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.

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.

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.

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.

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.

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.