Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome.

Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle fatigability and weakness. Heterozygous parents do not show any conserved clinical pathology but report multiple incidences of intra-uterine fetal death, which were also observed in an eighth family included in this study. In vivo studies of abcc9 loss-of-function in zebrafish revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility. Our findings define an ABCC9 loss-of-function-related phenotype, expanding the genotypic and phenotypic spectrum of AIMS and reveal novel human pathologies arising from KATP channel dysfunction.

Reversal and Preventive Pleiotropic Mechanisms Involved in the Antipsychotic-Like Effect of Taurine, an Essential ß-Amino Acid in Ketamine-Induced Experimental Schizophrenia in Mice.

Schizophrenia is a life disabling, multisystem neuropsychiatric disease mostly derived from complex epigenetic-mediated neurobiological changes causing behavioural deficits. Neurochemical disorganizations, neurotrophic and neuroimmune alterations are some of the challenging neuropathologies proving unabated during psychopharmacology of schizophrenia, further bedeviled by drug-induced metabolic derangements including alteration of amino acids. In first-episode schizophrenia patients, taurine, an essential ß-amino acid represses psychotic-symptoms. However, its anti-psychotic-like mechanisms remain incomplete. This study evaluated the ability of taurine to prevent or reverse ketamine-induced experimental psychosis and the underlying neurochemical, neurotrophic and neuroinmune mechanisms involved in taurine's clinical action. The study consisted of three different experiments with Swiss mice (n = 7). In the drug alone, mice received saline (10 mL/kg/p.o./day), taurine (50 and 100 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) for 14 days. In the preventive study of separate cohort, mice were concomitantly given ketamine (20 mg/kg/i.p./day) from days 8 to 14. In the reversal study, mice received ketamine for 14 days before taurine or risperidone treatments from days 8 to 14 respectively. Afterwards, stereotypy behaviour, social, non-spatial memory deficits, and body weights were assessed. Neurochemical (dopamine, 5-hydroxytryptamine, glutamic acid decarboxylase, (GAD)), brain derived-neurotrophic factor (BDNF) and pro-inflammatory cytokines [tumor necrosis factor-alpha, (TNF-α), interleukin-6, (IL-6)] were assayed in the striatum, prefrontal-cortex and hippocampal area. Taurine attenuates ketamine-induced schizophrenia-like behaviour without changes in body weight. Taurine reduced ketamine-induced dopamine and 5-hydroxytryptamine changes, and increased GAD and BDNF levels in the striatum, prefrontal-cortex and hippocampus, suggesting increased GABAergic and neurotrophic transmissions. Taurine decreases ketamine-induced increased in TNF-α and IL-6 concentrations in the striatum, prefrontal-cortex and hippocampus. These findings also suggest that taurine protects against schizophrenia through neurochemical modulations, neurotrophic enhancement, and inhibition of neuropathologic cytokine activities.

Thrombotic Risk Assessment in Patients with Lymphoid Neoplasm seen at the Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State.

BACKGROUND: Venous thromboembolism (VTE) is a cause of increased morbidity and mortality in cancer patients. VTE is the second leading cause of death in cancer patients. Risk assessment models have been developed to identify patients at risk of VTE for thromboprophylaxis. Risk scores of patients in our environment have not been adequately investigated. OBJECTIVE: The study evaluates the association of thrombotic risk assessment scores (using the modified Khorana risk assessment tool) and soluble P-selectin levels with thrombotic events in patients with lymphoid cancer. METHODS: This is a comparative cross-sectional study conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, Anambra State). Forty-five patients with lymphoid malignancy and 45 apparently healthy subjects participated in the study. The modified Khorana risk assessment score was used to assess cancer-associated thrombotic risk. Blood sample was collected for soluble P-selectin estimation. Data were analyzed with SPSS version 23. RESULTS: The age of subjects with lymphoid neoplasm and controls were 49.1±15.8 years, and 49.6±11.1 years respectively (p = 0.548). Subjects with lymphoid neoplasm consist of 26 (57.8%) males and 19 (42.2%) females while the controls consist of 25 (55.6%) males and 20 (44.4%) females. Non-Hodgkin's lymphoma was the most frequent of lymphoid neoplasm (18, 40.0%), followed by multiple myeloma (10, 22%), CLL (9, 20%), ALL (6, 13.0%) and Hodgkin's lymphoma (2, 4.0%). Thirty-five (77.8%) subjects with lymphoid neoplasm had intermediate risk scores and 10 (22.2%) had high-risk scores. Nineteen (42.2%) of the controls had intermediate risk and 26 (57.8%) low risk. The differences in proportion were statistically significant (p < 0.001). The median (IQR) levels of soluble P-selectin were significantly higher in patients with lymphoid neoplasm (12.2 vs. 7.0ng/mL, p <0.001). Three (6.6%) patients with lymphoid malignancies had deep vein thrombosis confirmed by a Doppler ultrasound scan. CONCLUSION: Lymphoid malignancy is associated with relatively higher thrombotic risk scores, sP-selectin levels, and venous thromboembolic events. CONTEXTE: La thromboembolie veineuse (TEV) est une cause de morbidité et de mortalité accrues chez les patients atteints de cancer. La TEV est la deuxième cause de décès chez les patients atteints de cancer. Des modèles d'évaluation des risques ont été mis au point pour identifier les patients présentant un risque de TEV en vue d'une thromboprophylaxie. Les scores de risque des patients dans notre environnement n'ont pas été étudiés de manière adéquate. OBJECTIF: L'étude évalue l'association des scores d'évaluation du risque thrombotique (en utilisant l'outil modifié d'évaluation du risque de Khorana) et des niveaux de P-sélectine soluble avec les événements thrombotiques chez les patients atteints d'un cancer lymphoïde. MÉTHODES: Il s'agit d'une étude transversale comparative menée au Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, État d'Anambra). Quarante-cinq patients atteints d'un cancer lymphoïde et 45 sujets apparemment sains ont participé à l'étude. Le score modifié d'évaluation du risque de Khorana a été utilisé pour évaluer le risque thrombotique associé au cancer. Un échantillon de sang a été prélevé pour l'estimation de la P-sélectine soluble. Les données ont été analysées avec SPSS version 23. RÉSULTATS: L'âge des sujets atteints de néoplasme lymphoïde et des témoins était respectivement de 49,1±15,8 ans et 49,6±11,1 ans (p = 0,548). Les sujets atteints de néoplasme lymphoïde sont 26 (57,8 %) hommes et 19 (42,2 %) femmes, tandis que les témoins sont 25 (55,6 %) hommes et 20 (44,4 %) femmes. Le lymphome non hodgkinien était le néoplasme lymphoïde le plus fréquent (18, 40 %), suivi du myélome multiple (10, 22 %), de la LLC (9, 20 %), de la LAL (6, 13 %) et du lymphome hodgkinien (2, 4 %). Trente-cinq (77,8 %) sujets atteints de néoplasmes lymphoïdes présentaient un score de risque intermédiaire et 10 (22,2 %) un score de risque élevé. Dix-neuf (42,2 %) des témoins présentaient un risque intermédiaire et 26 (57,8 %) un risque faible. Les différences de proportion étaient statistiquement significatives (p < 0,001). Les niveaux médians (IQR) de P-sélectine soluble étaient significativement plus élevés chez les patients atteints de néoplasme lymphoïde (12,2 vs. 7,0 ng/mL, p <0,001). Trois (6,6 %) patients atteints de tumeurs lymphoïdes ont présenté une thrombose veineuse profonde confirmée par une échographie Doppler. CONCLUSION: Les tumeurs malignes lymphoïdes sont associées à des scores de risque thrombotique, des taux de sP-sélectine et des événements thromboemboliques veineux relativement plus élevés. Mots-clés: Malignité lymphoïde, Thrombose, P-sélectine soluble, Scores d'évaluation du risqué.

KNOWLEDGE OF ANTIMICROBIAL DRUG RESISTANCE (AMR) AMONG PATIENTS IN A GENERAL OUTPATIENT CLINIC IN ABUJA MUNICIPAL AREA COUNCIL (AMAC), FEDERAL CAPITAL TERRITORY, NIGERIA.

Introduction: Antimicrobial resistance (AMR) is currently prevalent and has the potential to affect everyone, of any age, in any country. In humans, animals, and the environment, antimicrobial-resistant microbes are quickly emerging and spreading. This study aims to assess the knowledge of Antimicrobial Drug Resistance (AMR) among patients in a General Outpatient Clinic in Abuja Municipal Area Council (AMAC), Federal Capital Territory, Nigeria. Methodology: This was a descriptive cross-sectional study among 400 clients in a district hospital done in 2022 using a multistage sampling technique. Data was collected using a self-administered structured questionnaire and analyzed and presented as tables, proportions, and percentages using the IBM SPSS 28 Statistical Package for the Social Sciences. Ethical approval was granted by Bingham University Teaching Hospital Ethical Research Committee, Jos, and Plateau State. Results: The study revealed that 8.5% of female respondents had good knowledge, 20.75% had fair knowledge while 27.75% had poor knowledge. Of all the male respondents, 8.5% had good knowledge, 13% had fair knowledge and 21.5% had poor knowledge. Summarily, only 68 (17.0%) of participants had good knowledge of antimicrobial resistance, 135 (33.75%) had fair knowledge of antimicrobial resistance, and 197 (49.25%) had poor knowledge of antimicrobial resistance. Test of association between knowledge of antimicrobial resistance and socio-demographics showed that marital status (χ² = 44.28, p < 0.045), Education (χ²= 123.80, p < 0.001), and Age (χ² = 112.95, p < 0.001) were statistically significant. Conclusion: The Federal, State, and Local governments, health care providers, and community health workers should focus on increasing awareness of AMR risk factors through health campaigns and programs that will aid behavioral change.

Intergenus F1-hybrids of African weakly electric fish (Mormyridae: Gnathonemus petersii ♂ × Campylomormyrus compressirostris ♀) are fertile.

Hybridisation is an important element of adaptive radiation in fish but data are limited in weakly electric mormyrid fish in this respect. Recently, it has been shown that intragenus hybrids (Campylomormyrus) are fertile and are able to produce F2-fish. In this paper, we demonstrate that even intergenus hybrids (Gnathonemus petersii ♂ × Campylomormyrus compressirostris ♀) are fertile. Three artificial reproduction (AR) trials, with an average fertilisation rate of ca. 23%, yielded different numbers of survivals (maximally about 50%) of the F1-hybrids. The complete ontogenetic development of these hybrids is described concerning their morphology and electric organ discharge (EOD). Two EOD types emerged at the juvenile stage, which did not change up to adulthood. Type I consisted of four phases and Type II was triphasic. The minimum body length at sexual maturity was between 10 and 11 cm. Malformations, growth and mortality rates are also described.

Development and formulation of antidiabetic property of Anarcadium occidantale-based solid lipid microparticles.

Anacardium occidentale (AO) possesses potent anti-diabetic properties, owing to its high phytochemicals content. This study attempted to maximise the efficacy of AO by encapsulating it in a solid lipid microparticle (SLMs) formulation. Leaves of AO were extracted with water and formulated into SLMs using a lipid matrix composed of P90H and Dika fat. Characterisation of the SLMs include morphology, particle size, pH, encapsulation efficiency percentage, in vitro release and anti-diabetic properties. SLMs were spherical with sizes ranging from 16.7 ± 0.8 µm to 40.12 ± 2.34 µm and had a fairly stable pH over time. Highest drug entrapment was 87%. Batch A2 exhibited an even release of 89%, sustained over time, and a mean percentage reduction in glucose of 25.9% at 12 h after oral administration to study animals. Anacardium occidentale-loaded SLMs exhibited a good hypoglycaemic effect and can be used in the management of diabetes.

Demand for malaria rapid diagnostic test, health care-seeking behaviour, and drug use among rural community members with fever or malaria-like illness in Ebonyi state, Nigeria: a cross-sectional household survey.

BACKGROUND: A good understanding of the demand for malaria rapid diagnostic test (MRDT), malaria health care-seeking behavior, and drug use among community members is crucial to malaria control efforts. The aim of this study was to assess the demand (use and/or request) for MRDT, health care-seeking behavior, and drug use, as well as associated factors, among rural community members (both children and adults) with fever or malaria-like illness in Ebonyi state, Nigeria. METHODS: A cross-sectional household survey was conducted between October 1st and November 7th, 2018, in 18 rural geographical clusters. Data was collected using a structured interviewer-administered questionnaire. Descriptive analysis was done using summary statistics. Associated factors (socio-demographic, knowledge and opinion level) were assessed using bivariate and multivariate binomial logistic regressions while the overall effects of these factors were assessed using the "postestimation test" command in Stata. RESULTS: A total of 1310 children under 5 years of age and 2329 children ages 5 years and above and adults (excluding pregnant women) (3639 overall) participated in the study. Among the 1310 children under 5 years of age: 521 (39.8%) received MRDT of which the caregivers of 82 (15.7%) requested for the MRDT; 931 (71.1%) sought care with public/private sector providers (excluding traditional practitioners/drug hawkers) the same/next day; 495 (37.8%) sought care at government primary health centres, 744 (56.8%) sought care with the patent medicine vendors (PMVs); 136 (10.4%) sought care with traditional practitioners; 1020 (77.9%) took ACTs (=88.2%, 1020/1156 of those who took anti-malarial drugs). Generally, lower values were respectively recorded among the 2329 children ages 5 years and above and adults (excluding pregnant women). The most important overarching predictor of the demand for MRDT and care-seeking behaviour was the knowledge and opinion level of respondent female heads of households about malaria and malaria diagnosis. CONCLUSIONS: Among the rural community members with fever or malaria-like illness in Ebonyi state, Nigeria, while majority did not receive MRDT or diagnostic testing, and sought care with the PMVs, most took anti-malaria drugs, and mostly ACTs. Interventions are needed to improve the knowledge and opinion of the female heads of households about malaria and malaria diagnosis.

The pharmacological potential and possible molecular mechanisms of action of Inonotus obliquus from preclinical studies.

The use of mushrooms as functional foods and in the treatment of diseases has a long history. Inonotus obliquus is a mushroom belonging to the Hymenochaetaceae family and has possible anticancer, antiviral, and hypoglycemic properties. Chemical analysis of this mushroom has allowed the identification of various constituents such as melanins, phenolic compounds, and lanostane-type triterpenoids. A plethora of findings have highlighted the potential molecular mechanisms of actions of this mushroom such as its ability to scavenge reactive oxygen species, inhibit the growth of tumors, decrease inflammation and insulin resistance in type 2 diabetes, and stimulate the immune system. This review summarizes the relevant findings with reference to the therapeutic potential of this mushroom in countering the progression of cancers, diabetes mellitus, and antiviral activities, while highlighting its possible molecular mechanisms of action. The possible role of this mushroom as a therapeutic agent in addressing the pathogenesis of diabetes and cancer has also been suggested.

Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial.

Obinutuzumab is a type 2, glycoengineered, anti-CD20 antibody recently approved with chlorambucil for the initial therapy of chronic lymphocytic leukemia (CLL). In this nonrandomized, parallel-cohort, phase 1b, multicenter study, we explored the safety and preliminary efficacy of obinutuzumab-bendamustine (G-B) or obinutuzumab fludarabine cyclophosphamide (G-FC) for the therapy of previously untreated fit patients with CLL. Patients received up to 6 cycles of G-B (n = 20) or G-FC (n = 21). The primary end point was safety, with infusion-related reactions (88%, grade 3-4 20%) being the most common adverse event and grade 3-4 neutropenia in 55% on G-B and 48% on G-FC. Mean cycles completed were 5.7 for G-B and 5.1 for G-FC, with 2 and 7 early discontinuations, respectively. The objective response rate (ORR) for G-B was 90% (18/20) with 20% complete response (CR) and 25% CR with incomplete marrow recovery (CRi). The ORR for G-FC was 62% (13/21), with 10% CR and 14% CRi, including 4 patients not evaluable. With a median follow-up of 23.5 months in the G-B cohort and 20.7 months in the G-FC cohort, no patient has relapsed or died. We conclude that obinutuzumab with either B or FC shows manageable toxicity and has promising activity. This study was registered at www.clinicaltrials.gov as #NCT01300247.

Measuring intraocular pressure.

PURPOSE OF REVIEW: Tonometry is undergoing a long-overdue renaissance. Goldmann applanation tonometry (GAT) is 50-year-old technology. Although GAT is considered a 'reference standard', it has many limitations and confounders. This review compares GAT to some of the newer technologies that have recently been commercialized or are in development. RECENT FINDINGS: Dynamic contour tonometry is fairly cornea-independent, but requires technical skill to carry out. Rebound tonometry requires no anesthetic and is particularly useful in children. The ocular response analyzer quantifies corneal biomechanical factors and provides other useful measures relevant to glaucoma risk. A transpalpebral tonometer that claims to measure intraocular pressure (IOP) through the closed eyelid has been introduced, but studies comparing it to conventional tonometers suggest it is too unreliable for routine use. Various new technologies including IOP-sensing contact lenses and implantable sensors are in clinical evaluation. SUMMARY: There is no perfect tonometer, and clinicians must choose which to use in their daily practice, balancing accuracy, precision, convenience, and cost. Clinicians should recognize that a single IOP measurement is but an often error-prone snapshot of a widely varying physiologic parameter. IOP data should only be used in the context of the overall clinical picture.

At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1.

Lactobacilli have long been regarded as important constituents of the healthy human vagina. Lactobacillus iners is the most frequently detected bacterial species in the vagina, but little is known about its characteristics. We report a description of the whole-genome sequence of L. iners AB-1 along with comparative analysis of published genomes of closely related strains of lactobacilli. The genome is the smallest Lactobacillus reported to date, with a 1.3-Mbp single chromosome. The genome seems to have undergone one or more rapid evolution events that resulted in large-scale gene loss and horizontal acquisition of a number of genes for survival in the vagina. L. iners may exhibit specialized adaptation mechanisms to the vaginal environment, such as an iron-sulfur cluster assembly system, and several unique σ factors to regulate gene transcription in this fluctuating environment. A potentially highly expressed homolog of a cholesterol-binding lysin may also contribute to host cell adhesion or act as a defense mechanism against other microbes. Notably, there is a lack of apparent adhesion proteins, but several cell-anchor proteins were identified and may be important for interaction with the host mucosal tissues. L. iners is widely present in healthy females as well as those suffering from bacterial vaginosis or who have undergone antimicrobial therapy, suggesting that it is an important indigenous species of the vagina.

Polycyclic aromatic hydrocarbon in community drinking water, Nsisioken, Nigeria: Source and health risk assessment.

In 2011, the United Nations Environment Programme discovered high levels of hydrocarbon pollution in drinking water wells in Nsisioken Agbi Ogale Rivers State, Nigeria. However, the level of polycyclic aromatic hydrocarbons (PAHs) in the same community's water supply was unknown. A comprehensive study of PAHs in three household dug wells and three boreholes was conducted using Agilent 7890B gas chromatography and 5975A mass spectrometry. The detected PAHs were mainly 4 - 5 ringed PAHs, such as Chrysene, Fluoranthene, Pyrene, Benzo[a]anthracene, and Benzo[b]fluoranthene. The total mean concentration was 5.8 ± 2.3 µg/L, with values ranging from not detected in borehole 3 to 8.0 µg/L at well 2. Source identification analysis suggested that the PAHs originated from fuel and biomass combustion. The incremental lifetime cancer risk for children and adults due to groundwater ingestion and skin contact ranged from ND to 7.448 × 10-3 and ND to 1.83 × 10-3 respectively. The Risk index (RI) values from ingestion and dermal routes were 1.5 ×10-2 and 2.4 × 10-2, indicating high risk of cancer. The hazard quotient for the two non-carcinogenic PAHs was greater than 1, indicating high toxicity. The PAH concentrations exceeded the maximum contamination limits set by the World Health Organization and the U.S. environmental Protection Agency, highlighting potential health risks associated with water use in the community. Authorities should provide a safe alternative water source for the community.

Effect of Salt Solution Environment on the Aging of Styrene-Butadiene-Styrene (SBS)-Modified Asphalt.

The aim of this paper is to investigate the aging mechanism of asphalt in the sea salt erosion environment from a rheological point of view. In order to simulate the real pavement aging process in the sea salt erosion environment, base asphalt and Styrene-Butadiene-Styrene (SBS)-modified asphalt were selected for salt environment aging tests. The asphalt samples were aged via a thin film oven test (TFOT) and a pressure aging vessel (PAV) test. Then, thermo-oxidizing conditions were created after the samples were immersed in salt solution, mixed with four different concentrations of sodium chloride (NaCl) and sodium sulphate (Na2SO4), to investigate the aging state of asphalt. Temperature scan (TS), frequency scan (FS), and multiple stress creep and recovery (MSCR) tests performed using a Dynamic Shear Rheometer (DSR) were used to investigate the effects on the rheological properties of aged asphalt in a salt environment. The results showed that both base asphalt and SBS-modified asphalt were aged to different degrees under mixed salt solutions. The two asphalt samples aged in a salt environment showed increased hardness. SBS-modified asphalt exhibited higher aging resistance compared with base asphalt in the sea salt environment. However, due to the degradation of the SBS modifier and the aging of base asphalt, the properties of the SBS-modified asphalt showed more obvious complexity with changes in salt solution concentrations.

Nourishing the Mind: How Food Security Influences Mental Wellbeing.

Food insecurity is a significant public health problem worldwide and critical to mental health. There is a complex relationship between food security and mental health. We carried out a narrative review study aiming to address how food insecurity impacts mental wellbeing by focusing on the mental health repercussions of food insecurity, recognizing its pivotal role in attaining Sustainable Development Goals 2 (on hunger) and 3 (on enhancing global wellbeing). A comprehensive search was conducted on PubMed and Google Scholar, incorporating Google searches for pertinent reports and policy documents. To address these questions, we emphasized and elucidated the interconnectedness between food security and mental health. The review shows that food security and mental health share a profound relationship influenced by multifaceted factors like socioeconomic conditions, access to nutritious food, and societal inequalities. We then provide recommendations for integrating food security into mental health strategies based on the insights and conclusions drawn. Strategies ranging from sustainable farming practices to urban agriculture initiatives and digital mental health services demonstrate avenues for enhancing food safety and mental wellbeing. This highlights the need for collaborative interdisciplinary efforts and systemic reforms to address these interconnected challenges.

Assessment of Treatment Outcomes in the Management of Club foot using the Ponseti Technique: A cross-sectional study.

BACKGROUND: The Ponseti technique remains the preferred method for club foot treatment. Although measures of treatment outcomes have been well documented, there is no consensus on the determinants of those outcomes. This study aims to assess treatment outcomes and the factors which can influence treatment outcomes. MATERIALS AND METHODS: This is a cross-sectional study. A total of 472 children representing 748 feet in total were recruited. Patient characteristics such as age at presentation, gender, tenotomy, walking with or without deformity, parental educational status and occupation were documented. Outcomes of care were assessed using indictors such as parents' satisfaction with the outcome of treatment and the patients' ambulation without deformity. The relationships between the determinant factors and these outcomes were explored using multivariable binary logistic regression. RESULTS: Most of the children (69.1%) were aged below 2 years. Brace compliance was very high (89.9%). The pre-treatment average Pirani scores were 3.9 ± 1.8 and 4.3 ± 1.8 for the right and left feet, respectively. Majority (88.3%) of the children achieved ambulation without deformity, whereas most (87%) of the parents were satisfied with the treatment outcomes. In total, parental satisfaction with child's treatment outcomes was lower in parents who were not formally educated odds ratio (OR) = 0.19 (95% confidence interval [CI] 0.08-0.43), but parental satisfaction was lower if the child had higher Pirani score OR = 0.77 (95% CI 0.62-0.96). Children who had more casts applied to the affected foot were more likely to walk without deformity OR = 1.24 (95% CI 1.01-1.52). CONCLUSIONS: This study revealed that treatment outcomes in children with club foot can be determined by some sociodemographic and treatment-related factors.

Adverse drug reactions, adherence, and virologic outcomes in adult patients on dolutegravir-based antiretroviral therapy at a tertiary hospital, southeast Nigeria.

Objective: To assess the adherence, adverse drug reactions (ADR), and virologic outcomes of dolutegravir-based antiretroviral therapy. Design: This was a retrospective chart review. Setting: A tertiary health facility-based study in Abakaliki, Nigeria. Participants: Five hundred and fifteen (515) adult patients on dolutegravir were selected using a Random Number Generator. Demographic and clinical data were extracted from patients' case notes and analysed with IBM-SPSS version-25. Main outcome measures: Adherence to dolutegravir, ADRs, virologic outcome, and change in Body Mass Index (BMI) were estimated. Results: The mean age of the patients was 45.5±10.8 years; 68.2% of them were females; 97.1% of them had good self-reported adherence. The majority (82.9%) of them reported no ADRs and among those (17.1%) that did, headache (9.7%), body-itching (3.1%), and skin rash (2.7%) dominated. Most achieved viral suppression (94.4%) and did not have detectable viral particles (57.4%). There was a significant increase in the BMI of the patients with a mean weight increase of 0.9kg, a mean BMI increase of 0.3 kg/m2, and a 2.6% increase in the prevalence of overweight and obesity. Conclusions: Patients on dolutegravir reported low ADRs, good self-reported adherence, and a high viral suppression rate. However, dolutegravir is associated with weight gain. We recommend widespread use and more population-wide studies to elucidate the dolutegravir-associated weight gain. Funding: None declared.

Endoplasmic reticulum stress in pancreatic ß-cell dysfunction: The potential therapeutic role of dietary flavonoids.

Diabetes mellitus (DM) is a global health burden that is characterized by the loss or dysfunction of pancreatic ß-cells. In pancreatic ß-cells, endoplasmic reticulum (ER) stress is a fact of life that contributes to ß-cell loss or dysfunction. Despite recent advances in research, the existing treatment approaches such as lifestyle modification and use of conventional therapeutics could not prevent the loss or dysfunction of pancreatic ß-cells to abrogate the disease progression. Therefore, targeting ER stress and the consequent unfolded protein response (UPR) in pancreatic ß-cells may be a potential therapeutic strategy for diabetes treatment. Dietary phytochemicals have therapeutic applications in human health owing to their broad spectrum of biochemical and pharmacological activities. Flavonoids, which are commonly obtained from fruits and vegetables worldwide, have shown promising prospects in alleviating ER stress. Dietary flavonoids including quercetin, kaempferol, myricetin, isorhamnetin, fisetin, icariin, apigenin, apigetrin, vitexin, baicalein, baicalin, nobiletin hesperidin, naringenin, epigallocatechin 3-O-gallate hesperidin (EGCG), tectorigenin, liquiritigenin, and acacetin have shown inhibitory effects on ER stress in pancreatic ß-cells. Dietary flavonoids modulate ER stress signaling components, chaperone proteins, transcription factors, oxidative stress, autophagy, apoptosis, and inflammatory responses to exert their pharmacological effects on pancreatic ß-cells ER stress. This review focuses on the role of dietary flavonoids as potential therapeutic adjuvants in preserving pancreatic ß-cells from ER stress. Highlights of the underlying mechanisms of action are also presented as well as possible strategies for clinical translation in the management of DM.

Virus Load Kinetics in Lassa Fever Patients Treated With Ribavirin: A Retrospective Cohort Study From Southern Nigeria.

Background: The standard of care for Lassa fever is the use of ribavirin with supportive therapy. There is little information on the course of viremia and its relationship with clinical outcomes in patients treated with ribavirin. Methods: We conducted a retrospective analysis of virologic and clinical parameters of 152 reverse transcription polymerase chain reaction-confirmed Lassa fever cases admitted and treated with ribavirin therapy. We describe the Lassa virus RNA kinetics in blood in relation to the clinical course of the patients. Results: The overall mortality was 9%. The median duration (interquartile range [IQR]) of illness before admission was 8 (5-12) days. Median (IQR) Ct values on admission (t0 ) were lower among patients who died (21 [20-27]) than in those who survived (34 [30-37]; P < .01). The receiver operating characteristics curve of the association between outcome and Ct value at t0 had a high classification performance, with an AUC of 0.92 (95% CI, 0.86-0.98). The median time to viral clearance (IQR) was 10 (5-15) days. The viral load decreased steadily with the duration of treatment, and all survivors achieved viral clearance within 25 days of hospitalization. Conclusions: Our study demonstrates that the Ct value on admission has prognostic value and Lassa fever patients treated with ribavirin typically clear the virus within 3-4 weeks of hospitalization. This kinetics has implications for the design of clinical case management and future clinical trial protocols.