AIMIn the present study, a variety of high resolution microscopy techniques were used to visualize the organization and motion of lipids and proteins in the sperm's plasma membrane. We have addressed questions such as the presence of diffusion barriers, confinement of molecules to specific surface domains, polarized diffusion and the role of cholesterol in regulating lipid rafts and signal transduction during capacitation.

METHODSAtomic force microscopy identified a novel region (EqSS) within the equatorial segment of bovine, porcine and ovine spermatozoa that was enriched in constitutively phosphorylated proteins. The EqSS was assembled during epididymal maturation. Fluorescence imaging techniques were then used to follow molecular diffusion on the sperm head.

RESULTSSingle lipid molecules were freely exchangeable throughout the plasma membrane and showed no evidence for confinement within domains. Large lipid aggregates, however, did not cross over the boundary between the post-acrosome and equatorial segment suggesting the presence of a molecular filter between these two domains.

CONCLUSIONA small reduction in membrane cholesterol enlarges or increases lipid rafts concomitant with phosphorylation of intracellular proteins. Excessive removal of cholesterol, however, disorganizes rafts with a cessation of phosphorylation. These techniques are forcing a revision of long-held views on how lipids and proteins in sperm membranes are assembled into larger complexes that mediate recognition and fusion with the egg.

Cell Membrane ; physiology ; ultrastructure ; Humans ; Male ; Membrane Lipids ; physiology ; Microscopy, Atomic Force ; Sperm Capacitation ; physiology ; Sperm Maturation ; physiology ; Spermatozoa ; cytology ; physiology

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) encompasses a range of diseases from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and has been linked to cardiovascular disease and sub-clinical cardiac remodeling. This paper presents a retrospective study of biopsy-proven NAFL and NASH to examine the differences in subclinical cardiac remodeling. Methods: Patients were recruited from an institutional repository of patients with liver-biopsy-confirmed NAFLD. Patients with a transthoracic echocardiogram (TTE) within 12 months of the liver biopsy were included. The parameters of the diastolic dysfunction were reviewed for the differences between NAFL and NASH as well as between the stages and grades of NASH. Results: Thirty-three patients were included in the study, 17 with NAFL and 16 with NASH. The NASH patients were more likely to have lower platelets, higher AST, higher ALT, and higher rates of type 2 diabetes mellitus, coronary artery disease, and hypertension than the NAFL patients. The E/e’ ratio on transthoracic echocardiogram was significantly higher in NASH compared to NAFL, advanced-stage NASH compared to early stage, and high-grade NASH compared to low-grade. The E/e’ ratio was also significantly higher in NASH than NAFL in patients without diabetes mellitus. The presence of diastolic dysfunction trended toward significance. The other markers of diastolic dysfunction were similar. Logistic regression revealed a statistical association with E/e' and NASH. Conclusions NASH patients had evidence of a higher E/e’ ratio than NAFL, and there was a trend towards a significant diastolic dysfunction. Patients with NASH compared to NAFL should be closely monitored for signs and symptoms of cardiac dysfunction.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) encompasses a range of diseases from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and has been linked to cardiovascular disease and sub-clinical cardiac remodeling. This paper presents a retrospective study of biopsy-proven NAFL and NASH to examine the differences in subclinical cardiac remodeling. Methods: Patients were recruited from an institutional repository of patients with liver-biopsy-confirmed NAFLD. Patients with a transthoracic echocardiogram (TTE) within 12 months of the liver biopsy were included. The parameters of the diastolic dysfunction were reviewed for the differences between NAFL and NASH as well as between the stages and grades of NASH. Results: Thirty-three patients were included in the study, 17 with NAFL and 16 with NASH. The NASH patients were more likely to have lower platelets, higher AST, higher ALT, and higher rates of type 2 diabetes mellitus, coronary artery disease, and hypertension than the NAFL patients. The E/e’ ratio on transthoracic echocardiogram was significantly higher in NASH compared to NAFL, advanced-stage NASH compared to early stage, and high-grade NASH compared to low-grade. The E/e’ ratio was also significantly higher in NASH than NAFL in patients without diabetes mellitus. The presence of diastolic dysfunction trended toward significance. The other markers of diastolic dysfunction were similar. Logistic regression revealed a statistical association with E/e' and NASH. Conclusions NASH patients had evidence of a higher E/e’ ratio than NAFL, and there was a trend towards a significant diastolic dysfunction. Patients with NASH compared to NAFL should be closely monitored for signs and symptoms of cardiac dysfunction.

Objective. This study aimed to examine capacities and initiatives of the local government units (LGUs) in the Philippines in producing, recruiting and retaining human resources for health (HRH).

Methods. This 2-phase, descriptive, cross-sectional study employed multiple methods such as key informant interviews (KIIs), focus group discussions (FGDs) (for Phase 1) and surveys (for Phase 2) in rural municipalities across the country. Phase 1: We employed qualitative methods to develop a quantitative questionnaire in 22 purposefully selected municipalities. An exhaustive enumeration of responses from the guide questions of the FGDs and KIIs were then translated into a questionnaire. Phase 2: We administered the survey questionnaire from phase 1 to another 67 municipalities to obtain a greater representation of the intended study population as well as quantify results from the qualitative methods. We analyzed data with descriptive statistics.

Results. Initiatives in HRH production were mainly on provision of scholarships. Active recruitment was not done due to lack of available pool of applicants, lack of vacant positions, financial constraints leading to utilization of deployment programs and temporary nature of employment. Recruitment was influenced by budgetary constraints, political biases, dependency on deployment programs and other hired temporary HRH, and set health worker-to-population ratios. Initiatives to retain HRH were largely financial in nature based on pertinent policies. The capacities of LGUs to produce, recruit, and retain needed HRH were strongly dependent on the internal revenue allotment (IRA), along with their local income.

Conclusion. Rural municipalities in the Philippines have initiatives to produce, recruit, and retain HRH. However, these are not enough to meet the needed number of competent and highly motivated HRH that are expected to respond to the unique needs of the rural municipalities. Strategies to increase the capacity of LGUs, address the shortage of HRH, and increase motivation of HRH are recommended.

Economics ; Primary Health Care

First few ‘X’ (FFX) studies for COVID-19 involve data collection from confirmed cases and their close contacts. They remain relevant especially as many remain susceptible to infection, and as they can provide detailed insight into vaccine effectiveness and the epidemiology of variants of concern, helping to inform a proportionate health response.

Background: and Purpose We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. Methods: In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0–4 and LVO who underwent EVT 6–24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0–2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2–4) and those without (mRS score 0–1). Results: A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43–1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995). Conclusion A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.