Potential Alzheimer's disease drug targets identified through microglial biology research.

INTRODUCTION: Microglia, the primary immune cells in the brain, play multifaceted roles in Alzheimer's disease (AD). Microglia can potentially mitigate the pathological progression of AD by clearing amyloid beta (Aß) deposits in the brain and through neurotrophic support. In contrast, disproportionate activation of microglial pro-inflammatory pathways, as well as excessive elimination of healthy synapses, can exacerbate neurodegeneration in AD. The challenge, therefore, lies in discerning the precise regulation of the contrasting microglial properties to harness their therapeutic potential in AD. AREAS COVERED: This review examines the evidence relevant to the disease-modifying effects of microglial manipulators in AD preclinical models. The deleterious pro-inflammatory effects of microglia in AD can be ameliorated via direct suppression or indirectly through metabolic manipulation, epigenetic targeting, and modulation of the gut-brain axis. Furthermore, microglial clearance of Aß deposits in AD can be enhanced via strategically targeting microglial membrane receptors, lysosomal functions, and metabolism. EXPERT OPINION: Given the intricate and diverse nature of microglial responses throughout the course of AD, therapeutic interventions directed at microglia warrant a tactical approach. This could entail employing therapeutic regimens, which concomitantly suppress pro-inflammatory microglial responses while selectively enhancing Aß phagocytosis.

Progress towards universal health coverage and inequalities in infant mortality: an analysis of 4·1 million births from 60 low-income and middle-income countries between 2000 and 2019.

BACKGROUND: Expanding universal health coverage (UHC) might not be inherently beneficial to poorer populations without the explicit targeting and prioritising of low-income populations. This study examines whether the expansion of UHC between 2000 and 2019 is associated with reduced socioeconomic inequalities in infant mortality in low-income and middle-income countries (LMICs). METHODS: We did a retrospective analysis of birth data compiled from Demographic and Health Surveys (DHSs). We analysed all births between 2000 and 2019 from all DHSs available for this period. The primary outcome was infant mortality, defined as death within 1 year of birth. Logistic regression models with country and year fixed effects assessed associations between country-level progress to UHC (using WHO's UHC service coverage index) and infant mortality (overall and by wealth quintile), adjusting for infant-level, mother-level, and country-level variables. FINDINGS: A total of 4 065 868 births to 1 833 011 mothers were analysed from 177 DHSs covering 60 LMICs between 2000 and 2019. A one unit increase in the UHC index was associated with a 1·2% reduction in the risk of infant death (AOR 0·988, 95% CI 0·981-0·995; absolute measure of association, 0·57 deaths per 1000 livebirths). An estimated 15·5 million infant deaths were averted between 2000 and 2019 because of increases in UHC. However, richer wealth quintiles had larger associated reductions in infant mortality from UHC (quintile 5 AOR 0·983, 95% CI 0·973-0·993) than poorer quintiles (quintile 1 0·991, 0·985-0·998). In the early stages of UHC, UHC expansion was generally beneficial to poorer populations (ie, larger reductions in infant mortality for poorer households [infant deaths per 1000 per one unit increase in UHC coverage: quintile 1 0·84 vs quintile 5 0·59]), but became less so as overall coverage increased (quintile 1 0·64 vs quintile 5 0·57). INTERPRETATION: Since UHC expansion in LMICs appears to become less beneficial to poorer populations as coverage increases, UHC policies should be explicitly designed to ensure lower income groups continue to benefit as coverage expands. FUNDING: UK National Institute for Health and Care Research.

SARS-CoV-2 persistence and infectivity in COVID-19 corpses: a systematic review.

The persistence and infectivity of SARS-CoV-2 in different postmortem COVID-19 specimens remain unclear despite numerous published studies. This information is essential to improve corpses management related to clinical biosafety and viral transmission in medical staff and the public community. We aim to understand SARS-CoV-2 persistence and infectivity in COVID-19 corpses. We conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocols. A systematic literature search was performed in PubMed, Science Direct Scopus, and Google Scholar databases using specific keywords. We critically reviewed the collected studies and selected the articles that met the criteria. We included 33 scientific papers that involved 491 COVID-19 corpses. The persistence rate and maximum postmortem interval (PMI) range of the SARS-CoV-2 findings were reported in the lungs (138/155, 89.0%; 4 months), followed by the vitreous humor (7/37, 18.9%; 3 months), nasopharynx/oropharynx (156/248, 62.9%; 41 days), abdominal organs (67/110, 60.9%; 17 days), skin (14/24, 58.3%; 17 days), brain (14/31, 45.2%; 17 days), bone marrow (2/2, 100%; 12 days), heart (31/69, 44.9%; 6 days), muscle tissues (9/83, 10.8%; 6 days), trachea (9/20, 45.0%; 5 days), and perioral tissues (21/24, 87.5%; 3.5 days). SARS-CoV-2 infectivity rates in viral culture studies were detected in the lungs (9/15, 60%), trachea (2/4, 50%), oropharynx (1/4, 25%), and perioral (1/4, 25%) at a maximum PMI range of 17 days. The SARS-CoV-2 persists in the human body months after death and should be infectious for weeks. This data should be helpful for postmortem COVID-19 management and viral transmission preventive strategy.

Stunting Among Children Under Two Years in the Islands Areas: A Cross-sectional Study of the Maluku Region in Indonesia, 2021.

BACKGROUND: The Maluku region encompasses thousands of islands. The study analyzed factors related to stunting among children under two years old in the Maluku Region of Indonesia. Study Design: A cross-sectional study. METHODS: This cross-sectional study examined 4764 children under two years. In addition to nutritional status (stature), the study analyzed ten independent variables (province, residence, maternal age, marital status, maternal education, employment, wealth, children's age, gender, and early initiation of breastfeeding [EIBF]). Finally, the contribution of various factors to stunting was examined using logistic regression. RESULTS: Children in Maluku province were 1.13 times more likely than those in North Maluku province to become stunted. In addition, children aged 12-13 months were 4.09 times more likely than<12 months, and boys were 1.87 times more likely than girls to have the patterns of stunting. Children in rural areas were 1.10 times more likely to become stunted than those in urban areas (95% confidence interval: 1.06, 1.14). Divorced/widowed mothers were 1.88 times more likely than married mothers. Mothers of all education levels were more likely than those without formal education, and unemployed mothers were 1.07 times more likely than employed mothers to have stunted children. The possibility of becoming stunted was lower when the children were wealthier. CONCLUSION: Nine variables were related to stunted incidence, including province, residence, maternal age, marital status, maternal education, employment, wealth, children's age, and gender.

Utilization of Biang Fish Flour (Ilisha elongata) as an Enrichment Material for Sago Noodles Nutrient Value.

This study aims to determine the appropriate concentration of lead fish meal for enriching the nutritional value of sago noodles favored by consumers. The method used is an experimental design using Completely Randomized (CRD) with 4 concentration levels of lead fish meal, namely, 4% without a lead fish meal (M0), 6% (M1), 8% (M2), and 10% (M3). The analysis of sago noodles was performed and proximate by the AOAC method; amino acids by HPLC; fatty acids by GC; and minerals by HPLC. The results of the showed that the study getting the best treatment was a concentration of 8% (M2) with the characteristics of whole sago noodles' appearance: attractive, grayish-white color; a distinctive aroma of sago noodles with a hint of fish; a specific taste typical of sago noodles and fish prickly taste; delicious; slightly chewy texture. Sensory evaluation with a taste value of 8.9, an aroma of 8.6, a visual value of 8.9, and a texture value of 8.8. Its nutritional content is 5.58% protein content, air 22.35%, ash 1.69%, fat 1.41%, and carbohydrates 68.29%. The proximate values are protein 5.58%, water content 22.35%, ash 1.69%, fat content 1.41%, and carbohydrates (different) 68.29%. The mineral content is Ca.P.I, Mg, Zn, and Fe. Amino acids consist of 8 types of essential amino acids, namely, histidine, arginine, threonine, valine, alanine, methionine, isoleucine, leucine, phenylalanine, and 7 types of nonessential amino acids, namely, aspartic acid, glutamic acid, serine, glycine, tyrosine. Its fatty acid profile has 13 components of unsaturated fatty acids and 17 components of saturated fatty acids.

Assesment of Thyroid Function and Its Association with Free Thyroxin Hormone among Pregnant Women in Areas with Previous History Iodine Deficiency in Magelang, Indonesia.

Iodine deficiency in pregnant woman can affect growth and development of fetus. People who live in an area that had affected by previous iodine deficiency may continuously affect by abnormal thyroid function. The aim of the study is to assess thyroid function, that was measured by the concentrations of thyroid stimulating hormone, and its relationships with free thyroxine (fT4) among pregnant women in the two different geographic areas with previous history of iodine deficiency in Magelang, Central Java, Indonesia. Cross-sectional study was conducted in two types of location (replete and non-replete area) in Magelang, Central Java, Indonesia. A total of 243 aged between 15-45 y old with no pregnancy complication from two different geographics areas of iodine replete and sufficient were include in study. Blood biochemical markers such as free thyroxine hormone and thyroid stimulating hormone were assessed by Elisa method. Median of fT4 in non-replete and replete area was 1.18 (0.63-3.5) ng/dL; 1.12 (0.37-1.95) ng/dL, respectively. Whilst, median of TSH in replete area was 1.27 (0.09-8.21) ng/dL and non replete area was 1.3 (0.01-8.67) ng/dL. Correlation between fT4 and TSH showed significat relationship in non-replete area, r=-0.39 (<0.05), but it was not significant in replete area, r=-0.08 (>0.05). In addition, scatter plot showed the relationship between fT4 and TSH levels pattern in the replete area more widespread. Pregnant womens who live in areas that had affected severe iodine deficiency intake may have abnormal thyroid function but it still euthyroid maintain by adequate iodine intake.