The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

INTRODUCTION: We describe Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core progress including: the Biobank; cerebrospinal fluid (CSF) amyloid beta (Aβ1-42), t-tau, and p-tau181 analytical performance, definition of Alzheimer's disease (AD) profile for plaque, and tangle burden detection and increased risk for progression to AD; AD disease heterogeneity; progress in standardization; and new studies using ADNI biofluids. METHODS: Review publications authored or coauthored by ADNI Biomarker core faculty and selected non-ADNI studies to deepen the understanding and interpretation of CSF Aβ1-42, t-tau, and p-tau181 data. RESULTS: CSF AD biomarker measurements with the qualified AlzBio3 immunoassay detects neuropathologic AD hallmarks in preclinical and prodromal disease stages, based on CSF studies in non-ADNI living subjects followed by the autopsy confirmation of AD. Collaboration across ADNI cores generated the temporal ordering model of AD biomarkers varying across individuals because of genetic/environmental factors that increase/decrease resilience to AD pathologies. DISCUSSION: Further studies will refine this model and enable the use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic trials

Feto maternal outcome in pregnancy with fever

Background: Infection in pregnancy is a common clinical problem worldwide. The risk to the mother and the fetus is significantly increased in pregnancy complicated by fever. Effect of fever depends on the extent and duration of temperature elevation, socioeconomic status and nutritional status of mother, pre-existing co-morbidity, timing of exposure in pregnancy and several other factors. So, here we have carried out study on symptomatic antenatal patients to determine the fetomaternal outcome of various infections during pregnancy. Methods: This prospective observational study is done to determine fetomaternal outcome of 80 antenatal patients admitted during antepartum period with fever with infectious etiology at the department of obstetrics and gynecology, At SMT. SCL hospital, between 1st April 2023 to 30th September 2023, who were either delivered or aborted. Results: Out of 80 cases of fever in pregnancy, most common cause of fever was urinary tract infection (UTI) (31.3%) followed by upper respiratory infection (25%). fever was associated with antenatal complication such as abortion (13.8%), preterm delivery (23.7%), PROM, PPROM and etc. fetal outcome were preterm birth (23.7%), low birth weight (40%), neonatal mortality (2.5%). Conclusions: Infection during pregnancy is a commonly encountered feature that results in an extensive array of both maternal and fetal complications. The most common cause of fever was UTI. So, all women coming for first antenatal check-up should be investigated for the presence of asymptomatic genitourinary infection. early diagnosis and treatment of them adequately with the antimicrobials decreasing the associated neonatal and maternal morbidities

Finding a Way Forward: Conceptualizing Sustainability in Afghanistan's Community-Based Schools

Community-based educational (CBE) models have gained recognition across diverse contexts for closing access gaps, leveraging local assets, and shaping cost-effective and culturally relevant educational opportunities in marginalized communities. In protracted conflict contexts such as Afghanistan, CBE compensates for weak state capacity by cultivating community engagement and support. This article considers the impact of CBE in the voices of Afghanistan’s educational and community stakeholders, gained through interviews and observations with parents, teachers, students, educational officers, and school shuras (councils) across eight communities in two provinces. Against a backdrop of continued insecurity, resource shortages, and uncertain projections for future government and NGO support, conceptions of sustainability emerge as salient but poorly defined, and as lacking common understanding among stakeholders about the purposes and long-term prospects of CBE. We argue that the success of CBE models depends on how various actors define sustainability and what it is the model is seeking to sustain. The study underscores three dimensions of sustainability: (1) self-reported changed attitudes toward education, (2) decisions about student transitions from community to government schools, and (3) emergent indicators of community ownership over CBE. Across these measures of sustainable attitudes, actions, and community arrangements, quality education is positioned as a mechanism for long-term community commitment. However, increased community interest and capacity to sustain CBE is at odds with the current policy approach, which anticipates the eventual handover of all community-based schools to the government

SAFETY AND EFFECTIVENESS OF BUBBLE CONTINUOUS POSITIVE AIRWAY PRESSURE IN NEONATES WITH RESPI-RATORY DISTRESS AND ITS FAILURE FACTORS

Background: Studies on Bubble Continuous Positive Airway Pressure (B-CPAP) as respiratory support for neonates are few. The aim of our study was to determine the efficacy and safety of B-CPAP in preterm and term neonates requiring respiratory support and to study its failure factors, so we can come out of it and utilize this non-invasive cost effective method widely and successfully. Methods: A prospective observational study was done on 51babies both term and preterm babies admitted in NICU of SMIMER Hospital, Surat, requiring respiratory support for mild to moderate respiratory distress. Support was given with short nasal prongs with under water seal Bubble C Pap. Surfactant was administered when indicated. Monitoring was done clinically, with pulse oximeter, radiologically and with blood gases. Result: The mean gestational age of the study population was 32-34 weeks and birth weight was 1.501 g. 53% of the population were Very Low Birth Weight (VLBW) babies weighing less than 1500 g. C-PAP failure rate was higher in these babies. The most common disease for starting B-CPAP was RDS (80%) followed by pneumonia (17%), TTNB (0%) and MAS (2%). The commonest complications on B-CPAP were shock, apnea and nasal damage. Overall failure of BCPAP occurred in 21/51 cases or 40%. All babies who failed BCPAP were put on mechanical ventilation. Failures in RDS group were 18/41 or 43%. Failure rate in the pneumonia group was 3/9 or 33.3%. Higher cases of sepsis and pulmonary haemorrhage were seen in failure group (table2).Overall survival rate of the study population was 60 %. Conclusion: Bubble Continuous Positive Airway Pressure is safe, efficacious and easy to use in preterm& term neonates with mild to moderate respiratory distress. The major failure factors in our study were sepsis, recurrent apnea, and shock. The survival rate in our study was 60%

Effect of dehydration on the inactivation of Listeria monocytogenes and Salmonella enterica on enoki and wood ear mushrooms

Foodborne illness outbreaks in the U.S. associated with consumption of both fresh and dried specialty mushrooms have recently occurred. Dried wood ear mushrooms were implicated in a salmonellosis outbreak in 2020, while fresh enoki mushrooms were associated with two listeriosis outbreaks in 2020 and 2023. These specialty mushrooms are commercially available in both their fresh and dried states. Due to the short shelf life of mushrooms, dehydration is a common method used in both industry and by consumers to extend the shelf life and preserve quality. Therefore, the aim of this study was to evaluate the use of dehydration on the inactivation kinetics of both Listeria monocytogenes and Salmonella enterica on enoki and wood ear mushrooms. Fresh mushrooms were inoculated with four strain cocktails of either L. monocytogenes or S. enterica and dried at ambient conditions for 10 min. Following drying of the inoculum, mushrooms were placed into food dehydrators preheated to 70, 80, or 90°C and treated for up to 24 h. At treatment intervals, mushrooms were removed from the dehydrators for pathogen enumeration. Inactivation kinetics for both pathogens were modeled using the Weibull, log-linear with tail, and log-linear with shoulder models. Pathogen reductions of >4 log CFU/g were achieved on both enoki and wood ear mushrooms during dehydration at 90°C after only 2–4 h. At 70 and 80°C, log reductions of >4 log CFU/g were observed on wood ear mushrooms after 4–8 h. On enoki mushrooms, a tailing effect was observed with residual populations (>2 log CFU/g) of L. monocytogenes and S. enterica remaining even after 24 h of treatment at both 70 and 80°C. This study emphasizes the need for an individualized dehydration strategy for each mushroom type to ensure the effectiveness of dehydration as a process to reduce pathogen populations. Results of this study will aid in informing proper time and temperature combinations for dehydration of specialty mushrooms to ensure product safety

Disentangling the influence of reservoir abundance and pathogen shedding on zoonotic spillover of the <i>Leptospira </i>agent in urban informal settlements

Rats are major reservoirs for pathogenic Leptospira, the bacteria causing leptospirosis, particularly in urban informal settlements. However, the impact of variation in rat abundance and pathogen shedding rates on spillover transmission to humans remains unclear. This study aimed to investigate how spatial variation in reservoir abundance and pathogen pressure affect Leptospira spillover transmission to humans in a Brazilian urban informal settlement. A longitudinal eco-epidemiological study was conducted from 2013 to 2014 to characterize the spatial distribution of rat abundance and Leptospira shedding rates in rats and determine the association with human infection risk in a cohort of 2,206 community residents. Tracking plates and live-trapping were used to measure rat abundance and quantify rat shedding status and load. In parallel, four sequential biannual serosurveys were used to identify human Leptospira infections. To evaluate the role of shedding on human risk, we built three statistical models for: (1) the relative abundance of rats, (2) the shedding rate by individual rats, and (3) human Leptospira infection, in which “total shedding”, obtained by multiplying the predictions from those two models, was used as a risk factor. We found that Leptospira shedding was associated with older and sexually mature rats and varied spatially and temporally—higher at valley bottoms and with seasonal rainfall (December to March). The point estimate for “total shedding” by rat populations was positive, i.e., Leptospira infection risk increased with total shedding, but the association was not significant [odds ratio (OR) = 1.1; 95% confidence interval (CI): 0.9, 1.4]. This positive trend was mainly driven by rat abundance, rather than individual rat shedding (OR = 1.8; 95% CI: 0.6, 5.4 vs. OR = 1.0; 95% CI: 0.7, 1.4]. Infection risk was higher in areas with more vegetative land cover (OR = 2.4; 95% CI: 1.2, 4.8), and when floodwater entered the house (OR = 2.4; 95% CI: 1.6, 3.4). Our findings indicate that environmental and hydrological factors play a more significant role in Leptospira spillover than rat associated factors. Furthermore, we developed a novel approach combining several models to elucidate complex links between animal reservoir abundance, pathogen shedding and environmental factors on zoonotic spillover in humans that can be extended to other environmentally transmitted diseases.</p

A student-initiated and student-facilitated international health elective for preclinical medical students

Introduction: Global health education is becoming more important for developing well-rounded physicians and may encourage students toward a career in primary care. Many medical schools, however, lack adequate and structured opportunities for students beginning the curriculum. Methods: Second-year medical students initiated, designed, and facilitated a pass&#x2013;fail international health elective, providing a curricular framework for preclinical medical students wishing to gain exposure to the clinical and cultural practices of a developing country. Results: All course participants (N=30) completed a post-travel questionnaire within one week of sharing their experiences. Screening reflection essays for common themes that fulfill university core competencies yielded specific global health learning outcomes, including analysis of health care determinants. Conclusion: Medical students successfully implemented a sustainable global health curriculum for preclinical student peers. Financial constraints, language, and organizational burdens limit student participation. In future, long-term studies should analyze career impact and benefits to the host country

Treatment strategies for progressive immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome: case series

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A study of diabetic retinopathy in diabetic foot syndrome in Western Regional Institute of India

Background: Diabetes is a rapidly growing health challenge and potential epidemic across low-and-middle-income countries like India. Diabetic retinopathy (DR) is a consequence of diabetic microangiopathy, which may cause visual deterioration due to macular edema in any stage and vitreous hemorrhage or tractional retinal detachment in the advanced proliferative retinopathy stages. Aims and Objectives: The aim was to study the retinopathy status in diabetic patients with a risk of diabetic foot syndrome (DFS) visiting a western regional hospital in India. Materials and Methods: In this cross-sectional study, all patients with diabetes mellitus (DM) with a risk of DFS, visiting a tertiary care hospital during the study period, underwent an ophthalmological evaluation for documentation of their retinopathy status. Results: One hundred and fourteen patients diagnosed to have a risk profile for DFS were included in the study. Their mean age was 61.22 years and 81.6% were males. The mean duration of DM was 12.24 years, respectively. Of the 114 patients, 72 had DR. An increased presence of retinopathy in patients with an increased risk grade of diabetic foot (DF) was found significant by the Chi‐square test. (P<0.001). Conclusion: Our study found an increased presence of DR in Western Indian cohort with DFS. The severity of retinopathy was greater in patients with higher grades of risk for DF, therefore establishment of an association between DR and DFS will help in developing an integrated management strategy for these two grave consequences of diabetes

Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)–an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)

On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved