 7753 lncRNA transcripts, 1920 were novel intergenic (class code “u”), and 3748 transcripts were potentially novel isoform of lncRNAs. Gene ontology analysis revealed biological pathways associated with the stress response and immune signaling. Pairs of genes such as TP63-MSTRG.62, IL10-MSTRG.9783, IL10-MSTRG.9784, TK1-MSTRG.22826, and MSTRG.17881-GLI1 showed cis interactions, while DOCK10-MSTRG.30015, MSTRG.36357-LOC101268921, and MSTRG.34190-ENPP2 showed trans interactions. In this study, the role of lncRNAs in regulating the expression of the target genes was clearly identified. This finding is consistent with the regulatory processes of immune system responses mediated by cytokines, as well as the regulation of oxygen levels in response to viral infection. The information presented here highlights the various regulatory mechanisms of lncRNAs in the expression of immune system genes in fish treated with VHS virus.

Global warming and the associated increasing frequency of heatwaves are on the rise leading to numerous health complications. Diabetic patients are more vulnerable to heat exposure than healthy individuals, owing to their impaired sweating ability, however, little is known about how heat exposure may impact the function of skin cells, commonly keratinocytes. Our recent report provided the first proof-of-concept revealing that the metabolic composition of sweat EVs is associated with metabolic changes in healthy individuals and type 2 diabetes patients. Given this and the shared cellular proprieties of eccrine sweat glands with keratinocytes, we questioned whether the metabolic changes in sweat EVs may mirror the responses of keratinocytes upon heat exposure. To this, we exposed HaCat, which were maintained in low (mimicking healthy condition) and high glucose (mimicking diabetes condition) to acute (90 min), chronic (48 h), and repetitive heat exposure at 40 ⁰C. Through conducting a set of experiments including a targeted metabolomics approach, Greiss assay, western blotting analysis, and electron microscopy studies. The data demonstrate that heat exposure results in substantial changes of metabolite levels belonging to amino acids, pyrimidine metabolism, and glycolysis pathways in high glucose maintained HaCat cells when compared to those noted in low glucose condition. Exploring the molecular mechanisms through which heat exposure may impact the metabolic composition in keratinocytes, our discoveries highlight nitric oxide (NO) as a novel biomarker that the level is correlated with heat duration and frequency. Furthermore, data reveal that the HSP-70 protein levels and mitochondrial morphology are consequently altered. This study provides evidence of shared metabolic alterations in keratinocytes and sweat EVs collected from clinical study and proposes, for the first time, NO as a novel biomarker for monitoring changes in health and diabetes upon heat exposure.

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOC) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5,007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOC, including Alpha (n =714), Delta (n =1,877), and Omicron (n =1,802). Omicron isolates were further sub-typed as BA.1 (n =899), BA.2 (n =853), and BA.4/BA.5 (n =50); the remaining 614 isolates were classified as “Other”. Approximately 31.5% (1,577/5,007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p &lt;0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p &lt;0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p &lt;0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

Orthohantaviruses can cause two types of human infections: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is a zoonotic disease transmitted by multiple rodent species. Yunnan Province in southwest China is the natural foci of HFRS, and Dali Prefecture in Yunnan Province has the highest incidence of HFRS; however, the precise status of orthohantavirus infection in Dali Prefecture remains unknown. To this end, we obtained clinical data of HFRS patients from the medical records of the People's Hospital of Xiangyun County in Dali Prefecture from July 2019 to August 2021. We collected epidemiological data of HFRS patients through interviews and investigated host animals using the night clip or night cage method. We systematically performed epidemiological analyses of patients and host animals. The differences in the presence of rodent activity at home (2=8.75, P=0.031&lt;0.05), of rodent-proof equipment in the food (2=9.19, P=0.025&lt;0.05), and of rodents or rodent excrement in the workplace (2=10.35, P=0.014&lt;0.05) were statistically different in the four clinical types, including mild, medium, severe, and critical HFRS-associated diseases. Furthermore, we conducted molecular detection of orthohantavirus in host animals. The total orthohantavirus infection rate of rodents was 2.7% (9/331); the specific infection rate of specific animal species was 6.1% (5/82) for the Apodemus chevrieri, 100% (1/1) for the Rattus nitidus, 3.8% (2/53) for the Rattus norvegicus, and 12.5% (1/8) for the Crocidura dracula. In this study, a total of 21 strains of orthohantavirus were detected in patients and rodents. The 12 orthohantavirus strains from patients showed a closer relationship with Seoul orthohantavirus (SEOOV) L0199, DLR2, and GZRn60 strains; the six orthohantavirus strains from Rattus norvegicus and Apodemus chevrieri were closely related to SEOOV GZRn60 strain; One strains (XYRn163) from Rattus norvegicus and one strain (XYR.nitidus97) from Rattus nitidus were closely related to SEOOV DLR2 strain; the orthohantavirus strain from Crocidura dracula was closely related to the Luxi orthohantavirus (LUXV) LX309 strain. In conclusion, patients with HFRS in Xuangyun County of Dali Prefecture are predominantly affected by SEOOV, with multiple genotypes of orthohantavirus in host animals, and most importantly, these orthohantavirus strains constantly demonstrated zoonotic risk in humans.

Since the 20th century, numerous studies have detected or isolated parasites from the Trypanosomatidae family in various tick species. However, the status of ticks as vectors of medically or veterinary important Trypanosoma and Leishmania remains unclear. We conducted a systematic review and meta-analysis to pro-vide new insights into the potential vector status of Leishmania and Trypanosoma, which have medical and veterinary significance. We searched three databases (PubMed, Google Scholar, and Web of Science) from 1912 to June 30, 2023, resulting in 94 and 86 papers included in the qualitative and quantitative analyses, respectively. All identified field studies were conducted in endemic areas and investigated the presence of Trypanosoma and Leishmania parasite, DNA, or antigen in ticks. We recorded a pooled prevalence of Trypa-nosomatidae detection in ticks at 15.48% [7.99-24.61%], with significant variations depending on the year, detection method, and geographical area. Most of positive tick species belonged to the genera Amblyomma, Hyalomma, Ixodes, and Rhipicephalus. Experimental laboratory work on transmission routes proved potential vector competence in both the Argasidae and Ixodidae tick families. Although our systematic review and meta-analysis provide unambiguous evidence of the natural infection of ticks by Trypanosomatidae para-sites with some evidence of non-traditional transmission routes, it does not provide conclusive evidence on the role of ticks as biological or mechanical vectors for veterinary and medically interest protozoan Trypa-nosomatidae species. All these unambiguously demonstrates the need of additional investigations to address this point.

Cotton fiber is the leading natural textile material, and fiber elongation plays an essential role in the formation of cotton yield and quality. Although a wealth of components in the molecular network controlling cotton fiber elongation have been reported, a lot of players still need to be functionally dissected to understand the regulatory mechanism of fiber elongation comprehensively. In the present study, an R2R3-MYB transcription factor gene, GhMYB201, was characterized and functionally verified via CRISPR/Cas9 mediated gene editing. GhMYB201 was homologous to Arabidopsis AtMYB60, and both coding genes (GhMYB201At and Dt) were preferentially expressed in elongating cotton fibers. Knocking-out of GhMYB201 significantly reduced the rate and duration of fiber elongation, resulting in shorter and coarser mature fibers. It was found that GhMYB201 could bind and activate the transcription of cell wall loosening genes (GhRDLs), and also β-ketoacyl-CoA synthase (GhKCSs) genes to enhance very-long-chain fatty acid (VLCFA) levels in elongating fibers. Taken together, our data demonstrated that the transcription factor GhMYB201s play essential roles in promoting fiber elongation via activating genes related to cell wall loosening and VLCFA biosynthesis.

Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.

The social fear conditioning (SFC) paradigm, which is an animal model of social anxiety disorder, has been extensively used to investigate the cellular and molecular mechanisms underlying the psychopathology of this disorder. Studies using the SFC paradigm have suggested that the lateral septum plays a pivotal role in regulating social fear. While several lines of evidence have indicated the involvement of various neuronal mechanisms within the LS in modulating social fear, the role played by LS astrocytes in the tripartite synapses in regulating social fear expression is not yet fully understood. Over the years, astrocytes have emerged as key players in regulating synaptic transmission and a plethora of animal behaviors. Given their dynamic morphological and molecular response to various stimuli, studying astrocyte morphology remains an excellent tool for understanding their role in brain function and disease. By applying immunofluorescent-immunohistochemical methods, here we describe a protocol to characterize changes in the morphology of astrocytes in response to social fear acquisition using confocal microscopy.

As the world’s population age, Cognitive Frailty (CF) is becoming one of the most serious health problems and elucidating its biological mechanisms along with prevention and treatments becomes increasingly important also considering the associated health costs. This pilot study aims to investigate the potential cognitive and neuropsychological effects of a 5-week treatment with a therapy based on the regenerative properties of ozone (O3) in a cohort of patients stratified according to CF. We also study the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons have been recruited and randomly assigned to receive the active treatment (150cc of oxygen-O2-O3 mixture at the concentration of 30ug of O3 per cc of O2) or O2, or the placebo (air) for 5 weeks. The primary endpoint is a change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), 15 (T15) after treatment. The secondary endpoint is a change in biomarkers levels resulting from transcriptomics, proteomics and metabolomic patterns at the same times. This study will evaluate whether an intervention with the O2-O3 therapy could have potential cognitive, neuropsychological and biological effects on CF.

Many fundamental molecular techniques (PCR, Microarray, Southern and northern hybridization, siRNA, CRISPR/Cas9 etc.) developed so far shows errors. I wish to highlight these molecular techniques are developed on basis of Watson-Crick DNA model, ignoring the concept of parallel stranded DNA. Through this opinion article, I wish to highlight specificity and accuracy of these molecular techniques can be enhanced by considering both parallel and anti parallel hybridization of DNA. Hopefully my views will also solve issue of irreproducibility in life science research.

The development of a rapid, sensitive, specific method for detecting foodborne pathogens is paramount in supplying safe food to enhance public health safety. Despite the significant improvement in pathogen detection methods, key issues are still associated with rapid methods, such as distinguishing living cells from dead, pathogenic potential or health risk of the analyte at the time of consumption, detection limit, and sample-to-result. The mammalian cell-based assays analyze pathogens' interaction with the host cells and are responsive to only live pathogens or active toxins. In this study, a human embryonic kidney (HEK293) cell line expressing Toll-Like Receptor 5 (TLR-5) and chromogenic reporter system (HEK dual hTLR5) was used for the detection of viable Salmonella in a 96-well tissue culture plate. This cell line responds to low concentrations of TLR5 agonist flagellin. Stimulation of TLR5 ligand activates nuclear factor-kB (NF-κB) - linked alkaline phosphatase (AP-1) signaling cascade inducing the production of secreted embryonic alkaline phosphatase (SEAP). With the addition of a ρ-nitrophenyl phosphate as a substrate, a colored end product representing a positive signal is quantified. The assay's specificity was validated with the top 20 Salmonella enterica serovars and 19 non-Salmonella spp. The performance of the assay was also validated with spiked food samples. The total detection time (sample-to-result), including shortened pre-enrichment (4 h) and selective enrichment (4 h) steps with artificially inoculated outbreak-implicated food samples (chicken, peanut kernel, peanut butter, black pepper, mayonnaise, and peach) was 15 h when inoculated at 1–100 CFU/25 g sample. These results show the potential of HEK-DualTM hTLR5 cell-based functional biosensors for rapid screening of Salmonella.

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

Dearth of information on extent of genetic variability in cassava limits the genetic improvement of cassava in Sierra Leone. This study aimed at assessing the genetic variability and relationships within 103 cassava genotypes using agro-morphological and culinary markers. A field trial was conducted in the School of Agriculture and Food Sciences research site. The experiment was laid in an augmented randomized block design. Morphological classification based on qualitative and quantitative traits categorized the germplasm into three different groups. A total of ten principal components (PCs) in the qualitative and six PCs in the quantitative trait sets accounted for 66.74% and 67.27% of the total genetic variation, respectively. Traits with significantly strong and positive correlations included presence of fruit (PFRT) and presence of seed (PSE)(r = 0.86***),root yield per plant (RYPP) and number of storage root (NSR) (r = 0.76***), RYPP and number of commercial root (NCR) (r = 0.68***), length of leaf lobe (LLL) and width of leaf lobe (WLL) (r = 0.66***),and between NSR and NCR (0.84***). Cooking time, cooking percentage, texture, mealiness, taste and aroma varied widely among the accessions. Findings established that the cassava germplasm possess useful genetic variability that could be exploited through selection for short term release programme, genetic conservation of valuable germplasm and genetic improvement of the crop.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing in-creased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play im-portant roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB de-pendence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter en-dothelial function or the contractile response to phenylephrine in these arteries. In contrast, CIH exposure increased the systemic arterial pressure, and enhanced the contractile response to phenylephrine while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta, without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

The study investigated the application of Wastewater-Based Epidemiology (WBE) as a tool for monitoring SARS-CoV-2 prevalence in a city in Northern Italy from October 2021 to May 2023. Starting from a widely applied deterministic model, this study proposed a variation to take into account population characteristics and virus biodegradation in the sewer network. The model calculated virus loads and corresponding COVID-19 cases over time in different areas of the city and was validated with healthcare data while considering viral mutations, vaccinations, and testing variability. The correlation between the predicted and reported cases was high across the three waves that occurred in the considered period, demonstrating the model’s capacity to predict relevant fluctuations in the number of cases. Population characteristics did not substantially influence the predicted and reported infection rates. Conversely, biodegradation significantly reduced the virus load reaching the wastewater treatment plant, resulting in a 30% reduction in the total virus load produced in the study area. This approach can be applied for comparing virus load values across cities with varying population demographics and sewer network structures, enhancing the comparability of WBE data for effective surveillance and intervention strategies.

Our previous studies demonstrated a tight connection between simvastatin (SIM) inhibition of B16.F10 murine melanoma cell proliferation in vivo and in vitro and strong suppression of the subunit α of hypoxia inducible factor 1 (HIF-1) (HIF-1 α) production in these cancer cells. Since the translation of HIF-1α is modulated by signaling pathways coordinated by Akt, SIM effects on the link between these two regulatory factors and cancer cell metabolism under normoxia was investigated, which to our knowledge have never been described before. To achieve the proposed aim, SIM effects on cell metabolism were analysed at mRNA (via RNA-seq and RT-qPCR) as well as protein level (via western blot and catalytic activity of the key enzymes) Our data suggested that SIM might orientate glucose transport and metabolism to ensure replenishment of tricarboxylic acid (TCA) cycle activity. Moreover, it seems that SIM enhanced biosynthetic role of TCA over its energy role to further support synthesis of lipid-derived signaling molecules. Thus, under normoxia SIM treatment orientated lipid metabolism to stimulate isoprenoid and prostaglandin synthesis which might favor melanoma cell survival and aggressiveness.

Human serum albumin (HSA) corona formation at polymer microparticles of a spheroidal shape was studied using dynamic light scattering and laser Doppler velocimetry (LDV). Physicochemical characteristics of the albumin comprising, the zeta potential and the isoelectric point were determined as a function of pH for various ionic strengths. Analogous characteristics of the polymer particles were carried out. The adsorption of albumin on the particles was monitored by electrophoretic mobility measurements (LDV). The stability of the HSA functionalized particle suspensions under various pHs and their electrokinetic properties were determined. The deposition kinetics of the particles on mica, silica and gold sensors were determined in situ by optical microscopy, AFM and by the quartz microbalance (QCM) under diffusion and flow conditions. The obtained results were interpreted in terms of the coarse-grained random sequential adsorption model that allowed to estimate the range of applicability of QCM for determining deposition kinetics of virus and bacteria at abiotic surfaces.

Mpox, formerly known as Monkeypox, is a rare viral disease initially discovered in Africa in 1958. Since its first identification, several outbreaks have occurred in various African nations. Recently, the global community has witnessed a resurgence in the number of Mpox cases reported worldwide, prompting the World Health Organization (WHO) to declare the ongoing multi-country outbreak a public health emergency in July 2022. This study reports on the first cases of Mpox detected in Khartoum State, Sudan, outlining the epidemiology, preparedness, and public health response to this new challenge. A total of 55 suspected cases were identified, with two confirmed cases. The clinical manifestations observed in these cases align with the classic skin rash typical of Mpox, presenting alongside symptoms like fever, headache, and joint pain. The findings underscore the need for heightened surveillance, early detection, and timely intervention to prevent the domestic spread of Mpox and its potential impact on public health. Continued global efforts are needed to support effective screening, diagnostic, and control measures, ultimately enhancing preparedness and response in the face of this emerging disease.

The process of oxygenic photosynthesis is primarily driven by two multiprotein complexes known as photosystem II (PSII) and photosystem I (PSI). PSII facilitates the light–induced reactions of water–splitting and plastoquinone reduction, while PSI functions as the light–driven plastocyanin-ferredoxin oxidoreductase. In contrast to the highly conserved structure of PSII among all oxygen–evolving photosynthetic organisms, the structures of PSI exhibit remarkable variations, especially for photosynthetic organisms that grow in special environments. In this review, we make a concise overview of the recent investigations of PSI from photosynthetic microorganisms including prokaryotic cyanobacteria and eukaryotic algae from the perspective of structural biology. All known PSI complexes contain a highly conserved heterodimeric core; however, their pigment compositions and peripheral light-harvesting proteins are substantially flexible. This structural plasticity of PSI reveals the dynamic adaptation to environmental changes for photosynthetic organisms.

An HFMD outbreak spread over the city of Hải Phòng from Summer 2011 to Autumn 2012. This epidemic was chosen because it was the very first HFMD epidemic in North Vietnam, eliminating thus interferences with previous outbreaks. This epidemic displayed 3 separate waves. A complete dataset was collected for more than 9500 patients during this period, which enabled us to analyze this epidemic at different scales. Access to the healthcare system was crucial during this period, with a reorganization of the system in February-March 2012. An analysis at commune level enables us to track the epidemic along certain communication routes. The three-waves structure reveals a wide disparity at district level. We develop a mathematical model showing high accuracy at the adjustment of data for both the total number of cases and for the number of cases per week. As a consequence, the model was able to accurately determine the dates of beginning and end of each wave and to show that they overlapped. Using mathematical functions associated with this model, it was possible to calculate the probability for a patient to belong to a specific wave.