Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), facilitation of short-chain fatty acids (SCFAs) production, activation of the glucagon-like peptide 1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we have discussed research in other disease models that use probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

Severe malaria is a major public health concern in Angola, particularly among adults, with limited data on clinical outcomes and manifestations. The study therefore assessed the clinical manifestations and outcome of severe Plasmodium falciparum malaria in adult patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango, Angola. The study retrospectively reviewed the individual records of patients over 14 years old, admitted for severe malaria during the first trimester of 2021 and 2022. World Health Organization (WHO) criteria were used to define severity. A total of 640 patients were recorded into the study, 167 in 2021 and 473 in 2022, distributed across the departments; Intensive Care Unit (ICU; n=81), Medicine (MED; n=458) and Infectiology (INF; n=101). The median age was 26 years and 59.4% were males. The most common manifestation of severe malaria was renal impairment (37.4%). The overall mortality rate was 7% and decreased considerably from 10.2% in 2021 to 5.9% in 2022. The increase in malaria cases during 2022 with increased in prevalence of life-threatening signs like renal impairment, jaundice and impaired conscience, underscores the urgent need for enhanced malaria control and surveillance strategies to mitigate morbidity and mortality, highlighting the potential for antimalarial drug resistance.

Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria, whether IL-17A gene polymorphisms are involved in severe malaria susceptibility and the polymorphism’s influence on the IL-17A serum levels. 125 malaria patients and 48 free malaria controls were enrolled in this research. Malaria patients were classified into severe malaria (SM) and uncomplicated malaria (UM). IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum level and malaria outcome. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P<0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (GG). According to our results, it can be concluded that IL-17A may play a role in protection against fatal malaria outcomes.

(1) Background: Plasmodium vivax causes the largest malaria burden in Brazil, and chloroquine resistance poses a challenge to eliminating malaria by 2035. Illegal mining in the Roraima Yanomami indigenous territory can lead to the introduction of resistant parasites. This study aimed to investigate mutations in the pvcrt-o and pvmdr-1 genes to determine their potential as predictors of P. vivax chloroquine-resistant phenotypes. (2) Methods: Samples were collected in two health centers of Boa Vista. A questionnaire was completed, and blood was drawn from each patient. Then, DNA extraction, PCR, amplicon purification, and DNA sequencing were performed. After alignment with the Sal-1, the amplified fragment was analyzed. Patients infected with the mutant parasites were queried in the Surveillance Information System. (3) Results: 98% (157/164) of participants were from illegal mining areas. The pvcrt-o was sequenced in 151 samples, and the K10 insertion was identified in 13% of them. The pvmdr1 was sequenced in 80 samples: the MYF haplotype (958M) was detected in 92% of them, the TYF in 8%, while MYL was absent. No cases of recrudescence, hospitalization, or death were found. (4) Conclusions: Mutations in the pvcrt-o and pvmdr-1 genes have no potential to predict chloroquine resistance in P. vivax.

Severe malaria in adults is not well studied in Sahelian Africa. Clinical features and mortality associated with severe Plasmodium falciparum malaria in adult patients hospitalized in Kiffa, southern Mauritania, were analysed. Patients over 15 years old admitted for severe malaria between August 2016 and December 2019 were included in the present retrospective study. The World Health Organization (WHO) criteria were used to define severe malaria. The presenting clinical characteristics and outcome were compared. Of 4266 patients hospitalized during the study period, 573 (13.4%) had a positive rapid diagnostic test for malaria, and 99 (17.3%; mean age, 37.5 years; range 15–79 years; sex-ratio M/F, 2.1) satisfied the criteria for severe malaria. On admission, the following signs and symptoms were observed in more than one-fourth of the patients: fever (98%), impairment of consciousness (81.8%), multiple convulsions (70.7%), cardiovascular collapse (61.6%), respiratory distress (43.4%), severe anaemia ≤ 80 g/L (36.4%), haemoglobinuria (27.3%), and renal failure (25.3%). Patients were treated with parenteral quinine or artemether. Fourteen (14.1%) patients died. Multiple convulsions, respiratory distress, severe anaemia, haemoglobinuria, acute renal failure, jaundice, and abnormal bleeding occurred more frequently (P < 0.05) in deceased patients. Mortality due to severe falciparum malaria is high among adults in southern Mauritania. An adoption of the WHO-recommended first-line treatment for severe malaria, i.e. parenteral artesunate, is required to lower the mortality rate associated with severe malaria.

Dried blood spot (DBS) testing on confetti is one of the most common methods used to collect and extract DNA from field samples for molecular epidemiology of malaria studies. Here, we investigated whether ethanol or other solutions used to clean scissors are a source of sample contamination. DBS were prepared from 3 drops of blood from two Plasmodium falciparum cultures spotted on confetti, and 3 solutions (water, ethanol and DNase) were used to clean scissors between spots during DNA extraction. For each cleaning solution, two blank confetti were used as negative controls. Samples were analyzed by PCR-based genotyping of merozoite surface proteins 1 & 2 (msp-1 and msp-2), and P. falciparum chloroquine resistance transporter (Pfcrt). A total of 15 samples were analyzed. Based on msp-1 and msp-2 amplification, P. falciparum was detected on blank confetti when scissors were washed with ethanol. Based on Pfcrt amplification, DNA of P. falciparum was detected on blank confetti when scissors were cleaned with ethanol or water. No P. falciparum genes were detected on blank confetti when scissors were cleaned with DNase. Scissors cleaned with DNase prevented cross-contamination between samples during processing of dried blood spots, whereas ethanol (which is commonly used) fails to avert cross-contamination.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

In tropical developing regions, typhoid fever and malaria often co-occur, posing serious health risks. The two illnesses have similar symptoms, which makes diagnosis and treatment more difficult. Through a thorough analysis of existing literature on typhoid fever, malaria, and co-infection, including research articles, case studies, and review papers, this review seeks to understand the dynamic interactions between typhoid fever and malaria co-infection. The review highlights important problems with co-infection between typhoid and malaria, such as higher morbidity and death, diagnostics-related challenges, and antibiotic resistance. Overlapping symptoms and limitations in current diagnostic tests impede accuracy. Treatment plans are made more difficult by the advent of typhoid strains that are resistant to drugs. The analysis concludes by highlighting the necessity of developing more sensitive and specific diagnostic methods in order to accurately diagnose co-infections. Going forward, the review emphasizes the need for more investigation into the immunological connections between malaria and typhoid illnesses. Essentially, this paper offers a thorough summary of the difficulties and possibilities related to co-infection between typhoid and malaria. It provides a framework for upcoming studies and initiatives that seek to improve public health and patient outcomes in the face of these intricately linked health problems.

In the global fight against malaria, standard vector control methods such as indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are intended to protect inside residential structures and sleeping spaces. However, these methods can still leave individuals vulnerable to residual transmission from vectors that they may be exposed to outdoors. Nchelenge District in northern Zambia experiences high persistent malaria transmission even with ITNs and IRS in place. However, very few studies have examined outdoor vector activity. To assess diversity and abundance of outdoor foraging female anopheline mosquitoes, CDC light traps were used as proxy measures for mosquito host-seeking, set in three outdoor trapping schemes randomly assigned on different nights: 1) locations where people congregate at night outside of the house within the peri-domestic space, 2) animal pens or shelters, and 3) high human-trafficked areas, such as paths to latrines, where traps were baited with BG-Lure®. 1,087 total female anophelines were collected over a total of 74 trap nights. Anopheles funestus s.s. comprised the majority of the collection (86%), with An. gambiae s.s. (2%) and a highly diverse sampling of other anophelines (12%) making up the remainder. Plasmodium falciparum parasites were only detected in An. funestus (1%). No significant difference in species diversity or female anopheline abundance was detected between trapping schemes. Outdoor foraging anopheline mosquitoes, including a number of infectious An. funestus, may partially explain the difficulty of controlling malaria transmission in Nchelenge District where vector control is only targeted indoors. BG-Lure® shows some promise as an alternative to human-baited landing catch collections in this resource-poor setting.

Infection with the malaria parasite Plasmodium, remains a major cause of illness and death world-wide. The development of evasion strategies by the parasite from host immunity and its adaptability to antimalarial drugs has raised the urgency for developing new strategies to combat this disease. One promising avenue is targeting telomeres – sequences found at chromosome termini– and telomerase – the enzyme that catalysis synthesis of telomeres using an intrinsic RNA template. As telomeres shorten critically, cells undergo replicative senescence or apoptosis. Plasmodium, lacking telomerase activity in its human stages, exploits alternative mechanisms, accelerating telomere shortening, aging, and immune evasion. Chemical telomerase inhibitors show promise as antimalarials. In this review, we examine the potential of targeting this system in malaria therapy, with telomerase inhibitors offering a novel approach. A systematic search on PubMed using Boolean techniques identified 246 relevant articles from 1985 to March 31, 2024. After filtering, 43 articles met inclusion criteria, supplemented by snowball sampling. The telomerase inhibitor drug strategy is widely applicable against cancer. However, given the drugability of telomerase and the absolute requirement for active telomere maintenance in the vast majority of parasites including plasmodium, telomerase and telomere maintenance could well represent the Achilles heel of the parasite

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

This paper investigates the feasibility of a backend design for real-time, multiple-channel processing digital phased array system, particularly for high-performance embedded computing platforms constructed of using general purpose digital signal processors. Frist, we obtained the lab-scale backend performance benchmark from simulating beamforming, pulse compression, and Doppler filtering based on MicroTCA chassis using Serial RapidIO protocol in backplane communication. Next, a field-scale demonstrator of a multifunctional phased array radar is emulated by using the similar configuration. Interestingly, the performance of a barebone design is compared to that of emerging tools that systematically take advantage of parallelism and multicore capabilities, including Open Computing Language.

Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage or metabolic insult. Senescence is associated with aging and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) is not fully understood however, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated aging. This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases as controls. We show that senescence proteins CKAP4 and PTX3 are upregulated in AKI and CKD patients compared with controls with chronic diseases suggesting they may play in a role in overall kidney disease development. Additionally, CKAP4 was found to be differentially expressed in both AKI and CKD when compared to unhealthy controls hence this biomarker could be prognostic senescence biomarker of both AKI and CKD.

Antimicrobial resistance (AMR) is a public health problem exacerbated by the overuse and misuse of antibiotics and an inadequate capacity of laboratories to conduct AMR surveillance. This study assessed the capacity of laboratories in seven faith-based hospitals to conduct bacteriology, AMR testing and surveillance in Zambia. This multi-facility, cross-sectional exploratory study was conducted from February 2024 to April 2024. We collected and analysed data using the self-scoring Laboratory Assessment of Antibiotic Resistance Testing Capacity (LAARC) tool. This study found an overall score of 39%, indicating a low capacity of laboratories to conduct AMR surveillance. The highest capacity score was 47%, while the lowest was 25%. Only one hospital had full capacity (100%) to utilise a Laboratory Information System (LIS). Three hospitals had good capacity to perform data management with scores of 83%, 85%, and 95%. Only one hospital had full capacity (100%) to process specimens, and only one hospital had good safety requirements for a microbiology laboratory, with a score of 89%. This study demonstrates that all the assessed hospitals have a low capacity to conduct AMR surveillance. Therefore, there is an urgent need to strengthen the microbiology capacity of laboratories to enhance surveillance in faith-based hospitals in Zambia.

This study investigates the effects of Zinc (4wt.%) and severe plastic deformation on the mechanical properties of AZ61 magnesium alloy through the stir-casting process. The severe plastic deformation (equal channel angular pressing (ECAP)) has been done followed by T4 heat treatment. The microstructural examinations revealed that the addition of 4wt.%Zn enhances the uniform distribution of β-phase, contributing to a more uniformly corroded surface in corrosive environments. Additionally, dynamic recrystallization (DRX) significantly reduces the grain size of as-cast alloys after undergoing ECAP. The attained mechanical properties demonstrate that after a single ECAP pass, AZ61 + 4wt.%Zn alloy exhibits optimal yield strength (YS), ultimate compression strength (UCS), and hardness. This research highlights the promising potential of AZ61 + 4wt.%Zn alloy for enhanced mechanical and corrosion-resistant properties, offering valuable insights for applications in diverse engineering fields.

Background: Malaria is one of the most common diseased conditions across most developing countries caused by one of four species of Plasmodium. P. falciparum and P.vivax are the main agents responsible for malaria in Nigeria. Malarial infection has been shown to be associated with abnormalities in fluids, electrolytes and acid base balances. Electrolyte imbalance and mineral disturbances are majorly identified clinical symptoms in various infectious diseases including malaria. Electrolyte imbalance in malarial infection is capable of enhancing disease severity. The aim of this study was to investigate the effects of malarial infection on electrolytes parameters. Methods: Finger prick blood samples, Thick and Thin Giemsa-stained blood smears, were collected from 100 malaria-suspected individuals representing all age groups. The Giemsa-stained blood smears were examined microscopically. Demographic information was obtained using structured questionnaires. The electrolytes levels (Na, K, Cl^- and HCO_3-) in malarial patients were analyzed using standard procedures, Pearson's Correlation Coefficient correlation technique was used to investigate the relationship, and the strength of association between the variables. Results: The mean bound of patients’ sodium level was observed to fall within the specified normal limits of 125mmol/L – 145mmol/L; except for positive malaria patients belonging to the MP-(++) which will fall below the 125mmol/L (i.e. 126.25mmol/L – 1.77mmol/L = 124.48mmol/L). The spread of the sodium data taken from the patients were observed to fall within the normal limits leaving only the boxplot’s lower whisker out, that is, observations falling within the first quartile, except for MP-(++) patients with observations in the first to second quartile spreading outside the normal lower limit, in contrast for the negative tested patients, the box and its whiskers were almost engulfed within the normal limits. Conclusion: In our study we found that Plasmodium falciparum altered more in electrolytes parameters than Plasmodium vivax. The biochemical markers can be used as biomarkers to confirmation of malaria. This study discovered a significant linear relationship based on the Pearson product-moment correlation between creatinine and urea, potassium and chloride, potassium and creatinine, potassium and urea. The mean sodium and chloride level of positive malaria [MP-(++)] patients were observed to fall outside the normal limit.

Asthma is a chronic inflammatory disease for which the main anti-inflammatory drugs for better disease control are steroids or corticosteroids. The use of steroids in asthma patients, in particular in uncontrolled asthma patients, is associated with an increased risk of osteoporosis and fragility fractures. A single oral corticosteroids course increases the risk of osteoporosis and continual use of inhaled corticosteroids is correlated over time to an increased risk for both bone conditions. With the use of new, available biologic therapies for asthma, perhaps even anticipating the times of their use in what are the steps of therapeutic management, in the current guidelines and with targeted strategies of prevention it may be possible to improve asthma management, preventing some comorbidities, such as osteoporosis.

Background: Several studies recently confirmed the emergence of resistance to antimalarial drugs in sub-Saharan Africa. Multiple first-line treatment (MFT) is one of the measures envisaged to respond to the emergence and spread of this resistance. The aim of this study was to identify perceived advantages and disadvantages of several MFT deployment strategies and to better understand potential implementation drivers and barriers. Methods: A qualitative survey was conducted in seven sub-Saharan countries amongst key opinion-leaders, national decision-makers, and end users. A total of 200 individual interviews were conducted and findings were analyzed following a thematic inductive approach. Results: From a policy perspective, the new MFT intervention would require endorsement at the global, national, and regional levels to ensure its inclusion in guidelines. Funding of the MFT intervention could be a bottleneck due to costs associated with additional training of healthcare workers, adaptation of drug delivery mechanisms, and higher costs of drugs. Concerning the MFT deployment strategies, a slight preference for the segmentation strategy was expressed over the rotation and geographic approaches, due to the perception that a segmentation approach is already in place at country level. Conclusions: The findings highlighted the need for a collective approach to MFT deployment through the engagement of stakeholders at all levels of malaria management.

Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population-dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained through an extensive review of the literature, and additionally included target genes identified by the COVID-19 Host Genetic Initiative, as well as the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with severe COVID-19 outcome.

Malaria and Typhoid fever are prevalent diseases in tropical regions, exacerbated by unclear protocols, drug resistance, and environmental factors. Prompt and accurate diagnosis is crucial to improve accessibility and reduce mortality rates. Traditional diagnosis methods cannot effectively capture the complexities of these diseases due to the presence of confusable symptoms. Although machine learning (ML) models offer accurate predictions, they operate as "black boxes" with non-interpretable decision-making processes, making it challenging for healthcare providers to comprehend how the conclusions are reached. This study employs explainable AI (XAI) models such as Local Interpretable Model-agnostic Explanations (LIME), and Large Language Models (LLMs) like ChatGPT, Gemini, and Perplexity, to clarify diagnostic results for healthcare workers, building trust and transparency in medical diagnostics. The models were implemented on Google Colab and Visual Studio Code because of their rich libraries and extensions. Results showed that the Random Forest model outperformed Extreme Gradient Boost and Support Vector Machines and important features for predicting Malaria and Typhoid were identified with the LIME plots. Among LLMs, ChatGPT 3.5 demonstrates a comparative advantage over Gemini and Perplexity, hence highlighting how crucial it is to use a hybrid strategy that combines ML, XAI, and LLMs to improve diagnostic performance and reliability in healthcare applications. The study recommends implementing the integrated ML, LIME, and LLM processes because it streamlines the development and maintenance process's workflow overall, makes use of resources more effectively, and improves explainability by allowing the LLM to consider the complete context that LIME provides.

7046 aluminum alloy has good fatigue property, corrosion resistance and weld property, but the moderate strength and plasticity limit its wider application and development. In the present study, severe plastic deformation (SPD) was applied prior to T6 treatment to significantly strengthen and toughen the 7046 aluminum alloy. Results indicate that the alloy processed by 4 passes of equal channel angular pressing (ECAP) at 300 ℃ prior to T6 treatment exhibits an excellent mechanical performance, with ultimate tensile strength (UTS) and elongation (EL) of 485 MPa and 19%, exhibiting an improvement of 18.6% and 375% compared to that of the T6 alloy, respectively. The mechanical properties of the alloy are further improved by the additional room temperature (RT) rolling process, with UTS of 508 MPa and EL of 23.4%. There are more precipitates of η' and Al6Mn phases in the 300℃4P-R80%-T6 and 300°C4P-T6 alloys, which contribute to the strengthening and toughening enhancement by SPD processed T6 alloy. The results of this work may shed some light on enhancing 7046 aluminum alloy.

In sub-Saharan Africa, malaria is a leading cause of mortality and morbidity. As a result of the interplay between many factors, the control of this disease can be challenging. However, few studies have demonstrated malaria's complexity, control, and modeling although this perspective could lead to effective policy recommendations. This paper aims to be a didactic material providing the reader with an overview of malaria. More importantly, using a system approach lens, we intend to highlight the debated topics and the multifaceted thematic aspects of malaria transmission mechanisms, while showing the control approaches used as well as the model supporting the dynamics of malaria. As there is a large amount of information on each subject, we have attempted to provide a basic understanding of malaria that needs to be further developed. Nevertheless, this study illustrates the importance of using a multidisciplinary approach to designing next-generation malaria control policies.

Thalassemia is a common monogenic autosomal disorder prevalent in India. HbE beta thalassemia is a compound heterozygous state of two different beta globin mutations (HBB), predominant in the Eastern India. In HbE-beta thalassemia (β⁺/β°) patients, one HBB mutation does not produce any functional protein (β°); another mutation produces a structural altered haemoglobin, variant E (β⁺). It has been observed that in HbE-beta thalassemia patients with same type of HBB mutations, there exist diverse phenotypic presentation ranging from very severe, with regular transfusion-dependence to clinically non severe requiring very less transfusion or no transfusion. To explore this phenotypic mystery, we performed trio based expanded whole exome sequencing (WES) of two extreme phenotypes of HbE beta thalassemia subjects with similar HBB genotype and their parents. For WES library preparation, Agilent Sure select V6+UTR kit was used and sequencing was done through the Illumina HiSeq 2500 platform. This study aimed to search for de novo or inherited variants associated with the clinical severity. Six significant inherited variants were found in the genes, ATOH8, TTLL4, P2RX7, PRSS54, SLC9C2 and VRK2 in severe subject, however only one significant inherited variant in MTRR gene was found in non-severe subject. Bioinformatic analysis also confirms that each variant significantly changes in respective protein structure. The identified genes were either associated with iron absorption, oxidative stress, hematopoietic stem cell differentiation, structural organization of RBC cytoskeleton or regulating anemia. No significant de novo variant were identified associated with clinical severity. The finding of this study indicates that the combined effect of mutation load in major pathways may responsible for severe phenotype.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic disease in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search differences in clinical features. Methods: 713 patients belonging to CTO Bone Unit because of osteoporosis and fragility fractures were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 10.8%. When compared to patients without DM, the median age at the time of first fracture was similar (72 years ± 14 IQR vs 71 years ± 12 IQR); prevalence of combination of vertebral and hip fractures was higher (p=0.039), as well as prevalence of males, although not significantly (p=0.051). Bone mineral density (BMD) at all sites was higher in DM group; Trabecular Bone Score (TBS), instead, was significantly lower (p&lt;0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and therefore should be used as a diagnostic tool in clinical practice.

Severe combined immunodeficiency (SCID) is a primary inherited immunodeficiency that could be fatal, usually due to opportunistic infections caused by bacteria, viruses, fungi, and protozoa if left untreated. Opportunistic infections are the most common presentation of SCID these include viral, fungal, or intracellular bacteria, and infection should prompt immunological investigation. This review aimed to provide a comprehensive approach to the microrganisms associated with severe combined immunodeficiency (SCID) and its management. The authors described SCID as a syndrome and summarized the different microorganisms that affect children and how they are managed.

Cameroon introduced the malaria vaccine in its routine immunization programme on 22 January 2024, in the 42 districts out of 200, among the most at risk of malaria. A cross-sectional analysis of data on vaccine key events in the introduction roadmap and vaccine uptake during the first 30 days was conducted. In addition to available gray literature related to the introduction of the malaria vaccine, data on malaria vaccine uptake by vaccination session, collected through a digital platform, were analyzed. A total of 1,893 reports were received from 22 January 2024 to 21 February 2024 from 766 health facilities (85% of overall completeness). Two regions out of 10 recorded less than 80% of completeness. As of 21 February 2024, 13,811 children have received the first dose of the malaria vaccine, including 7,124 girls (51.6%) and 6,687 boys (48.4%). Thirty six percent of children were vaccinated through outreach sessions versus 61.5% through sessions in fixed posts. The overall monthly immunization coverage with the first dose was 37%. Early results have shown positive attitudes towards and acceptance of malaria vaccines. Suboptimal completeness of data reporting and low coverage highlight persistent gaps and challenges in vaccine rollout.

Ion channels serve many cellular functions including ion homeostasis, volume regulation, signaling, nutrient acquisition, and developmental progression. Although the complex lifecycles of malaria parasites necessitate ion and solute flux across membranes, whole genome sequencing of the human pathogen, Plasmodium falciparum, revealed remarkably few orthologs of known ion channel genes. Contrasting with this, biochemical studies have implicated channel-mediated flux of ions and nutritive solutes across several membranes in infected erythrocytes. Here, I review advances in the cellular and molecular biology of ion channels in malaria parasites. These studies have implicated novel parasite genes in the formation of at least two ion channels, with additional ion channels likely present at various membranes and parasite stages. Computational approaches that rely on homology to known channel genes from higher organisms will not be very helpful in identifying the molecular determinants of these activities. Given their unusual properties, novel molecular and structural features, and essential roles in pathogen survival and development, parasite channels should be promising targets for therapy development.

The gut microbiota has recently been associated with susceptibility/resistance to malaria in animal models and humans, yet the impact of the gut microbiota on the risk of a malaria attack remains to be assessed. This study aims at assessing the influence of the gut microbiota on malaria attacks and Plasmodium parasitæmia in children living in a malaria-endemic area in Mali. Three hundred healthy children were included in a 16-months cohort study in Bandiagara. Their gut bacteria and fungi community structures were characterised via 16S and ITS metabarcoding from stool samples collected at inclusion. Clinician team monitored the occurrence of malaria attacks. Asymptomatic carriage of Plasmodium was assessed by qPCR. Over the 16-month period, 107 (36%) children experienced at least one occurrence of malaria attacks, and 82 (27%) at least one asymptomatic Plasmodium parasitæmia episode. A higher gut bacteria richness was independently associated with susceptibility to asymptomatic parasitæmia episodes and malaria attacks; while the Shannon H diversity and Chao-1 richness index of gut fungi community structure was relatively homogeneous in children who were and were not infected with P. falciparum. Using a linear discriminant effect size analysis of operational taxonomic units assigned to the species level, 17 bacteria, including Clostridiaceae, Eubacteriaceae, Senegalimassilia sp., Atopobiaceae and Lachnosipraceae, and seven fungi, including Dioszegia fristigensis, Ogataea polymorpha and Cutaneotrichosporon cyanovorans, were associated with susceptibility; whereas eight bacteria, including, Bifidobacterium spp., Weissela confusa and Peptostreptococcacea, and 3 fungi, Malassezia sp., Niesslia exosporoides, and Didymocrea leucaenae, were associated with resistance to malaria. Moreover, 15 bacteria, including Coproccus eutactus, Terrisporobacter petrolearius, Klebsiella pneumoniae and Ruminococcaceae, and 13 fungi, including Wallemia mellicola, were associated with susceptibility, whereas 19 bacteria, including Bifidobacterium spp., Bacteroides fragilis, Peptostreptococcacea, and Lactobacillus ruminis, and three fungi, including Cryptococcus neoformans, were associated with resistance to asymptomatic Plasmodium parasitæmia episodes. Further studies are needed to confirm these findings that point the way towards strategies aiming to reduce the risk of malaria by modulating gut microbiota components in at-risk populations.

Background: Despite a range of available treatments, there is a remaining unmet need for patients with severe post-partum hemorrhage (sPPH). Objective: This manuscript evaluated efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 [NCT04723979], OS-2, OS-3 and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligation, arterial embolization or hysterectomy) and safety (incidence of thromboembolic events [TE] and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa exposed women only. Results: A total of 446 women exposed to rFVIIa and 1,717 non-exposed controls were included. In the RCT, fewer rFVIIa exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio 0.11, 95% confidence interval 0.03–0.35). In OS-1, more rFVIIa exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio 2.46, 95% confidence interval 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio 0.33, 95% confidence interval 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa in the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

We report the case of a 61-year-old woman who was referred to the Oral Surgery and Implantology Unit of the University Hospitals of Geneva to take care edentulous sites after dental avulsions of teeth 11 and 21 following traumatic shock due to endotracheal intubation under general anaesthesia. The dental history revealed that the patient had a history of generalized chronic periodontitis that had been treated several years earlier. Treatment consisted, for the first time to our knowledge, of immediate insertion of implants at sites 11 and 21 with simultaneous bone augmentation in a single surgical procedure and immediate restorations.

Community engagement involves five phases: informing, consulting, involvement, collaboration, and empowerment. This study explored the experiences of community stakeholders during the collaborative phase of community engagement co-developed by researchers and community members for the implementation of projects. The study was carried out in uMkhanyakude District, South Africa. A qualitative case study approach was used to explore the collaboration phase. Data was collected from key community stakeholders through key informant interviews, focus group discussions, and direct observations. The findings indicated that village headmen, community advisory board members and community research assistants can collaborate as trustworthy partners to address community health challenges. Community research assistants complement the role of participatory-based research appropriately, as they get to be involved hands-on together with the researchers. However, despite the significant role community research assistants played in the projects implemented by the KwaZulu-Natal Ecohealth Program, maintaining collaborative relationships was marred with unforeseen difficulties due to many barriers which included stretched work hours, lack of breaks, miscommunication around compensation, inappropriate behavior from the research team, and humiliation/oppression over language. Initiatives for community-based participatory research have proven to be effective as a collaborative approach that combines methodical research, involvement, and action to address health-related problems. However, it is necessary to consider the local socio-cultural aspects that could lead to barriers and misunderstandings between the locals and the researchers. Collaborative partnerships should ultimately result in community empowerment.

In tropical areas, simultaneous transmission of several vector-borne diseases is common due to ecological factors that are shared by arthropod vectors. Malaria and dengue virus, transmitted by Anopheles and Aedes mosquitoes, respectively, are among the top vector-borne diseases that cause significant morbidity and mortality in endemic areas. Notably, tropical areas often have suitable conditions for the co-existence of these mosquito species, highlighting the importance of identifying markers that accurately indicate the risk of acquiring each specific disease entity. Aedes are daytime-biting mosquitoes, while Anopheles preferentially bite during the night. These biting patterns raises the possibility of concurrent exposure to bites from both species. This pattern is important since mosquito saliva, deposited in the skin during blood feeding, induces immune responses that modulate pathogen establishment and infection. Previous studies have focused on characterizing such effects on the vector-pathogen interface for an individual pathogen and its mosquito vector. In this study, we evaluated associations between immune responses to salivary proteins from non-dengue and non-malaria vector mosquito species with clinical characteristics of malaria and dengue, respectively. Surprisingly, antibody responses against Anopheles antigens in dengue patients correlated with red blood cell count and hematocrit, while antibody responses against Aedes proteins were associated with platelet count in malaria patients. Our data indicate that concurrent exposure to multiple disease-carrying mosquito vectors and their salivary proteins with differing immunomodulatory properties could influence the transmission, pathogenesis, and clinical presentation of malaria, dengue fever, and other vector-borne illnesses.

Malaria is a critical fevered illness caused by Plasmodium parasites transmitted among people through the bites of infected female Anopheles mosquitoes. Public awareness about the disease is important for the control of disease. This article proposes a mathematical model to study the dynamics of malaria disease transmission with the influence of awareness-based control interventions. We found two equilibria of the model, namely the disease-free and endemic equilibrium. Disease-free equilibrium is stable globally if basic reproduction number (R0) is less than unity (R0&lt;1). Some basic mathematical properties of the proposed model, such as nonnegativity and boundedness of solutions, the feasibility of the equilibrium points and their stability properties, have been studied. Finally, we adopted optimal control to minimize the cost of disease control and solve the problem by formulating Hamiltonian functional. The optimal use of insecticides for controlling the mosquito population is determined. Numerical simulations have been provided for the confirmation of the analytical results. We conclude that media awareness with optimal control approach is best for cost-effective malaria disease management.

Background: The increasing prevalence of severe obesity among children and adolescents poses a significant challenge for pediatricians and general practitioners. This study aimed to investigate the relationships between biochemical results, anthropometry, blood pressure measurements and bioimpedance analysis (BIA)-derived parameters, to identify potential cardiometabolic complications associated with severe obesity. Methods: The study included 347 children (162 boys, 185 girls) aged 0-19 years, meeting criteria for severe obesity based on BMI thresholds for different age groups. Patients were recruited in four pediatric endocrinology centers in Poland (Zabrze, Cracow, Rzeszow, Szczecin). Each participant underwent anthropometric measurements, pubertal stage assessment, blood pressure measurement, biochemical and hormonal tests and BIA. Results: BMI showed significant associations with fat mass percentage (FM%) and waist-to-height ratio (WHtR), but not waist-to-hip ratio (WHR). The relationship between BMI and FM% was stronger in girls and prepubertal children. Metabolic syndrome (MetS) Z-score showed a strong positive correlation with BMI in pubertal children. Negative correlation between HDL and triglycerides was observed only in boys. Prepubertal children exhibited more significant correlations despite a smaller sample size and shorter duration of obesity. Conclusions: Considering multiple parameters beyond BMI alone provides a better understanding of cardiometabolic risks associated with severe obesity in children. MetS Z-score was not a reliable indicator of increased cardiometabolic risk in younger children. Early-onset severe obesity was associated with a higher risk of metabolic complications. Early intervention is crucial to mitigate metabolic complications in this population.

Malaria is a long-standing disease and one of the top life-threatening diseases, yet its treatment has not changed, while the world has already embraced the Fourth Industrial Revolution (4IR). A wave of research on digitizing monitoring mechanisms of such a deadly disease has surfaced. Automated malaria screening is one of the detection processes which are gaining popularity in the research domain. However, the process needs to be coupled with other processes aiming a nationally or regionally contextualised malaria monitoring system. This paper proposes a digital malaria monitoring system in the context of an African country or region. One advantage of such a digital system is that is enables a novel disease spread forecasting model based on the dynamics of different malaria types. The architecture of the diagnosis system is described, and the disease spread model is mathematically modelled in terms of a SPITR (Susceptible- Protected- Infected-Treated- Recovered) epidemic model which is further analysed. The forecasting model is expressed and analysed whereas experiments are conducted using a Monte Carlo simulation method. The design of the monitoring system has inspired how predictions can be made in the complex cases such as mixed infections. Results show that reinforcing the model parameter makes a significant improvement on the disease prediction.

There are a number of Anopheles species playing either primary or secondary roles in malaria transmission. Hence, understanding the species composition, their bionomics, and behaviors are all important in designing and implementing vector control intervention tools. Moreover, accurate identification of different species is vital. This study aimed to assess species composition, sporozoite infection rate, and blood meal origins of malaria mosquitoes in two malaria-endemic villages of Boreda district in Gamo zone, southwest Ethiopia. Thirty houses, 20 for Centers for Disease Control and Prevention (CDC) light traps and 10 for Pyrethrum Spray Catches (PSC), were randomly selected for bimonthly mosquito collection from October 2019 to February 2020. Enzyme-linked-immunosorbent assay (ELISA) test was done to detect the blood meal origins and circumsporozoite proteins (CSPs). The entomological inoculation rate (EIR) was calculated by multiplying the sporozoite and human biting rates from PSCs. Anopheles gambiae and An. funestus complexes were further identified into species by polymerase chain reaction (PCR). Anopheles species with some morphological structures confusing with An. gambiae or An. funestus complexes were father confirmed by PCR. A total of 15 Anopheles species were documented, of which An. demeilloni was the dominant one. Only An. arabiensis was positive for P. falciparum CSP. The overall P. falciparum CSP rate of An. arabiensis was 0.54%. The overall estimated P. falciparum EIR of An. arabiensis from PSC was 1.5 infectious bites/person/five months. Of the 145 freshly fed Anopheles mosquitoes tested for blood meal source, 57.9% (84/145) had bovine blood meal, 22 (15.2%) had human blood meal origin alone and 24 (16.5%) had mixed blood meal origins of human and bovine. An. demeilloni mainly fed on bovine blood (102/126 = 80.9%). Among 420 morphologically classified An. demeilloni, 11 (2.6%) were confirmed as An. lessoni (one of the An. funestus complexes) by PCR. A substantial number of morphologically classified An. salbaii, An. maculipalpis and An. fuscivenosus were found to be An. arabiensis by PCR. Regardless of the high diversity of Anopheles mosquitoes, An. arabiensis is playing the primary role in malaria transmission. Morphological misclassification of species could be a challenge in malaria mosquito monitoring and surveillance, and hence it should be supported by more sensitive techniques for confirmation.

Wastewater-based surveillance has emerged as an important method for monitoring SARS-CoV-2. This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time PCR. Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and two sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia.

In this review, severe plastic deformation (SPD) is considered as a materials processing technology. The deformation mode is the principal characteristic differentiating SPD from common forming operations. For large plastic strains, deformation mode depends on the distribution of strain rates between continuum slip lines and can be varied from pure shear to simple shear. A scalar, invariant and dimensionless coefficient of deformation mode is introduced as a normalized speed of rigid rotation. On this basis, simple shear provides the optimum mode for structure modification and grain refinement whereas pure shear is "ideal" for forming operations. Special experiments and SPD practice confirm this conclusion. Various techniques of SPD are classified and described in accordance with simple shear realization or approximation. It is shown that correct analyses of the processing mechanics and technological parameters are essential for comparison of SPD techniques and the development of effective industrial technologies.

Buruli ulcer is a chronic ulcerative disease of skin and subcutaneous tissues caused by infection with Mycobacterium ulcerans. Although Australian possums are known to be susceptible to Buruli ulcer, many aspects of the disease in possums, including welfare impacts, remain largely unreported. Severe clinical Buruli ulcer was identified in four common ringtail possums (Pseudocheirus peregrinus) from Melbourne, Victoria. All four possums were euthanised due to welfare concerns and poor prognosis, based on the presence of deep ulcerative lesions to paws, some of which exposed carpal or tarsal bones. These lesions were considered likely to cause partial or complete loss of limb function, which would severely affect the welfare and survival of these wild arboreal animals. Histologically, there was severe ulcerative necrotising pyogranulomatous dermatitis, panniculitis, and myositis, with intralesional acid-fast bacteria. M. ulcerans was detected by real-time PCR in all swabs and biological tissues collected from all four cases. Buruli ulcer may be an important and under-recognised cause of poor possum welfare in endemic areas. In addition to severe cutaneous lesions, infection extends to underlying bones and joints, and the systemic distribution of M. ulcerans throughout all major tissues and internal organs, as observed in these four cases, may further impact the health and fitness of infected possums. Further research is needed to investigate the epidemiology, pathogenesis and impacts of Buruli ulcer in possums, and to inform the design of interventions that may protect the health and welfare of possums and other affected animal species.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella-zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKi), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. In twenty-four RA patients with new-onset HZ and forty-two without HZ, serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ inducible protein-10 (IP-10) were measured by ELISA. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21pg/ml, interquartile range (IQR) 77.63-150.30pg/ml versus 142.3pg/ml, IQR 106.7-175.6pg/ml, p&lt;0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8ng/ml, IQR 21.0-38.2ng/ml versus 10.5ng/ml, IQR 9.9-15.0ng/ml, p&lt;0.005). In conclusion, patients with HZ had significantly lower MCP-1 levels than those without HZ, and patients with severe HZ had significantly higher titers of anti-IFN-γ than those with non-severe HZ. Given small sample size, our results need further validation in future studies.

Malaria comprises a spectrum of disease syndromes and the immune system is a major participant in malarial disease. This is particularly true in relation to the immune responses elicited against blood stages of Plasmodium-parasites that are responsible for the pathogenesis of infection. Mouse models of malaria are commonly used to dissect the immune mechanisms underlying disease. While no one mouse model of Plasmodium infection completely recapitulates all the features of malaria in humans, collectively the existing models are invaluable for defining the events that lead to the immunopathogenesis of malaria. Here we review the different mouse models of Plasmodium infection that are available, and highlight some of the main contributions these models have made with regards to identifying immune mechanisms of parasite control and the immunopathogenesis of malaria.

In central Senegal malaria incidences have declined from 2000 to 2010 in response to scaling-up of control measures and then remained stable, making elimination improbable. Additional control measures are needed to reduce transmission. We simulated chemoprophylaxis interventions targeting malaria hotspots, using a meta-population mathematical model based on differential equation framework and incorporating human mobility. The model was fitted to weekly malaria incidences from 45 villages. Three approaches for selecting intervention targets were compared: a) villages with malaria cases during the low transmission season of the previous year; b) villages with highest incidences during the high transmission season of the previous year; c) villages with highest connectivity with adjacent populations. Our modeling, considering human mobility, showed that the intervention strategies targeting hotspots would be effective in reducing malaria incidence in both targeted and untargeted areas. But whatever the intervention, pre-elimination stage (1-5 cases per 1,000 per year) would not be reached without simultaneously increasing vector control by more than 10%. Targeted interventions allow increasing overall malaria control and elimination potential.

The human malaria parasite, Plasmodium falciparum, accounts for more than 500,000 deaths worldwide per year. From 2000 to 2019, the malaria global death toll fell from 864,000 to 576,000 deaths; however, progress on reducing this toll has since slowed, with the COVID-19 pandemic contributing to an increase in the mortality rate since 2020. The emergence of widespread resistance in P. falciparum to first-line treatment drugs has highlighted the need for new antimalarial drugs, and smarter approaches, including better combination therapies and mass drug administration. Nevertheless, recent successes of the first malaria vaccine (RTS,S/AS01) and the approval of a second (R21/MM), have renewed the promise of widely applicable vaccines in the future. Since 2015, the Eastern Mediterranean Region has experienced an overall increase in malaria cases and deaths. In the Arabian Peninsula, while most of the Gulf Cooperation Council (GCC) countries have been declared free of indigenous malaria (Bahrain, Kuwait, Qatar, and the United Arab Emirates), malaria is still endemic in two GCC countries (Saudi Arabia and Oman) and its neighbors (Yemen). Furthermore, a number of factors threaten malaria control in this region, at the level of the parasite (antimalarial drug resistance), the mosquito (the emergence of highly invasive species), the environment (climate change and increasing average temperatures), and society (imported malaria). In this review, we assess the current world-wide status of malaria in terms of public health, prevention and treatment, before providing an Arabian regional perspective, with a critical evaluation of the malaria situation in the GCC countries.

The global malaria community has picked up the theme of malaria elimination in greater than 90 % of the world’s population in the next decade. The recent reports of P. vivax in all sub-Saharan Africa, including Duffy negative individuals, threaten the efforts to achieve elimination. This is not only in view of strategies that are tailored only to P. falciparum elimination, but also due to currently revealed biological characteristics of P. vivax concerning the relapse patterns of hypnozoites and conservation of a large biomass at cryptic sites in the bone marrow and spleen. A typical scenario has been observed in Botswana from the period between 2008 to 2018, which palpably projects how P. vivax could endanger efforts at malaria elimination where the two parasites co-exist. The need for the global malaria community, NMPs, funding agencies and relevant stakeholders to engage in a forum to discuss and recommend clear pathways for sub-Saharan Africa regarding malaria elimination including P. vivax, is warranted.

Technology-based approaches for upper limb (UL) motor rehabilitation after stroke are designed mostly for severely affected patients to increase their recovery chances. However, the available randomised controlled trials (RCTs) focused on efficacy of technology-based interventions often include patients with a wide range of motor impairment. This scoping review aims at overviewing the actual severity of stroke patients enrolled in RCTs which claim to specifically address UL severe motor impairment. The literature search was conducted on Scopus and PubMed databases and included articles from 2008 to May 2024, specifically RCTs investigating the impact of technology-based interventions on UL motor functional recovery after stroke. Forty-eight studies were selected. They showed that upon patients’ enrolment the values of the UL Fugl-Meyer Assessment and Action Research Arm Test covered the whole range of both scales, thus revealing the non-selective inclusion of severe impaired patients. Heterogeneity in terms of numerosity, characteristics of enrolled patients, trial design, implementation, and reporting were present across studies. No clear difference in the severity of the included patients according to the intervention type was found. Patient stratification upon enrolment is crucial to best direct resources to those patients who will benefit the most from a given technology-assisted approach (personalised rehabilitation).

The malaria parasite resides within erythrocytes during one stage of its life cycle. During this intraerythrocytic period, the parasite ingests the erythrocyte cytoplasm and digests approximately two-thirds of the host cell hemoglobin. This digestion occurs within a lysosome-like organelle called the digestive vacuole. Several proteases are localized to the digestive vacuole and these proteases sequentially breakdown hemoglobin into small peptides, dipeptides, and amino acids. The peptides are exported into the host cytoplasm via the chloroquine-resistance transporter and an amino acid transporter has also been identified on the digestive vacuole membrane. The environment of the digestive vacuole also provides appropriate conditions for the biocrystallization of toxic heme into non-toxic hemozoin by a poorly understood process. Hemozoin formation is an attribute of Plasmodium and Haemoproteus and is not exhibited by other intraerythrocytic protozoan parasites. The efficient degradation of hemoglobin and detoxification of heme likely plays a major role in the high level of replication exhibited by malaria parasites within erythrocytes. Unique features of the digestive vacuole and the critical importance of nutrient acquisition provide therapeutic targets for the treatment of malaria.

Background: First-line biological diagnosis of malaria in Mali is based on the use of rapid diagnostic tests (RDT), which detect in the blood the Histidin Rich Protein 2 antigen, specific to Plasmodium falciparum. Our study, based on a real-time polymerase chain reaction (qPCR) gold-standard diagnosis, aims to evaluate the performance of RDTs used in Mali and to describe the distribution of Plasmodium species in each administrative regions of Mali; Methods: We collected RDT cassettes in 47 sites of the nine regions of Mali. We randomly selected 150 malaria-negative and up to 30 malaria-positive RDTs from each regions. DNA was extracted from the RDTs’ nitrocellulose strip and then assayed with a pan-Plasmodium qPCR. Positive samples were then analyzed with qPCRs specific for P. falciparum, P. malariae, P. vivax, and P. ovale; Results: Of the 1,389 tested by qPCR RDTs, 258 (18.6%) were positive for Plasmodium spp. P.falciparum was the most predominant (97.3%). However, the prevalence of P.vivax reach 21.1% in the Ménaka region in the north; Conclusion: Overall, RDT diagnostic indices are adequate for the biological diagnosis of malaria in Mali. Our finding support the adjustment of RDTs to the local epidemiology.

An SIRS (Susceptible–Infected–Removed-Susceptible) mathematical model for the transmission dynamics of the Transfusion–Transmitted Malaria (TTM) model with optimal control pair u₁(t) and u₂(t) was developed and studied in this research work. The model Transfusion–Transmitted Malaria disease–free equilibrium and endemic equilibriums points were determined. The model exhibited two equilibriums; disease-free and endemic equilibrium. It is shown that the disease–free equilibrium was locally asymptotically stable if the associated basic reproduction numbers R₀ is less than unity while the disease persists if R₀ is greater than unity. The global stability of the Transfusion–Transmitted Malaria model at the disease-free equilibrium was established using the comparison method. The optimality system was derived and an optimal control model of blood screening and drug treatment for the Transfusion–Transmitted Malaria model was investigated. Conditions for the optimal control were considered using Pontryagin’s Maximum Principle and solved numerically using the Forward and Backward Finite Difference Method (FBDM). Numerical results obtained are in perfect agreement with our analytical results.

Aortic stenosis continues to be still the most frequently valvular pathology in the elderly population of the Western countries. According to the latest guidelines, the therapeutic choice of aortic stenosis depends on the age of the patient (&lt;75 years or &gt;75 years) and the risk class (STS-Prom/ Euroscore II &lt; o &gt; 4%). Therefore, if the surgical indication is clear in young and low risk patients and percutaneous treatment is the gold standard in older and high-risk patients, the therapeutic choice is still debated in intermediate-risk patients. In this group of patients the aortic valve stenosis treatment depends on the patient's global evaluation, on the experience of the center and no less important on the patient's will. Two main therapeutic options are debated: surgical aortic valve replacement with sutureless prosthesis versus transcatheter aortic valve implantation. In addition, the progressive development of mininvasive techniques for aortic valve surgery (right -anterior minitoracotomy) has also reduced the peri and post -operative risk in this group of patients. The goal of our review is to analyze the literature evidence of the best therapeutic choice in intermediate risk patients with severe aortic stenosis.

Plasmodium vivax malaria is a neglected tropical disease, despite being more geographically widespread than any other form of malaria. The documentation of P. vivax infections in different parts of Africa where Duffy-negative individuals are predominant suggested that there are alternative pathways for P. vivax to invade human erythrocytes. Duffy-negative individuals may be just as fit as Duffy-positive individuals and are no longer resistant to P. vivax malaria. In this review, we describe the complexity of P. vivax malaria, characterize pathogenesis and candidate invasion genes of P. vivax, and host immune responses to P. vivax infections. We provide a comprehensive review on parasite ligands in several Plasmodium species that further justify candidate genes in P. vivax. We also summarize previous genomic and transcriptomic studies related to the identification of ligand and receptor proteins in P. vivax erythrocyte invasion. Finally, we identify topics that remain unclear and propose future studies that will greatly contribute to our knowledge of P. vivax.

This case report describes a 71-year-old female with multiple comorbidities who presented with symptoms suggestive of stroke and was subsequently found to have severe acute kidney injury (AKI) due to acute interstitial nephritis (AIN). The patient has normal kidney function at baseline. She has been on hydrochlorothiazide and metoprolol succinate for hypertension for several years. Due to severe acute kidney injury, a kidney biopsy was performed, revealing severe Acute Interstitial Nephritis secondary and multiple intratubular oxalate crystals. The patient's renal function improved after withdrawing HCTZ, volume repletion and initiating prolonged prednisone taper. We attempt to provide some insights through our paper into the mechanism of acute renal failure from crystal nephropathy and its management.

Snakebite envenomation remains a major cause of morbidity and mortality in rural populations. This study aimed to identify factors associated with complications from snakebite envenomation reported in health facilities in the Cascades region of Burkina Faso. This cross-sectional study used routine data of patients admitted for snakebite envenomation in five health facilities between January 1, 2016, and December 31, 2021. Data were collected on sociodemographic, clinical, and therapeutic characteristics of patients showing signs of envenomation. Bivariate and multivariate analyses were conducted to determine factors associated with complications. Among the 846 patients with envenomation, 355 (42%) experienced complications. Local complications at the bite site included wounds (21.5%) and skin necrosis (12.5%). Systemic complications included hemorrhage (30.5%), shock (16.3%), and coma (4.3%), with a mortality rate of 3.2%. Factors significantly associated with complications were rural residence (AOR: 4.80; 95% CI: 2.21-11.4), incision at the bite site (AOR: 4.31; 95% CI: 2.51-7.52), tourniquet application (AOR: 5.52; 95% CI: 1.42-30.8), bleeding (AOR: 14.2; 95% CI: 8.80-23.4), abnormal vital signs (AOR: 14.3; 95% CI: 9.22-22.7), and non-administration of antivenom serum (AOR: 2.92; 95% CI: 1.8-4.8). These findings highlight the importance of antivenom availability and public awareness to reduce complications from snakebite envenomation.

Background/Purpose: Multimorbidity of malaria, anaemia, and malnutrition (MAMM) is a condition in which an individual cohabits with two or more of these health outcomes and is becoming an emergent public health concern in sub-Saharan African countries. The independent associations of a child’s demographic variables and socioeconomic disparities with a child’s health outcomes have been established in literature. However, the effects of the intersection of these factors on MAMM, while accounting for other covariates have not been studied. Therefore, this study aimed to determine how children’s sex, age and socioeconomic status interact to explain the variations in MAMM among children aged 6-59 months in Nigeria. Methods: Data from the 2018 Nigeria Demographic and Health Survey and the 2018 National Human Development Report (NHDR) were used. The study includes weighted samples of 10,184 children aged 6-59 months in Nigeria. A three-level multilevel mixed effect ordinal logistic regression model such that individual characteristics at level 1 are nested in communities at level 2 and nested in states at level 3 was used. Subsequently, predictive probability charts and average adjusted probability tables were used to interpret the intersectional effects. Five models were created in this scenario. Model 1 is the interaction between the child's sex and wealth status; model 2, child's sex and age; model 3 is between child's age and wealth status; model 4 has the three 2-way interactions of child's sex, age, and household wealth status, and model 5 includes model 4 and the 3-way interactions between a child's sex, age, and wealth quintiles. Results: The prevalence of children with ‘none of the three diseases’ outcomes was 17.3% (1767/10,184), while, 34.4% (3499/10,184) had ‘only one of the diseases’, and 48.3% (4,918/10,184) cohabit with ‘two or more’ of MAMM. However, in the multivariate analyses, model 3 was the best fit compared with other models, so, that the two-way interaction effects of a child's age and wealth status are significant predictors in the model. Children aged 36-47 months living in the poorest households have the probability of 0.11, 0.18, and 0.32 of contracting MAMM above the probability of children of the same age and live in the middle, more prosperous and richest households, respectively, while all other covariates are held constant. Thus, the variation in MAMM over a child's age differs depending on the household wealth quintile. In other words, as the children grow older, variations in MAMM become more evident between the rich and the poor household. Conclusion: Therefore, it is recommended that policies that are geared toward economic redistribution will help bridged the disparities observed in multiple diseases among children aged 6-59 months in Nigeria

Anxiety in older individuals is understudied despite its prevalence. Investigating its occurrence can be challenging, yet understanding the factors influencing its recurrence is important for improved management. This study aimed to model the recurrence of anxiety symptomatology in an older population within a five-month timeframe. Data included baseline socio-demographic and general health information for older adults aged 60 years or older with at least mild depressive symptoms. A Bayesian network model explored the relationship between baseline data and recurrent anxiety symptomatology. Model evaluation employed the Area Under the Receiver Operating Characteristic Curve (AUC). The Bayesian model was also compared to three machine learning models. The model achieved an AUC of 0.821 on the test data, using a threshold of 0.367. This result surpassed both the Logistic Regression and XGBoost models, but slightly behind SGDClassifier. Key factors associated with recurrence of anxiety symptomatology were: “Not being able to stop or control worrying”; “Becoming easily annoyed or irritable”; “Trouble relaxing”; and “depressive symptomatology severity”. The model demonstrated generalisation abilities and outperformed some machine learning models while being less complex and more explainable. These findings indicate a prioritised sequence of predictors to identify individuals most likely to experience recurrent anxiety symptomatology.

The discovery of interesting inter-relationships between the different malaria epidemiological parameters is essential towards the disease control. However, existing associative rule-based machine learning algorithms for pattern discovery are slow while working on high-dimensional Malaria Indicator Survey (MIS) data, with the further challenge of data under fitting and inadequate result visualization. Hence, this work proposed a novel and efficient associative rule-based machine-learning algorithm with enhanced graphical visualization capacity for rigorous and confident biological result interpretation for malaria control. Through empirical and asymptotic comparative time-complexity performance evaluations, the proposed algorithm scaled better than other existing associative rule-based machine learning algorithms while maintaining its accuracy. The algorithm was applied to two real MIS data sets obtained from the Demographic and Health Survey repository and other supplementary literature source using Nigeria as a case study. The resulting interesting malaria epidemiological discovered novel trends were: a) the malaria disease might not be associated with the anemia symptom; b) there was no significant association between the anemia symptom and the wealth indices of individuals; c) there were other parameters associated with the insecticide resistance capacity of the malaria vector asides the knock down resistance alleles; d) the population dynamics of the malaria vector was not associated with the malaria disease endemicity. In conclusion, this work developed a computationally efficient and user-friendly associative rule-based machine-learning algorithm called E_Apriori for the control of the malaria disease.

The purpose of this study is to estimate the mean transitioning probabilities from a Healthy state to malaria positive uncomplicated state or to malaria positive severe state. It also classifies the various transitioning probabilities of moving through the various states based on some baseline characteristics. Malaria test results for 2019 over a 12-month period were collected from the University of Ghana school clinic. An H-U model for the study was developed and the transition rates from the cross-sectional data are indicated. With two states Healthy (H) and Uncomplicated (U) forming a state space, there were four possible transitions. The results show that the probability of transitioning from a Healthy state to a malaria positive state is 0.03% while the probability that an individual will remain at Healthy state (H) after the test is 99.73%. It was found that if an individual is already positive and has taken medication the probability that its second test came out negative is 6.45% while the chances that it will remain positive but uncomplicated is 93.55%. The study also showed that in the long run, about 95.98% of persons who visited the student clinic with malaria symptoms recorded negative tests for malaria parasite while about 4% recorded positive for malaria. In terms of disaggregation by gender, it was realized that the number of reported negative test results were higher for females (97.08%) than for males (96.13%). However, the infection rate is higher for males (3.87%) than females (2.92%). It is recommended that in as much as the University of Ghana has two health centers (a clinic and hospital), there should be a centralized system to track students’ health so research done would not be biased.

This paper investigates existing mathematical morphology based techniques applied for performing malaria parasites detection and identification in both Giemsa and Leishman stained blood smears images. Malaria is an epidemic health disease and a rapid, accurate diagnosis is necessary for proper intervention. Generally, pathologists visually examine blood stained slides for malaria diagnosis; this kind of visual inspection is subjective, errorprone and time consuming. In order to cope with such issues, computer-aided methods have been increasingly evolved for abnormal erythrocyte and/or parasites detection, segmentation and semi/fully automated classification. The aim of this paper is to present a review of recent mathematical morphology based methods for malaria parasite detection.

SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at the time of hospital admission are still missing. Here, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 participants, including 20 uninfected and 37 acutely SARS-CoV-2-infected CVD patients and 37 healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T cell subsets. Moreover, we identified an immune signature characterised by mucosal-associated invariant T (MAIT) cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.

Malaria is a prevalent disease in several tropical and subtropical regions, including Brazil, where remains a significant public health concern. Despite control efforts, reintroduction of endemics in areas without cases for decades poses a challenge. To assess factors influencing ma-laria risk, regional outbreak cluster analysis and a spatio-temporal models were developed for the Brazilian Amazon, incorporating climate, land use/cover interactions, endemic bird, and amphibian richness. Results showed that amphibian, bird richness and endemism correlated with a reduction in malaria risk. Presence of forest had a positive effect on risk, but it depended on its juxtaposition with anthropic land uses. Biodiversity and landscape composition, rather than forest formation presence alone, modulated malaria risk in the period. Areas with low en-demic species diversity and high human activity, predominantly anthropogenic landscapes posed high malaria risk. This study underscores the importance of considering the broader eco-logical context in malaria control efforts.

Introduction: Chronic wounds caused by diabetes or lower-extremity artery disease are intractable because the wound healing mechanism is no longer effective due to the poor environment of the wound bed. Biosheet obtained using in-body tissue architecture (iBTA) is a collagen-based membranous tissue that is created within the body and autologously contains various growth factors and somatic stem cells including pluripotent stem cells. When applied to a wound, granulation formation can be promoted and even epithelialization may be achieved. Hearin, we report our clinical treatment experience with seven cases of intractable diabetic foot ulcers. Cases: From 46- to 93-year-old 7 patients had large foot ulcers including heel area, which was failed to heal with standard wound treatment. Methods: Two or four Biosheet-forming molds were implanted subcutaneously in the chest or abdomen, and after 3 to 6 weeks, the molds were removed. Biosheets that formed inside the mold were obtained and applied directly to the wound surface. Results: In all cases, there were no problems with the mold embedding and removal procedures, and Biosheets were formed without any infection or inflammation during the implantation period. The Biosheets were simply applied to the wounds, and in all cases, they adhered within one week, did not fall of, and became integrated with the wound surface Complete wound closure was achieved within 8 weeks in two cases and within 5 months in two cases. One patient was lost due to infective endocarditis from septic colitis. One case required lower leg amputation due to the wound recurrence, and one case achieved wound reduction and wound healing in approximately 9 months. Conclusion: Biotube obtained via iBTA promoted wound healing and were extremely useful for intractable diabetic foot ulcers involving heel area.

Background/Objectives: The purpose of this study was to evaluate the relationship between 1-year mortality and health insurance benefit extension policy items in severe pneumonia pa-tients requiring mechanical ventilation using a South Korean nationwide cohort. Methods: A nationwide population-based retrospective study was conducted using the Korean National Health Insurance database. A total of 1,099 patients (542 patients in the health insurance benefit item group and 557 patients in the control group) were included. The primary outcome was 1-year mortality. Results: Among patients with health insurance benefit extension policy items, 203 patients (37.5%) were diagnosed with hemato-oncological disease, who were categorized as group A, and 339 patients (62.5%) were diagnosed with cerebrovascular, cardiovascular, or rare diseases, who were categorized as group B. Group B had lower 1-year mortality (50.7% vs. 62.5%, P

Pediatric psychology action in the pediatric clinical-surgical high complexity unit has become increasingly necessary. It allows for the possibility of integrating complex pediatric clinical-surgical operations by reducing painful effects on the emotional world of children and adolescents. The pediatric psychologist in a pediatric unit continuously oversees children and adolescents (C/A) throughout the entire therapeutic process, extending activity to parents and healthcare personnel. In ill children and adolescents, physical pain and psychological suffering follow, with minimal temporary variations, the same clinical path with continuous changes which put a strain on the ability of children, adolescents, parents and healthcare staff to cope with stress.

Accurate Quantitative Precipitation Estimation (QPE) is fundamental for a large number of hydrometeorological applications, especially when addressing extreme rainfall phenomena. This paper presents a comprehensive comparison of various rainfall estimation methods, specifically those relying on weather radar data, rain gauge data, and their fusion. The study evaluates the accuracy and reliability of each method in estimating rainfall for a severe event that occurred in Tuscany, Italy. The obtained results indicate that merging radar and rain gauge data outperform both individual approaches by reducing errors and improving the overall reliability of precipitation estimates. The study highlights the importance of data fusion in enhancing the accuracy of QPE and also supports its application in operational contexts, providing evidence for the greater reliability of merging methods

Malaria remains a life-threatening disease in many tropical countries. Honduras has successfully reduced malaria transmission as different control methods have been applied focusing mainly on indoor mosquitoes. The selective pressure exerted by the use of insecticides inside the households could modify the feeding behavior of the mosquitoes forcing them to search for available animal hosts outside the houses. These animal hosts in the peridomicile could consequently become an important factor in maintaining vector populations in endemic areas. Herein, we investigated the blood meal sources and Plasmodium spp. infection on anophelines collected outdoors in endemic areas of Honduras. Individual PCR reactions with species-specific primers were used to detect five feeding sources on 181 visibly engorged mosquitoes. In addition, a subset of these mosquitoes where chosen for pathogen analysis by a nested PCR approach. Most mosquitoes fed on multiple hosts (2 to 4), and 24.9% of mosquitoes were fed on a single host, animal or human. Chicken and bovine were the most frequent blood meal sources (29.5% and 27.5% respectively). The average human blood index (HBI) was 22.1%. None of the mosquitoes was found to be infected with Plasmodium spp. Our results show the opportunistic and zoophilic behavior of Anopheles mosquitoes in Honduras.

(1) Background: The severity of malaria is associated with low bioavailability of antioxidants and high concentration of free radicals that induce oxidative damage in cerebral and pulmonary microcirculation. This can be prevented by the action of consumable antioxidants present in foods. Therefore, we investigated the protective role of lycopene (LYC) on the oxidative changes induced by Plasmodium berghei (Pb); (2) Methods: Mice were infected by intraperitoneal injection of 106 parasitized red blood cells and treated via gavage with LYC (3.11 mg/kg bw/day) or NAC (62 mg/kg bw/day). They were then evaluated for 1, 4, 8 or 12 days after infection. Levels of thiobarbituric acid reactive substances (TBARS), antioxidant capacity by inhibition of ABTS radicals (AC-ABTS) and DPPH (AC-DPPH), uric acid (UA), and nitric oxide (NO) were measured in brain and lung tissues; (3) Results: The infection caused oxidative stress confirmed by increased levels of TBARS, AC-ABTS, AC-DPPH, UA, and NO in the tissues leading to the death of the animals. LYC prevented the increase in TBARS, AU, and NO levels compared to Pb (p&lt; 0.0001) and NAC+Pb groups (p&lt;0.0001), reaching values similar to those of Sham animals; (4) Conclusions: These results are striking evidence of the beneficial effect of lycopene supplementation on oxidative stress in experimental malaria in vivo and emphasize the importance of antioxidant supplementation in the treatment of the disease.

Malaria is a disease spread by female mosquitos of the Anopheles genus. It is acutely prevalent in Sub-Saharan Africa, where 90% of malaria deaths occur annually. One Sub-Saharan African country historically impacted by malaria is Ethiopia. In the past twenty years, malaria prevalence has decreased throughout Sub-Saharan Africa; yet, anthropogenic environmental changes are changing the landscape of malaria. Scholarly literature has cited a positive relationship between hydroelectric dams and malaria in Sub-Saharan Africa. Ethiopia is currently expanding their hydroelectric infrastructure. The Gilgel Gibe III Dam is located on the Omo River in Southwestern Ethiopia. It began generating electricity in 2015 and its reservoir has a capacity of 14,700 million m3 of water. This research utilized Geographic Information Systems and Remote Sensing to identify populations at an increased risk of malaria due to Gilgel Gibe III Dam. Two different techniques were employed: the proximity approach and the remote sensing approach. The proximity approach was based on distance from the reservoir. It identified all populations living within three kilometers of the reservoir as being at an increased risk. The remote sensing approach evaluated the slope, elevation, water content, and land surface temperature of the study area to create a mosquito breeding habitat risk map. Then, populations living within three kilometers of the two main High-Risk areas were identified. This study suggests that mosquito breeding habitat risk is not equally distributed throughout the Gilgel Gibe III Reservoir. This causes certain populations to be at a heightened risk of malaria.

Disease control programs need to identify breeding sites of mosquitoes which transmit malaria and other diseases to target interventions and identify environmental risk factors. Increasing availability of very high resolution drone data provides new opportunities to find and characterize these vector breeding sites. Within this study, we identified land cover types associated with malaria vector breeding sites in West Africa. Drone images from two malaria endemic regions in Burkina Faso and Côte d’Ivoire were assembled and labeled using open-source tools. We developed and applied a workflow using region of interest-based and deep learning methods to classify these habitat types from very high resolution natural color imagery. Analysis methods achieved a dice coefficient ranging between 0.68 and 0.88 for different vector habitat types; however, this classifier consistently identified the presence of specific habitat types of interest. This establishes a framework for developing deep learning approaches to identify vector breeding sites and highlights the need to evaluate how results will be used by control programs.

Malaria is a constant reminder of the climate change impacts on health. Many studies have investigated the influence of climatic parameters on the of malaria transmission. Climate conditions can modulate malaria transmission through increased temperature, which reduces the duration of the parasite's reproductive cycle inside the mosquito. The intensity and frequency of the rainfall modulate the development of the mosquito population. In this study, the Liverpool Malaria Model (LMM) is used to simulate the spatio-temporal variation of the malaria incidence in Senegal. The simulations are based on the WATCH Forcing Data applied to ERA-Interim data (WFDEI) used as a point of reference, and biased-corrected CMIP6 models, separating historical and projections for 3 Shared Socio-economic Pathways scenarios (SSP126, SSP245 and SSP585). Our results highlight a strong increase in temperatures, especially towards eastern Senegal under the SSP245 but mainly the SSP585 scenarios. The ability of the LMM model to simulate the seasonality of malaria incidence is assessed. The model reveals a period of high malaria transmission between September and November with a maximum reached in October. Results indicate a decrease in malaria incidence in certain regions of the country for the far future and for the extreme scenario. This study is importance for the planning, prioritization, and implementation of control activities in Senegal.

Malaria remains an important cause of death, especially in sub-Saharan Africa with about 228 million malaria cases worldwide and an estimated 405,000 deaths in 2019. Currently, malaria is diagnosed in the health facility using a microscope (BS) or rapid malaria diagnostic test (MRDT) and with area where these tools are inadequate the presumptive treatment is performed. Apart from that self-diagnosis and treatment is also practiced in some of the households. With the high-rate self-medication on malaria drugs, this study aimed at computing the most significant features using feature selection methods for best prediction of malaria in Tanzania that can be used in developing a machine learning model for malaria diagnosis. A malaria symptoms and clinical diagnosis dataset were extracted from patients’ files from four (4) identified health facilities in the regions of Kilimanjaro and Morogoro. These regions were selected to represent the high endemic areas (Morogoro) and low endemic areas (Kilimanjaro) in the country. The dataset contained 2556 instances and 36 variables. The random forest classifier a tree based was used to select the most important features for malaria prediction. Regional based features were obtained to facilitate accurate prediction. The feature ranking as indicated that fever is universally the most influential feature for predicting malaria followed by general body malaise, vomiting and headache. However, these features are ranked differently across the regional datasets. Subsequently, six predictive models, using important features selected by feature selection method, were used to evaluate the features performance. The features identified complies with malaria diagnosis and treatment guideline provided with WHO and Tanzania Mainland. The compliance is observed so as to produce a prediction model that will fit in the current health care provision system in Tanzania.

COVID-19 was an inflammatory pneumonia caused by a respiratory infection with a coronavirus named SARS-CoV-2. Severely ill COVID-19 patients could die of acute pulmonary and systemic inflammation. Thus, there was a theory that long COVID-19 shared many similarities with systemic autoimmune diseases. There was also a theory that the SARS-CoV-2 virus could infect many cell- and tissue-types distributed throughout multiple organ systems of the body. I aim to review the above theories using unbiased high-throughput datasets cataloguing gene expression. Studies reviewed used the technology of next generation sequencing, either as bulk tissue RNA sequencing, or as single-cell RNAs sequencing; ingenious methods for signal deconvolution were then used to identify individual cell types. Datasets reviewed suggested that severe COVID-19 induced expression of genes associated with pro-inflammatory signaling, tissue development or remodeling, scarring, or cell death. The datasets also provided evidence for several inflammatory syndromes associated with COVID-19, such as neuronal COVID, acute respiratory disease syndrome, vascular inflammation, or multisystem inflammatory syndrome. Indeed, inflammatory signal during severe COVID-19 was reported in many cell types, for example in structural cells, in infiltrating immune cells, in the vascular system, or in circulating cells in the blood. There was also frequently a change in proportions of immune cell-types in the blood, epithelial cells in the lungs, or among infiltrating immune cells.

Dementia is a rising public health concern. Feeding and nutritional problems increase as the disease progresses, affecting clinical course and caregiver burden. While some guidelines advise against percutaneous endoscopic gastrostomy (PEG) and tube feeding in advanced dementia, conflicting evidence exists. This study aims evaluating nutritional status and the influence of PEG-feeding on outcome and evolution of nutritional/progonosis markers of patients with severe dementia (PWSD) who underwent gastrostomy for nutritional support. We conducted a 16-year rectrospective study on 100 PEG-fed PWSD with strong familiar support. We evaluated survival PEG-feeding period, safety, and objective nutritional/progonosis data at the gastrostomy day and after 3 months: Body Mass Index (BMI), Mid Upper Arm Circumference, Tricipital Skinfold, Mid-Arm Muscle Circumference, albumin, transferrin, total cholesterol and hemoglobin. Most patients presented low values in these nutritional/progonosis parameters. No major life-threatening PEG complications were reported. The mean survival time after gastrostomy was 27.9 months (median of 17 months). Female sex, BMI recovery at 3 months, and higher baseline hemoglobin levels were associated with a reduced risk of death and increased survival time. The study concluded that, in carefully selected PWSD with strong familiar support, PEG feeding can improve nutritional status and have a positive impact on survival.

The quality assurance of malaria microscopy unit was established by National Malaria Control Program, Ministry of Health (MoH) in 2009 to respond to the internal malaria microscopy validation process, in microscopy training for malaria diagnosis in the country, monitoring and supervision, and other relevant activities regarding laboratory diagnosis of malaria in Timor-Leste is described. Trained laboratory technicians who are working in the relevant unit. There are two ways of malaria microscopy validation process such as onsite validation and monthly validation after received malaria blood smear from senior analyst at the municipality level. The aim of this work is to describe the quality assurance of malaria microscopy system in Timor-Leste. The management of quality assurance service support, the importance of quality assurance of malaria microscopy, the role of quality assurance of malaria microscopy, challenge and opportunities encountered by quality assurance microscopy unit, National Health Laboratory are highlighted. Key words: Quality assurance of malaria microscopy, system, Timor-Leste.

Malaria is one of the life-threatening disease caused by the Anopheles mosquitoes affecting the human red blood cells. It is the global health concern which is quite common in tropical as well as sub-tropical parts of the World. Therefore, it is an important to have an effective computer aided system in place for early detection and treatment. State of the art machine learning techniques are used to detect the infected malaria cells from the pool of images. As the visual heterogeneity of the malaria dataset is highly complex and dynamic, therefore higher number of images are needed to train the machine learning models effectively. However, hospitals as well as medical institutions do not share the medical image data for collaboration due to general data protection regulation (GDPR) and data protection act (DPA). To overcome this collaborative challenge, our research is inspired to use the real-time medical image data while using the framework of federated learning (FL) framework that will ensure the data privacy while mutual collaboration of hospitals and medical institutes. We have used the state of the art machine learning models that include the Resnet50 and densenet in a federated learning framework. We have experimented both models in different settings and our preliminary results showed that the densenet model performed better in accuracy (75%) in contrast to resnet50 (72%) while considering 8 clients, while the trend is observed common in 4 clients with the similar accuracy of 94% and 6 client showed that the densenet model performed quite well with the accuracy of 92% while resnet50 achieving only 72%.

Polymerase chain reaction (PCR) technique is one of the molecular methods in amplifying DNA for the detection of malaria. However, the limitations of PCR especially when used for routine clinical practice can hamper its sensitivity and specificity. With that, this study focuses on designing a microfluidic device that will mimic the function of a conventional genus-specific PCR based on 18S rRNA gene to detect malaria parasites (Plasmodium falciparum) at low grade parasitemia. The design was drawn and simulated using ANSYS 14.5 Computational Fluid Dynamics (CFD). The simulation shows that adding loops to the design increases its relative deviation but to a minimal extent as compared to having only a straight path design, which indicates that looping is acceptable in designing a microfluidic device to minimize chip length. Also, increasing the cross-sectional area of the fluid path decreases the efficiency of the design, thus, the design with a relatively smaller cross-sectional area is favored. And lastly, among the three materials utilized, the chip made of polypropylene is the most efficient with a relative deviation of 0.94 as compared to polycarbonate and polydimethylsiloxane which have relative deviations of 2.78 and 1.92, respectively.

Malaria remains a primary public health challenge in Africa, and there is growing interest in leveraging artificial intelligence (AI) to raise malaria interventions. This research examines the possible influence, challenges, and recommendations for implementing AI-based personalized malaria interventions in Africa. AI offers several opportunities in malaria management, including early detection and prediction of outbreaks, improved diagnosis, personalized interventions, optimal treatment recommendations, surveillance and response, resource optimization, and research innovation. However, the implementation of AI in malaria interventions faces various challenges. These include data availability and quality, infrastructure and resource constraints, contextual relevance and generalizability, ethical and privacy considerations, integration into healthcare workflows, and the need to build trust and acceptance among stakeholders. To address these challenges, it is recommended to strengthen data infrastructure, build local capacity in AI technologies, contextualize AI models to local settings, address ethical considerations, establish monitoring and evaluation frameworks, promote collaboration and knowledge sharing, and secure sustainable funding and long-term commitment. By considering these recommendations, stakeholders can work towards implementing AI-based personalized malaria interventions in Africa that can contribute to improving malaria control outcomes, reducing the weight of the disease, and advancing public health in the region.

This is a single center retrospective study to assess safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. Retrospective chart review was performed on 58 infants and data was collected at baseline, 1, 6, 12, 24, 48, and 72 hours of iloprost initiation. Primary outcomes were change in heart rate (HR), fraction of inspired oxygen (FiO2), mean airway pressures (MAP), blood pressure (BP) and oxygenation index (OI). Secondary outcomes were need for extracorporeal membrane oxygenation (ECMO) and death. 51 patients treated for > 6 hours were analyzed in 2 age groups, neonate (≤28 days: n=32) and infant (29-365 days: n=19). FiO2 (p

Background: Malaria remains a serious public health concern worldwide, particularly in tropical and subtropical regions, and the leading causes of mortality and morbidity in children especially among those aged under five in developing countries. Malaria can be fatal if not promptly and accurately diagnosed, especially in children.This study was carried out to determine the level of malaria infection and its associated risk factors among febrile children.Methods: Blood samples were collected and analyzed from two- hundred (200) systematically selected febrile children aged 1-10 years old. assay of samples collected were carried out using standard methods.data were collected using a pretested structured questionnaire. Results: Results obtained from study subjects shows that, of the eighty-seven (87) infected subjects, 34 (39.1%) were aged 1-5 years, while 52 (59.8%) were within the range of 6 years and above.severity of infection showed 48 (55.2%) with scanty parasitic infection while 25 (28.7%) showed moderate infection, and 13 (14.9%) showed heavy infection.The association of age and level of parasitemia showed that 34 (58.8% ) subjects below 5 years, recorded scanty malaria compared to 14.7% with severe malaria within the age range.Considering gender, of the 33 infected female subjects, 45.5% had scanty malaria, 36.4% showed moderate malaria, while 18.2% had severe malaria, compared to the males subjects.Conclusion: This study reveals the prevalence of malaria infection with some level of severity among children at our study location.The need for prompt diagnosis and improved access to all malaria interventions becomes relevant,with a special focus on the high risk group.

Plasminogen activator inhibitor-1 (PAI-1) has a significant role in fibrinolysis, atherogenesis, cellular senescence, and chronic inflammation. OSA (obstructive sleep apnea) leads to increased PAI-1 levels and the development of cardiovascular disease (CVD). The aim of this study was to determine the effects of CPAP therapy in patients with severe OSA on coagulation parameters and PAI-1. This prospective, controlled study enrolled 57 patients who were newly diagnosed with severe OSA, 37 of whom had had a good CPAP adherence after 6 months of therapy (usage of the device for at least 4 h per night), and their data were analyzed. The analysis showed a statistically significant increase in D-dimer values (415 (316.5-537.5) before CPAP therapy vs. 499 (327-652) after therapy, p = 0.0282) and a decrease in fibrinogen values (3.665 ± 0.752 before CPAP therapy vs. 3.365 ± 0.771) after therapy, p = 0.0075)). The PAI-1 concentration values before and after CPAP therapy did not differ significantly (17.35±7.01 ng/ml before CPAP therapy vs. 17.42±6.99 ng/ml after therapy, p = 0.9367). This study shows a tendency to improve the fibrinolytic capacity in patients with OSA after CPAP therapy although PAI-1 levels did not differ significantly.

Endothelial autocrine signaling is essential to maintain vascular hemostasis. There is limited in-formation about the role of endothelial autocrine signaling in regulating severe pulmonary vas-cular remodeling during the onset of pulmonary arterial hypertension (PAH). In this study, we employed the first severe PAH mouse model, Egln1Tie2Cre (Tie2Cre-mediated disruption of Egln1) mice, to identify the novel autocrine signaling mediating the pulmonary vascular endothelial cells (PVECs) hyperproliferation and the pathogenesis of PAH. PVECs isolated from Egln1Tie2Cre lung expressed upregulation of many growth factors or angiocrine factors such as CXCL12, and exhib-ited hyperproliferative phenotype in coincident with upregulation of proliferation specific tran-scriptional factor FoxM1. Treatment of CXCL12 on PVECs increased FoxM1 expression, which was blocked by CXCL12 receptor CXCR4 antagonist AMD3100 in culture human PVECs. Endo-thelial specific deletion of Cxcl12 (Egln1/Cxcl12Tie2 Cre) or AMD3100 treatment in Egln1Tie2Cre mice downregulated FoxM1 expression in vivo. We then generated and characterized a novel mouse model with endothelial specific FoxM1 deletion in Egln1Tie2Cre mice (Egln1/Foxm1Tie2Cre), and found that endothelial FoxM1 deletion reduced pulmonary vascular remodeling and right ventricular systolic pressure. Together, our study identified a novel mechanism of endothelial autocrine sig-naling in regulating PVECs hyperproliferation and pulmonary vascular remodeling in PAH.

Severe cancer pain significantly diminishes patients' quality of life, leading to increased reliance on caregivers. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD) with symptoms such as nausea, vomiting, drowsiness, and constipation. While controlled-release oxycodone is a viable option, its prolonged use can lead to opi-oid-induced constipation (OIC). Addressing this, a relative novel formulation - a fixed 2:1 ratio of oxycodone and naloxone in prolonged release - aims to provide analgesia while alleviating OIC. This review critically assesses the evidence on the efficacy, safety, and patient experience of ox-ycodone/naloxone prolonged release in managing severe cancer pain, emphasizing the necessity for a targeted approach in this patient population.

Abstract: Background: Vasoplegic shock syndrome(VSS) after an off-pump coronary artery bypass graft (OPCABG) is an extremely rare condition. Inotropic support is usually the first-line therapy though it can precipitate several complications or be ineffective. We report the first case of severe refractory VSS after OPCABG successfully treated with hydroxycobalamin. Methods: A 77-year-old gentleman underwent OPCABG for three vessels coronary artery disease. Preoperative LV ejection fraction was 28%, and the patient before surgery started sacubi-tril/valsartan titrated, then, to the highest dose. Surgery was uneventful and, by the end of the procedure, TEE showed improved biventricular contractility. Results: The patient was transferred to the ICU without inotropic support but he developed soon hypotension. TEE ruled out pericardial tamponade and confirmed fair contractility. Norepineph-rine was titrated to a medium-high dose, vasopressin was started and a Swan-Ganz catheter was placed. SVR was 480 dyn·s·cm−5. Despite aggressive pharmacologic treatment (including Methylprednisolone and Methylene blue), no improvements were noticed. 10 g of hydroxycobalamin were administered. One hour later hemodynamic status re-assessment showed SVR > 800 dyn·s·cm−5. Afterward, vasopressors were gradually reduced. Conclusions: Our case demonstrated the importance of adequate early treatment in VSS after OPCABG. For the first time, hydroxycobalamin was effectively used to restore homeostasis.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

Diarrhoea contributes significantly in the under-five childhood morality and mortality worldwide. This cross-sectional study was carried out in a tertiary care hospital in Ujjain, India from July 2015 to June 2016. Consecutive children aged 1 month to 12 years having “some dehydration” and “dehydration” according to World Health Organization classification were eligible to be included in the study. Other signs and symptoms used to assess severe dehydration were capillary refill time, urine output, and abnormal respiratory pattern. A questionnaire was administered to identify risk factors for severe dehydration, which was the primary outcome. Multivariate logistic regression modeling was used to detect independent risk factors for severe dehydration. The study included 332 children, with mean ± standard deviation age of 25.62 ± 31.85 months; out of which, 70%(95% confidence interval [CI] 65 to 75) were diagnosed to have severe dehydration. The independent risk factors for severe dehydration were: child not exclusive breast fed in the first six months of life (AOR 5.67, 95%CI 2.51 to 12.78; p<0.001), history of not receiving oral rehydration solution before hospitalization (AOR 1.34, 95%CI 1.01 to 1.78; p=0.038), history of not receiving oral zinc before hospitalization (AOR 2.66, 95%CI 1.68 to 4.21; p<0.001) and living in overcrowded conditions (AOR 5.52, 95%CI 2.19 to 13.93; p<0.001). The study identified many risk factors associated with severe childhood dehydration; many of them are modifiable though known and effective public health interventions.

The emergence of resistance to first-line antimalarial drugs calls for development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4-aminoquinoline hydrazone analogues were tested on Plasmodium falciparum strains: IC50 values after a 48-hour cycle ranged from 0.60 - 49 µM, while the 72-hour cycle ranged from 26-219 nM on the multi-drug resistant K1 strain. Time-course assays were carried out to define the activity of the lead compounds which inhibited over 50 % growth in 24 hours and 90% growth in 72 hours. Cytotoxicity assays with HepG2 cells showed IC50 values of 0.87-11.1 M, whereas in MDBK cells IC50 values ranged from 1.66-11.7 M. High selectivity indices were observed for the lead compounds screened at 72 hours on P. falciparum. Analyses of stage-specificity revealed that the ring stage of the parasite life cycle were most affected. Based on antimalarial efficacy and in vitro safety profiles, lead compound 4-(2-benzylidenehydrazinyl)-6-methoxy-2-methylquinoline 2 was progressed to drug combination studies for the detection of synergism, with a combinatory index of 0.599 at IC90 for the combination of with artemether, indicating a synergistic antimalarial activity. Compound 2 was screened on different strains of P. falciparum (3D7, Dd2) which maintained similar activity to K1, suggesting no cross-resistance between multi-drug resistance and sensitive parasite strains. In vivo analysis with 2 showed suppression of parasitaemia with P. yoelii NL treated mice (20 mg/kg and 5 mg/kg).

Lead pollutants mainly from urban agricultural practices, Leaded paints, Leaded fuels spillages, Lead-contaminated air, soils, and water sources pause a health threat to urban children in Uganda. Prolonged Lead exposure affects iron metabolism, by competitively blocking iron absorption leading to anemia. Blood Lead (BL) inhibits key enzymes ferrochelatase and aminolevulinic acid dehydrogenase (ALAD) involved in hemoglobin (Hb) biosynthesis even at very low levels. Lead poisoning and malaria infection geographically overlap, and both produce similar hematological outcome especially in children. Malaria parasites cause anemia by destroying parasitized red blood cells, therefore, co-existence of BL and malaria parasites infection worsens the anemia status of the host. This study aimed at expounding the extent of heme synthesis inhibition by BL levels among a study group of malaria positive children by measuring levels of free erythrocyte protoporphyrin (FEP) in blood samples. Briefly venous blood samples from 198 children were analyzed for malaria parasite densities by the thick smear method, hemoglobin (Hb) concentrations determined by the standard cyan methemoglobin method, BLL were analyzed on an atomic absorption spectrophotometer and FEP levels were fluorometrically measured. The results showed means of BLL (9.3 µg/dL), Hb (7.5 g/dL), FEP/Hb (8.3 µg/g) and parasite density (PD) (3.21×10³ parasites / µL) among the study group. A majority of 151/198 (76.3%) of the children were moderately anemic while 8/198 (4%) were severely anemic. There was weak correlation between PD and Hb (R²= -0.15, P-value < 0.001), as compared to one between FEP/Hb and Hb (R²= -0.6, P-value=0.001). The study concludes that BL is a significant contributor to malaria anemia and should be considered in the management of anemia in malaria-endemic areas.

The World Health Organization (WHO) documents malaria as one of the leading causes of high morbidity and mortality worldwide. The disease affects millions and kills thousands of people annually. Efforts to reduce the global burden of malaria have prompted WHO to recommend prevention strategies like using anti-malarial drugs. However, these strategies have been ineffective because of anti-malarial drug resistance. The only efficacious malaria treatment is Artemisinin-based Combination Therapy (ACT). However, the extended ACTs clearance times, linked to the emergence of artemisinin monotherapy resistance recorded most recently in Africa and the Great Mekong region, pose a danger to its efficacy. Therefore, better efficacious malaria drugs are required. Since P. falciparum heat shock protein 90 (PfHsp90) is a well-characterized malaria drugs target, this study uses it to discover more efficacious malaria drugs. An in-silico approach was used to discover PfHsp90 inhibitors with pharmacological properties against Plasmodium malaria using molecular dynamics simulation (MDS) and hierarchical virtual screening. Geldanamycin (GDM), a well-known anti-PfHsp90 compound, was used to identify PfHsp90 inhibitors with pharmacological properties against Plasmodium malaria by screening it against the ZINC database via the ZINCPHARMER web server. This virtual screening process resulted in 17 hits. These ZINCPHARMER hits were subjected to drug-likeness and pharmacokinetics properties analysis in the SwissADME web server, and 9 of them satisfied the requirements. The 9 ZINC compounds were docked with PfHsp90 using the PyRx software to understand their interactions. From the molecular docking results, ZINC09060002 (-8.2 kcal/mol), ZINC72133064 (-7.8 kcal/mol), ZINC72163401 (-7.7 kcal/mol), ZINC72358537 (-8.1 kcal/mol), and ZINC72358557 (-7.6 kcal/mol) had better binding affinities to PfHsp90 than GDM (-7.5 kcal/mol). The stability of these molecularly docked protein-inhibitor complexes was assessed through MDS using GROMACS 2022. ZINC72163401, ZINC72358537, and ZINC72358557 formed stable complexes with PfHsp90. The lead compounds were subjected to in vitro validation for their inhibitory capability. They showed promising inhibition of parasite growth with IC50 values ranging between 200 – 400 ng/ml. In this regard, the three PfHsp90 inhibitors can be used as anti-malarial drugs. However, further structural optimization studies and clinical (in vivo) tests are necessary to ascertain the antimalarial activity of these compounds in humans.

We have considered a SEIR-SEI Vector-host mathematical model which captures malaria transmission dynamics, described and built on 7-dimensional nonlinear ordinary differential equations. We compute the basic reproduction number of the model; examine the positivity and boundedness of the model compartments in a region using well established methods viz: Cauchy’s differential theorem, Birkhoff & Rota’s theorem which verifies and reveals the well-posedness, and carrying capacity of the model respectively, the existence of the Disease-Free (DFE) and Endemic (EDE) equilibrium points were determined and examined. Using the Gaussian elimination method and the Routh-hurwitz criterion, we convey stability analyses at DFE and EDE points which indicates that the DFE (malaria-free) and the EDE (epidemic outbreak) point occurs when the basic reproduction number is less than unity (one) and greater than unity (one) respectively. We obtain a solution to the model using the Variational iteration method (VIM) (an unprecedented method) to each population compartments and verify the efficacy, reliability and validity of the proposed method by comparing the respective solutions via tables and combined plots with the computer in-built Runge-kutta-Felhberg of fourth-fifths order (RKF-45). We illustrate the combined plot profiles of each compartment in the model, showing the dynamic behavior of these compartments; then we speculate that VIM is efficient and capable to conduct analysis on Malaria models and other epidemiological models.

Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it doesn't provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using Spot-synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: 40 IgA epitopes were identified, with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90-99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes, except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.

This study examines the performance of the Indian Monsoon Data Assimilation and Analy-sis (IMDAA) in predicting five extremely severe cyclonic storms (ESCS) over the Bay of Bengal. The Advanced Research version of the WRF (ARW) model is utilized for this analysis over the last two decades. The initial and lateral boundary conditions are derived from the IMDAA datasets with a horizontal resolution of 0.12° × 0.12°. Five ESCSs from the past two decades are considered: Sidr 2007, Phailin 2013, Hudhud 2014, Fani 2019, and Amphan 2020. The model is integrated up to 96 hours using double nested domains of 12 km and 4 km. Model performance is evaluated using the 4 km results, compared with available observational datasets, including the best-fit data from the India Meteorological Department (IMD), The Tropical Rainfall Measuring Mission (TRMM) satellite, and Doppler Weather Radar (DWR). The results indicate that IMDAA provides accurate forecasts for ESCSs Fani, Hudhud, and Sidr in terms of track, intensity, and mean sea level pressure, aligning well with IMD observational datasets. However, Sidr's track deviates more from the observations. The calculated mean absolute maximum sustained wind speed errors range from 8.4 m/s to 10.6 m/s from day-1 to day-4, while mean track errors range from 114 km to 496 km during the same period. Statistical analysis, including bias, mean error, and standard deviation, underscores the significance of ESCS prediction. The discussion also covers rainfall prediction, maximum reflectivity, and the associated structure of the storms.

Climate change is impacting the spread/intensity of vector-borne diseases, including malaria, and accelerating evolutionary/adaptive changes in vector species. These changes including chromoso-mal inversions and overexpression and/or changes in allele frequencies of thermotoler-ance-associated genes, may facilitate insecticide resistance through pleiotropy. This study investi-gated the impact of thermotolerance on pyrethroid resistance in four populations of malaria vector An. gambiae, from savanna/sub-Sahel of northern Nigeria. Anopheles coluzzii and An. gambiae were the only malaria vectors found, sympatric in all the sites, with the former species predominant. High thermotolerance was observed, with no mortality at 38°C, and LT50 of ~44°C. Significantly high permethrin resistance was observed (mortality <50%) in heat-hardened (44°C) larvae from two sites, BUK and Pantami, compared with control, and heat-hardened adult females from Auyo (mortality = 3.00%±1.20, χ2 = 5.83, p<0.01) compared with control (12.00%±4.65). The 2La chromosomal inver-sion was detected at ~50% in larvae and 58% in adult females. Significant association was observed (OR = 7.2, p<0.03) between permethrin resistance and 2La/+a rearrangement compared with 2L+a/+a, in BUK larvae. For all sites permethrin resistance correlated with 2La/a homozygosity in adult fe-males [OR = 5.02, p=0.01). qRT-PCR identified 6 genes commonly induced/overexpressed, including heat shock protein 70 (AGAP004581) which was 2468x and 5x overexpressed in heat-hardened and permethrin-resistant females, respectively, trehalose-6-phosphate synthase (AGAP008227), and ionotropic glutamate receptor genes, IR25a (AGAP010272) and IR21a (AGAP008511). This study highlights challenges associated with insecticide-based malaria vector control, and the epidemiological significance of taking climate variables into account for design/choice of control measures.

In Brazil, malaria transmission is mostly confined to the Amazon, where substantial progress has been achieved towards disease control in the past decade. Vector control has been historically considered a fundamental part of the main malaria control programs implemented in Brazil. However, the conventional vector-control tools have been insufficient to eliminate local vector populations due to the complexity of the Amazonian rainforest environment and ecological features of malaria vector species in the Amazon, especially Anopheles darlingi. Malaria elimination in Brazil and worldwide eradication will require a combination of conventional and new approaches that takes into account the regional specificities of vector populations and malaria transmission dynamics. Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, these new vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put on research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the development of such innovative tools.

Hong Kong was under the direct hit of Severe Typhoon Koinu (2314) on 8 and 9 October 2023, necessitating the issuance of the Increasing Gale or Storm Signal, No. 9. Koinu was a very challenging case for TC forecasting and warning services due to its compact size and erratic movement over the northern part of the South China Sea. This paper reviews the difficulties and challenges on the forecasting aspect of the severe typhoon. The predicted tropical cyclone track and intensity from both conventional models and emerging artificial intelligence models are examined, as well as local wind and rainfall forecast. Experience in this case study showed that while deterministic global models only performed moderately and were not able to adequately support early warning, a regional model and AI models could more effectively support decision making for operational tropical cyclone warning service.

Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially to those with co-morbidities, the elderly and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analysis of transcriptomic RNAseq and single-cell sequencing datasets comparing between severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examined the existing literature summarizing the characteristics of MDSCs, the evidence of MDSCs in facilitating severe COVID-19 pathogenesis and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualise the temporal changes of specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution at https://temporal-severe-covid.streamlit.app/, based on our previous study described by Ong et al., 2021.

Strong convective storms can be a serious threat to modern society, influencing both the economy and human life. Thunderstorms can bring much-needed rain after a dry spell, but the nature of thunderstorm mostly causes damage due to high wind associated with it and heavy intensity rain that mostly causes quick overlandflow and flashfloods. The paper focused on the 2011 Pukkelpop event in Belgium where due to heavy thunderstorm a lot of financial damage occurred, and five casualties. In this paper we look into the basic elements that enforces the creation of a thunderstorm like CAPE and windshear. A representative grid has been taken from the Alaro-0 model of 12.5 km resolution for the analysis of the thunderstorm over Belgium which is detailed out in the methodology. The model runs of Alaro-0 from Royal Meteorological Institute of Belgium (RMI) is used for historical and future years for CAPE and Shear. We look into STEnv which is a composite number that can provide some insight on occurrence of thunderstorm, and STEnv is when CAPE*Shear exceeds certain threshold. In this study the threshold has been chosen as 97%. Only summer months have been taken into account into this study as summer(s) has the most thunderstorm in Belgium. The analysis of CAPE and STEnv over historical period (1977-2005), near future (2041-2069) and far future (2071-2099) shows significant increase in occurrence of thunderstorm in the 2071-2099s, specially in extreme cases such as 97% and 99% quantile. CAPE (J/Kg) increases in all future scenarios compared to the historical period. In 2071-2099s, CAPE increases from 2100 J/Kg to 2300 J/Kg (90% quantile) and from 3500 J/Kg to 3900 J/Kg (99% quantile) compared to the historical period. The number of STEnv increases from 300 to 378 in top 10% storm case (90% quantile), 158 to 218 in top 5% storm (95% quantile), 97 to 153 in top 3% storm (97% quantile) and 33 to 66 in top 1% storm (99% quantile) with a 90% confidence interval overall. Shear mostly remains unchanged. The study also shows spatial variation of CAPE, shear and STEnv over Belgium for present and future scenarios in different extremities (90%, 95%, 97% and 99% quantiles). There is a good indication that increase in CAPE translates to increase in STEnv, which is an accepted measure to predict occurrence of thunderstorm. Future climate change also amplifies the occurrence of thunderstorm, which is coherent with relevant studies. The uncertainty related to the study can be reduced with more detailed dataset and involvement of numerical weather prediction models beyond data statistics.

The incidence of Severe Combined Immunodeficiency (SCID) in Manitoba, (1/15,000), is at least three to four times higher than the national average and that reported from other jurisdictions. It is overrepresented in two population groups: Mennonites (ZAP70 founder mutation) and First Nations of Northern Cree ancestry (IKBKB founder mutation). We have previously demonstrated that in these two populations the most widely utilized T-cell receptor excision circle (TREC) assay is an ineffective newborn screening test to detect SCID as these patients have normal numbers of mature T-cells. We have developed a semi-automated, closed tube, high resolution DNA melting procedure to simultaneously genotype both of these mutations from the same newborn blood spot DNA extract used for the TREC assay. Parallel analysis of all newborn screening specimens utilizing both TREC analysis and the high resolution DNA procedure should provide as complete ascertainment as possible of SCID in the Manitoba population.

Abstract: To obtain bovine oocytes in high quality, effects of vitamin C (VC) on in vitro maturation (IVM) of bovine oocytes and early embryo development were investigated. The results showed that: 1) The IVM medium containing 50 µg/mL VC improved the oocyte maturation rate, while no effects on the development of parthenogenetic embryos; 2) The in vitro culture (IVC) medium containing 20 µg/mL VC increased the cleavage rate of the in vitro fertilized (IVF) embryos, enhanced the mRNA levels of pluripotency gene Oct4, Sox2, Cdx2 and Nanog in the blastocysts, but no effect on the blastocyst rate; 3) Combing supplemention of 50 µg/mL in IVM medium + 20 µg/ml VC in IVC medium (VC 50/20) increased the cleavage rate of IVF embryos and enhanced the mRNA levels of Oct4, Sox2, Cdx2 and Nanog in the blastocysts; 4) Combination of VC 0/20 and VC 50/20 enhanced the expression of anti-apoptotic gene Bcl-2 and VC 50/0 weakened the expression of pro-apoptotic gene Bax, while VC 0/40 and VC 0/60 increased Bax expression and decreased the Bcl-2/Bax ratio in blastocysts. Together, VC supplementation at tuned concentration as well its combination in IVM and IVC media improves the developmental rates of bovine oocytes and embryos.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.