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Background: The accumulation of β-amyloid (Aβ) peptides into insoluble plaques is an early pathological feature of Alzheimer's disease (AD). BACE1 is the sole β-secretase for Aβ generation, making it an attractive therapeutic target for AD therapy. While BACE1 inhibitors have been shown to reduce Aβ levels in people with AD, clinical trials targeting BACE1 have failed due to unwanted synaptic deficits. Understanding the physiological role of BACE1 in individual cell types is essential for developing effective BACE inhibitors for the treatment of AD. Recent single-cell RNA transcriptomic assays revealed that oligodendrocytes are enriched with genes required for generating Aβ. However, the contribution of oligodendrocytes to amyloid plaque burden in AD and the side effects of oligodendrocyte-specific Bace1 deletion remain to be explored., Methods: We generated an oligodendrocyte-specific Bace1 knockout model (Bace1 fl/fl ;Olig2-Cre) to monitor potential disruptions in myelination using standard electron microscopy. Long-term potentiation (LTP) was monitored to measure synaptic integrity. We crossed the Bace1 fl/fl ;Olig2-Cre model with heterozygous App NL-G-F/wt knock-in AD mice to generate AD mice lacking oligodendrocyte Bace1 (Bace1 fl/fl ;Olig2-Cre; App NL-G-F/wt ) and examined amyloid plaque number and insoluble Aβ levels and gliosis in these animals. Single nuclei RNA sequencing experiments were conducted to examine molecular changes in response to Bace1 deficiency in oligodendrocytes in the wild type or APP knock-in background., Results: Bace1 deletion in oligodendrocytes caused no change in myelin thickness in the corpus callosum but a marginal reduction in myelin sheath thickness of the optic nerve. Synaptic strength measured by LTP was not different between Bace1 fl/fl ;Olig2-Cre and age-matched Bace1 fl/fl control animals, suggesting no major effect on synaptic plasticity. Intriguingly, deletion of Bace1 in 12-month-old heterozygous AD knock-in mice (Bace1 fl/fl ;Olig2-Cre; App NL-G-F/wt mice) caused a significant reduction of amyloid plaques by ~ 33% in the hippocampus and ~ 29% in the cortex compared to age-matched AD mice (Bace1 fl/fl ;App NL-G-F/wt ). Insoluble Aβ 1-40 and Aβ 1-42 levels were reduced comparably while more astrocytes and microglia were observed in surrounding amyloid plaques. Unbiased single-nuclei RNA sequencing results revealed that deletion of oligodendrocyte Bace1 in APP NL-G-F/wt knock-in mice increased expression of genes associated with Aβ generation and clearance such as ADAM10, Ano4, ApoE, Il33, and Sort1., Conclusion: Our results provide compelling evidence that the amyloidogenic pathway in oligodendrocytes contributes to Aβ plaque formation in the AD brain. While specifically targeting BACE1 inhibition in oligodendrocytes for reducing Aβ pathology in AD is likely challenging, this is a potentially explorable strategy in future studies., Competing Interests: Declarations Ethical Approval and Consent to participate All experimental protocols were approved by the Institutional Animal Care and Use Committee of the University of Connecticut School of Medicine in compliance with the guidelines established by the Public Health Service Guide for the Care and Use of Laboratory Animals. Consent for publication All authors have read and approved the final manuscript. Competing interests All authors declare no conflict of interests., (© 2024. The Author(s).)

Purpose: Understanding the technical efficiency of health facilities is essential for an optimal allocation of scarce resources to primary health sectors. The COVID-19 pandemic may have further undermined levels of efficiency in low-resource settings. This study takes advantage of 2019 and 2020 data on characteristics of health facilities, health services inputs and output to examine the levels and changes in efficiency of Ghanaian health facilities. The current study by using a panel dataset contributes to existing evidence, which is mostly based on pre-COVID-19 and single-period data., Methods: The analysis is based on a panel dataset including 151 Ghanaian health facilities. Data Envelopement Analysis (DEA) technique was used to estimate the level and changes in efficiency of health facilities across two years.., Results: The results show a net increase of 26% in inputs, influenced mostly by increases in temporary non-clinical staff (131%) and attrition of temporary clinical staff and permanent non-clinical staff, 40% and 54% respectively. There was also a net reduction in output of 34%, driven by a reduction in in-patient days (37%), immunization (11%), outpatients visits and laboratory test of 9%. Nowithstanding the COVID-19 pandemic, the results indicate that 59 (39%) of sampled health facilities in 2020 were efficient, compared to 48 (32%) in 2019. The results also indicate that smaller-sized health facilities were less likely to be efficient compared to relatively bigger health facilities., Conclusion: Based on the findings, it will be essential to examine factors that accounted for efficiency improvements in some health facilities, to enable health facilities lagging behind to learn from those on the efficiency frontier. In addition, the findings emphasise the need for CHAG to work with health facility managers to optimise inputs allocation through a redistribution of staff. Most importantly, the findings are suggestive of the resilience of CHAG health facilities in responding to a health shock such as the COVID-19 pandemic., (© 2024. The Author(s).)

The activity of γ-secretase is critical to the pathogenesis of Alzheimer's disease (AD). How its activity is regulated is intriguing and highly important for any AD therapy that focuses on reduction of toxic amyloid peptides and amyloid deposition in patients. Recently, interferon-induced transmembrane protein 3 (IFITM3) has been identified as a novel regulator of γ-secretase through a specific interaction. This commentary highlights this exciting study and provides an updated link of γ-secretase activity to innate immunity through IFITM3.

Background: Qnr genes are known to confer a low-level resistance to fluoroquinolone in Enterobacteriaceae . They are often found on the same resistance plasmids as extended spectrum β-lactamase (ESBL) and constitute the most common antibiotic resistance mechanism. This study aimed to detect the presence of qn r genes in ESBL -producing E. coli and Klebsiella spp ., Methods: From May 2013 to July 2015, 91 E. coli and 64 Klebsiella spp. strains with phenotypic resistance to quinolone were collected from several specimens and analyzed for the detection of qnrA, qnrB, qnrS genes and the β-lactamase resistance genes ( blaCTX-M , blaTEM , blaSHV ) using simplex and multiplex PCR., Results: In the present study, 107 (69%; 61 E. coli and 46 Klebsiella spp. ) of 155 bacterial strains tested were found harboring at least one qnr gene consisting of 74 (47.74%) qnrB , 73 (47.10%) qnrS and 4 (2.58%) qnrA . Of the 107 strains encoding qnr genes, 102, 96 and 52 carried CTX-M1 , TEM and SHV type ESBL respectively., Conclusion: This study identified quinolone resistance ( qnr ) gene in ESBL -producing E. coli and Klebsiella spp. in Togo. These finding which suggest a possible resistance to quinolone are of high interest for better management of patients and control of antimicrobial resistance in Togo., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: There is some evidence to suggest that within the household, family and community settings, women in sub-Saharan Africa often have limited autonomy and control over their reproductive health decisions. However, there are few studies that examine how intra-familial decision-making power may affect women's ability to access and use maternal health services. The purpose of this paper is to examine how intra-familial decision-making affects women's ability to access and use maternal health services., Methods: We conducted 12 focus group discussions and 81 individual interviews with a total of 185 expectant and lactating mothers in six communities in Ghana. In addition, 20 key informant interviews were completed with healthcare providers. Attride-Stirling's thematic network analysis framework was used to analyse the data., Results: Findings suggest that decision-making regarding access to and use of skilled maternal healthcare services is strongly influenced by the values and opinions of husbands, mothers-in-law, traditional birth attendants and other family and community members, more than those of individual childbearing women. In 49.2%, 16.2%, and 12.4% of cases in which women said they were unable to access maternal health services during their last pregnancy, husbands, mothers-in-law, and husband plus mothers-in-law, respectively, made the decision. Women themselves were the final decision-makers in only 2.7% of the cases. The findings highlight how the goal of improving access to maternal healthcare services can be undermined by women's lack of decision-making autonomy through complex processes of gender inequality, economic marginalisation, communal decision-making and social power., Conclusion: Interventions to improve women's use of maternity services should move beyond individual women to target different stakeholders at multiple levels, including husbands and mothers-in-law.