Background Recent studies indicate that donor innate immune responses participate in initiating and accelerating innate responses and allorecognition in the recipient. These immune responses negatively affect recipient outcomes and predispose recipients to allograft coronary artery vasculopathy (CAV). We hypothesized that donor cause of death (COD) associated with higher levels of innate immune response would predispose recipients to more adverse outcomes post-transplant, including CAV. Methods We performed a single-institution retrospective analysis comparing donor characteristics and COD to recipient adverse cardiovascular outcomes. We analyzed the medical records of local adult donors (age 18-64) in a database of donors where adequate data was available. We linked donor characteristics and COD to recipient adverse cardiac outcomes after transplant, including cardiovascular (CV) death and incidence of significant antibody-mediated rejection (pAMR) after transplant (>2 episodes of pAMR within 90 days post-transplant). The data were analyzed using logistic regression, log-rank test of differences, and Tukey Contrast. Results Donor advanced age, female sex, and CODs of motor vehicle accident and intracranial hemorrhage were significantly associated with a higher incidence of recipient CV death and early pAMR compared to other donor characteristics and CODs. Conclusions In this single institution study, we found that recipients with hearts from donors over 40 years, donors who were female, or donors who died with a COD of motor vehicle accidents or intracranial hemorrhage had a higher frequency of CV related deaths and early pAMR. Donor monitoring and potential treatment of innate immune activation may decrease subsequent recipient innate responses and allorecognition stimulated by donor derived inflammatory signaling which lead to adverse outcomes.

This paper concentrates on the general birth-death processes with two different types of catastrophes. The Laplace transform of transition probability function for birth-death processes with two-type catastrophes are is successfully expressed with the Laplace transform of transition probability function of the birth-death processes without catastrophe. The first effective catastrophe occurrence time is considered. The Laplace transform of its probability density function, expectation and variance are obtained.

The regulation of cell death is a fundamental issue in cell biology and continues to be intensely investigated worldwide. The significance of research in this field persists because understanding the determinants of cell lifespan directly impacts the maintenance of multicellular organism homeostasis and, consequently, is crucial for addressing biomedical challenges associated with various diseases. It is recognized that the initiation of cell death can be prompted by both specific signals (such as cytokines or hormones) and nonspecific stimuli, including radiation, temperature increase, or oxidants. When these factors affect a cell, numerous signaling pathways are triggered in the cell, leading to neutralization of the effects of their negative effects or, in case of irreparable damage, to cell elimination. This removal of damaged cells occurs through apoptosis or programmed cell death, a highly regulated process. Numerous signaling molecules participate in orchestrating the apoptotic process, many of which also govern other essential functions within the organism. Physiological factors capable of triggering the apoptotic program in cells include nitric oxide (NO), which serves as one of the key signaling molecules regulating the functions of the cardiovascular, nervous, and immune systems of the organism. The unique chemical nature of NO, along with its numerous intracellular targets and physiologically active redox forms, raises questions about the specific mechanisms through which NO exerts its damaging effects on cells. Utilizing pharmacological preparations- such as sources (donors) of exogenous nitric oxide- represents an approach to investigating the initiation and execution of the apoptotic program in sensitive target cells. Furthermore, this approach holds promise as a direction for discovering new selective drugs.

Wildfires have short- and long-term impacts on the geoenvironment, including the changes to biogeochemical and mechanical properties of soils, landfill stability, surface- and groundwater, air pollution, and vegetation. Climate change has increased the extent and severity of wildfires across the world. Simultaneously, anthropogenic activities—through the expansion of urban areas into wildlands, abandonment of rural practices, and accidental or intentional fire-inception activities—are also responsible for a majority of fires. This paper provides an overall review and critical appraisal of existing knowledge about processes induced by wildfires and their impact on the geoenvironment. Burning of vegetation leads to loss of root reinforcement and changes in soil hydromechanical properties. Also, depending on the fire temperature, soil can be rendered hydrophobic or hydrophilic and compromise soil nutrition levels, hinder revegetation, and, in turn, increase post-fire erosion and debris flow susceptibility of hillslopes. In addition to direct hazards, wildfires pollute air and soil with smoke and fire suppression agents releasing toxic, persistent, and relatively mobile contaminants into the geoenvironment. Nevertheless, the mitigation of wildfires’ geoenvironmental impacts does not fit within the scope of this paper. In the end, in no exhaustive way, some areas of future need for research are highlighted.

In India, the divorce rate is rising year after year. Divorces are thought to have increased by more than a factor of two during the past two decades. India has great cultural diversity, and each of its states has something unique to offer. The divorce rate in India, which differs from state to state, is among the most frequently discussed subjects. More than 30% of marriages end in divorce in big cities like Delhi, Mumbai, Chennai, and Bangalore. Divorce applications have nearly tripled in the past few years in cities like Delhi, Bangalore, Mumbai, Kolkata, and Lucknow. In India, the divorce rate has increased, especially in small cities. Hence, the reasons behind divorce in India were explored in this article. In order to analyze the causes of divorce, the current study aimed to combine the critical components of TOPSIS and COPRAS methodologies in a fuzzy environment. Additionally, it is shown that a comparison study may pinpoint the characteristics that influence divorces the most.

Epidemic diseases that arise from infectious RNA viruses, particularly influenza viruses, pose a constant threat to the global economy and public health. Viral evolution has undermined the efficacy of acquired immunity from vaccines and the antiviral effects of FDA-approved drugs. As such, there is an urgent need to develop new antiviral lead agents. Natural compounds, owing to their historical validation of application and safety, have become a promising solution. In this light, a novel marine bacterium, Pseudomonas sp. M20A4R8, has been found to exhibit significant antiviral activity [half maximal inhibitory concentration (IC50) = 1.3 µg/mL, selectivity index (SI) = 919.4] against influenza virus A/Puerto Rico/8/34, surpassing the activity of chloroquine. The antiviral response by M20A4R8 extract was induced during post-entry stages of the influenza virus, indicating suitability for post-application after the establishment of viral infection. Furthermore, post-treatment with M20A4R8 extract protected the host from virus-induced apoptosis, suggesting its potential use in acute respiratory disease complexes resulting from immune effectors' overstimulation and autophagy-mediated self-apoptosis. The extract demonstrated an outstanding therapeutic index against influenza virus A/Wisconsin/15/2009 (IC50 = 8.1 µg/mL, SI = 146.2) and B/Florida/78/2015 Victoria lineage (IC50 = 3.5 µg/mL, SI = 343.8), indicating a broad anti-influenza virus activity with guaranteed safety and effectiveness. This study provides a new perspective on mechanisms for preventing a broad spectrum of viral infections through antiviral agents from novel and natural origins. Future studies on a single or combined compound from the extract hold promise, encouraging its use in preclinical challenge tests with various influenza virus strains.

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with a progressive loss of biochemical processes and degeneration of molecular material, however, the mechanisms of diminishing function are not simply a result of aberrant expression of these pathways. Natural selection pressures are at their highest in youthful periods to select genes advantageous to maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene function once beneficial for developmental growth, but pathogenic later in life. Due to this selective ‘shadowing’ in ageing, mechanisms to counter hyperfunctional genes are unlikely to evolve within a given species. These genetic ‘run-on’ programmes are not dysfunctional per se and, in fact, remain highly robust. Thus, interventions capable of optimising gene function during the ageing process represent as attractive therapeutic modalities. Caenorhabditis elegans offers a unique model to explore high-throughput screening of interventions to combat hyperfunctional pathways involved in ageing. However, the majority of research to date employ whole-life vs late-life pathway manipulation of developmental/growth-related systems to claim ageing attenuation, despite significant impairments in early-life fitness and discordance with healthspan. Here, we discuss data supporting hyperfunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutants alter these dynamics. We later discuss the relevance of such mutant models for exploring mechanisms of ageing, highlighting that post-reproductive gene manipulation represents a far more translatable approach for C. elegans research not routed within pleiotropic constraints. More so, lifespan has become a routine readout for quantifying ‘ageing’, however, we make the argument that a compression of gerospan vs lifespan extension is a more meaningful goal for anti-ageing regimes with current knowledge. Similarly, mechanisms governing lifespan are distinct from those regulating health, and slowing senescent pathology accumulation appears more applicable for the abstraction to human ageing.

Food insecurity remains a significant developmental challenge, particularly in rural areas, despite ongoing efforts to mitigate it. To better understand the persistence of this issue, this study investigates the causes of household food insecurity and the coping strategies employed by households in Zorkor Goo, Zorkor Kanga, and Zorkor Kadaare communities within the Bongo District of Ghana’s Upper East Region. A descriptive cross-sectional survey was conducted, sampling 196 households systematically from these communities. Data were collected through a structured questionnaire covering socio-demographic factors, causes of food insecurity, household coping strategies, and dietary intake. The analysis was performed using SPSS (Version 21.0), with food security status and dietary intake assessed via the FANTA Household Food Insecurity Access Scale (HFIAS) and Food Consumption Score, respectively. The study identified key factors contributing to food insecurity, including soil infertility, poor rainfall patterns, food spoilage, extravagant funerals, large family size, high unemployment, and lack of education. Major coping strategies among households included meal skipping, reducing meal size and frequency, migration, asset sales, and basket weaving. The findings revealed that 96.4% of households were severely food insecure, and over two-thirds (67.3%) exhibited poor dietary consumption. Notably, household employment levels, education, and food consumption scores were significantly associated with food insecurity (P<0.001). These findings underscore the need for targeted interventions addressing the root causes of food insecurity and enhancing household resilience in these communities.

Various strategies have been employed to improve the reliability of 2D, 3D, and co-culture in vitro models of nonalcoholic fatty liver disease, including using extracellular matrix proteins, such as collagen I, to promote cell adhesion. While studies have demonstrated the significant benefits of culturing cells on collagen I, its effects on HepG2 and HepaRG cell lines after exposure to palmitate (PA) have not been investigated. Therefore, this study aimed to assess the effects of PA-induced lipotoxicity in HepG2 and HepaRG cultured in the absence or presence of collagen I. HepG2 and HepaRG cultured in the absence or presence of collagen I were exposed to PA, followed by analyses that assessed cell proliferation, viability, adhesion, cell death, mitochondrial respiration, reactive oxygen species production, gene and protein expressions, and triacylglycerol accumulation. Culturing HepG2 on collagen I was associated with increased cell proliferation, adhesion, expression of integrin receptors, and improved cellular spreading compared to culturing them in the absence of collagen I. PA-induced lipotoxicity was greater in collagen I-cultured HepG2 than those cultured in the absence of collagen I. In summary, the present study demonstrated for the first time that collagen I-cultured HepG2 exhibited exacerbated cell death following exposure to PA through integrin-mediated death. The findings from this study may serve as a caution to those using 2D models or 3D scaffold-based models of HepG2 in the presence of collagen I.

This study aims to unravel the paradox of perceptions and knowledge of the flood victims towards the causes of the disaster in both internal and external context. Internal context comprises of a comparison of perceptions and knowledge based on individual characteristics (age, gender, education and income). Whereas, the external context includes the factors of the awareness of the victims towards the amount of rainfall, the impact of land use changes as well as the negligence of the responsible parties. The main objective of this study is to determine the differences of perception and knowledge of December 2014 flood victims in Kelantan towards the factors that lead to the flood. This disaster had resulted in huge amount of money loss as well as traumatize the victims in which can be felt to this day. Since that incident, there were various points of view and different perceptions in finding the cause of the disaster occurred. Besides that, the study found that the level of perception and knowledge as to the cause of the disaster is different in the internal context (individual characteristics). This difference has a significant influence on the awareness of the causes of the floods that occurred in the external context. Significant relationships at the level of p <0.05 has existed between perception and knowledge of the causes of the disaster victims affected by environmental changes in the last 10 years. This indicates that although the victim is aware of the physical environment changes happening around them, but all that is seen as not a major contributing factor to the cause of the floods in Kelantan in 2014.

During the COVID-19 pandemic, the spread of the SARS-CoV-2 virus forced many individuals to confront their mortality and worry about losing loved ones also because social distancing policies often made it impossible to say goodbye. Those not directly experiencing loss were inundated with information about COVID-19-related deaths through various media, leading to vicarious grief. This study aims to explore the long-term effects of direct and vicarious mourning on people's mental health during the COVID-19 pandemic. A sample of 171 adults (65% female) aged 19 to 66 years (mean age = 25.8, SD = 8.57) voluntarily participated in an online survey assessing self-reported psychological measures of complicated grief, anxiety, stress, depression, dispositional neuroticism, and situational anxiety using the Fear of COVID-19 Scale. MANOVA tests revealed that individuals experiencing direct mourning had extremely severe scores for anxiety, stress, and fear of COVID-19, while those without personal losses had moderate scores. Participants reporting high media exposure had higher scores for depression and stress. In line with Terror Management Theory, the study supported that people during the COVID-19 pandemic engaged more in proximal defenses than distal ones, taking health-protective measures, experiencing increased anxiety levels toward SARS-CoV-2 infection, and feeling more distressed. Additionally, vicarious mourning was more strongly associated with depression due to emotional empathy with others. The discussion also addresses the strengths and limitations of the study.

Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. The risk of these cancers is increased even in people who have only one alcoholic drink per day. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect has been overlooked probably because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of endogenous and exogenous DNA-damaging agents (e.g., reactive oxygen species, acetaldehyde and tobacco carcinogens). Alcohol consumption probably increases the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Because the cytotoxic activity of ethanol is concentration-dependent, the risk of these cancers will not only increase with increasing amounts of ethanol, but also with increasing concentrations; an ounce of whisky is probably more carcinogenic when taken undiluted than when taken mixed with non-alcoholic beverages. The local cytotoxic effect of ethanol can also explain the known synergistic effect of alcohol and tobacco use on the risk of these cancers. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.

Historical analysis of Australian bushfire data spanning 170 years addresses whether the strength of recent fire events has been exacerbated by human-induced climate change. The question of “cause” looks at the characteristics of a wider range of natural hazards. Fire characteristics are compared with earthquake hazard characteristics: (1) energy – termed “magnitude”; (2) severity – termed “intensity”; and (3) resultant damage to people and structures – termed “impact”.Published global, Northern and Southern hemisphere temperature data are shown to vary consistently in phase over 170 years, but vary in amplitude with statistical significance. CO₂ levels north and south of the Equator have tracked quite consistently. Thus, Southern Hemisphere bushfire magnitude and intensity is compared with the Southern Hemisphere climate record, rather than a global data set.28 major bushfires and associated droughts since 1850 show neither apparent drought extent, nor area burned, nor bushfire intensity, correlates with changes in Southern Hemisphere climate. Average rainfall from 1900 shows a wetter, rather than drier trend. Cyclone energy shows no significant trend with climate. Planet-wide “greening”, through CO₂ fertilisation, is an insignificant contributor to bushfire magnitude. Combustion theory shows recorded “global warming” could have had no significant influence on bushfire magnitude or intensity. Any increase in Australian bushfire impact, as judged by lives lost, similarly, shows no correlation with bushfire magnitude, nor indeed, any observed Southern Hemisphere global warming.Thus, bushfire magnitude seems much more likely driven by fuel load and any anomalous bushfire intensity is likely driven by anomalous ground level fuel load. The evidence suggests that any CO₂ emissions reduction will have no impact on future bushfire “severity.

The objective of this research is to ascertain the elements that have an impact on and drive domestic violence in Saudi Arabia, a phenomenon that has a prevalence rate of around 35% among women globally. The researchers administered a survey to a sample of 550 individuals and using exploratory factor analysis (EFA) to analyze the collected data. The findings revealed three factors: lack of familial unity, encouragement of detrimental characteristics, and economic turmoil. The authors examined the consequences of these characteristics on preventive and intervention programs and proposed suggestions for policy makers and researchers. This research enhances the existing body of knowledge on domestic violence by doing a statistical analysis to examine the factors that lead to it and the resulting outcomes within a particular cultural setting.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We retrospectively evaluated mortality events from inpatient admissions to Cardiology Department between 2010-2019. Data were collected from morbidity &amp; mortality meeting presentations which evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1,182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI) (53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%) and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019 while there was an apparent increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, p&lt;0.001) and other cardiac reasons (3.0% vs. 0.4%, p&lt;0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant decline in the proportion of deaths due to AMI in recent years with an increase in deaths due to HF.

In recent decades the Mediterranean area observed an increase in large fires, despite the decrease in the number of fire ignitions, following a worldwide tendency. Climate change has been the main culprit for large burnt areas, and alterations of forest ecosystems, resulting in the increased recurrence of forest fires. In Portugal, the analogous trend resulted in the destruction of large rural, urban and industrial areas, where after the 2017 months of June and October catastrophic events, the government implemented the 2019 specific policies for preventing fire outbreaks and defending the forest against fires. This compulsory policy demanded that landowners and local governments alike needed to contact specific authorities requesting authorization for their intentions to clean properties in and around urban areas, roads, and forest limits. Despite policy and careful monitoring, ignitions still occur, and in many cases resulting from the implementation of such policies. The study analyses the before and after policy implementation, considering 6904 ignitions records from the period between 2014 and 2023 from the central area of Portugal, covering the transition area between the agricultural fields of the Tagus valley and the Monte-junto-Estrela Mountain range, the district of Santarém. The authorization to use fire in clearance practices is granted according to a set of weather conditions, temperature, wind intensity, and relative humidity, when analyzing fire ignitions with the average daily wind intensity at the site of the occurrence, we observed that more than half of wildfires occur on days with winds between 10 and 20 Km/h, whereas intensities greater than 30 Km/h only 1% of the total occurrences, and of these 22% occurred due to the use of fire in the burning of agricultural leftovers and cut and piled bushes. The circulation of the thermal depression in the Iberian Peninsula gives rise to increasing intensity throughout the day, reaching a maximum in the late afternoon, this factor combined with the misjudgment of safe conditions leads us to suggest stricter intervals and the need for awareness of daily variation in conditions.

Pipelines are widely used globally, particularly in Nigeria, to transport raw and processed hydrocarbon fluids, including crude oil, from the point of production to the shore for export, processing facilities and distribution of refined products to depots for sales and consumption. Although pipelines are designed to withstand environmental and physical shocks, intermittently, pipelines are exposed to natural or human-induced conditions that damage pipelines and disrupt their functionality. These disruptions could result from operational defects or vandalism, causing an economic loss of up to US$ 658.5 million as observed in the Niger Delta from 1990 to 2022. Furthermore, product loss of about 705,100 barrels observed over the same period has caused environmental and social impacts, damaging the natural environment, destroying livelihoods supported by the ecosystem, and deteriorating the health of residents as documented in several literatures. To mitigate these issues and ensure the safe and reliable conveyance of crude oil in pipelines, measures must be taken to timely detect spillages and intervene during oil spillages to minimize damage and loss. Such detection methods include external, visual/ biological and internal/computation-based approaches. This paper uses a mixed-method approach to review the literature on the causes and impact of crude oil pipeline leakage in the Niger Delta region of Nigeria and highlights some methods that could be applied to detect pipeline leakage, as well as their strengths and inefficiencies. This paper further assesses the joint investigation visit mechanisms for oil spill response used in the oil and gas industry in Nigeria and identified that between 2006 to 2021, it took an average of 4 days to report oil spill occurrence, and 21 days to respond. Also, for 18 percent of the spill occurrences in that period, there were no JIV. This study suggests that the gap in the JIV mechanism can be addressed by integrating technology to enhance detectability and minimize the cost of monitoring. The paper also guides the way forward to develop and improve the reliability of pipeline leak detection systems.

Background and Objectives: Down syndrome (DS) is the most common chromosomal disorder in the world. It is caused by the imbalance of the chromosomal constitution of 21, by free trisomy, translocation or mosaicism. Children and adolescents with Down syndrome have immune dysregulation and are more susceptible to infections. This study aims to evaluate hospitalizations of children and adolescents with DS in the pediatric ward of Botucatu Clinics Hospital (HCFMB), to classify the population of children included in the study regarding age, diagnosis, outpatient follow-up, length of stay and need for Intensive Care Unit (ICU). Thus, it will be possible to improve care for these children, aiming to reduce these hospitalizations. Materials and Methods: It was an observational, cross-sectional study, with retrospective data collection from the last 10 years of hospitalization, from January 2013 to December 2021, of children and adolescents with DS, in the pediatric ward, emergency room and ICU of HCFMB. Children hospitalized in this period in the pediatric ward and ICU, in the age range of 30 days to 15 years (age of acceptance for admission to this service) were included in this study. Those who at some point had the exclusion of the diagnosis of DS were excluded. The evaluation of comorbidities that culminated in the need for hospitalization in this population can be the focus of actions to improve diagnoses and conducts for this population, to prevent worsening and hospitalizations in future populations. Results: The statistical analysis of the data was performed. In this analysis, 80 children with DS were evaluated, with a total of 283 hospitalizations and it was noticed that 46 of them had more than one hospitalization in this period. The most prevalent age group was 1 to 3 years, and the main cause was due to problems in respiratory system (99 cases). Among respiratory causes, the main cause of hospitalization was due to pneumonia, in 50% of cases, followed by acute respiratory failure, in 14%. The average hospitalization time was 8 days and in 49 hospitalizations the children required the ICU. The main cause of hospitalization in the ICU was due to respiratory causes (36%), followed by cardiac malformations (14%). During the ICU hospitalizations, there were 13 deaths, and we observed a higher prevalence of heart conditions and, in some cases, positive urine cultures in these children. Conclusions: preventive actions, such as vaccinations and improved monitoring of these children, without outpatient follow-up or during hospitalization, should be carried out. Thus, it has been developed a proposal for a risk score for mortality in children and adolescents with DS admitted to the ICU, and those patients with five or more points should be monitored more closely. A meeting will be held with the genetics, cardiology, and pediatric ICU teams to discuss this score and propose a surveillance plan for these patients at the HCFMB and potentially for the pediatric community in the future.

The Drosophila spermatogenesis has the renewal of germline stem cells, meiosis of spermatocytes, and morphological transformation of spermatids into mature sperm. We previously demonstrated that Ocnus (ocn) plays an essential role in spermatogenesis. ValRS-m (Valyl-tRNA synthetase, mito-chondrial) gene was downregulated in ocn RNAi testes. By hatchability testing, we found that ValRS-m-knockdown induced complete sterility of male flies. We also concluded that ValRS-m-knockdown inhibited the transition from spermatogonia to spermatocytes and caused accumulated spermatogonia in testes. To understand the intrinsic reason for this destruction, we further conducted transcriptome sequencing analysis in ValRS-m RNAi testes. A total of 7710 dif-ferentially expressed genes (DEGs) were identified to have at least a 2-fold change with a p-value of

Oxidative stress and chronic inflammation, both at the systemic and central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose. To investigate the oxidative stress, inflammatory, and Tau-phosphorylation lowering effects of pomegranate polyphenols (PP) (punicalagin, ellagic acid, peels, and arils extracts). Methods. We used flow cytometry to quantify protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific markers (CD86 and CD163) expression in human microglia HMC3 cells. IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PP on human amyloid beta 1-42 (Aβ1-42)-induced oxidative stress was assessed in microglia by measuring ROS generation and lipid peroxidation, using respectively two ′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substances (TBARS) tests. Neuronal viability and cell apoptotic response to Aβ1-42 toxicity were assayed using the MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and the annexinV-FITC apoptosis detection kit; respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PP to modulate Aβ1-42-induced Tau-181 phosphorylation (pTau-181). Results. Our data indicate that PP was significantly (p<0.05) effective in countering Aβ1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) (in U373-MG astrocytes and THP1 macrophages) and decreasing proinflammatory markers (IL-1β) expression in THP1 macrophages. PP was also significantly (p<0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p<0.05) beneficial impact on oxidative stress, illustrated in the reduction of TBARS and ROS generation. Our treatments have significant (p<0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ1-42 significantly (p<0.05) increases pTau-181. This effect was significantly (p<0.05) attenuated by arils, peels, and punicalagin and drastically reduced by ellagic acid treatments. Conclusion. Our results are attributed to PP's anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau pathology potential. Future studies should aim to extend our knowledge of the potential role of PP on A1-42-induced neurodegeneration, mainly its association with the tauopathy involved in AD.

The present study aimed to date the death of Korean red pine (Pinus densiflora Siebold &amp; Zucc.) at Sogwang-ri, where is famous for the Korean red pine forests in Korea, using a dendrochronological method, and to investigate the effect of climatic factors on the death and growth decline of the pine trees. For the study, 51 Korean red pines were selected from three stands (Jungmi-gol A, Jungmi-gol B, and Neonam-gol) in the study area, and for the ring-width measurement the increment cores were extracted from the selected trees. The stand chronologies for the Jungmi-gol and Neonam-gol were established using the mean values of individual time series of the living trees from each site, and the chronologies were further used for cross-dating with individual time series of the dead trees to date their death. The abrupt growth reduction was also investigated based on the consecutive ring-width growth decline trend to know the vitality during the living. Results revealed that the red pines at Jungmi-gol A were dead in 2020, at Jungmi-gol B in 2012 or 2013, and at Neonam-gol in 2019. So, it was verified that the death of the red pines at the study sites occurred from high to low elevations. In the analysis of the role of climate in the annual ring growth, the trees at Jungmi-gol A and B located on the southwest slope showed more ring-width growth when precipitation in April, July, and August were increasing, at Neoman-gol located on the north slope when precipitation only in July was increasing. Although the correlations of the ring-width growths at the sites with temperature and precipitation were somehow different from each other, Drought Stress Index (DSI) from May to September at all sites were all negative. Therefore, water stress caused by increased temperature and decreased precipitation is the most significant climatic parameter for the death or growth decline of the pine trees in the study area.

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in controlling inflammation and cell death. Its function is tightly controlled through post-translational modifications, enabling its dynamic switch between promoting cell survival and triggering cell death. Phosphorylation of RIPK1 at various sites serves as a critical mechanism for regulating its activity, exerting either activating or inhibitory effects. Perturbations in RIPK1 phosphorylation status have profound implications for the development of severe inflammatory diseases in humans. This review explores the intricate regulation of RIPK1 phosphorylation and dephosphorylation and highlights the potential of targeting RIPK1 phosphorylation as a promising therapeutic strategy for mitigating human diseases.

Keywords: lactic acid; ceramide; folate; nicotinamide; Alzheimer’s disease

Big Epidemiology is an innovative framework that extends the interdisciplinary approach of Big History to understand disease patterns, causes, and effects across human history on a global scale. This comprehensive methodology integrates epidemiology, genetics, environmental science, sociology, history, and data science to address contemporary and future public health challenges through a broad historical and societal lens. The foundational research agenda involves mapping the historical occurrence of diseases and their impacts on societies over time, utilizing archaeological findings, biological data, and historical records. By analyzing skeletal remains, ancient DNA, and artifacts, researchers can trace the origins and spread of diseases, such as Yersinia pestis in the Black Death. Historical documents, including chronicles and medical treatises, provide contextual narratives and quantitative data on past disease outbreaks, societal responses, and disruptions. Modern genetic studies reveal the evolution and migration patterns of pathogens and human adaptations to diseases, offering insights into co-evolutionary dynamics. This integrative approach allows for temporal and spatial mapping of disease patterns, linking them to social upheavals, population changes, and economic transformations. Big Epidemiology also examines the roles of environmental changes and socioeconomic factors in disease emergence and re-emergence, incorporating climate science, urban development, and economic history to inform public health strategies. The framework reviews historical and contemporary policy responses to pandemics, aiming to enhance future global health governance. By addressing ethical, legal, and social implications, Big Epidemiology seeks to ensure responsible and effective epidemiological research and interventions. This approach aims to profoundly impact how we understand, prevent, and respond to diseases, leveraging historical perspectives to enrich modern scientific inquiry and global public health strategies.

Coronaviruses are a large family of diverse enveloped RNA viruses found in numerous animal species. They are well-known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in human populations. In contrast, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we discuss the significance and perspectives of broad-spectrum therapeutics and vaccines.

BACKGROUNDBrain death in most countries requires supplementation of clinical diagnosis with ancillary tests such as EEG, cerebral angiography, or radionuclide imaging. Transcranial Doppler sonography (TCD) is one such non-invasive, real-time, bedside test that sidesteps the logistic hurdles associated with some of the tests mentioned above. OBJECTIVETo substantiate the utility of TCD as a reliable ancillary test to diagnose brain death with more certainty and reliability.METHODOLOGYMeta-analysis was performed with the use of statistical and analytical software to obtain data and estimate Sensitivity, Specificity, positive predictive value(PPV), diagnostic odds ratio (DOR), and relative risk with 95 percent confidence intervals to examine critical clinical outcomes(CI).RESULTSInitial dataset of 31 studies of which 16 studies, with a total of 1317 patients was used considering the reliability of the data. The pooled sensitivity and specificity of TCD were 0.91 (95% CI range: 0.89-0.93) and 0.99 (95% CI range: 0.97-0.99) respectively. The summary of the ROC curve showed an area under the curve of 0.9750 and an overall diagnostic odds ratio (DOR) was 323.26 with the Younden Index being 0.9. Summary of Fagan plot analysis of all studies showed a prior probability of 63% (1.7); a Positive Likelihood Ratio of 56, a post-test probability of 99% (96); a Negative likelihood ratio of 0.09, and a post-test probability of 13% (0.2).CONCLUSIONOur study emphasizes that clinical diagnosis is sufficiently adequate to declare a patient cerebrally dead. However, for ambiguous cases, TCD is a practical and fast method showing close correspondence to angiography and is superior to other bedside tests like EEG.

From the evening of 1st May 2023 to 3rd May 2023, severe hydro-meteorological events occurred in the Italian Emilia-Romagna region, particularly in the provinces of Forlì-Cesena, Ravenna, Bologna, Modena, and Reggio Emilia. Additionally, on 16th-17th May, another intense meteorological event occurred, impacting the Romagna provinces. Such events caused extensive flooding, landslides, isolation of many areas, evacuation of numerous families, and significant damages to infrastructure, agriculture, buildings, and essential services. Many hilly municipalities were cut off, and thousands of civilians had to be evacuated, losses of life occurred. The consequences beyond the recorded immediate impacts on infrastructure and life were impressive, and extended to the regional economy, specifically in the Fruit Valley, where, in addition to immediate yield losses, long-term damage to orchard production is expected due to persistent flooding. The civil and cultural building heritage has also been heavily affected, both in the countryside and in inhabited centers. Some of the damage, direct and indirect, caused by flooding on buildings will also see an evolution in the medium to long term that will have to be addressed. This paper analyzes the reasons that led to the atmospheric phenomenon to understand the increasing potential occurrence of similar events from the perspective of climate change. This paper document analyzes the causes and effects of these events, additionally considering the future impacts of similar hazards potentially occurring in the context of climate change. It is crucial indeed to remark how such events, when occurring in high density agricultural areas, have the potential to threat the entire regional production system for extended periods. For example, the alteration of direct physiological processes due to root drowning may compromise production of entire productive agricultural extensions and many years will be required to their replacement.

The spread of viral pathogens both between and within hosts is inherently a spatial process. While the spatial aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread within infected hosts are still understudied. Recent experimental studies, however, have started to shed more light on the mechanisms and spatial dynamics of viral spread within hosts. Here, we review these experimental studies as well as the limited number of computational modeling efforts that have begun to integrate spatial considerations for understanding within-host viral spread. We limit our review to influenza virus to highlight key mechanisms affecting spatial aspects of viral spread for pathogens of the respiratory tract. There is considerable empirical evidence for highly spatial within-host spread of influenza virus, yet few computational modeling studies that shed light on possible factors that structure the dynamics of this spatial spread. In existing modeling studies, there is also a striking absence of theoretical expectations of how spatial dynamics may impact the dynamics of viral populations. To mitigate this, we turn to the extensive ecological and evolutionary literature to provide informed theoretical expectations for what viral and host factors may impact the spatial patterns of within-host viral dynamics and for how spatial spread will affect the genetic composition of within-host viral populations. We end by discussing current knowledge gaps related to the spatial component of within-host influenza virus spread and the potential for within-host spatial considerations to inform the development of disease control strategies.

Neuronal cell death in the central nervous system has always been a challenging process to decipher. In physiological condition, neuronal cell death is restricted in the adult brain even as people ages. However, in pathological conditions of various neurodegenerative diseases, the cell death and shrinkage of a specific brain region represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe the evidence of the cell deaths in the context of common neurodegenerative diseases individually, discussing our current understandings of cell death in connecting with the renowned pathogenic proteins, including tau, amyloid-beta, alpha-synuclein, huntingtin, and TDP-43.

The work proposes a backtesting analysis in comparison between the Lee-Carter and the Cairns-Blake-Dowd mortality models, employing Italian data. The mortality data come from the Italian National Statistics Institute (ISTAT) database and span the period 1975-2014, over which we computed back-projections evaluating the performances of the models in comparisons with real data. We propose three different backtest approaches, evaluating the goodness of short-run forecast versus medium-length ones. We find that both models were not able to capture the improving shock on the mortality observed for the male population on the analyzed period. Moreover, the results suggest that CBD forecast are reliable prevalently for ages above 75, and that LC forecast are basically more accurate for this data.

Electricity price signal is a direct reflection of the attributes of electric power commodities, but due to the influence of market supply and demand, power producers' offer, line capacity and other factors, electricity price signals often show a variety of abnormal forms. The identification and traceability of abnormal tariff signals is an important daily work of power trading centers at all levels. However, at present, it is common to rely on manual experience to analyze the causes of abnormal tariffs, which is inefficient and difficult to ensure the objective and scientific traceability of abnormal tariff causes. Since different types of abnormal tariff signals are caused by different dominant factors, if the key features of abnormal tariffs can be classified and matched, the identification efficiency can be effectively improved. For this reason, this paper proposes a traceability method of abnormal tariffs based on the comparison analysis of key features. First of all, based on the characteristics of historical tariff data, this paper completes the classification of tariff spike magnitude anomaly and tariff mean value anomaly, further establishes the key features of each type of abnormal tariff signal based on principal component analysis, and finally calculates the influence degree of each element within the key features one by one based on alternative algorithms, and then realizes the screening and traceability of the causes of abnormal tariffs based on the importance of the degree of influence ordering. The effectiveness of the proposed method has been verified in a large number of examples constructed based on the actual data of the electricity market, and the average correctness rate of the proposed method for the traceability of the causes of the average value and spike anomalies of the electricity price reaches more than 85%, which can reduce the labor cost in the process of the traceability of the causes of the anomalous electricity price.

Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain on eye movements. Typical ON is associated with Multiple Sclerosis and is generally mild and steroid-responsive, whereas atypical forms are characterized by unusual features, such as optic disc edema, poor treatment response and bilateral involvement, and are often associated with autoantibodies against aquaporin-4 (AQP4) and Myelin Oligodendrocyte Glycoprotein (MOG). However, in rare cases AQP4 and MOG antibodies will come back negative, plunging the clinician in a diagnostic conundrum. Seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis is greatly different. The scope of this review is to describe possible, rarer etiologies of ON when AQP4 and MOG antibodies are negative and discuss their diagnosis and treatment.

Time can be a difficult concept to understand. Albert Einstein, who viewed time as an illusion, explained the passage of time is relative to the observer’s frame of reference in the space-time continuum. However, the state of consciousness of the observer also influences the passage of time. This paper examines the relationship between the experience of time and different states of consciousness including near-death experiences, mystical states of consciousness, and psychedelic medicine-induced states of consciousness. Two different experiences of time are described. These are Chronos and Kairos. Chronos is described as 4th dimensional time whereas Kairos is 5th dimension time. Methods for facilitating the experience of Kairos are discussed and the potential benefits of experiencing Kairos are reviewed.

Cerebral ischemic stroke poses a significant global cause of death, with ischemia-reperfusion injury contributing to neuronal cell death and tissue damage. However, significant therapeutic approaches with meaningful treatment effects for patients with ischemic stroke in actual clinical practice are lacking. This study investigated the potential neuroprotective effects of sildenafil, a phosphodiesterase-5 inhibitor, in a global cerebral ischemia model. We explored the impact of sildenafil on GFAP and AQP-4 expression, which are markers associated with astrocyte activation and water homeostasis, respectively. The immunofluorescence analysis revealed that the number of cells co-expressing the markers, which increased in the ischemia-induced group, was significantly reduced in sildenafil-treated groups, suggesting a potential mitigating effect on ischemia-induced astrocyte activation. Additionally, we conducted diverse behavioral tests, including the open-field test, novel object recognition, Barnes maze, Y-maze, and passive avoidance tests, to assess the effect of sildenafil on the cognitive function impaired by ischemia. Cognitive improvements were observed following sildenafil administration (20mg/kg) compared to the untreated group. Taken together, the results presented here suggest sildenafil's potential as a neuroprotective agent for alleviating delayed neuronal cell death and cognitive function impaired by ischemia.

Background: Suicide is a major health problem. The aim of this study was a comparative study of the causes and methods of completed suicide referred to legal Medicine Organization in Bushehr Province during the years 2006- 2015. Methods: This consideration has been done as a retrospective cross-sectional study; the data were collected by the check list. After coordination to the medico legal 343 cases of completed suicide lead to death over a ten year period from 2006 to 2015 were extracted and the data were analyses by SPSS software. Results: The rate of completed suicide was 2.43 and 1.12 suicides per 100,000 people in male and female, respectively. The mean age were 29.25 and 27.61 years in male and female, respectively p>0.05. A higher completed suicide rate was found among single people. The most common ways of a suicide among people who live in Bushehr were hanging out 184(53.6%), self-Immolation 83(24.2%) and firearms 37(10.8%). Motive of suicide was psychological disorders, Physical disease, Conflict with family and substance abuse. 43(12.5%) people smoking and 22(6.4%) people were both smoking and opioid. During the ten year period of studied, throughout the all years that frequency of hanging out has been higher than others. Conclusion: Due to the high incidence of completed suicide in young people and unmarried individuals also hanging out in male and self-burning in females are prevalent. So determination of preventive measures appears to be necessary. Social factors such as psychological disorders and family conflicts have a noticeable role from .Bushehr people.

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those involving costly resource reallocation, and exhibiting endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

Extracellular vesicles (EVs) have been identified as novel mediators of intercellular communication. They work via delivering the sequestered cargo to cells in close vicinity as well as distant sites in the body, regulating pathophysiological processes. Cell death and inflammation are biologically crucial processes in both normal physiology and pathology. These processes are indistinguishably linked with their effectors modulating the other process. For instance, during an unresolvable infection, the upregulation of specific immune mediators leads to inflammation causing cell death and tissue damage. EVs have gained considerable interest as mediators of both cell death and inflammation during conditions such as sepsis. This review summarizes the types of extracellular vesicles known to date and their roles in mediating immune responses leading to cell death and inflammation with specific focus on sepsis and lung inflammation.

The main features of the instrumental global mean surface temperature (GMST) are reasonably well described by a simple linear response model driven by anthropogenic, volcanic and solar forcing. This model acts as a linear long-memory filter of the forcing signal. The physical interpretation of this filtering is the delayed response due to the thermal inertia of the ocean. This description is considerably more accurate if El Ni\~{n}o Southern Oscillation (ENSO) and the Atlantic Multi-decadal Oscillation (AMO) are regarded as additional forcing of the global temperature and hence subject to the same filtering as the other forcing components. By considering these as predictors in a linear regression scheme, more than 92\% of the variance in the instrumental GMST over the period 1870-2017 is explained by this model, and in particular all features of the 1998 -- 2015 hiatus, including its death. While the more prominent pauses during 1870 -- 1915 and 1940 -- 1970 can be attributed to clustering in time of strong volcanic eruptions, the recent hiatus is an unremarkable phenomenon that is attributed to ENSO and a small contribution from solar activity.

Drug-induced movement disorders (DIMDs) are a group of neurological conditions caused by the use of certain medications. These disorders can significantly impact a person's quality of life and are essential to recognize and manage. This article provides an overview of the causes, symptoms, and treatment of DIMDs. DIMDs can manifest in various forms, including parkinsonism, tardive dyskinesia, dystonia, and akathisia. They are most commonly associated with medications such as neuroleptics, antidepressants, antipsychotics, antiemetics, and anticonvulsants. Risk factors for developing DIMDs include age, genetics, duration of medication use, and dose of medication. Symptoms of DIMDs can range from mild to severe and may include tremors, rigidity, bradykinesia, and involuntary movements. These symptoms can significantly impact a person's ability to perform daily activities and lead to social isolation and decreased quality of life. DIMD diagnoses are based on clinical evaluation, including a thorough medical history and physical examination. Imaging studies such as MRI or CT scans may also be used to rule out other possible causes of symptoms. Treatment of DIMDs involves the withdrawal of the offending medication if possible. Pharmacological treatments such as anticholinergic drugs, benzodiazepines, and dopamine agonists may also be used to manage symptoms. Non-pharmacological treatments such as physical, occupational, and speech therapy can also be beneficial. DIMDs are necessary neurological conditions that can significantly impact a person's quality of life. Early recognition and management of these disorders are essential for optimizing outcomes. Further research is needed to understand the underlying mechanisms of DIMDs better and to develop more effective treatments.

Chronic stress is a major risk factor for various psychiatric diseases, including depression; it induces a range of cellular and structural adaptations, culminating in altered neurocircuitry and subsequent depression. Accumulating evidence suggests that microglial cells orchestrate stress-induced depression. Preclinical studies of stress-induced depression revealed microglial inflammatory activation in regions of the brain that regulate mood. Although studies have identified several molecules that trigger inflammatory responses in microglia, the pathways that regulate stress-induced microglial activation remain unclear. Understanding the exact triggers that induce microglial inflammatory activation can help find therapeutic targets to treat depression. In the current review, we summarize the recent literature on possible sources of microglial inflammatory activation in animal models of chronic stress-induced depression. In addition, we describe how microglial inflammatory signaling affects neuronal health and causes depressive behavior. Finally, we propose ways to target the microglial inflammatory cascade to treat depressive disorders.

As technology evolves, our digital footprint keeps increasing. Now, everything we do is largely related to us being online, connected and logged. Therefore, if someone’s online data is exposed, then their life will be compromised. This is called identity theft and in this era of technology, it has become one of the most serious forms of crime. When someone’s data is compromised, there is a huge chance of harming the person financially, morally and socially. New technology and the knowledge gap it creates when it first comes out is perfect for identity thieves to exploit. If we are not cautious, our future will be very different than what we dream of due to the very technology created to make it better. Hence, we need to understand the technology, identify the loopholes and educate ourselves to avoid being held captive by our digital footprint.

Our previous study has found the anti-tumor activity of oleandrin in osteosarcoma cells in vitro, but the signal transduction process of cell apoptosis induced by oleandrin is uncertain, which is explored in this study. Fluorescence staining and flow cytometry (FCM) was performed to detect the cell apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). Caspase-3 activity was detected using a commercial kit. The protein expression of cytoplasmic cytochrome c, mitochondrial cytochrome c, bcl-2, bax, caspase-9, Fas, FasL, caspase-8 and caspase-3 was detected using western blot. A pan-caspase inhibitor, z-VAD-fmk, was applied to block the apoptotic pathway and the apoptosis status were re-tested. We found that oleandrin significantly induced the increased apoptosis of U2OS cells. Meanwhile, the intracellular ROS was elevated, but the MMP decreased. The cytochrome c in mitochondria was notably decreased but increased in cytoplasm. The caspase-3 activity was also enhanced with the increase of drug concentration and treatment time. Oleandrin also down-regulated the level of bcl-2, but remarkably up-regulated the expression of bax, cleaved caspase-9, Fas, FasL, cleaved caspase-8 and cleaved caspase-3. Furthermore, the pre-treatment with z-VAD-fmk almost completely reverted the oleandrin-induced apoptosis. The results suggested that oleandrin induces the apoptosis of osteosarcoma cells via mitochondrial- and death receptor-dependent pathways.

Introduction: Cerebral palsy is the most common childhood disability Aims: Analyze and determine the main risk factors for the development of cerebral palsy in the population of Kazakhstan Materials and methods: Retrospective, analytical "case" - "control". Core group "case" - medical records of 100 pregnant women whose children at different ages has been diagnosed with cere-bral palsy Results: Thus, a retrospective analysis revealed the following features and complications in the perinatal period, which could promote the formation of cerebral palsy in children. Analytical results of the study are set significant results in cerebral palsy development Conclusion: Premature birth and urinary tract infections turned out to be the largest contribu-tors to the development of cerebral palsy, however, according to statistics, the rate of preterm birth, as well as the detection of infections, stably remains at the same level, while the number of cerebral palsy has been steadily growing since the early 1990s in Kazakhstan.

Introduction: Cholelithiasis and consumption of alcohol are the most frequent causes of acute pancreatitis (AP), accounting for about 30 to 40% of the cases, respectively. The frequency of acute biliary pancreatitis is high in a certain population in Brazil. Objective: To estimate the global frequencies of acute biliary pancreatitis (ABP), acute alcoholic pancreatitis (AAP) and the cases considered as acute idiopathic pancreatitis (AIP) in studies published from October 2006 to December 31, 2018. Methods: A systematic review of observational studies was performed from October 2006 to December 31, 2018. A meta-analysis by the random effects model was used to calculate the frequencies of global ABP, AIP and AAP and subgroups. Results: Forty-six studies representing 2,341,007 AP cases were included in 36 countries. The overall estimate for acute biliary pancreatitis (ABP) was 41.6% (95% CI 39.2-44.1), followed by acute alcoholic pancreatitis (AAP) with 20.5% (95% CI) 16.6- 24.6) and acute idiopathic pancreatitis (AIP) in 18.3% (95% CI 15.1-27.7). Conclusion: ABP is the most prevalent etiology of AP, being two times more frequent than second-placed pancreatitis. Latin America has a frequency for ABP much higher than the rest of the world. The importance of the etiologic diagnosis is the treatment of the cause for prevention of recurrence.

Bangladeshi construction industry suffers a lot of safety and accidental issues than other developing countries in the world. Among many of these, accident of construction project goes far beyond and shape a horrific figure of death for every year. The aims of this study is that analysis and discussion of causes of accident at construction project in Bangladesh. A widespread statistical data collection and data analysis take place to identify the causes and design the questionnaire. The questionnaire-based survey was used to elicit the attitude of four stakeholders as workers, owners, consultants, and contractors towards passive causes of fatal accident at construction site. These study also identify 77 passive causes under 14 major groups and ranked them based on Relative Importance Index (RII). The top 5 major group of causes are (1) Management related, (2) Consultant related, (3) Technology related, (4) Labour related and (5) Contractor related. The top 5 passive causes are: (1) Unaware of safety-related issue, (2) Lack of personal protective equipment, (3) Lack of safety eliminating/ avoiding design, (4) Unfit equipment, (5) Lack of knowledge and training on equipment.

This article explores the enduring mysteries of consciousness and the afterlife, two enigmatic topics that have fascinated humanity for ages. Despite extensive scientific efforts, the existence of an afterlife remains unproven, and understanding consciousness remains a significant challenge. The research introduces new hypotheses through simple experiments with empirical evidence and theoretical foundations. It delves into the complexities of consciousness, its relationship with the brain, and the need for interdisciplinary approaches. Boldly contemplating the probability of a continuous consciousness after death, the study argues that existing evidence strongly supports this idea. In other words, if we do not accept the hypothesis of an afterlife, we may not be able to discuss the experimental results in the context of any alternative theories. Beyond theoretical implications, it envisions practical outcomes, suggesting that insights into these mysteries could enhance human well-being and contribute to a more harmonious world. This article sheds light on age-old questions about consciousness and the afterlife. Through fresh methodologies, it seeks to provide new perspectives that could reshape our understanding of existence and inspire intellectuals to positive individual and societal advancements including psychological well-being and intelligence.

To maintain proteostasis, cells must integrate information and activities that supervise protein synthesis, protein folding, conformational stability, and also protein degradation. Extrinsic and intrinsic conditions can both impact on normal proteostasis, causing the appearance of proteotoxic stress. Initially, proteotoxic stress elicits adaptive responses aimed to restore proteostasis, allowing cells to survival the stress condition. However, if the proteostasis restoration fails, a permanent and sustained proteotoxic stress can be deleterious and cell death ensues. Many cancer cells convive with high levels of proteotoxic stress and this condition could be exploited in a therapeutic perspective. Understanding the cell death pathways engaged by proteotoxic stress is instrumental to better hijack the proliferative fate of cancer cells.

Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccha-rides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and as-sociated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) sug-gest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.

The genetic bases of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have been comprehensively studied, which is not the case for atypical cases not classified into these diagnoses. In the present study, we aim to contribute to the molecular understanding of the development of non-AD and non-FTD dementia by surveying rare pathogenic variants. The analysis was performed on 91 patients, the DNA samples of which were pooled and then subjected to whole exome sequencing. Among detected variants two are rare pathogenic and show significant difference in frequency between the analyzed pool and gnomAD Bulgarian control exomes. The rs373478202, G&gt;T, B9D1 variant, most likely present in heterozygous state; is causative for the autosomal recessive ciliopathy- Joubert syndrome, which involves specific CNS malformation. The rs148918985, C&gt;T, ASS1 variant leads to arginosuccinate enzyme deficiency and in compound heterozygosity with other rare pathogenic variant detected in the same gene causes the late-onset form of citrullinemia type I. This disorder causes high ammonia levels, which can lead to cerebral dysfunction. In conclusion, the detected rare pathogenic variants suggest that, in certain cases, the development of non-AD and non-FTD dementia can be mediated by structural alterations in neuronal cilia or by hyperammoniemia.

Eukaryotic plasma membrane (PM) transporters face critical challenges that are not widely present in prokaryotes. The two most important issues are proper subcellular traffic and targeting to the PM, and regulated endocytosis in response to physiological, developmental or stress signals. Sorting of transporters from their site of synthesis, the Endoplasmic Reticulum (ER), to the PM has been long thought, but not formally shown, to occur via the conventional Golgi-dependent vesicular secretory pathway. Endocytosis of specific eukaryotic transporters has been studied more systematically and shown to involve ubiquitination, internalization, and sorting to early endosomes, followed by turnover in the MVB/lysosomes/vacuole system. In specific cases internalized transporters have been shown to recycle back to the PM. However, the mechanisms of transporter forward trafficking and turnover have been overturned recently through systematic work in the model fungus Aspergillus nidulans. In this review we present evidence that shows that transporter traffic to the PM takes place through Golgi-bypass and transporter endocytosis operates via a mechanism that is distinct from that of recycling membrane cargoes essential for fungal growth. We discuss these findings in relation to adaptation to challenges imposed by cell polarity in fungi as well as in other eukaryotes and provide a rationale why transporters and possibly other housekeeping membrane proteins ‘avoid’ routes of polar trafficking.

Mental health issues can have significant impacts on individuals and communities and hence on social sustainability. There are several challenges facing mental health treatment, however, more important is to remove the root causes of mental illnesses because doing so can help prevent mental health problems from occurring or recurring. This requires a holistic approach to understanding mental health issues that are missing from the existing research. Mental health should be understood in the context of social and environmental factors. More research and awareness are needed, as well as interventions to address root causes. The effectiveness and risks of medications should also be studied. This paper proposes a big data and machine learning-based approach for the automatic discovery of parameters related to mental health from Twitter data. The parameters are discovered from three different perspectives, Drugs & Treatments, Causes & Effects, and Drug Abuse. We used Twitter to gather 1,048,575 tweets in Arabic about psychological health in Saudi Arabia. We built a big data machine learning software tool for this work. A total of 52 parameters were discovered for all three perspectives. We defined 6 macro-parameters (Diseases & Disorders, Individual Factors, Social & Economic Factors, Treatment Options, Treatment Limitations, and Drug Abuse) to aggregate related parameters. We provide a comprehensive account of mental health, causes, medicines and treatments, mental health and drug effects, and drug abuse, as seen on Twitter, discussed by the public and health professionals. Moreover, we identify their associations with different drugs. The work will open new directions for social media-based identification of drug use and abuse for mental health, as well as other micro and macro factors related to mental health. The methodology can be extended to other diseases and provides a potential for discovering evidence for forensics toxicology from social and digital media.

To determine the fracture rate of ceramic crowns and causes of ceramic crown failure, this study used keywords—namely “endocrown,” “veneered fixed dental prosthesis,” “monolithic lithium disilicate (LS2),” and “all-ceramic single crown”—to search for articles published in English from 2005 to 2023 in the PubMed electronic database. Rather than using the Boolean logic algorithm between MESH terms and keywords, we accurately calculated the numbers of final clinically tracked cases with crown fractures from the contents of articles. The titles and abstracts of many related articles focused on implant or abutment fracture, while crown fracture was investigated and mentioned only in the main texts of the articles. Our studies included those crowns as well as having more complete data collection. Our search yielded 228, 93, 404, and 358 articles for the keywords “endocrown,” “veneered fixed dental prosthesis,” “monolithic lithium disilicate (LS2),” and “all-ceramic single crown,” respectively. We used the Newcastle–Ottawa Scale (NOS) to assess article quality, and our inclusion criteria were randomized controlled trials (RCT) and cohort study articles involving more than 3 years of follow-up and more than 20 cases. After reviewing, 16 high-quality articles were selected for analysis. The 4.4% crown fracture rate recommended on the basis of most clinical results was achieved in only 6 of the 16 articles. In these 6 articles, the researchers concluded the following reasons that may cause the crown fractures: the thickness of the veneer ceramic material; the connector dimensions; pontic span of the fixed prosthesis; the type of cement; the treatment of the ceramic surface before luting. Other articles inferred that the computer-aided design libraries that were insufficient for the creation of appropriate anatomically supported frameworks for prostheses with ceramic veneers; the thermal expansion coefficient and fracture toughness of the framework material did not match those of the veneer ceramic, resulting in an insufficient area supporting the ceramic veneer then leads to premature crown failure after a long period chewing. The future prospective for material developing could focus on solving those problems and have better clinical results.

The study aims to evaluate the rate of readmission in patients affected by diabetic foot ulcers (DFUs), causes and the outcomes of patients requiring a new hospitalization. This study is a retrospective observational study including consecutive patients requiring hospitalization since January 2019 to September 2022 due to a DFU. Once they were discharged, patients were regularly followed as outpatients. After 6 months of follow-up, the rate of hospital readmission for a diabetic foot problem was recorded. According to the readmission or not, patients were divided in two groups, readmitted and not readmitted patients respectively. Hence, all patients were followed for six months more and outcomes for the two groups were analyzed and compared. The mean age was 6812yrs, with a prevalence of male (72.6%); the majority of patients were affected by type 2 diabetes (>90%) with a mean diabetes duration of approximately 20yrs. After 6 months of follow-up, 68 (21.9%) patients were readmitted. The main reason of hospital readmission were the presence of critical limb ischaemia (CLI) in the contralateral limb (6.1%), the recurrence of CLI in the previous treated limb (4.5%) and the onset of new infected DFU in the contralateral foot (4.5%). Readmitted patients reported lower rate of healing (51.5vs89.2%,p<0.0001) and higher rate of major amputation (10.3vs4.5%,p=0.04) in comparison to not readmitted patients. CLI and dialysis resulted independent predictors of hospital readmission. Hospital readmission is frequent issue among patients with DFUs, increasing the risk of non-healing and major amputation. CLI resulted the main cause of new hospitalization.

The important topic of climate change is discussed in this article, with a focus on the historical background and present effects. It draws attention to the differences between climate change and global warming and attributes the faster pace of climate change to human activity, specifically the release of greenhouse gases into the atmosphere. Agricultural practices, deforestation, and the combustion of fossil fuels are examined in conjunction with natural contributors like volcanic emissions. There is discussion of the far-reaching effects of climate change, such as increased temperatures, rising sea levels, harsh weather, and effects on water supplies. The article emphasizes how crucial it is to mitigate and adapt to the effects of climate change by putting in place climate-resilient infrastructure, switching to renewable energy sources, and lowering greenhouse gas emissions. While recognizing the difficulties involved, it examines several approaches, including nuclear energy, wind power, carbon capture and storage, and green building techniques. To successfully address the global challenge of climate change, the conclusion emphasizes the urgent need for joint efforts by scientists, environmentalists, communities, and governments.

Humans have extremely variable skin pigmentation and melanin production influenced by genetics, UV exposure, and some medications. A significant number of skin illnesses that result in pigmentary abnormalities have an impact on patients’ physical appearance as well as their psychological and social well-being. Skin pigmentation can be divided into two basic categories: hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced. Albinism, melasma, vitiligo, Addison's disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosine, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. This review article explores the numerous types of pigmentation problems, their causes, and treatments, as well as the 25 plants, four marine species, and 17 topical and oral medications now on the market that have been clinically tested to treat skin diseases.

Background Hop creep continues to present an unresolved issue for the brewing industry, specifically stemming from those hops added to beer during fermentation. Hops have been found to contain four dextrin-degrading enzymes: alpha amylase, beta amylase, limit dextrinase, and an amyloglucosidase. One recent hypothesis predicts that these dextrin-degrading enzymes could originate from microbes rather than the hop plant itself. Scope and Approach This review begins by describing how hops are processed and used in the brewing industry. It will then discuss hop creep’s origins with a new beer style, antimicrobial factors from hops and resistance mechanisms that bacteria use to counter them, and finally microbial communities that inhabit hops, focusing on whether they can produce the starch degrading enzymes which drive hop creep. After initial identification, microbes with possible links to hop creep were then run through several databases to search the genomes (if available) and for those specific enzymes. Key Findings and Conclusions Several bacteria and fungi contain alpha amylase as well as unspecified glycosyl hydrolases, but only one contains beta amylase. Finally, this paper closes with a short summary of how abundant these organisms typically are in other flowers.

The Metabolic Food Waste [MFW (kg of food)], first time developed in 2016 as a new indicator by Serafini and Toti, indicates the amount of food consumed over the nutritional requirements and the impact of this overconsumption on the environment. It is necessary to identify the causes and to develop potential methods to prevent and reduce MFW, at the same time with increasing consumer awareness about unsustainable diets and changing diet habits toward more environmentally conscious consumption patterns. By analysing and corroborating external data available for food waste, nutritional requirements, environmental impact of food waste and consumer behaviour, we identified as primary causes for MFW the lack of nutritional education and little understanding of the nutritional requirements amongst all categories of consumers, no access to appropriate food resources or reduced availability of fresh produced food. We conclude that for the quantification of the negative impact of MFW on both the environment and human health, we need a decisive action to raise consumer awareness for healthy and sustainable diets, together with an uniform worldwide distribution of the nutritious food.

Infant mortality remains a major global concern. Sudden unexpected death in infancy (SUDI) is reported globally and in the Western Cape of South Africa it accounted for 40% of all infant deaths between 2012 and 2016. Research highlighting molecular typing of respiratory viruses in SUDI cases is lacking. A total of 116 PCR-positive human rhinovirus (HRV) and respiratory syncytial virus (RSV) swab samples collected from the lungs and trachea of SUDI cases admitted to Tygerberg Medico-legal Mortuary in Cape Town between 2015 and 2019 were included and underwent sequencing and phylogenetic analysis. Three distinct HRV species were identified; HRV-A (n=28), HRV-C (n=11), and HRV-B (n=4), including eight HRV-A, seven HRV-C and one HRV-B genotypes. For RSV, both RSV-A (n=5) and -B (n=5) were detected, but no RSV-A. After amino acid alignment indicating 20 amino acid duplication and nine substitutions, two BA9 genotypes were confirmed. This study describes the first molecular and phylogenetic characterisation of respiratory viruses in SUDI cases in South Africa. The rapid decline in viral viability in post-mortem samples and the retrospective study design employed for the current study did not allow for any correlations between viral genotypes and cause of death and future prospective studies should investigate temporality and specific viral strains associated with clinical disease severity.

This paper presents a study conducted to identify, assess, rank, and compare the most influencing factors causing schedule delay during construction phase of petrochemical projects in Saudi Arabia. The methodology followed in this research to achieve the main aims is a combination of comprehensive review of the literature and interviewing number of local experts, which have resulted in identifying of 23 factors. Through a web-based questionnaire survey, the identified factors were ranked. Total of 90 completed responses were gathered from 106 received responses. The completed responses gathered from 38 contractors and 52 owners. Of 90 participants, there are 32 project managers, 22 project engineers, 7 construction supervisors and the other 31 having different positions in projects departments The study has found that the most influencing factors causing schedule delay during construction in petrochemical projects in Saudi Arabia are “Poor site management and supervision by contractors”; “Conflict between main contractor and subcontractor”; “poor planning and scheduling of projects by contractor”; “Delay of material or equipment delivery”; and followed by “Delay in Handing Over Construction Site to Contractor”. This paper is original in the sense that the areas of knowledge and practice covered in the identified factors were distributed and not available in one source. The factors are derived from personal interviews with selected project managers, project engineers, construction supervisors and the others from different positions in project department and from the relevant literature.

This paper presents a theoretical analysis of an International conflict, i.e. East Pakistan Crisis, 1971, and reveals that unequal development creates conflict in society. Natural resource scarcity and environmental degradation can also become a source of conflict, so marginalised and excluded people fight for their rights through non-peaceful means. This essay supports the theoretical approaches of poverty, environment, and conflict nexus and reveals that unequal development and resource scarcity deepens the poverty and creates conflicts in the society, causing harm to the environment. The degraded environment increases the poverty as environment and poverty are interlinked, and the poor have limited choices other than to degrade the environment for their survival. This vicious downward spiral link between poverty and degradation of the environment requires working extensively for poverty alleviation to reverse the environmental decline.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

Aneuploidy describes the gain or loss of entire chromosomes or chromosome arms. Already more than 100 years ago, aneuploidy was described to be featured in cancer and it is known today to be present in 68-90 % of cancers, depending on tumour entity. Aneuploidy is implicated to affect cancer growth, therapy response and frequently affects prognosis. Chromosomal instability (CIN) is recognized as the main cause of aneuploidy and is characterised as the fluent process of gaining or losing chromosomes. Chromosomally instable cells need to be kept in check, or cleared, to prohibit the sampling of aneuploid karyotypes able to drive tumorigenesis. Of note, even aneuploid cancer cells often show CIN, a feature that promotes therapy related drug-resistance. Here, we review how CIN can be prevented or limited to spread by the induction of cell death and the relevance of different p53 responses triggered in response to mitotic perturbations to prohibit the formation of cancer driving aneuploidies.

Abstract Objectives To assess the causes and risk factors of posttraumatic stress disorder (PTSD) in adult asylum seekers and refugees. To explore whether the causes and risk factors of PTSD, between male and female adult refugees/ asylum seekers is different. Study design Systematic review of current literature. Data Sources PubMed, Web of Science, Scopus and Google Scholar up until February 2019 Method A structured systematic search was conducted in the relevant databases. Papers were excluded, if they failed to meet the inclusion and exclusion criteria. Afterwards, a qualitative assessment was performed on the selected papers. Results 12 Studies were included for the final analysis. All papers were either case studies/report or cross sectional studies. The number of traumatic events experienced by refugees/asylum seekers, is the most frequently reported pre-migration causes for PTSD development. Whilst acculturative stress, is the most common post migration stressor. There were mixed reports, regarding the causes of PTSD between both genders of refugees/asylum seekers. Conclusion This reviews’ findings, have potential clinical application into helping clinicians, to risk stratify refugees/asylum seekers for PTSD development and thus aid in embarking on earlier intervention measures. However, more rigorous research similar to this one, is needed for it to be implemented into clinical practice.

This review examines eutrophication in freshwater ecosystems, a widespread environmental issue stemming from excessive nutrient input, largely due to human activities. The study explores the origins, consequences, evaluation techniques, and control methods for eutrophication. Primary causes include agricultural discharge, urban development, and climate shifts. The effects are far-reaching, impacting biodiversity, water quality, and socio-economic factors. The assessment utilizes a combination of chemical, physical, and biological markers, with cutting-edge technologies like remote sensing improving monitoring efforts. Mitigation strategies are diverse, incorporating preventative actions (such as nutrient limitation and land management), corrective measures (including bio-manipulation and chemical applications), and regulatory initiatives (like water quality guidelines and nutrient exchange schemes). While case studies demonstrate successful interventions, they also reveal ongoing challenges, particularly ecosystem unpredictability and climate change influences. The research highlights the promise of emerging technologies, notably machine learning, in enhancing management practices. Knowledge gaps persist, especially regarding eutrophication-biodiversity dynamics in tropical environments and the socio-economic ramifications of interventions. The study emphasizes the importance of flexible, comprehensive approaches that blend scientific insights with practical solutions and strong policy structures to tackle this intricate environmental challenge in an era of climate change.

Although adult spontaneous (non-diabetic) hypoglycaemia is rare, its recognition is important for the preventative or curative treatment of the underlying cause. Establishing Whipple’s triad; low blood glucose, neuroglycopaenia and resolution of neuroglycopaenia on increasing blood glucose levels to normal or above, is essential to verify hypoglycaemia. Awareness that hypoglycaemia may occur in severely ill patients is important for its prevention. Further investigation in such cases is unnecessary unless another cause of hypoglycaemia is suspected. Patients are often asymptomatic and normoglycaemic at review. History of medication, self-medication, access to hypoglycaemic drugs, alcohol and comorbidity may provide aetiological clues. The investigation involves obtaining blood samples during symptoms for laboratory glucose measurement or provoking fasting or postprandial hypoglycaemia as directed by symptoms. If confirmed, insulin, c-peptide, proinsulin, beta-hydroxybutyrate are analysed in hypoglycaemic samples. These will classify hypoglycaemia due to non-ketotic hyperinsulinaemia, non-ketotic hypoinsulinaemia and ketotic hypoinsulinaemia and direct investigations to identify the underlying cause. There are, however, many pitfalls, which may mislabel healthy individuals as “hypoglycaemic” or misdiagnose treatable or preventable causes of spontaneous hypoglycaemia. Clinical acumen and appropriate investigations will mostly identify hypoglycaemia and its cause.

The aim of the present research to identify the differences between the social acceptance, attention, and emotional and social loneliness feeling in women suffering from Alzheimer's and normal. The sample was analyzed in this study included 39 women age 51 to 69 years with the scope of that 19 of them with Alzheimer's disease (AD) and 18 people had normal cognitive function and healthy in the city of Gorgan in the winter 1395 in the study. Identification of Alzheimer's sufferers and healthy based on the diagnosis of the physician and cognitive status questionnaire (SPMSQ) and they were asked to answer the social acceptance of the scale questionnaire Marlow and Craven, affective and social adults alone feel scale (SELSA-S), Spotlight questionnaire (FAQ). The data using analysis of variance, multivariate factor test method (MANOVA) were studied. The results of this test indicate that it is totally focused attention between petty scale, the Spotlight focused on the notion of social acceptance of social interaction and social-emotional feeling lonely scale in women suffering from Alzheimer's and normal according to the analysis of the one-way variance of a significant difference in the context of manova level (P < 0.001). But in the other scale retail spotlight focused on his research, a significant difference was not observed. According to the results of the research in general can be found stating that to provide family-centered care and the implementation of the health-welfare interventions by relevant organs with different educational, supportive, emotional and consultation approaches, can be effective on health promotion of public health and the actual need in the community.

Late-life diseases result from the poorly understood process of senescence (aging), that is largely genetically determined. According to a recently proposed evolutionary physiology-based account, the multifactorial model, senescence is largely caused by evolved but non-adaptive programmatic mechanisms specified by the wild-type (i.e. normal) genome. These act together with disruptions to wild-type function (due e.g. to infectious pathogens, mechanical injury and malnutrition) in a variety of combinations to generate diverse late-life diseases. Here the utility of this model is explored by testing its capacity to provide an account of one complex, late-life disease, osteoarthritis (OA), and a framework for understanding OA etiology suggested. In this framework, the core OA disease mechanism is a futile endochondral ossification quasi-program (non-adaptive developmental program), in which hypertrophic articular chondrocytes alter joint architecture. Programmatic changes prime chondrocytes for quasi-program activation, which can be triggered by secondary causes of OA (e.g. joint mechanical injury). A suggested evolutionary cause of this priming, involving antagonistic pleiotropy, is selection to maximize early life tissue repair benefits at the expense of late-life programmatic costs.

Objective: We aim to assess the reporting discrepancy and the difference between confirmed and unreported COVID-19-like death counts.Study Design: The study is based on time-series data.Methods: We used publicly available data to explore the differences between confirmed death counts and deaths with Codiv-19 symptoms between March 8, 2020, and July 11, 2020, in Bangladesh.Results: During the week ending May 9, 2020, the unreported COVID-19-like death count was higher than the confirmed COVID-19 death count; however, it was lower in the following weeks. On average, unreported COVID-19-like death counts were similar to the confirmed COVID-19 death counts during the same period. However, the reporting authority neither considers these deaths nor adjusts for potential seasonal influenza or other related deaths, which might produce incomplete COVID-19 data and respective mortality rates. Conclusions: Documenting unreported deaths with COVID-19 symptoms needs to be included in provisional death counts because it is essential to estimate a robust COVID-19 mortality rate and to offer data-driven pandemic response strategies. An urgent initiative is needed to prepare an acceptable guideline for COVID-19 death reporting.

Curcumin, found in the rhizome of turmeric, has extensive therapeutic promises via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown curcumin to be an effective treatment for multiple cancers. These effects are drived by curcumin's ability to induce G2/M cell cycle arrest, induction of autophagy, activation of apoptotic pathways, disruption of molecular signaling, inhibition of invasion and metastasis, and by increasing the efficacy of existing chemotherapeutics. Here we focused on the hormetic behaviour of curcumin. Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress whereas high dose activates acute responses like autophagy and cell death. This phenomenon is referred to as hormesis. Many molecules that cause cell death elicite an initial autophagic step that is a cytoprotective mechanism relying on elimination of dysfunctional structures intracellular, notably by mitophagy. This phenomenon is considered as a primarily protective mechanism against stressors. At higher doses, cells undergo mitochondrial outer membrane permeabilization due to calcium release from the endoplasmic reticulum and die. Herein, we address the complex crosstalk between the induced mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy and cell death that can also be at play.

Super-Resolution Microscopy enables non-invasive, molecule-specific imaging of the internal structure and dynamics of cells with sub-diffraction limit spatial resolution. One of its major limitations is the requirement for high-intensity illumination, generating considerable cellular phototoxicity. This factor considerably limits the capacity for live-cell observations, particularly for extended periods of time. Here, we overview new developments in hardware, software and probe chemistry aiming to reduce phototoxicity. Additionally, we discuss how the choice of biological model and sample environment impacts the capacity for live-cell observations.

COVID-19 is a potentially fatal viral infection. This study investigates geography, demography, socioeconomics, health conditions, hospital characteristics, and politics as potential explanatory variables for death rates at the state and county levels. Data from the Centers for Disease Control and Prevention, the Census Bureau, Centers for Medicare and Medicaid, Definitive Healthcare, and USAfacts.org were used to evaluate regression models. Yearly pneumonia and flu death rates (state level, 2014-2018) were evaluated as a function of the governors’ political party using repeated measures analysis. At the state and county level, spatial regression models were evaluated. At the county level, we discovered a statistically significant model that included geography, population density, racial and ethnic status, three health status variables along with a political factor. State level analysis identified health status, minority status, and the interaction between governors’ parties and health status as important variables. The political factor, however, did not appear in a subsequent analysis of 2014-2018 pneumonia and flu death rates. The pathogenesis of COVID-19 has greater and disproportionate effect within racial and ethnic minority groups, and the political influence on the reporting of COVID-19 mortality was statistically relevant at the county level and as an interaction term only at the state level.

Lewis et al. published an important and timely necessary article about the determination of death by neurological criteria, revising the Uniform Determination of Death.The acceptance of brain death (BD) has been progressively accepted beginning at the late 1950s. Nonetheless, contentious brain-death cases have recently raised new controversies about the diagnosis of BD, such as the Jahi McMath case, extensively covered by the US and international press. Jahi McMath meant a terrible tragedy for her and her family. But further than this gloomy story, the case has also raised confusion and challenging qualms about a fundamental query: how we confirm whether a person is dead or alive? Since 1981, the Uniform Determination of Death Act (UDDA) has served as the legal foundation for the medical practice of determining death. But, although death by neurologic criteria is considered legal death throughout the United States, several recent lawsuits have quizzed the rightfulness the authority of the UDDA to declare death by neurological criteria. This issue explains the importance of Lewis’s et al. paper. In this article I want to present the historical procedure for issuing a law in Cuba for the determination and certification of death. Of course, it is impossible to compare our country with USA. Cuba is a small and developing country, in which a law encompasses a national scenery, in contrast with USA, a multistate nation.

Poultry eggs are a critical source of protein, vitamins, and minerals for people worldwide; facing the current global egg shortage is a significant concern. The shortage results from various factors, including avian flu outbreaks, changes in consumer demand, and supply chain disruptions caused by the COVID-19 pandemic. The economic crisis caused by the pandemic has also impacted the availability and affordability of eggs, particularly in low-income countries. The global egg shortage has implications for public health, particularly for vulnerable populations who rely on eggs for essential nutrients. One Health, an approach that recognizes the interconnectedness of human, animal, and environmental health, provides a useful framework for understanding and addressing the egg shortage. One Health approaches to the egg shortage involve collaboration between agriculture and environmental sectors to address the root causes of the lack and ensure the sustainable production and distribution of eggs. Addressing the global egg shortage requires a multifaceted approach considering the complex social, economic, and environmental factors. One Health perspectives offer a way to understand and address the interconnected factors contributing to the shortage to ensure access to affordable, nutritious eggs for all in a healthy way

There are several causes of hypoxia during and after surgery, and atelectasis is a common symptom that occurs during surgery. In particular, elderly patients are more vulnerable to hypoxia due to their existing lung diseases or respiratory muscle weakness. This study presents the cases of two elderly patients who developed hypoxia during total hip arthroplasty under general anesthesia. Positive end expiratory pressure, recruitment maneuver, and increased fraction of inspired oxygen improved hypoxia only temporarily, and patients’ oxygen saturation level again dropped to 79%–80%. We suspected that hypoxia was caused by atelectasis and, therefore, re-sumed spontaneous respiration. Thereafter, both the patients showed an improvement in hypoxia. Intraopera-tive hypoxia that is suspected to be caused by atelectasis can be improved by securing sufficient lung volume for respiration through increased muscle tone with spontaneous respiration

Bayesian analysis for masked data under competing risk frameworks is studied for the purpose of assessing the impact of covariates on the hazard functions when the failure time is exactly observed for some subjects but only known to lie in an interval of time for the remaining subjects. Such data, known as partly interval-censored data, usually result from periodic inspection. Dirichlet and Gamma processes are assumed as priors for masking probabilities and baseline hazards. The Markov Chain Monte Carlo (MCMC) technique is employed for the implementation of the Bayesian approach. The effectiveness of the proposed model is tested through numerical studies, including simulated and real data sets.

Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel Aspidosperma-Aspidosperma bisindole alkaloid isolated from the Malayan plant Tabernaemontana corymbosa. Herein, we report conofolidine’s anticancer activity together with that of three other bisindoles - conophylline, leucophyllidine and bipleiophylline against human-derived carcinoma cell lines. Remarkably, conofolidine was able to induce apoptosis (as observed in MDA-MB-468 breast cancer cells) or senescence (as detected in HT-29 colorectal carcinoma cells). Annexin V-FITC/PI, caspase activation and PARP cleavage confirmed the former while positive β-gal staining corroborated the latter. Evident cell cycle perturbations were observed comprising S-phase depletion, accompanied by downregulated CDK2, and cyclins (A2, D1) with p21 upregulation. Confocal imaging of HCT-116 cells revealed induction of aberrant mitotic phenotypes - multi-nucleation, membrane blebbing and DNA-fragmentation. The DNA integrity assessment of HCT-116 and MDA-MB-468 showed irreparable damage identified by increased fluorescent γ-H2AX during the G1 cell cycle phase. Furthermore, γ-H2AX foci were visually validated in HCT-116 and MDA-MB-468 cells using confocal microscopy. Conofolidine increased oxidative stress, preceding apoptosis- and senescence-induction in most carcinoma cell lines as seen by enhanced ROS levels accompanied by NQO1 expression. Collectively, we present conofolidine as a potential anticancer candidate capable of inducing heterogeneous modes of cancer cell death in vitro, encouraging further preclinical evaluation of this natural product.

The COVID-19 disease has infected many countries with generalised impacts on the different income categories. To test this hypothesis, we carried out a survey among households (n = 412) representing different income groups in Nigeria. We used validated food insecurity experience and socio-psychologic tools. We analysed the data obtained using descriptive and inferential statistics. The earning capacities of the respondents range from US$145/month for the low-income earners to US$1945/month for high-income earners. A total of 173 households (42%) ran out of food during the COVID-19 pandemic. All categories of households have experienced increasing dependency from the general public and perception of increasing insecurity, with the high-income earners having the greatest shift. In addition, increasing levels of anger and irritations have been experienced with all categories. Of the socio-demographic variables, only gender (p = 0.012), level of education of household head (p = 0.000), work hours per day (p = 0.006), and family income based on society class (p = 0.000) were significantly associated with food security and hunger due to the COVID-19 pandemic. Household heads with medium (OR: 4.36, 95% CI: 2.64 – 7.21, p &lt; 0.001) and high (OR: 30.27, 95% CI: 3.99 – 229.90, p &lt; 0.001) family income based on society class were more likely to have satisfactory experience on food security and hunger than respondents with low family income. Irrespective of the social class of the respondents, some respondents had negative experiences such as movement/change of location within the same city (17.68%), begin a new relationship (14.43%), recent change of job/loss of job (11.55%), movement to another city (10.81%), and separation from spouse or long-term relationship (10.07%). However, 231 (60.16%) reported satisfaction with their jobs despite the pandemic. Psychological stress due to impact of COVID-19 was observed to be more in the low income earning group than others. It is recommended that socio-economic groups should be mapped and support systems should target each group as per the needed support in terms of health, social, economic, and mental wellness; the government should show political commitments and transparency in food security and counselling supports. National authorities should prioritize empirical-based interventions on resources allocation during crises.

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

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

Abstract: Fanconi anemia (FA), a chromosome instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, that cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired, and accumulation of toxic DNA double strand breaks occurs. In order to repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, that may lead to the formation of gross structural chromosome aberrations of which radial figures are the epitome and origin of subsequent aberrations like translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, that results in tissue attrition, selection of malignant clones and cancer onset. Moreover, the effect of the FA/BRCA pathway in germinal cells, evidenced by infertility in patients with FA attests of chromosomal instability and cell death also occurring in the germinal compartment.

Jamoytius kerwoodi, is a primitive, eel-like jawless vertebrate found uniquely in an Early Silurian (Llandovery epoch; 444-433 Ma) horizon near Lesmahagow, Scotland. This species is a rare component of a low-diversity dominantly nektonic detritus and herbivorous fauna living over an anoxic bottom and is found at the transition from a marine-influenced, probably brackish-water, deep-water basin to a shallower-water, less saline and likely freshwater basin. In the absence of true teeth, Jamoytius was probably a detritivore or herbivore feeding on Ceratiocaris. Jamoytius may be a direct ancestor of living lampreys, especially as their ectoparasitic mode of life might have evolved from ancestral microphagous filterers or herbivores.

Apoptosis, necroptosis, and autophagy are cellular mechanisms by which cells are programmed to die under a wide range of physiological and developmental stimuli. A multitude of protein mediators of programmed cell death have been identified and apoptosis, necroptosis, and autophagy signals have been found to utilize common pathways elucidating the proteins involved. This narrative review focuses on caspase-dependent and caspase-independent programmed cell death systems. Included studies of caspase-dependent programmed cell death include extrinsic pathway apoptotic mechanisms including phosphatidylserine (PS), FAS (APO-1/CD95), Tumor Necrosis Factor (TNF) Receptor type 1 (TNF-R1) and TNF-Related Apoptosis-Inducing Ligand (TRAIL) and intrinsic or mitochondrial pathway such as Cytochrome C, the Bcl-2 family of proteins and Smac/Diablo. The Bcl-2 family has apoptotic mediators Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), Bcl-2-Interacting Protein BIM (Bim), Bcl-2 agonist of cell death (Bad), Bid, Bcl-2 adenovirus E1B 19kDa-interacting protein 1 NIP3 (Bnip3), BMF, HRK, Noxa and PUMA and anti-apoptotic proteins such as Bcl-2 itself, Mcl-1, Bcl-w, A1, and Bcl-XL. Moreover, caspase-independent programmed cell death pathways include the mitochondrial pathway with the protein mediators Apoptosis Inducing Factor (AIF), and Endonuclease G, the pathways Necroptosis, and Autophagy. Understanding programmed cell death from those reported in this review could shed substantial light on the processes of biological homeostasis. In addition, identifying specific proteins involved in these processes is mandatory to identify molecular biomarkers as well as therapeutic targets. This knowledge could provide the ability to modulate the programmed cell death response and could lead to new therapeutic interventions in a wide range of diseases.

ABSTRACT Two years after first patients approached the emergency rooms of hospitals in Wuhan becouse of respiratory distress,thousend of SARS-CoV-2 infected persons continue to die every day worldwide.SARS-CoV-2-infected patients undergo a process of dehydration and malnutrition before they develop respiratory problems and approach the emergency room of a hospital.This is,in many cases, the consequence of high fever which causes massive loss of fluids. In addition loss of appetite, is responsible for the deficit of protein intake.Most of the virus-infected patients admitted to the emergency room are therefore hypovolemic and hypoproteinemic and suffer of respiratory distress accompanied by ground grass opacities at CT-scan of the lungs.Critically ill patients are treated following the guidelines for treatment of septic shock but with „conservative“ fluid replacement and administration of diuretics to assure sufficient hourly urine production. The combination of conservative fluid administration with reduced protein content in the enterally administered diet, together with administration of diuretics, has severe hemodynamic consequenses in mostly aged,dehydrated,critically ill patients. Many of them will develop acute kidney injury in the next 24 hours.In most of the cases, patients continue to loose weight by loosing skeletal muscle mass. Ischemic damage in the lung capillaries is responsible for the acute respiratory distreass syndrome (ARDS) and for the hallmark of autoptic findings,diffuse alveolar damage (DAD) characterized by hyaline membrane formation,fluid invasion of the alveoli recruitment of some inflammatory cells and progressive arrest of blood flow in the pulmonary vessels.The consequence is progressive congestion , increase of lung weight and progressive hypoxia (progressive severity of ARDS).Sequestration of blood in the lungs worsen hypovolemia and ischemia in different organs.This is most probably responsible for recruitment of inflammatory cells and for persistance of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autoptic studies have been performed mostly in patients who died in the ICU after SARS-CoV-2-infection because of progessive ARDS.In those patients, tubulus epithelium necrosis in the kidney is a frequent finding as it has been the case in the first SARS-CoV-1 pandemic.In the death certification charts, many times weeks after first symptoms have started ,cardiac arrest is the cause of death after respitatory insufficiency.Replacement therapy with sufficient amount of fluid and albumin should be part of the early individualized life-saving supportive measures avoiding mechanical ventilation.

Abstract. The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in R&D by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.

High-grade gliomas are the most common and aggressive adult primary brain tumors with a median survival of only 12-15 months. Current standard therapy consists of maximal safe surgical resection followed by DNA-damaging agents, such as irradiation and chemotherapy that can delay but not prevent inevitable recurrence. Some have interpreted glioma recurrence as evidence of glioma stem cells which persist in a relatively quiescent state after irradiation and chemotherapy, before the ultimate cell cycle re-entry and glioma recurrence. Conversely, latent cancer cells with a therapy-induced senescent phenotype have been shown to escape senescence, giving rise to more aggressive stem-like tumor cells than those present in the original tumor. Therefore, approaches are needed to either eliminate or keep these glioma-initiating cells in a senescent state for a longer time to prolong survival. In our current study, we demonstrate that the radiation-induced cell cycle inhibitor P21 can provide a powerful route to induce cell death in short-term explants of PDXs derived from three molecularly diverse human gliomas. Additionally, cells not killed by P21 overexpression were maintained in a stable senescent state for longer than control cells. Collectively, these data suggest that P21 activation may provide an attractive therapeutic target to improve therapeutic outcomes.

Hox genes represent an important gene family that is involved in the segmentation pattern and identity of the segments during the formation of the body plan in metazoans. For many years, several studies have sought to establish a correlation between the evolution of these genes and the evolution of large groups of metazoans. Here, we use publicly available sequences of Hox gene clusters to reconstruct the evolutionary history of anterior Hox genes. We show that information harbored by these genes, in part, reflects the evolution and diversification of most animal archetypes, but in many cases, there were conflicts between the evolutionary history of some genes and the history of large groups, these cases may have occurred due to specific and similar selective pressures in relatively distant groups, which may have led to evolutionary convergences. Our findings also reveal that the evolution of Hox genes (and clusters) as a multigene family is consistent to a birth-and-death model constrained by development, where there is a trade-off between a relatively fast gene turnover and their central developmental roles

Excessive activation of frog eggs, so called overactivation, can be initiated by strong oxidative stress, leading to expedited calcium-dependent non-apoptotic cell death. Overactivation also occurs spontaneously, albeit with a low frequency, in natural populations of spawned frog eggs. Currently, cytological and biochemical events of the spontaneous process are not characterized. In the present study, we demonstrate that spontaneous overactivation of Xenopus frog eggs, similarly to oxidative stress- and mechanical stress-induced overactivation, is characterized by the fast and irreversible contraction of the egg’s cortical layer, increase in the egg size, depletion of intracellular ATP, drastic increase in the intracellular ADP/ATP ratio, and degradation of M phase-specific cyclin B2. These events manifest in eggs in the absence of caspase activation within just one hour of triggering overactivation. Importantly, large amounts of ATP and ADP leak from the overactivated eggs, indicating that plasma membrane integrity is compromised in these cells. The rapture of the plasma membrane and acute depletion of intracellular ATP define explicitly necrotic cell death. Finally, we report that egg overactivation can occur in the frog’s genital tract. Our data argue that mechanical stress may be a key factor promoting egg overactivation during natural spawning in frogs.

Fire-related deaths are issues for forensic pathologists particularly in ascertaining if death occurred before or during fire. The authors highlight a unique bronchiolar epithelial cytological clue (nuclear heat-induced elongation) determined by active inhalation of hot gases and fumes, not yet described in the literature at distal small airways level.

In the paper, we measure the digital financial inclusion index of 31 provinces in China from 2011 to 2020 based on three dimensions: coverage breadth, depth of use and digitalization degree. By means of weighted Dagum Gini coefficient and quantile standardization, we explored the degree of imbalance and insufficiency of the development of digital inclusive finance in China and four major regions and its structural causes. Using Kernel density estimation method and Markov chain analysis method, we further investigates the evolution trend of imbalance and insufficiency. The study finds that (1) the Digital Inclusive Financial Index in China and the four major regions rise significantly, with the COVID-19 epidemic reducing its growth rate. Of these, the eastern region has the highest development level. (2) The imbalance level of digital inclusive finance development obviously has reduced. The level of imbalance is highest within the eastern region, and the development gap between the eastern and western regions is the widest. The imbalance of overall development is mainly due to the regional imbalance. The imbalance of coverage breadth and depth of use is the main structural cause of unbalanced development in the four major regions. There is a trend of bipolarization or multipolarization in China and the other three major regions, with the exception of the central region. (3) The western region is the least developed. The development shortcoming of digital inclusive finance in China and the four major regions is the breadth of coverage. There are "Club Convergence" and "Matthew Effect" in the eastern, central and western regions.

Extramedullary hematopoiesis is a compensatory response in chronic hemolytic anemia, such as thalassemia, and can lead to spinal cord compression. This case report describes a 36-year-old woman with β-thalassemia who presented with lower extremity motor deficiency, pelvic paresthesia, and bladder dysfunction. The patient had a history of low back pain, bilateral lower limb weakness, and poor compliance with iron chelation therapy. MRI revealed compression of the spinal cord due to extramedullary hematopoiesis. Surgical intervention was not feasible, and the patient underwent hypertransfusion and iron chelation therapy. Neurological symptoms improved, but urinary retention persisted. The patient continues to receive iron chelation treatment and undergoes transfusions. Extramedullary hematopoiesis is a common complication in thalassemia and requires an individualized treatment approach.

The vacuolar H+-ATPase is a multisubunit enzyme which plays an essential role in the acidification and functions of lysosomes, endosomes, and synaptic vesicles. Many genes encoding subunits of V-ATPases, namely ATP6V0C, ATP6V1A, ATP6V0A1 and ATP6V1B2, have been associated with neurodevelopmental disorders and epilepsy. The autosomal dominant ATP6V1B2 p.Arg506* variant can cause both deafness, congenital, with onychodystrophy, autosomal dominant (DDOD) and deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndromes (DOORS). Some but not all individuals with this truncating variant have intellectual disability and/or epilepsy, suggesting incomplete penetrance and/or variable expressivity. To further explore the impact of the p.Arg506* variant in neurodevelopment and epilepsy, we generated Atp6v1b2emR506* mutant mice and performed standardized phenotyping using the International Mouse Phenotyping Consortium (IMPC) pipeline. In addition, we assessed the EEG profile and seizure susceptibility of Atp6v1b2emR506* mice. Behavioral tests revealed that the mice present locomotor hyperactivity and show less anxiety-associated behaviors. Moreover, EEG analyses indicate that Atp6v1b2emR506* mutant mice have interictal epileptic activity and that both heterozygous (like patients) and homozygous mice have reduced seizure thresholds to pentylenetetrazol. Our results confirm that variants in ATP6V1B2 can cause seizures and that the Atp6v1b2emR506* heterozygous mouse model is a valuable tool to further explore the pathophysiology and potential treatments for vacuolar ATPases-associated epilepsy and disorders.

Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data show that Aldh2+/- mice exhibits impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in CoQ biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.

The fate of a viral infection in the host begins with various types of cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, and pyroptosis are the three major types of regulated cell death mechanisms that play critical roles in viral infection response. Cell shrinkage, nuclear condensation, bleb formation, and retained membrane integrity are all signs of osmotic imbalance-driven cytoplasmic swelling and early membrane damage in necroptosis and pyroptosis. Caspase-driven apoptotic cell demise is considered in many circum-stances as an anti-inflammatory, and some pathogens hijack the cell death signaling routes to initiate a targeted attack against the host. In this review, we selected mechanisms by which viruses interfere with cell death are discussed in-depth and are used to illustrate the general principles and cellular signaling mechanisms of virus-host specific molecule interactions.

Background: New controversies have raised on brain death (BD) diagnosis when lesions are localized in the posterior fossa. Objective: To discuss the particularities of diagnosis BD in patients with posterior fossa lesions. Material and Methods. The author made a systematic review of literature on this topic. Results and Conclusions: A supratentorial brain lesion usually produces a rostrocaudal transtentorial brain herniation, resulting in forebrain and brainstem loss of function. In secondary brain lesions [i.e., cerebral hypoxia], the brainstem is also affected like the forebrain. Nevertheless, some cases complaining posterior fossa lesions [i.e., basilar artery thrombotic infarcts, or hemorrhages of the brainstem and/or cerebellum] may retain intracranial blood flow and EEG activity. In this article I discuss that if a posterior fossa lesion does not produce an enormous increment of intracranial pressure, a complete intracranial circulatory arrest does not occur, explaining the preservation of EEG activity, evoked potentials, and autonomic function. I also address Jahi McMath, who was declared braindead, but ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to “Mother Talks” stimulus, rejecting the diagnosis of BD. Jahi McMath’s MRI study demonstrated a huge lesion in the pons. Some authors have argued that in patients with primary brainstem lesions it might be possible to find a in some cases partial recover of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath.

Despite significant milestones in armed conflict research generally and climate security research specifically, methodologically tight explanation of naturally caused armed conflict still leaves much to be desired. In this article we unpack the black box of the climate-security nexus and advance causal modelling of armed conflict. To infer effects of natural causes on armed conflict outcomes, we apply recent advances in causal methods to conflict outcomes that have been non-experimentally observed across Iraqi municipalities. Retrieval of an entire empirical causal structure of climate-conflict pathways allows us to corroborate the existence of a cause-and-effect relationship between climatological, environmental, and demographic variables and armed conflict. We confirm that soil temperature, population density, and variability of latent energy cause an increase in fatalities, while rice production decreases fatalities. We discuss our findings, their limitations, and future research directions, and reflect on their relevance for policy interventions.

Abstract. The remarks by the Supreme Leader of the Islamic Revolution on the toll of the famines that afflicted occupied Iran in World War I and World War II indicate a desire to incorporate these calamities in Iran’s national narrative and collective memory. His criticism of famine historiography and stated toll numbers, and the unfolding catastrophic famine in Gaza, justify and necessitate a fresh look at each famine’s historiography and toll. This article re-estimates the toll of each famine by including many overlooked and neglected primary sources and in ways not previously done. It builds a trajectory of Iran’s demographic development from 1810 to 1944, and derives the toll of each famine. The World War II famine and typhus epidemics had claimed 5.5 million. World War I famine was also more deadly, though the 1869-73 famine was not far behind. At least 15.5 million Iranians died in the two world wars, a fact nowhere reflected in the history of the conflicts. Iran’s 1944 population of 12 million was unchanged from that of 1850 and a century of population growth obliterated

More than fifty million people over the age of fifty have osteoporosis issues due to low bone mass, disease contribution, and not exercising continuously. Certain most important risk factors and causes of osteoporosis contain age, gender, hormones, visits to inexperienced doctors, and certain medical conditions. In this manuscript, we diagnosed certain frank operational laws under the availability of complex intuitionistic fuzzy (CIF) information. Furthermore, using the evaluated operational laws, we pioneered the theory of CIF frank weighted averaging (CIFFWA), CIF frank ordered weighted averaging (CIFFOWA), CIF frank hybrid averaging (CIFFHA), CIF frank weighted geometric (CIFFWG), CIF frank ordered weighted geometric (CIFFOWG), CIF frank hybrid geometric (CIFFHG) operators, and described their beneficial and valuable results with certain useful properties. Moreover, we aim to evaluate the most dangerous type of osteoporosis based on their symptoms, causes, and risk factors using diagnosed approaches. Finally, to enhance the worth of the evaluated operators, we compare the diagnosed result with certain prevailing results and illustrated their geometrical representation with the help of MATLAB.

Environment pollution is one of the major problem that faces by our civilization . Textile industry is one of the factor for pollute the environment. In this study various causes that occurs by textile industry and pollute the environment will be shown and described. In textile industry for energy to run the factory various kind of fuel are used and in the industry there are many chemicals and dyes are used for the textile products. Plastic is one of the main substance for making the synthetic fabric. They pollute the air, water, soil and also they pollute the ecosystem of the various animals and destroy the ozone surface of the earth. For various kind of pollution that causes by textile industry the life of normal life hampered. They got ill and many time men and women lost their organs and sometimes they got attacked by various life taking illness.

Dysfunction and selective loss of retinal ganglion cells (RGCs) is a known cause of vision loss in glaucoma and other neuropathies where ocular hypertension (OHT) is the major risk factor. We investigated the impact of transient non-ischemic OHT spikes (spOHT) on RGC function and viability in vivo to identify cellular pathways linking low-grade repetitive mechanical stress to RGC pathology. We found that repetitive spOHT had an unexpectedly high impact on intraocular homeostasis and RGC viability, while exposure to steady OHT (stOHT) of similar intensity and duration failed to induce pathology. The repetitive spOHT induced a rapid activation of the inflammasome, marked by the upregulation of NLRP1, NLRP3, AIM2, caspases -1, -3/7, -8, gasdermin D (GsdmD) and the release of interleukin-1β (IL-1β) and other cytokines into the vitreous. Similar effects were also detected after 5 weeks of exposure to chronic OHT in an induced glaucoma model. The onset of these immune responses in both spOHT and glaucoma models preceded a 50% deficit in pattern electroretinograms (PERG) amplitude, and significant loss of RGCs at 7 days post-injury. Inactivation of inflammasome complexes in NLRP1-/- , Casp1-/- and GsdmD-/- knockout animals, significantly suppressed the spOHT induced inflammatory response and protected RGCs. Our results demonstrate that mechanical stress produced by acute repetitive spOHT or chronic OHT is mechanistically linked to inflammasome activation, which leads to RGC dysfunction and death.