MEK inhibition enhances the antitumor effect of radiation therapy in NF1-deficient glioblastoma.

Individuals with neurofibromatosis type 1 (NF-1), an autosomal dominant neurogenetic and tumor predisposition syndrome, are susceptible to developing low-grade glioma (LGG) and, less commonly, high-grade glioma (HGG). These gliomas exhibit loss of the neurofibromin gene (NF1), and 10-15% of sporadic HGG have somatic NF1 alterations. Loss of NF1 leads to hyperactive RAS signaling, creating opportunity given the established efficacy of MEK inhibitors (MEKi) in plexiform neurofibromas and some individuals with LGG. We observed that NF1-deficient glioblastoma neurospheres were sensitive to the combination of a MEKi (mirdametinib) with irradiation, as evidenced by synergistic inhibition of cell growth, colony formation, and increased cell death. In contrast, NF1-intact neurospheres were not sensitive to the combination, despite complete ERK pathway inhibition. No neurosphere lines exhibited enhanced sensitivity to temozolomide combined with mirdametinib. Mirdametinib decreased transcription of homologous recombination genes and RAD51 foci, associated with DNA damage repair, in sensitive models. Heterotopic xenograft models displayed synergistic growth inhibition to mirdametinib combined with irradiation in NF1-deficient glioma xenografts, but not those with intact NF1. In sensitive models, benefits were observed at least three weeks beyond the completion of treatment, including sustained phosphor-ERK inhibition on immunoblot and decreased Ki-67 expression. These observations demonstrate synergistic activity between mirdametinib and irradiation in NF1-deficient glioma models and may have clinical implications for patients with gliomas that harbor germline or somatic NF1 alterations.

Investigating antimicrobial resistance genes in Kenya, Uganda and Tanzania cattle using metagenomics.

Antimicrobial resistance (AMR) is a growing problem in African cattle production systems, posing a threat to human and animal health and the associated economic value chain. However, there is a poor understanding of the resistomes in small-holder cattle breeds in East African countries. This study aims to examine the distribution of antimicrobial resistance genes (ARGs) in Kenya, Tanzania, and Uganda cattle using a metagenomics approach. We used the SqueezeMeta-Abricate (assembly-based) pipeline to detect ARGs and benchmarked this approach using the Centifuge-AMRplusplus (read-based) pipeline to evaluate its efficiency. Our findings reveal a significant number of ARGs of critical medical and economic importance in all three countries, including resistance to drugs of last resort such as carbapenems, suggesting the presence of highly virulent and antibiotic-resistant bacterial pathogens (ESKAPE) circulating in East Africa. Shared ARGs such as aph(6)-id (aminoglycoside phosphotransferase), tet (tetracycline resistance gene), sul2 (sulfonamide resistance gene) and cfxA_gen (betalactamase gene) were detected. Assembly-based methods revealed fewer ARGs compared to read-based methods, indicating the sensitivity and specificity of read-based methods in resistome characterization. Our findings call for further surveillance to estimate the intensity of the antibiotic resistance problem and wider resistome classification. Effective management of livestock and antibiotic consumption is crucial in minimizing antimicrobial resistance and maximizing productivity, making these findings relevant to stakeholders, agriculturists, and veterinarians in East Africa and Africa at large.

An audit of chemical pathology laboratory investigation request forms received at a private tertiary hospital in Nigeria

Context: Laboratory testing constitutes an integral part of patient management and has an extensive influence on medical decision-making. The completion of laboratory investigation request forms is a vital aspect of the highly variable pre-analytical phase of laboratory testing.Aim: We aimed to assess the adequacy of completion of investigation request forms received at our laboratory.Methods: An audit of systematically selected laboratory investigation request forms received over a six-month period at our laboratory was performed to assess the degree of completion of these forms by requesting clinicians. Data was analysed using Microsoft Excel®.Results: Two hundred and fifty four request forms were reviewed. None of the reviewed forms was adequately completed. The clinician's contact number was missing in all the request forms. About two-thirds of the request forms did not have the patient's hospital number (66.1%) and the referring clinician's signature (66.9%) available on them. The clinical diagnosis of the patient was not stated in 18.9% of the request forms. The patient's name, gender and age were the most frequently completed parameters in 100.0%, 98.4% and 97.2% of the request forms respectively.Conclusion: Basic information required for the accurate interpretation of laboratory results are missing in several request forms. This may have deleterious impact on laboratory turn around time, healthcare costs and patient management as most medical decisions are influenced by laboratory results

Knowledge, attitude and use of seat belt among commercial drivers in Sokoto Metropolis

Background: Every year about 1.2 million people are killed on the world's roads and up to 50 million are injured or disabled as a result of road traffic accidents. The effectiveness of seat belt usage in reducing the severity of the sequelae of road traffic accidents is widely known. The aim of this study was to determine the knowledge, attitude and use of seat belt among commercial drivers in Sokoto Metropolis.Methods: The study design was cross-sectional and descriptive. Pre-tested, structured, interviewer administered questionnaires were used for data collection. Each correct response to the knowledge questions was scored one mark and wrong response or non-response was scored zero.Results: A total of 430 questionnaires were analyzed. The mean knowledge score (%) of the study subjects was high (64.8±17.7). Majority (57.9%) of the respondents had positive attitude towards compulsory use of seat belt. 363 (84.4%) of the respondents reported that they use seat belt when they drive. There were statistically significant associations between age (p<0.0001), ethnicity (p=0.02), education (p=0.001) as well as attendance of driving school (p=0.000002) and the reported use of seat belt.Conclusion: This study has identified high level of knowledge, positive attitude and reported use of seat belt. It is recommended that public awareness of the safety benefits of seat belts and strong enforcement are necessary to achieve optimal use of seat belt