Exploring the inhibitory potential of phytochemicals from Vernonia glaberrima leaves against snake venom toxins through computational simulation and experimental validation.

Phospholipase A2 (PLA2) is an enzyme present in appreciable quantity in snake venoms which catalyze the hydrolysis of glycerophospholipids at sn-2 position and promote the release of lysophospholipids and fatty acids. 5-methylcoumarin-4-ß-glucoside (5MC4BG) and lupeol were previously isolated from the leaves of V. glaberrima. The aim of this research was to evaluate effect of these compounds as potential inhibitors of snake venom toxins of Naja nigricollis using an in vitro and in silico studies. Antisnake venom studies was conducted using acidimetry while the molecular docking analysis against PLA2 enzyme from N. nigricollis was performed using Auto Dock Vina and ADME-Tox analysis was evaluated using swissADME and ProTox-II online servers. The two compounds (5MC4BG and Lupeol) were able to inhibit the hydrolytic actions of PLA2 enzyme with percentage inhibition ranging from 23.99 to 72.36 % and 21.97-24.82 % at 0.0625-1.00 mg/mL respectively while the standard ASV had 82.63 % at 1.00 mg/mL after 10 min incubation at 37 °C. Similar effects were observed after 30 min incubation, although there was significant increase in percentage inhibition of 5MC4BG and lupeol ranging from 66.51 to 83.73 % and 54.87-59.60 % at similar concentrations. Furthermore, the compounds were able to bind to the active site of PLA2 enzyme with high affinity (-7.7 to -6.3 kcal/mol); the standard ligand, Varespladib had a docking score of -6.9 kcal/mol and they exhibited favorable drug-likeness and pharmacokinetic properties and according to toxicity predictions, the two compounds are toxic. In conclusion, the leaf of V. glaberrima contains phytoconstituents with antisnake activity and thus, validates the hypothesis that, the phytoconstituents of V. glaberrima leaves has antisnake venom activity against N. nigricollis venom and thus, should be studied further for the development as antisnake venom agents.

Darier-Roussy Subcutaneous Sarcoidosis Masquerading as Multiple Abscesses: A Report of a Rare Case.

Sarcoidosis is an idiopathic multisystemic granulomatous disease that mainly affects the lungs. Darier-Roussy subcutaneous sarcoidosis is among the specific and least encountered skin manifestations of sarcoidosis. In this case study, we report how subcutaneous sarcoidosis could mimic multiple abscesses presentation and hinder reaching a definitive diagnosis. A 65-year-old female presented with five, multiple, deep-seated skin lesions on the forearm, chest, and scalp. The lesions showed redness and tenderness. The patient also experienced arthralgia in the right ankle. Laboratory workup of the patient showed a high erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell (WBC) count. The patient was suspected to have multiple abscesses, which were managed with antibiotics with no response. Thus, a computed tomography (CT) scan of the chest was done and showed mediastinal lymphadenopathy. A biopsy was taken from one of the right forearm skin lesions, and it revealed characteristic features consistent with sarcoidosis. The patient was managed with hydroxychloroquine and a tapering dose of prednisone. Therefore, subcutaneous sarcoidosis should be included in the differential diagnosis of subcutaneous lumps.

Treatment response amplitude and timing in chronic inflammatory demyelinating polyneuropathy with routine care: Study of a UK cohort.

BACKGROUND AND PURPOSE: The amplitude, timing, and determinants of improvement with available treatments are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). Our primary objective was to quantify categorized outcomes with routine care. METHODS: We retrospectively studied treatment response within 36 months from initiation in 112 consecutive subjects with CIDP. Response was classified into a proposed new "CIDP treatment-response category" (CT-RC), based on achieved endpoints. Determinants of the CT-RC, of timing of maximum improvement, and of treatment discontinuation were ascertained. RESULTS: The CT-RC demonstrated high concurrent validity with current outcome measures. Thirty-six subjects (32.1%) achieved a "complete response," 37 (33%) a "good partial response," 10 (8.9%) a "moderate partial response," and 15 (13.4%) a "poor partial response." Fourteen subjects (12.5%) were "nonresponsive." The CT-RC was independently predicted only by age. Mean time to maximum improvement was 12.1 months (range = 1-36) and was not associated with any pretreatment covariate. Treatment discontinuation occurred in 24 of 62 (38.2%) partial responders and was only associated with shorter pretreatment disease duration. Nonresponders were older and received a similar number of treatments compared to responders. CONCLUSIONS: CT-RC classification indicates persistent disability in >60% of treatment responders in CIDP. Timing of maximum improvement is variable, frequently delayed, and unpredictable. Treatment withdrawal without deterioration is achievable in approximately 40% of subjects and may be more likely with prompt treatment. Treatment withdrawal in partial responders and limited escalation in nonresponders suggest implication of physician- and patient-related factors in suboptimal response. More effective treatments/treatment methods and better understanding of other factors influencing response are needed in CIDP.

Electrodiagnostic subtyping in Guillain-Barré syndrome patients in the International Guillain-Barré Outcome Study.

BACKGROUND AND PURPOSE: Various electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. METHODS: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. RESULTS: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. CONCLUSIONS AND DISCUSSION: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.

An assessment of priorities in handling climate change impacts on infrastructures.

Climate change (CC) will likely significantly impact the world's infrastructure significantly. Rising temperatures, increased precipitation, and rising sea levels are all likely to stress critical infrastructures (CI). Rising temperatures can lead to infrastructure damage from extreme heat events. This can cause roads and bridges to buckle or crack, leading to costly repairs and potential traffic disruptions. In addition, heat waves can damage vital electrical infrastructure, leading to widespread power outages. In light of this context, this article reports on a study which examined the connections and impacts of CC on infrastructure. The study employed a mixed-method approach, combining bibliometric analysis for the period 1997-2022 with a series of relevant case studies from the five continents to offer insight into the impact of CC on infrastructure. The article fills a research gap in respect of assessments of the extent to which climate change (CC) negative influences the infrastructure, with a special focus on developing countries. It also showcases CI projects and adaptation measures being currently deployed, to address CC. The results show that the current infrastructure is vulnerable to CC. The selected case studies on CI adaptation show that in developing and industrialised countries, there is a perceived need to understand better the connections and potential impacts of CC on critical areas such as transport, settlements, and coastal infrastructure. In order to protect infrastructure from CC impacts, governments need to invest in measures such as flood control, early warning systems, and improved building codes. Additionally, they need to work to reduce greenhouse gas emissions more actively, which are the primary cause of CC.

A comprehensive measure of Golgi sphingolipid flux using NBD C6-ceramide: evaluation of sphingolipid inhibitors.

Measurements of sphingolipid metabolism are most accurately performed by LC-MS. However, this technique is expensive, not widely accessible, and without the use of specific probes, it does not provide insight into metabolic flux through the pathway. Employing the fluorescent ceramide analogue NBD-C6-ceramide as a tracer in intact cells, we developed a comprehensive HPLC-based method that simultaneously measures the main nodes of ceramide metabolism in the Golgi. Hence, by quantifying the conversion of NBD-C6-ceramide to NBD-C6-sphingomyelin, NBD-C6-hexosylceramides, and NBD-C6-ceramide-1-phosphate (NBD-C1P), the activities of Golgi resident enzymes sphingomyelin synthase 1, glucosylceramide synthase, and ceramide kinase (CERK) could be measured simultaneously. Importantly, the detection of NBD-C1P allowed us to quantify CERK activity in cells, a usually difficult task. By applying this method, we evaluated the specificity of commonly used sphingolipid inhibitors and discovered that 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, which targets glucosylceramide synthase, and fenretinide (4HPR), an inhibitor for dihydroceramide desaturase, also suppress CERK activity. This study demonstrates the benefit of an expanded analysis of ceramide metabolism in the Golgi, and it provides a qualitative and easy-to-implement method.

Prevalence and determinants of moderate-to-severe anaemia in the third trimester of pregnancy: a multicenter cross-sectional study in Lagos, Nigeria.

The high burden of anaemia during pregnancy underscores the urgent need to gain a comprehensive understanding of the factors contributing to its widespread occurrence. Our study assessed the prevalence and the trends of moderate-to-severe anaemia (MSA) in late pregnancy (28 to 36 weeks) and then investigated the key determinants driving this prevalence among women in Lagos, Nigeria. We conducted a secondary data analysis involving 1216 women enrolled in the Predict-PPH study between January and March 2023. We employed a multivariate binary logistic regression model with a backward stepwise selection approach to identify significant predictors of MSA. The study revealed a 14.5% prevalence of MSA during pregnancy. Independent predictors of MSA included having given birth to two or more children (adjusted odds ratio = 1.46, 95% confidence interval: 1.03-2.07), having a maternal body mass index (BMI) of 28 kg/m2 or higher (adjusted odds ratio = 1.84, 95% confidence interval: 1.29-2.61), having less than tertiary education (adjusted odds ratio = 1.51, 95% confidence interval: 1.08-2.11), and being unemployed (adjusted odds ratio = 1.97, 95% confidence interval: 1.19-3.26). It is crucial for pregnant women, particularly those with higher parities and elevated BMI, to be monitored regularly for anaemia and its consequences during their antenatal care. Additionally, addressing the link between low education, unemployment, and anaemia necessitates comprehensive strategies that empower women in terms of education and economic status to enhance the overall well-being of individuals and communities, ultimately reducing the prevalence of anaemia and associated health issues in pregnancy.

The Role of the Insula in Chronic Pain and Associated Structural Changes: An Integrative Review.

Chronic pain affects a substantial portion of the global population, significantly impacting quality of life and well-being. This condition involves complex mechanisms, including dysfunction of the autonomic nervous system, which plays a crucial role in pain perception. The insula, a key brain region involved in pain processing, plays a critical role in pain perception and modulation. Lesions in the insula can result in pain asymbolia, where pain perception remains intact but emotional responses are inappropriate. The insula is anatomically and functionally divided into anterior and posterior regions, with the posterior insula processing nociceptive input based on intensity and location before relaying it to the anterior insula for emotional mediation. Understanding the insula's intricate role in pain processing is crucial, as it is involved in encoding prediction errors and mediating emotional dimensions of pain perception. The focus of this review was on synthesizing existing literature on the role of the insula in chronic pain and associated structural changes. The goal was to integrate findings from various sources to provide a comprehensive overview of the topic. The search strategy included a combination of Medical Subject Headings (MeSH) and relevant keywords related to insula and chronic pain. The following databases were surveyed: PubMed, Embase, Scopus, and Web of Science. We identified a total of 2515 articles, and after following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline based on eligibility criteria, 46 articles were used to synthesize this review. Our study highlights the pivotal role of the insula in chronic pain processing and associated structural changes, integrating findings from diverse studies and neuroimaging investigations. Beyond mere pain sensation, the insula contributes to emotional awareness, attention, and salience detection within the pain network. Various chronic pain conditions reveal alterations in insular activity and connectivity, accompanied by changes in gray matter volume and neurochemical profiles. Interventions targeting the insula show promise in alleviating chronic pain symptoms. However, further research is needed to understand underlying mechanisms, which can aid in developing more effective therapeutic interventions for pain.

Pericardial Diseases Mortality Trends in Brazil From 2000 to 2022.

Background Pericardial diseases manifest in various clinical forms, including acute pericarditis, constrictive pericarditis, pericardial effusion, and cardiac tamponade, with acute pericarditis being the most prevalent. These conditions significantly contribute to mortality rates. Therefore, this article aimed to analyze mortality trends in the Brazilian population based on age and sex, shedding light on the impact of pericardial diseases on public health outcomes. Methods  This is a retrospective time-series analysis of pericardial disease mortality rates in Brazil (2000-2022). Data was obtained from the Department of Informatics of the Unified Health System (DATASUS), and the 10th edition of the International Classification of Diseases (ICD-10) codes: I30, I31, and I32 were included for analysis. We gathered population and demographic data categorized by age range and sex from the Brazilian Institute of Geography and Statistics (IBGE). Subsequently, we computed the age-standardized mortality rate per 100,000 individuals and assessed the annual percentage changes (APCs) and average annual percentage changes (AAPCs) using joinpoint regression, along with their corresponding 95% confidence intervals (CIs). Results  In terms of mortality trends based on sex, overall mortality rates remained stable for males and combined sexes over the study period. However, there was a notable increase in mortality rates among females (AAPC=1.18), particularly between 2020 and 2022, with a significant APC of 27.55. Analyzing pericardial diseases across different age groups (20 to 80 years and above), it wasobserved that mortality rates significantly increased in the 70-79 and 80 years and above age groups throughout the study period (AAPC=1.0339 and AAPC=3.4587, respectively). These two age groups experienced the highest significant rise in mortality between 2020 and 2022. Other age groups did not exhibit a significant change in AAPC. Conclusions  This comprehensive analysis spanning two decades (2000-2022), examined the mortality trends of pericardial diseases in Brazil and revealed relative stability overall. Males exhibited an overall higher mortality number due to pericardial diseases; however, females showed the most significant increase in mortality trend throughout the whole period. In the first segment (2000-2015), mortality rose across all cohorts, which was attributed to substandard healthcare facilities and infectious diseases like tuberculosis. The second segment (2016-2020) saw a decline in mortality, likely due to improved healthcare, particularly the increased availability of echocardiograms. However, the third segment (2020-2022) witnessed a sharp rise in mortality, coinciding with the COVID-19 pandemic, with post-COVID-19 symptoms, particularly pericarditis. Pericarditis-related death rates declined compared to pericardial effusion, and mortality rates correlated directly with age, with older cohorts experiencing higher mortality due to increased comorbidities, and decline in health and immunocompetency.

Lower Third Leg Trauma Management Algorithm; Kasr Alainy Protocol.

Background: Soft tissue defects in the lower third of the leg present significant challenges for surgeons. Despite various options available for soft tissue coverage, selecting the most suitable option is limited by potential complications. In response to this challenge, some surgeons have sought to develop algorithms to guide decision-making in the management of lower leg trauma. Methods: This prospective observational cross-sectional study included 53 patients with traumatic injuries to the lower third leg and ankle regions. Each patient underwent a management plan based on our proposed algorithm, which incorporated the utilization of negative pressure wound therapy and dermal substitutes. Outcomes were assessed in terms of the ability to achieve complete coverage, complication rates, duration of hospital stay, and return to normal daily activity. Results: The proposed algorithm proved to be comprehensive and easily applicable, achieving complete coverage in 98.1% of cases. The mean duration for definitive coverage was 21.89 ±â€…12.84 days, and the majority of cases (81.1%) returned to normal daily activity within a mean duration of 60.69 ±â€…56.7 days. The use of dermal substitutes resulted in achieving coverage in wounds with exposed structures, with favorable outcomes in cases with a mean size of 11.39 ±â€…10.05 cm². Conclusions: Our algorithm provides a safe and effective approach to manage traumatic defects of the lower third leg and ankle, considering the patient's general condition and the complexity of the wound. Proper utilization of dermal substitutes and negative pressure wound therapy is emphasized in the algorithm.

Integrated management of groundwater quantity, physicochemical properties, and microbial quality in West Nile delta using a new MATLAB code and geographic information system mapping.

Groundwater is an excellent alternative to freshwater for drinking, irrigation, and developing arid regions. Agricultural, commercial, industrial, residential, and municipal activities may affect groundwater quantity and quality. Therefore, we aimed to use advanced methods/techniques to monitor the piezometric levels and collect groundwater samples to test their physicochemical and biological characteristics. Our results using software programs showed two main types of groundwater: the most prevalent was the Na-Cl type, which accounts for 94% of the groundwater samples, whereas the Mg-Cl type was found in 6% of samples only. In general, the hydraulic gradient values, ranging from medium to low, could be attributed to the slow movement of groundwater. Salinity distribution in groundwater maps varied between 238 and 1350 mg L-1. Although lower salinity values were observed in northwestern wells, higher values were recorded in southern ones. The collected seventeen water samples exhibited brackish characteristics and were subjected to microbial growth monitoring. Sample WD12 had the lowest total bacterial count (TBC) of 4.8 ± 0.9 colony forming unit (CFU mg L-1), while WD14 had the highest TBC (7.5 ± 0.5 CFU mg L-1). None of the tested water samples, however, contained pathogenic microorganisms. In conclusion, the current simulation models for groundwater drawdown of the Quaternary aquifer system predict a considerable drawdown of water levels over the next 10, 20, and 30 years with the continuous development of the region.

Predictive models for short-term load forecasting in the UK's electrical grid.

There are global efforts to deploy Electric Vehicles (EVs) because of the role they promise to play in energy transition. These efforts underscore the e-mobility paradigm, representing an interplay between renewable energy resources, smart technologies, and networked transportation. However, there are concerns that these initiatives could burden the electricity grid due to increased demand. Hence, the need for accurate short-term load forecasting is pivotal for the efficient planning, operation, and control of the grid and associated power systems. This study presents robust models for forecasting half-hourly and hourly loads in the UK's power system. The work leverages machine learning techniques such as Support Vector Regression (SVR), Artificial Neural Networks (ANN), and Gaussian Process Regression (GPR) to develop robust prediction models using the net imports dataset from 2010 to 2020. The models were evaluated based on metrics like Root Mean Square Error (RMSE), Mean Absolute Prediction Error (MAPE), Mean Absolute Deviation (MAD), and the Correlation of Determination (R2). For half-hourly forecasts, SVR performed best with an R-value of 99.85%, followed closely by GPR and ANN. But, for hourly forecasts, ANN led with an R-value of 99.71%. The findings affirm the reliability and precision of machine learning methods in short-term load forecasting, particularly highlighting the superior accuracy of the SVR model for half-hourly forecasts and the ANN model for hourly forecasts.

Mental Health Burden and Facilitators Among Frontline Healthcare Professionals in Nigeria Amid COVID-19 Pandemic: A Cross-sectional Study.

BACKGROUND: During the COVID-19 pandemic, the frontline healthcare providers faced significant mental health stressors. Previous pandemics have revealed the need for psychosocial support and healthy coping mechanisms to mitigate mental health risks. AIM: The study aimed to assess psychological impact and supportive mechanisms experienced by frontline healthcare workers treating COVID-19 patients in Kaduna State. METHODS: This study involved 38 frontline healthcare providers mainly from Kaduna State Infectious Disease Treatment Center. Participants' mental health burden was captured through Hospital Anxiety and Depression Scale. Mental health facilitators were assessed through six tools: Ten-Item Values Inventory, healthy defense section of the Defense Style Questionnaire, Existential Anxiety Questionnaire, Brief Resilience Scale, Oslo Social Support Scale, and the Insomnia Severity Index. RESULTS: The mean age of the study participants was 35.5 ± 6.6 years, with the majority being males (68.4%) and doctors (39.5%). More than a quarter of the participants showed appreciable symptoms of depression and anxiety. Psychosocial facilitators such as moral values, openness to change, self-transcendence, sublimation, anticipation, and humor scored above average for more than half of the participants. Most participants demonstrated moderate resilience and social support, with few experiencing sleep challenges. Comparisons of variables indicated "openness to change" was significantly higher among males, whereas symptoms of depression and anxiety were associated with higher levels of existential concerns and sleep challenges. CONCLUSION: Our study finds that Nigerian frontline health workers experienced significant mental health challenges during the COVID-19 pandemic. It identified specific facilitators linked to gender and psychological burdens, informing the need for tailored support interventions.

Prenatal anaemia and risk of postpartum haemorrhage: a cohort analysis of data from the Predict-PPH study.

BACKGROUND: Most previous clinical studies investigating the connection between prenatal anaemia and postpartum haemorrhage (PPH) have reported conflicting results. OBJECTIVES: We examined the association between maternal prenatal anaemia and the risk of PPH in a large cohort of healthy pregnant women in five health institutions in Lagos, Southwest Nigeria. METHODS: This was a prospective cohort analysis of data from the Predict-PPH study that was conducted between January and June 2023. The study enrolled n = 1222 healthy pregnant women giving birth in five hospitals in Lagos, Nigeria. The study outcome, WHO-defined PPH, is postpartum blood loss of at least 500 milliliters. We used a multivariable logistic regression model with a backward stepwise conditional approach to examine the association between prenatal anaemia of increasing severity and PPH while adjusting for confounding factors. RESULTS: Of the 1222 women recruited to the Predict-PPH study between January and June 2023, 1189 (97·3%) had complete outcome data. Up to 570 (46.6%) of the enrolled women had prenatal anaemia while 442 (37.2%) of those with complete follow-up data had WHO-defined PPH. After controlling for potential confounding factors, maternal prenatal anaemia was independently associated with PPH (adjusted odds ratio = 1.37, 95% confidence interval: 1.05-1.79). However, on the elimination of interaction effects of coexisting uterine fibroids and mode of delivery on this association, a sensitivity analysis yielded a lack of significant association between prenatal anaemia and PPH (adjusted odds ratio = 1.27, 95% confidence interval: 0.99-1.64). We also recorded no statistically significant difference in the median postpartum blood loss in women across the different categories of anaemia (P = 0.131). CONCLUSION: Our study revealed that prenatal anaemia was not significantly associated with PPH. These findings challenge the previously held belief of a suspected link between maternal anaemia and PPH. This unique evidence contrary to most previous studies suggests that other factors beyond prenatal anaemia may contribute more significantly to the occurrence of PPH. This highlights the importance of comprehensive assessment and consideration of various maternal health factors in predicting and preventing this life-threatening obstetric complication.

Deciphering the interactions of scopoletin and scopolin from Catunaregam nilotica roots against Naja nigricollis phospholipase A2 enzyme.

Catuneragam nilotica has been used in ethnomedicine to treat snakebite, inflammation, and diarrhea among others. The aim of this research is to isolate, and characterize potential potential phospholipase A2 (PLA2) inhibitors from the roots of C. nilotica. The plant material was collected, authenticated, and sequentially extracted using solvents of increasing polarity starting from n-hexane, ethyl acetate, and methanol. The extracts as reported in our previous work, were screened in vitro for their inhibitory activity against PLA2 enzyme from N. nigricollis venom using acidimetric assay. In line with the bio-activity guided isolation, methanol extract (being the most active) was subjected to chromatographic separation using silica gel and sephadex LH-20 which resulted in the isolation and characterization of scopoletin, and scopolin; the compounds were able to inhibit the hydrolytic actions of PLA2 enzyme with percentage inhibition ranging from 67.82 to 100.00 % and 65.76-93.15 %, respectively while the standard Antisnake Venom (ASV) had 74.96-85.04 % after 10 min incubation at 37 °C. The molecular docking of the compounds against PLA2 enzyme was performed using Auto Dock Vina while ADME-Tox analysis was evaluated using swissADME and ProTox-II online servers; The findings indicated that both compounds were able to bind to the active site of PLA2 enzyme with high affinity (-6.5 to -6.2 kcal/mol) and they exhibited favorable drug-likeness and pharmacokinetic properties, and according to toxicity predictions, scopolin was found to be non-toxic (LD50 of 5000 mg/kg) while scopoletin has a slight chance of being toxic (LD50 of 3800 mg/kg). In conclusion, the findings of the research revealed that the roots of C. nilotica contains phytoconstituents with anti-PLA2 enzyme activity and thus, validates the ethnomedicinal claim of the use of the plant as herbal therapy against N. nigricollis envenomation.

New additions to the crabronid fauna of the Arabian Peninsula and Saudi Arabia (Hymenoptera: Apoidea (Spheciformes): Crabronidae), new distribution records and new species.

The present study is based on specimens collected in coffee orchards on the mountains in the Jazan Province (southwestern Saudi Arabia) using Malaise traps. The genera Carinostigmus Tsuneki, 1954, and Polemistus de Saussure, 1892 are first recorded for the Arabian Peninsula, each with a single species. Three new species: Bembecinus similis Gadallah & Edmardash, Crossocerus arabicus Gadallah & Edmardash, and Oxybelus coffeae Edmardash & Gadallah are described and illustrated. The previously unknown female of Nysson ohli (Schmid-Egger 2011) (UAE) is discovered, described and illustrated.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Current Therapeutic Approaches and Future Outlooks.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable autoimmune disorder, for which different treatment options are available. Current first-line evidence-based therapies for CIDP include intravenous and subcutaneous immunoglobulins, corticosteroids and plasma exchanges. Despite lack of evidence, cyclophosphamide, rituximab and mycophenolate mofetil are commonly used in circumstances of refractoriness and, more debatably, of perceived overdependence on first-line therapies. Rituximab is currently the object of a randomized controlled trial for CIDP. Based on case series, and although rarely considered, haematopoietic autologous stem cell transplants may be effective in refractory disease, with low mortality and high remission rates. A new therapeutic option has appeared with efgartigimod, a neonatal Fc receptor blocker, recently shown to significantly lower relapse rate versus placebo, after withdrawal from previous immunotherapy. Other neonatal Fc receptor blockers, nipocalimab and batoclimab, are under study. The C1 complement-inhibitor SAR445088, acting in the proximal portion of the classical complement system, is currently the subject of a new study in treatment-responsive, refractory and treatment-naïve subjects. Finally, Bruton Tyrosine Kinase inhibitors, which exert anti-B cell effects, may represent another future research avenue. The widening of the therapeutic armamentarium enhances the need for improved evaluation of treatment effects and reliable biomarkers in CIDP.

Characterisation of colistin resistance in Gram-negative microbiota of pregnant women and neonates in Nigeria.

A mobile colistin resistance gene mcr was first reported in 2016 in China and has since been found with increasing prevalence across South-East Asia. Here we survey the presence of mcr genes in 4907 rectal swabs from mothers and neonates from three hospital sites across Nigeria; a country with limited availability or history of colistin use clinically. Forty mother and seven neonatal swabs carried mcr genes in a range of bacterial species: 46 Enterobacter spp. and single isolates of; Shigella, E. coli and Klebsiella quasipneumoniae. Ninety percent of the genes were mcr-10 (n = 45) we also found mcr-1 (n = 3) and mcr-9 (n = 1). While the prevalence during this collection (2015-2016) was low, the widespread diversity of mcr-gene type and range of bacterial species in this sentinel population sampling is concerning. It suggests that agricultural colistin use was likely encouraging sustainment of mcr-positive isolates in the community and implementation of medical colistin use will rapidly select and expand resistant isolates.

A ticket to where? Dwindling snow cover impacts the winter tourism sector as a consequence of climate change.

Climate change affects human activities, including tourism across various sectors and time frames. The winter tourism industry, dependent on low temperatures, faces significant impacts. This paper reviews the implications of climate change on winter tourism, emphasising challenges for activities like skiing and snowboarding, which rely on consistent snowfall and low temperatures. As the climate changes, these once taken-for-granted conditions are no longer as commonplace. Through a comprehensive review supported by up-to-date satellite imagery, this paper presents evidence suggesting that the reliability of winter snow is decreasing, with findings revealing a progressive reduction in snow levels associated with temperature and precipitation changes in some regions. The analysis underscores the need for concerted efforts by stakeholders who must recognize the reality of diminishing snow availability and work towards understanding the specific changes in snow patterns. This should involve multi-risk and multi-instrument assessments, including ongoing satellite data monitoring to track snow cover changes. The practical implications for sports activities and the tourism industry reliant on snow involve addressing challenges by diversifying offerings. This includes developing alternative winter tourism activities less dependent on snow, such as winter hiking, nature walks, or cultural experiences.

Neutral Sphingomyelinase 2 Inhibition Limits Hepatic Steatosis and Inflammation.

Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear. Here, we report studies that address this question. After 14 weeks on a high-fat diet (HFD) with high sucrose, C57BL/6 mice revealed a phenotype of liver steatosis. Transcriptional profiling analysis of the liver tissues was performed using RNA sequencing (RNA-seq). Our RNA-seq data revealed 692 differentially expressed genes involved in processes of lipid metabolism, oxidative stress, immune responses, and cell proliferation. Notably, the gene encoding neutral sphingomyelinase, SMPD3, was predominantly upregulated in the liver tissues of the mice displaying a phenotype of steatosis. Moreover, nSMase2 activity was elevated in these tissues of the liver. Pharmacological and genetic inhibition of nSMase2 prevented intracellular lipid accumulation and TNFα-induced inflammation in in-vitro HepG2-steatosis cellular model. Furthermore, nSMase2 inhibition ameliorates oxidative damage by rescuing PPARα and preventing cell death associated with high glucose/oleic acid-induced fat accumulation in HepG2 cells. Collectively, our findings highlight the prominent role of nSMase2 in hepatic steatosis, which could serve as a potential therapeutic target for NAFLD and other hepatic steatosis-linked disorders.