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IntroductionIn malaria management, insecticides play a crucial role in targeting disease vectors. Benzothiazole derivatives have also been reported to possess insecticidal properties, among several other properties they exhibit. The female Anopheles mosquito is responsible for transmitting the malaria parasite when infected. Anopheles gambiae (Ag) and Anopheles funestus (Af) are two of the most notable Anopheles species known to spread malaria in Nigeria. Trehalase is an enzyme that breaks down trehalose. Recent research has proposed it as a viable target for inhibition since it aids in flight and stress adaptation.MethodsThis study aimed to investigate benzothiazole derivatives as potential inhibitors of trehalase of Anopheles funestus (AfTre) and Anopheles gambiae (AgTre) using toxicity profiling, molecular docking, and dynamic simulation for future insecticidal intervention. A total of 4,214 benzothiazole-based compounds were obtained from the PubChem database and subjected to screening against the 3D modelled structure of AfTre and AgTre. Compounds with some toxicity levels were optimised, and the obtained lead compounds were further investigated through molecular docking studies. Furthermore, the best hit was subjected to parameters such as RMSD, RMSF, SASA, Rg, and hydrogen bond to confirm its stability when in a complex with AfTre, and these parameters were compared to that of validamycin A (control ligand).Results and discussionThe post-screening analysis showed binding affinities of −8.7 and −8.2 kcal/mol (compound 1), −8.2 and −7.4 kcal/mol (compound 2), compared to −6.3 and −5.1 kcal/mol (Validamycin A, a known inhibitor) against AfTre and AgTre, respectively. The molecular dynamics simulation showed that compound 1 (the best hit) had good stability when in complex with AfTre. These findings suggest that these best hits can serve as potential inhibitors for the development of novel insecticides in the control of malaria vectors.

Malaria remains a significant global health concern causing numerous fatalities and the emergence of antimalarial drug resistance highlights the urgent need for novel therapeutic options with innovative mechanisms of action and targets. This study aimed to design potential inhibitors of Plasmodium falciparum 6-pyruvoyltetrahydropterin synthase (PfPTPS), synthesize them, and experimentally validate their efficacy as antimalarial agents. A structure-based approach was employed to design a series of novel derivatives, including amidinyl, amidoximyl and hydroxamic acid analogs (1c, 1d, 2b, and 3b), with a focus on their ability to bind to the Zn2+ present in the active site of PfPTPS. The syntheses of these compounds were accomplished through various multi-step synthetic pathways and their structural identities were confirmed using 1H and 13C NMR spectra, mass spectra, and elemental analysis. The compounds were screened for their antiplasmodial activity against the NF54 strain of P. falciparum and in vitro cytotoxicity testing was performed using L-6 cells. The in vivo acute toxicity of the compounds was evaluated in mice. Docking studies of the compounds with the 3D structure of PfPTPS revealed their strong binding affinities, with compound 3b exhibiting notable metal–acceptor interaction with the Zn2+ in the protein binding pocket thereby positioning it as a lead compound for PfPTPS inhibition. The in vitro antiplasmodial studies revealed moderate efficacies against the Pf NF54 strain, particularly compounds 1d and 3b which displayed IC50

The inhibition of O-acetyl sulphydrylase synthase isoforms has been reported to represent a promising approach for the development of antibiotic adjuvants. This occurs via the organism developing an unpaired oxidative stress response, causing a reduction in antibiotic resistance in vegetative and swarm cell populations. This consequently increases the effectiveness of conventional antibiotics at lower doses. This study aimed to predict potential inhibitors of Salmonella typhimurium ortho acetyl sulphydrylase synthase (StOASS), which has lower binding energy than the cocrystalized ligand pyridoxal 5 phosphate (PLP), using a computer-aided drug design approach including pharmacophore modeling, virtual screening, and in silico ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) evaluation. The screening and molecular docking of 4254 compounds obtained from the PubChem database were carried out using AutoDock vina, while a post-screening analysis was carried out using Discovery Studio. The best three hits were compounds with the PubChem IDs 118614633, 135715279, and 155773276, possessing binding affinities of −9.1, −8.9, and −8.8 kcal/mol, respectively. The in silico ADMET prediction showed that the pharmacokinetic properties of the best hits were relatively good. The optimization of the best three hits via scaffold hopping gave rise to 187 compounds, and they were docked against StOASS; this revealed that lead compound 1 had the lowest binding energy (−9.3 kcal/mol) and performed better than its parent compound 155773276. Lead compound 1, with the best binding affinity, has a hydroxyl group in its structure and a change in the core heterocycle of its parent compound to benzimidazole, and pyrimidine introduces a synergistic effect and consequently increases the binding energy. The stability of the best hit and optimized compound at the StOASS active site was determined using RMSD, RMSF, radius of gyration, and SASA plots generated from a molecular dynamics simulation. The MD simulation results were also used to monitor how the introduction of new functional groups of optimized compounds contributes to the stability of ligands at the target active site. The improved binding affinity of these compounds compared to PLP and their toxicity profile, which is predicted to be mild, highlights them as good inhibitors of StOASS, and hence, possible antimicrobial adjuvants.

Introduction: Quinazolin-4(3H)-one derivatives have attracted considerable attention in the pharmacological profiling of therapeutic drug targets. The present article reveals the development of arylidene-based quinazolin-4(3H)-one motifs as potential antimicrobial drug candidates.Methods: The synthetic pathway was initiated through thermal cyclization of acetic anhydride on anthranilic acid to produce 2-methyl-4H-3,1-benzoxazan-4-one 1, which (upon condensation with hydrazine hydrate) gave 3-amino-2-methylquinazolin-4(3H)-one 2. The reaction of intermediate 2 at its amino side arm with various benzaldehyde derivatives furnished the final products, in the form of substituted benzylidene-based quinazolin-4(3H)-one motifs 3a–l, and with thiophene-2-carbaldehyde to afford 3 m. The purified targeted products 3a–m were effectively characterized for structural authentication using physicochemical parameters, microanalytical data, and spectroscopic methods, including IR, UV, and 1H- and 13C-NMR, as well as mass spectral data. The substituted arylidene-based quinazolin-4(3H)-one motifs 3a–m were screened for both in silico and in vitro antimicrobial properties against selected bacteria and fungi. The in silico studies carried out consisted of predicted ADMET screening, molecular docking, and molecular dynamics (MD) simulation studies. Furthermore, in vitro experimental validation was performed using the agar diffusion method, and the standard antibacterial and antifungal drugs used were gentamicin and ketoconazole, respectively.Results and discussion: Most of the compounds possessed good binding affinities according to the molecular docking studies, while MD simulation revealed their levels of structural stability in the protein–ligand complexes. 2-methyl-3-((thiophen-2-ylmethylene)amino) quinazolin-4(3H)-one 3 m emerged as both the most active antibacterial agent (with an minimum inhibitory concentration (MIC) value of 1.95 μg/mL) against Staphylococcus aureus and the most active antifungal agent (with an MIC value of 3.90 μg/mL) against Candida albicans, Aspergillus niger, and Rhizopus nigricans.

Plasmodium falciparum Apicomplexan Apetala 2 Invasion ( Pf AP2-I) transcription factor (TF) is a protein that regulates the expression of a subset of gene families involved in P. falciparum red blood cell (RBC) invasion. Inhibiting Pf AP2-I TF with small molecules represents a potential new antimalarial therapeutic target to combat drug resistance, which this study aims to achieve. The 3D model structure of Pf AP2-I was predicted ab initio using ROBETTA prediction tool and was validated using Save server 6.0 and MolProbity. Computed Atlas of Surface Topography of proteins (CASTp) 3.0 was used to predict the active sites of the Pf AP2-I modeled structure. Pharmacophore modeling of the control ligand and Pf AP2-I modeled structure was carried out using the Pharmit server to obtain several compounds used for molecular docking analysis. Molecular docking and postdocking studies were conducted using AutoDock vina and Discovery studio. The designed ligands’ toxicity predictions and in silico drug-likeness were performed using the SwissADME predictor and OSIRIS Property Explorer. The modeled protein structure from the ROBETTA showed a validation result of 96.827 for ERRAT, 90.2% of the amino acid residues in the most favored region for the Ramachandran plot, and MolProbity score of 1.30 in the 98th percentile. Five (5) best hit compounds from molecular docking analysis were selected based on their binding affinity (between −8.9 and −11.7 Kcal/mol) to the active site of Pf AP2-I and were considered for postdocking studies. For the absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties, compound MCULE-7146940834 had the highest drug score (0.63) and drug-likeness (6.76). MCULE-7146940834 maintained a stable conformation within the flexible protein’s active site during simulation. The good, estimated binding energies, drug-likeness, drug score, and molecular dynamics simulation interaction observed for MCULE-7146940834 against Pf AP2-I show that MCULE-7146940834 can be considered a lead candidate for Pf AP2-I inhibition. Experimental validations should be carried out to ascertain the efficacy of these predicted best hit compounds.

Plasmodium falciparum (Pf) 5-aminolevulinic acid synthase (5-ALAS) is an essential enzyme with high selectivity during liver stage development, signifying its potential as a prophylactic antimalarial drug target. The aim of this study was to identify important potential lead compounds which can serve as inhibitors of Pf 5-ALAS using pharmacophore modeling, virtual screening, qualitative structural assessment, in silico ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) evaluation and molecular dynamics simulation. The best model of the tertiary structure of Pf 5-ALAS was obtained using MolProbity, while the following databases were explored for the pharmacophore-based virtual screening: CHEMBL, ChemDiv, ChemSpace, MCULE, MCULE-ULTIMATE, MolPort, NCI Open Chemical Repository, LabNetwork and ZINC databases. 2,621 compounds were screened against the modeled Pf 5-ALAS using AutoDock vina. The post-screening analysis was carried out using Discovery Studio while molecular dynamics simulation was performed on the best hits using NAMD-VMD and Galaxy Europe platform. Compound CSMS00081585868 was observed as the best hit with a binding affinity of -9.9 kcal/mol and predicted Ki of 52.10 nM, engaging in seven hydrogen bonds with the target’s active site amino acid residues. The in silico ADMET prediction showed that all ten best hits possessed relatively good pharmacokinetic properties. The qualitative structural assessment of the best hit, CSMS00081585868, revealed that the presence of two pyridine scaffolds bearing hydroxy and fluorine groups linked by a pyrrolidine scaffold contributed significantly to its ability to have a strong binding affinity with the receptor. The best hit also showed stability in the active site of Pf 5-ALAS as confirmed from the RMSD obtained during the MD simulation.

Quinoline is one of the most common nitrogen-containing heterocycles owing to its fascinating pharmacological properties and synthetic value in organic and pharmaceutical chemistry. Functionalization of this moiety at different positions has allowed for varying pharmacological activities of its derivative. Several publications over the last few decades have specified various methods of synthesis. This includes classical methods of synthesizing the primary quinoline derivatives and efficient methods that reduce reaction time with increased yield employing procedures that fulfill one of the twelve green chemistry principles, “safer solvent”. The metal nanoparticle-catalyzed reaction also serves as a potent and effective technique for the synthesis of quinoline with excellent atom efficiency. The primary focus of this review is to highlight the routes to synthesizing functionalized quinoline derivatives, including hybrids that have moieties with predetermined activities bound to the quinoline moiety which are of interest in synthesizing drug candidates with dual modes of action, overcoming toxicity, and resistance amongst others. This was achieved using updated literature, stating the biological activities and mechanisms through which these compounds administer relief. The ADMET studies and Structure-Activity Relationship (SAR) of novel derivatives were also highlighted to explore the drug-likeness of the quinoline-hybrids and the influence of substituent characteristics and position on the biological activity of the compounds.

Abstract Introduction The outcomes of transfemoral (TF) compared with transapical (TA) access for transcatheter aortic valve replacement (TAVR) in diabetics are unknown. Methods We queried the NIS database (2011–2014) to identify diabetics who underwent TAVR. We performed a propensity matching analysis comparing TF-TAVR versus TA-TAVR. Results The analysis included 14.555 diabetics who underwent TAVR. After matching, in-hospital mortality was not different between TF-TAVR and TA-TAVR. (3.5 vs. 4.4%, p = 0.11). TF-TAVR was associated with lower rates of cardiogenic shock (2.7 vs. 4.7%, p = 0.02), use of mechanical circulatory support (2.0 vs. 2.9%, p = 0.03), acute renal failure (17.8 vs. 26.5%, p

Trehalase inhibitors are considered safe alternatives for insecticides and fungicides. However, there are no studies testing these compounds on Anopheles gambiae, a major vector of human malaria. This study predicted the three-dimensional structure of Anopheles gambiae trehalase (AgTre) and identified potential inhibitors using molecular docking and molecular dynamics methods. Robetta server, C-I-TASSER, and I-TASSER were used to predict the protein structure, while the structural assessment was carried out using SWISS-MODEL, ERRAT, and VERIFY3D. Molecular docking and screening of 3022 compounds was carried out using AutoDock Vina in PyRx, and MD simulation was carried out using NAMD. The Robetta model outperformed all other models and was used for docking and simulation studies. After a post-screening analysis and ADMET studies, uniflorine, 67837201, 10406567, and Compound 2 were considered the best hits with binding energies of −6.9, −8.9, −9, and −8.4 kcal/mol, respectively, better than validamycin A standard (−5.4 kcal/mol). These four compounds were predicted to have no eco-toxicity, Brenk, or PAINS alerts. Similarly, they were predicted to be non-mutagenic, carcinogenic, or hepatoxic. 67837201, 10406567, and Compound 2 showed excellent stability during simulation. The study highlights uniflorine, 67837201, 10406567, and Compound 2 as good inhibitors of AgTre and possible compounds for malaria vector control.

Abstract Introduction Little is known about ethnic and gender disparities for transcatheter aortic valve replacement (TAVR) procedures in the United States. Methods We queried the Nationwide Inpatient Sample (NIS) database (2011–2014) to identify patients who underwent TAVR. We described the temporal trends in the uptake of TAVR procedures among various ethnicities and genders. Results Our analysis identified 39,253 records; 20,497 (52.2%) were men and 18,756 (47.8%) were women. Among all TAVRs, 87.2% were Caucasians, 3.9% were African Americans (AA), 3.7% were Hispanics, and 5.2% were of other ethnicities. We found a significant rise in the trend of TAVRs in all groups: in Caucasian men (coefficient = 0.946, p

Background: Hepatocellular carcinoma (HCC) is a common and leading cancer around the globe. This study investigated the anticancer properties of extract of Annona senegalensis in N-diethylnitrosamine (DEN) - induced hepatocellular carcinoma in male Wistar rats. Methods: Rats were simultaneously induced with a combination of 100 mg/kg b.wt of DEN and 0.5 mL/kg of carbon tetrachloride (CCl4) intraperitoneally once a week for three weeks in a row. Thereafter, animals were treated with 100 mg/kg and 200 mg/kg b.wt of A. senegalensis extract daily for 21days. Analysis using gas chromatography-mass spectrometry (GC–MS) was carried out to discover the phytoconstituents contained in the n-hexane extract of A. senegelensis. The levels of liver function parameters and antioxidant enzyme activities were determined via spectrophotometric analysis. Reverse transcriptase-polymerase chain reaction technique was used to assess the gene expression patterns of BCL-2, P53, P21, IL-6, FNTA, VEGF, HIF, AFP, XIAP, and EGFR mRNAs. Results: Treatment of DEN-induced hepatocellular carcinoma Wistar rats with the extract caused significant (p

Background There is a paucity of data on the trends and outcomes of reoperative coronary artery bypass graft (CABG) surgery during the current decade in the United States. Methods and Results We queried the National Inpatient Sample database (2002–2016) for all hospitalizations with isolated CABG procedure. We reported the temporal trends and outcomes of reoperative CABG versus primary CABG procedures. The main outcome was in‐hospital mortality. Among 3 212 768 hospitalizations with CABG, 46 820 (1.5%) had reoperative CABG. Over the 15‐year study period, there were no changes in the proportion of reoperative CABG (1.8% in 2002 versus 2.2% in 2016, Ptren=0.08), and the related in‐hospital mortality (3.7% in 2002 versus 2.7% in 2016, Ptrend=0.97). Reoperative CABG was performed in patients with increasingly higher risk profile. Compared with primary CABG, hospitalizations for reoperative CABG were associated with higher in‐hospital mortality (3.2% versus 1.9%, P

Abstract Introduction The impact of therapeutic hypothermia (TH) on outcomes of percutaneous coronary intervention (PCI) and the optimal antiplatelet treatment remains debatable. Methods Electronic databases were searched for randomized trials and observational studies to evaluate the available clinical evidence comparing the use of clopidogrel versus newer P2Y12 antagonists in cases of TH after PCI. The primary outcome was in-hospital definite stent thrombosis while the secondary outcomes were in-hospital mortality and major bleeding. Fixed-effects risk ratios (RRs) were estimated using Mantel–Haenszel method. Results The final analysis included five studies with a total of 290 patients. There was no difference in the incidence of stent thrombosis (RR 0.92; 95% CI 0.35–2.38), in-hospital mortality (RR 1.38; 95% CI 0.72–2.65), and major bleeding (RR 0.89; 95% CI 0.33–2.40) between patients receiving clopidogrel versus those receiving newer agents. Conclusions This meta-analysis showed no difference between clopidogrel and newer antiplatelet agents in the incidence of stent thrombosis or in-hospital mortality for PCI in cases of TH. Further randomized studies are needed to explore the optimal dual antiplatelet treatment in TH.

Plasmodium falciparum adenylosuccinate lyase ( Pf ADSL) is an important enzyme in purine metabolism. Although several benzimidazole derivatives have been commercially developed into drugs, the template design as inhibitor against Pf ADSL has not been fully explored. This study aims to model the 3-dimensional (3D) structure of Pf ADSL, design and predict in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) of 8 substituted benzo[ d ]imidazol-1-yl)methyl)benzimidamide compounds as well as predict the potential interaction modes and binding affinities of the designed ligands with the modelled Pf ADSL. Pf ADSL 3D structure was modelled using SWISS-MODEL, whereas the compounds were designed using ChemDraw Professional. ADMET predictions were done using OSIRIS Property Explorer and Swiss ADME, whereas molecular docking was done with AutoDock Tools. All designed compounds exhibited good in silico ADMET properties, hence can be considered safe for drug development. Binding energies ranged from −6.85 to −8.75 kcal/mol. Thus, they could be further synthesised and developed into active commercial antimalarial drugs.

Background: Extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria are emerging and impacting significantly on the management of patients and hospital costs. Besides, they are not being routinely sought after in diagnostic laboratories thus contributing to treatment failure. Materials and Methods: Bacterial isolates from wounds of 45 patients were identified using commercial identification kits and antibiotic susceptibility was evaluated by the Bauer-Kirby method. Screening and phenotypic confirmation of ESBL production were done as prescribed by the Clinical and Laboratory Standards Institute. The conjugation experiment was performed by the mating assay in broth between the ESBL producers and E. coli ATCC 25922 as the recipient. Results: Out of 102 Gram-negative bacteria isolated, 36 were positive for ESBL mainly of the Enterobacteriaceae family (33) and the rest were oxidase-positive bacilli (3). The predominant bacteria were Klebsiella spp. and E. coli. Others were Serratia rubidae, Citrobacter freundii, Morganella morgannii, Proteus spp., Providencia stuartii, and Enterobacter spp. There was a significant association between treatment with third-generation cephalosporins (3GCs) and isolation of ESBLs ( p=0.0020 ). The ESBL producers were multiply resistant and moderately sensitive to colistin. The conjugation experiment showed that the ESBL gene was transferred horizontally and tetracycline, cotrimoxazole, nitrofurantoin, gentamicin, and aztreonam resistance genes were co-transferred. No mortality was recorded but the mean length of stay in the hospital was 82 days. Conclusion: The development and spread of ESBL among Gram-negative bacteria and possible horizontal transfer calls for concern, especially in view of treatment failure, high treatment cost, and consequent discomfort to patients.

Abstract Hypertensive disorders of pregnancy (HDP), such as preeclampsia and eclampsia, present significant risks to maternal and fetal health. While immediate complications are well-documented, emerging research highlights potential neurocognitive impacts on both mothers and their offspring. This narrative review synthesizes evidence on these neurocognitive outcomes associated with HDP, focusing on preeclampsia and eclampsia. A literature search was conducted for studies published from 2000 to February 2024. Maternal outcomes, including memory, executive function, and psychosocial well-being, were assessed across 11 studies, while fetal and neonatal neurocognitive outcomes were explored in five studies. Consistent findings indicate that preeclampsia and eclampsia are linked to impairments in maternal cognitive functions and psychosocial health. Offspring exposed to these conditions in utero also show cognitive deficits and alterations in brain connectivity. Contributing factors include placental dysfunction, altered angiokine levels, maternal stress, and socioeconomic variables. To mitigate these impacts, future research should focus on clarifying the underlying mechanisms and developing early interventions. This review emphasizes the necessity of multidisciplinary approaches to improve neurocognitive outcomes for both mothers and their children affected by preeclampsia and eclampsia.

Abstract Ischaemic stroke, a leading cause of global morbidity and mortality, necessitates effective biomarkers for enhanced diagnostic and prognostic stratification. MicroRNAs (miRNAs), particularly miR-210, have emerged as promising candidates due to their intricate regulatory roles in cellular responses to hypoxia and neuroprotective effects. This study explores the potential of miR-210 as a biomarker for ischaemic stroke, considering its expression patterns, regulatory functions and diagnostic/prognostic implications. A literature search was conducted on PubMed, Scopus, Google Scholar and Web of Science to identify studies focusing on miR-210 in ischaemic stroke. Inclusion criteria comprised reports on miR-210 expression in ischaemic stroke patients, excluding non-English studies, reviews, commentaries and conference abstracts lacking primary data. Studies investigating miR-210 levels in ischaemic stroke patients revealed significant alterations in expression patterns compared to healthy controls. Diagnostic potential was explored, indicating miR-210’s sensitivity and specificity in distinguishing ischaemic stroke from other neurological conditions. Prognostic value was evident through associations with infarct size, functional outcomes and long-term survival. Challenges included variability in miR-210 levels, limited diagnostic specificity, absence of standardised assays and concerns regarding cost-effectiveness and accessibility. While miR-210 holds promise as an ischaemic stroke biomarker, challenges must be addressed for its successful integration into clinical practice. Standardised reference ranges, validation studies in diverse populations and collaborative efforts for assay standardisation are crucial. Despite challenges, miR-210’s diagnostic and prognostic potential, particularly in predicting therapeutic responses, suggests a significant role in advancing ischaemic stroke management.

Abstract This review explores the immunomodulatory potential of Teplizumab and its impact on pancreatic β-cell function in T1D. Characterized by the autoimmune destruction of insulin-producing beta cells, T1D’s management involves maintaining glycemic control through exogenous insulin. Teplizumab, a humanized monoclonal antibody targeting the CD3 antigen, has shown promise in delaying T1D onset and preserving residual β-cell function. The review employs a narrative approach, synthesizing evidence from diverse clinical trials and studies gathered through a meticulous literature search. It scrutinizes Teplizumab’s mechanisms of action, including its influence on autoreactive CD8 + T cells and regulatory T cells, offering insights into its immunological pathways. The synthesis of findings from various trials demonstrates Teplizumab’s efficacy in preserving C-peptide levels and reducing exogenous insulin requirements, particularly in recent-onset T1D. Considering Teplizumab’s real-world implications, the paper addresses potential obstacles, including side effects, patient selection criteria, and logistical challenges. It also emphasizes exploring combination therapies and personalized treatment strategies to maximize Teplizumab’s benefits. The review contributes a nuanced perspective on Teplizumab’s clinical implications and future directions in T1D management, bridging theoretical understanding with practical considerations.

Abstract Renal diseases pose significant challenges to global health. With conditions like chronic kidney disease (CKD) on the rise, there is an urgent need for deeper insights into their underlying mechanisms and risk factors to improve patient outcomes. Genomic research has emerged as a powerful tool in unraveling the complex genetic architecture of renal diseases, offering opportunities for personalized medicine, early diagnosis, and targeted therapies. This paper provides an overview of recent advancements in genomic research related to renal diseases and their implications for clinical practice. Through genomic analyses such as genomic-wide association studies (GWAS), whole exome sequencing (WES), and functional genomics, researchers have identified numerous genetic variants, metabolic pathways, and molecular mechanisms contributing to different kidney diseases. Furthermore, through functional genomic approaches and polygenic risk scores (PRS), studies have made significant strides in predicting disease risk and stratifying high-risk individuals for early intervention. The integration of genomic insights into clinical practice enables more accurate risk assessment and tailored treatment strategies, although challenges such as genetic heterogeneity and population-specific variations remain. The search for effective biomarkers in nephrology has gained momentum in recent years, driven by the limitations of traditional markers like serum creatinine and the need for more precise diagnostic and prognostic tools. Despite significant progress, challenges remain in translating these findings into clinical practice, including the need for cost-effective validation methods and the integration of genomic data into routine patient care.

Abstract This paper explores the potential of stem cell therapies in revolutionising stroke recovery, addressing the limitations of current treatments and emphasising regenerative medicine as a promising alternative. Stroke, a leading cause of disability and death worldwide, necessitates innovative approaches due to the temporal constraints and regenerative deficiencies in existing therapeutic modalities. The review explores the diverse mechanisms underlying stem cell-mediated recovery, encompassing neuroprotection, neurogenesis, angiogenesis, modulation of inflammatory responses, and induction of host brain plasticity. We searched prominent databases (PubMed, Scopus, Google Scholar, and Web of Science) from inception to January 2024 for studies on “stem cell therapy” or “regenerative medicine” combined with “stroke recovery” or “cerebrovascular accident”. Studies in humans and animals, published in peer-reviewed journals, and investigating the impact of stem cell therapy on stroke recovery were included. We excluded non-English publications and those lacking sufficient outcome data. Evidence from animal studies demonstrates the efficacy of various stem cell types, while human studies, though limited, contribute valuable insights into safety and potential efficacy. Safety considerations, crucial for successful clinical application, emphasise the need for rigorous preclinical and clinical studies, long-term follow-up data, and ethical standards. Challenges in the field, such as study design heterogeneity, optimising stem cell delivery methods, and identifying subpopulations likely to benefit, require concerted efforts to overcome. Standardising methodologies, refining delivery routes, and personalising interventions based on biomarkers are essential. This review positions stem cell therapies as promising for comprehensive neural tissue recovery following stroke.

Abstract Gestational Diabetes Mellitus (GDM) poses significant health risks to mothers and infants. Early prediction and effective management are crucial to improving outcomes. Machine learning techniques have emerged as powerful tools for GDM prediction. This review compiles and analyses the available studies to highlight key findings and trends in the application of machine learning for GDM prediction. A comprehensive search of relevant studies published between 2000 and September 2023 was conducted. Fourteen studies were selected based on their focus on machine learning for GDM prediction. These studies were subjected to rigorous analysis to identify common themes and trends. The review revealed several key themes. Models capable of predicting GDM risk during the early stages of pregnancy were identified from the studies reviewed. Several studies underscored the necessity of tailoring predictive models to specific populations and demographic groups. These findings highlighted the limitations of uniform guidelines for diverse populations. Moreover, studies emphasised the value of integrating clinical data into GDM prediction models. This integration improved the treatment and care delivery for individuals diagnosed with GDM. While different machine learning models showed promise, selecting and weighing variables remains complex. The reviewed studies offer valuable insights into the complexities and potential solutions in GDM prediction using machine learning. The pursuit of accurate, early prediction models, the consideration of diverse populations, clinical data, and emerging data sources underscore the commitment of researchers to improve healthcare outcomes for pregnant individuals at risk of GDM.

Abstract Background Familial hypercholesterolemia (FH) poses a substantial risk of cardiovascular diseases. The recent approval of evinacumab signifies a breakthrough in FH management. This review synthesizes evidence from diverse clinical trials, examining evinacumab’s efficacy, safety, and broader impact on hypercholesterolemia. Body As highlighted by multiple trials, Evinacumab demonstrates robust efficacy in reducing LDL-C levels, particularly in refractory cases. Its sustained impact, evidenced by enduring reductions in LDL-C levels throughout extended treatment periods, positions it as a potential long-term solution. While the safety profile appears favorable, instances of deaths underline the importance of holistic clinical management and ongoing surveillance. The clinical implications are profound, suggesting evinacumab’s potential inclusion in guidelines for managing severe lipid disorders. Conclusion Future research directions emphasize inclusivity, diversity, and real-world applications to establish sustained efficacy and safety across diverse populations. Integrating evinacumab into clinical guidelines requires evidence-based recommendations, necessitating collaboration between researchers, clinicians, and guideline developers.

Abstract Background Nanoplastics (NPs) have emerged as significant environmental pollutants, raising concerns due to their ubiquitous presence and potential adverse effects on human health. The migration and fate of NPs in the environment are subjects of intense study, with human exposure pathways expanding through ingestion, inhalation, and dermal contact. Body Studies indicate that NPs can infiltrate the cardiovascular system, potentially causing adverse effects. Mechanistic insights from in vitro and animal studies suggest that oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction contribute to nanoplastic-induced cardiovascular toxicity. Animal models demonstrate altered heart rate, myocardial fibrosis, and dysfunction following NPs exposure, with specific adverse effects observed in cardiac valves and mitochondrial structure. Clinical studies provide further evidence of NPs accumulation in cardiovascular tissues, with implications for cardiovascular pathologies such as atherosclerosis and myocardial infarction. Notably, patients with higher levels of nanoplastics in carotid plaque exhibit an increased risk of adverse cardiovascular outcomes. Conclusion However, challenges in studying nanoplastics persist, including methodological limitations, ethical considerations, and the need for standardized detection methods. Addressing these challenges requires interdisciplinary collaboration, innovative research approaches, and robust regulatory measures to mitigate NPs pollution and protect cardiovascular health.

Abstract This mini-narrative review explores the relationship between diabetes and dementia, focusing on the potential mitigating role of metformin in reducing cognitive decline among individuals with type 2 diabetes. The interplay of factors such as glycemic control, diabetic complications, and lifestyle influences characterises diabetes-related dementia. This review emphasises the significance of comprehensive diabetes management in addressing the heightened risk of dementia in this population. Methodologically, the review synthesises evidence from 23 studies retrieved through searches on PubMed, Embase, Google Scholar, and Scopus. Current evidence suggests a predominantly positive association between metformin use and a reduced risk of dementia in individuals with diabetes. However, the review shows the complex nature of these outcomes, revealing variations in results in some studies. These discrepancies show the importance of exploring dose–response relationships, long-term effects, and demographic diversity to unravel the complexities of metformin's impact on cognitive health. Limitations in the existing body of research, including methodological disparities and confounding variables, necessitate refined approaches in future studies. Large-scale prospective longitudinal studies and randomised controlled trials focusing specifically on cognitive effects are recommended. Propensity score matching and exploration of molecular mechanisms can enhance the validity of findings in clinical practice. From a clinical perspective, metformin can serve as a potential adjunctive therapy for individuals with diabetes at risk of cognitive decline.

Background. Pediatric critical care in low-resource settings faces challenges like inadequate infrastructure, limited personnel, financial constraints, and cultural considerations, leading to poor outcomes for critically ill children. Methods. This review synthesizes information from 2 articles on pediatric intensive care units (PICUs) in low- and middle-income countries (LMICs). It identifies challenges such as high care costs, cultural preferences, and resource allocation issues. Results. Challenges include the financial burden of care, limited resources, and the need for external funding. Family preferences impact healthcare decisions, leading to ethical dilemmas. Resource allocation issues affect patient outcomes, including delayed diagnoses and high mortality rates. Conclusion. Addressing these challenges requires a multifaceted approach involving governments, healthcare providers, and international stakeholders. Standardizing care, investing in infrastructure and training, and promoting collaboration are essential to improving pediatric critical care and ensuring equitable access.

Abstract Background Neuropsychiatric disorders significantly burden individuals and society, necessitating the exploration of innovative treatment approaches. Non-invasive brain stimulation techniques have emerged as promising interventions for these disorders, offering potential therapeutic benefits with minimal side effects. This narrative review provides a comprehensive overview of non-invasive brain stimulation techniques' current applications and future directions in managing neuropsychiatric disorders. Methods A thorough search of relevant literature was conducted to identify studies investigating non-invasive brain stimulation techniques in neuropsychiatric disorders. The selected studies were critically reviewed, and their findings were synthesised to provide a comprehensive overview of the current state of knowledge in the field. Results The review highlights the current applications of non-invasive brain stimulation techniques in neuropsychiatric disorders, including major depressive disorder, Parkinson's disease, schizophrenia, insomnia, and cognitive impairments. It presents evidence supporting the efficacy of these techniques in modulating brain activity, alleviating symptoms, and enhancing cognitive functions. Furthermore, the review addresses challenges such as interindividual variability, optimal target site selection, and standardisation of protocols. It also discusses potential future directions, including exploring novel target sites, personalised stimulation protocols, integrating with other treatment modalities, and identifying biomarkers for treatment response. Conclusion Non-invasive brain stimulation techniques offer promising avenues for managing neuropsychiatric disorders. Further research is necessary to optimise stimulation protocols, establish standardised guidelines, and identify biomarkers for treatment response. The findings underscore the potential of non-invasive brain stimulation techniques as valuable additions to the armamentarium of neuropsychiatric treatments.

Abstract Background Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that Cannabidiol (CBD) offer therapeutic benefits for DS. This review aims to evaluate the efficacy and safety of CBD in pediatric patients with DS based on data from ten clinical trials. Methods A review was conducted to identify clinical trials assessing the efficacy and safety of CBD in pediatric patients diagnosed with DS. PubMed, MEDLINE, Scopus, Web of Science, and relevant grey literature were systematically searched for relevant articles up to October 2023, and clinical trials within the last 10 years were included. The search strategy incorporated controlled vocabulary terms and keywords related to "Cannabidiol," "Dravet Syndrome," and "pediatric patients." Results The analysis revealed promising efficacy outcomes. Notably, CBD demonstrated substantial reductions in seizure frequency, with some patients achieving seizure freedom. The findings emphasised the consistency of CBD's efficacy across different patient subgroups. The safety profile of CBD was generally acceptable, with adverse events often being manageable. Conclusion This review consolidates evidence from multiple clinical trials, affirming the potential of CBD as a promising treatment option for pediatric patients with DS. While further research is needed to address existing knowledge gaps, CBD's efficacy and acceptable safety profile make it a valuable addition to the therapeutic tools for DS.

Abstract Background Emergency airway management in resource-limited settings presents multifaceted challenges due to shortages in essential medical resources, healthcare professionals, and infrastructure. Methods We conducted a literature search using keywords “Emergency Airway Management” “Low Resource” “Africa” “Asia” from databases such as Pubmed, and Google Scholar, from where we extracted relevant literature for our study. Findings These limitations resulted in delayed interventions, suboptimal care, and higher complication rates during intubation procedures. However, innovative solutions have emerged to address these challenges, including cost-effective airway management devices and training programs tailored for non-medical personnel. Capacity building and local empowerment are critical components of improving emergency airway management in these settings. Additionally, advocating for policy support and investment in healthcare infrastructure is essential to ensure access to essential equipment and adequate staffing. Collaboration and knowledge-sharing networks among healthcare professionals and organisations are pivotal in disseminating best practices and advancing healthcare delivery in resource-limited regions. Conclusion Future efforts should focus on tailored training programs, rigorous research, innovative device development, telemedicine solutions, sustainable capacity building, and advocacy to enhance emergency airway management in resource-limited settings.

Aims Autism Spectrum Disorder (ASD) poses unique challenges for social interaction and communication skills development in children. Various interventions, including virtual reality (VR) and social skills training, have emerged as potential approaches to address these challenges. This systematic review aims to evaluate and compare the effectiveness of VR Social Skills Training with Standard In-Person Social Skills Training in improving social interaction skills and reducing social anxiety levels in children with ASD. Methods A search was conducted across electronic databases (PubMed, PsycINFO, Cochrane Library and Scopus) for relevant studies published from 2000 to December 2023. Inclusion criteria include randomised controlled trials (RCTs) and observational studies comparing VR Social Skills Training with Standard In-Person Social Skills Training in children diagnosed with ASD within the specified age range. Two independent reviewers assessed study eligibility, conducted data extraction, and evaluated study quality. The primary outcomes included changes in social interaction skills and reduced social anxiety levels. Results From 1,239 studies initially identified, 25 met inclusion criteria post-screening. VR interventions (n = 12) showed significant improvements (80%) in social interaction skills (15% average anxiety reduction). Varied platforms were utilised, including virtual social scenarios. Using conventional techniques, standard interventions (n = 13) demonstrated improvements (75%) with a 12% average anxiety reduction. Comparative effectiveness between VR and Standard approaches lacked consistent significance. Subgroup analyses showed shorter interventions (4–8 weeks) induced rapid skill improvements, while longer-term ones (12+ weeks) sustained anxiety reduction. Younger participants (6–8 years) exhibited more pronounced skill enhancements and higher baseline anxiety correlated with greater improvement. Conclusion This review provides an overview of the current evidence on the comparative effectiveness of VR Social Skills Training and Standard In-Person Social Skills Training for children with ASD. The implications of this review extend to clinicians, educators, and policymakers involved in developing and implementing interventions aimed at improving social outcomes in children with ASD.

Abstract Background Minority stress from racism and heterosexism may uniquely interact to impact the mental health of racialized sexual minorities. We examined variations in anxiety and depressive symptoms by reported by ethno-racial identity among gay, bisexual, and other men who have sex with men (gbMSM) in Vancouver, Canada. Methods We recruited gbMSM aged ≥ 16 years from February 2012 to February 2015 using respondent-driven sampling (RDS). Participants completed computer assisted self-interviews (CASI) at enrollment and every 6 months until February 2017. We examined factors associated with moderate/severe anxiety and depression scores (> 10) on the Hospital Anxiety and Depression Scale (HADS) and differences in key explanatory variables including sociodemographic, psychosocial, and substance use factors. We used multivariable mixed effects models to assess whether moderate/severe scores were associated with ethno-racial identity across all visits. Results After RDS-adjustment, of 774 participants, 79.9% of participants identified as gay. 68.6% identified as white, 9.2% as Asian, 9.8% as Indigenous, 7.3% as Latin American, and 5.1% as other ethno-racial identities. Participants contributed a median of 6 follow-up visits (Q1-Q3: 4–7). In the multivariable analysis, Asian participants had decreased odds of moderate/severe anxiety scores compared to white participants (aOR = 0.39; 95% CI: 0.18–0.86), and Latin American participants had decreased odds of moderate/severe depression scores compared to both white (aOR = 0.17; 95% CI: 0.08–0.36) and Asian (aOR = 0.07; 95% CI: 0.02–0.20) participants. Conclusion Asian and Latino gbMSM reported decreased mental health symptoms compared to white participants. Asian and Latino gbMSM in Vancouver appear to manage multiple minority stressors without adversely affecting their mental health.

Abstract This paper examines the far-reaching implications of Triple Artemisinin-Based Combination Therapy (TACT) in the global battle against malaria. Artemisinin-Based Combination Therapy (ACT) is recognized for its cost-effectiveness, lower likelihood of adverse events, and widespread acceptance by patients and healthcare providers. However, TACT introduces novel dimensions to the fight against malaria that make them a superior choice in several aspects. TACT has been demonstrated to address resistance, offer a broader spectrum of action, reduce the risk of treatment failure, and can be tailored to meet regional needs, strengthening the global effort to combat malaria. However, maximizing these benefits of TACT depends on accessibility, particularly in resource-limited regions where malaria is most prevalent. Collaborative efforts among stakeholders, sustainable pricing strategies, efficient supply chains, and public–private partnerships are essential to ensure that TACT reaches needy populations. Moreover, dispelling prevalent malaria myths through health education campaigns is critical in this endeavour. The paper underscores the significance of collaborative initiatives and partnerships among governments, international organizations, research institutions, acadaemia, pharmaceutical companies, and local communities. Together, these efforts can pave the way for the acceptance, adoption, and success of TACT, ultimately advancing the global goal of a malaria-free world.

Abstract Malaria affects millions of lives annually, particularly in tropical and subtropical regions. Despite being largely preventable, 2021 witnessed 247 million infections and over 600,000 deaths across 85 countries. In the ongoing battle against malaria, a promising development has emerged with the endorsement by the World Health Organization (WHO) of the R21/Matrix-M™ Malaria Vaccine. Developed through a collaboration between the University of Oxford and Novavax, this vaccine has demonstrated remarkable efficacy, reaching 77% effectiveness in Phase 2 clinical trials. It is designed to be low-dose, cost-effective, and accessible, with approval for use in children under three years old. This perspective paper critically examines the R21/Matrix-M malaria vaccine, its development, potential impact on global malaria eradication efforts, and the challenges and opportunities it presents.

Abstract Background The association between the Mediterranean-DASH (Dietary Approaches to Stop Hypertension) Diet Intervention for Neurodegenerative Delay (MIND) diet and cognitive decline has garnered substantial attention in recent research. This review aims to comprehensively analyse the existing evidence regarding the potential impact of the MIND diet on cognitive health. Methods A literature search was conducted to identify relevant studies exploring the relationship between the MIND diet and cognitive decline. A narrative synthesis approach was employed to summarise and interpret the findings from diverse study designs. Results The review reveals consistent evidence suggesting a positive association between adherence to the MIND diet and improved cognitive performance. Several longitudinal studies demonstrate potential preventive effects against cognitive decline, emphasising the significance of dietary habits in preserving cognitive function. Conclusion The MIND diet's positive impact on cognitive health is well-supported by numerous studies. Additionally, the review highlights the exciting opportunity to connect research findings with practical dietary guidance and targeted interventions, particularly for high-risk populations, to enhance cognitive health promotion.

Abstract Cholera continues to severely threaten public health, particularly in regions with inadequate access to clean water and sanitation. Zimbabwe, a southern African nation, has witnessed recurrent cholera outbreaks, highlighting the enduring vulnerabilities faced by communities grappling with these underlying challenges. The 2023 cholera outbreak in Chegutu resulted in a devastating impact, with approximately 100 reported deaths and nearly 5000 confirmed and suspected cases. Beyond its immediate health consequences, the outbreak has strained the already fragile healthcare system, exacerbated issues of malnutrition, and disrupted education, particularly affecting vulnerable populations. The Zimbabwean government, non-governmental organisations (NGOs), and international agencies have initiated comprehensive efforts to combat the outbreak, encompassing medical treatment, surveillance, public health measures, infrastructure improvement, and community empowerment. Policy recommendations and future directions are discussed, emphasising risk communication, stakeholder engagement, standardisation, evaluation, resource allocation, and capacity-building to bolster prevention and control measures.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare and fatal neurodegenerative disorder with no known cure. Early diagnosis of sCJD is crucial for appropriate patient management, but currently, there is no single definitive diagnostic test. However, recent research has shown promising results in identifying novel biomarkers that may aid in the early diagnosis and management of sCJD. This review summarises the current state of biomarker research for sCJD, focusing on the potential of various biomarkers, including cerebrospinal fluid (CSF) biomarkers, neuroimaging techniques, and other potential biomarkers such as blood, urine, and saliva. Using these biomarkers has significantly improved the premortem diagnosis of sCJD, providing patients with valuable information about their condition and enabling them to make necessary plans for the future. Additionally, biomarkers have contributed to our understanding of the disease, paving the way for future therapies and management strategies. While biomarker research for sCJD has shown promising results, there are still several challenges and limitations that need to be addressed. Future research directions include the development of more sensitive and specific biomarkers, the standardisation of diagnostic criteria, and the validation of biomarkers across different patient populations.

AbstractBackground Stroke rehabilitation presents a complex challenge, necessitating innovative approaches to optimise functional recovery. Virtual Reality-Based Rehabilitation (VRBR) has emerged as a promising intervention that capitalises on immersive technology to engage stroke survivors in their recovery journey. This review aims to examine the efficacy of VRBR in stroke rehabilitation, focusing on its advantages and challenges.Methods A comprehensive search of relevant literature was conducted to gather evidence on the efficacy of VRBR in stroke survivors. Studies that investigated the impact of VRBR on patient engagement, functional recovery, and overall rehabilitation outcomes were included. The review also assessed the ability of VRBR to simulate real-life scenarios and facilitate essential daily activities for stroke survivors.Results The review highlights that VRBR offers a unique immersive experience that enhances patient engagement and motivation during rehabilitation. The immersive nature of VRBR fosters a sense of presence, which can positively impact treatment adherence and outcomes. Moreover, VRBR’s capacity to replicate real-world scenarios provides stroke survivors with opportunities to practice vital daily activities, promoting functional independence. In contrast, conventional rehabilitation methods lack the same level of engagement and real-world simulation.Conclusion VRBR holds promise as an efficacious intervention in stroke rehabilitation. Its immersive nature enhances patient engagement and motivation, potentially leading to better treatment adherence and outcomes. The ability of VRBR to simulate real-life scenarios offers a unique platform. However, challenges such as cost, equipment, patient suitability, data privacy, and acceptance must be addressed for successful integration into stroke rehabilitation practice.

Abstract Introduction Anaemia remains a major public health concern, particularly, in sub-Saharan Africa (SSA), where it is one of the causes of maternal death. The most common cause of maternal anaemia is iron deficiency or malnutrition. This study examined the prevalence of and risk factors for anaemia among women that participated in the Nigerian Demographic Health Survey. Method We used data of 14,454 women that participated in the 2018 Nigeria Demographic and Health Survey (NDHS). We extracted information such as demographic, social and housing, dietary characteristics and haemoglobin concentration. The descriptive statistic results, prevalence and 95% confidence interval (CIs) of anaemia with the selected respondents background characteristics were presented. The Poisson regression model with robust variance was used to assess the risk of anaemia among women of reproductive age. All analyses were weighted and adjusted for the complex survey design. Statistical significance was interpreted at p value

Copper-containing intrauterine device (IUD) is a common method of contraception with a low failure rate and high acceptability. However, complications could follow its use including expulsion and migration of the device out of the uterus. When migration occurs, the device could pierce other structures in the pelvis such as the rectum, sigmoid colon, small bowel, or urinary bladder. The pattern of the patient's complaints will guide the clinician on the possible organ involved and the manner of care. This case report presents a 44-year-old woman with IUD migration into the urinary bladder with resulting stone formation. She presented with pelvic pain and hematuria. Following ancillary investigations, she had laparotomy and removal of the IUD along with bladder stones. She had a satisfactory recovery after the surgery and had a complete resolution of all her preoperative symptoms.

Therapeutic intervention in cyclin-dependent kinase-like 5 (CDKL5) deficiency disorders (CDDs) has remained a concern over the years. Recent advances into the mechanistic interplay of signalling pathways has revealed the role of deficient tropomyosin receptor kinase B (TrkB)/phospholipase C γ1 signalling cascade in CDD. Novel findings showed that in vivo administration of a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), resulted in a remarkable reversal in the molecular pathologic mechanisms underlying CDD. Owing to this discovery, this study aimed to identify more potent TrkB agonists than 7,8-DHF that could serve as alternatives or combinatorial drugs towards effective management of CDD. Using pharmacophore modelling and multiple database screening, we identified 691 compounds with identical pharmacophore features with 7,8-DHF. Virtual screening of these ligands resulted in identification of at least 6 compounds with better binding affinities than 7,8-DHF. The in silico pharmacokinetic and ADMET studies of the compounds also indicated better drug-like qualities than those of 7,8-DHF. Postdocking analyses and molecular dynamics simulations of the best hits, 6-hydroxy-10-(2-oxo-1-azatricyclo[7.3.1.05,13]trideca-3,5(13),6,8-tetraen-3-yl)-8-oxa-13,14,16-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1,3,6,9,11,15-hexaen-5-one (PubChem: 91637738) and 6-hydroxy-10-(8-methyl-2-oxo-1H-quinolin-3-yl)-8-oxa-13,14,16-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1,3,6,9,11,15-hexaen-5-one (PubChem ID: 91641310), revealed unique ligand interactions, validating the docking findings. We hereby recommend experimental validation of the best hits in CDKL5 knock out models before consideration as drugs in CDD management.

Abstract The empirical analysis examines the asymmetric effect of financial development and remittance on economic growth in MINT nations (Mexico, Indonesia, Nigeria, and Turkey). The present study utilized panel data covering the period from 1980 to 2019. The research objectives are to address the questions: (a) Is there a long-run association between economic growth and the regressors? (b) Do financial development and remittance trigger MINT nations' economic growth? Moreover, the present study applied both linear panel ARDL and the novel panel nonlinear ARDL to capture the asymmetric impact of development and remittance on economic growth. The outcomes of the linear ARDL disclosed that both financial development and remittance triggers economic growth positively. Furthermore, the outcomes of the NARDL disclosed that both positive and negative shocks in financial development increase economic growth. In addition, a positive and negative shock in remittance increases economic growth in the long-run.

Masturbation, a common sexual behaviour, may result in life-threatening injuries. Here, the authors present a case of 40-year-old female patient, P2L2 who presented to the Gynaecological Emergency unit, on account of a three-hour history of bleeding per vagina following candlestick masturbation which resulted in a 4 cm right lateral vaginal fornix laceration and accompanying Hypovolaemic shock. She was separated from her husband for a period of two years. She underwent examination under anaesthesia and repair of vaginal laceration. Postoperatively, she had one unit of blood transfused and was discharged home on haematinics, broad spectrum antibiotics and analgesics. Counselling on marital stress and sexual distress was provided, while encouraging the use of adult sex toys in favour of improvised ones when necessary.

There is an exponential increase of apprehension in the uptake, affordances and the excessive use of smartphones by multiple categories of users and the impact on the society. The research evaluates excessive use within a user community in a developing country landscape. It is estimated that many young people spend too much time on their phones and the projections suggest even higher numbers with disturbing estimations. The unravelling of contexts surrounding the excessive use of digital devices such as smartphones and the elements that lead to it are mostly unexplored. Consequently, the study illuminated the fundamental mechanisms that influence excessive use of smartphones by learners using perspectives from the Incentive-sensitization Theory (IST) to add scope and breadth. A total of 110 undergraduate students participated in the study. The fundamental results showed that the increase in the volume of activities such as online games, virtual world games and social media was responsible for excessive use. The findings provided an understanding of the relationship between depression-like behaviour and anxiety and shed new light on the influence of excessive use, smartphone stress and depression-related symptoms on students. The study outlined the implications of the results for prevention and regulation.