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Background An elevated neutrophil–lymphocyte ratio (NLR) in blood has been associated with Alzheimer’s disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau), as well as the trajectories of these CSF measures obtained longitudinally. Results A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p  < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p  = 0.042), higher BMIs (27.94 vs. 25.79, p  < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p  < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p  = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β = -12.193, p  = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p  = 0.019) and p-tau (β = 3.441, p  = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ + ( n  = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p  = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. Conclusions We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.

Introduction We determined whether slow wave sleep is associated with plasma levels of Aβ40, Aβ42, Aβ42/Aβ40, Tau, tau/Aβ42 and NfL and whether this relationship differed between Blacks/African-Americans and non-Hispanic Whites. Methods This was a cross-sectional analysis of baseline data from 171 community-dwelling cognitively normal older-adults, participating in ongoing NYU studies on memory, sleep and aging. Non-rapid eye movement sleep (NREM) slow wave sleep (SWS) duration was calculated from 2 nights of in-lab NPSGs. Plasma Aβ40, Aβ42, Tau and NfL were determined using single molecule array (SIMOA). Associations of NREM SWS duration and plasma AD biomarker levels were assessed using adjusted generalized linear models and Pearson correlation analysis after data normalization. Analyses were adjusted for age, sex, BMI, race, and education. Results Of the 171 subjects (128 non-Hispanic Whites and 43 Blacks/African-Americans), 112 (65.5%) were females, and mean (SD) age was 68.6 (6.6) years, BMI was 27.6 (6.1) kg/m**2, and education was 16.9 (2.1). There were no racial differences in age, sex, BMI, NREM SWS and AHI4%. Compared to non-Hispanic Whites, Blacks/African-Americans had significantly lower years of education (14.2 vs. 17.2, p <.01), plasma Aβ40 (248.3 vs. 262.5 pg/ml) and NfL levels (11.4 vs. 15.2 pg/ml) p<.05 for both. There were no significant racial differences in levels of plasma Aβ42, Aβ42/Aβ40, Tau, Tau/Aβ40 and Tau/Aβ42 (p>.05 for all). NREM SWS duration was not associated with plasma Aβ42, Aβ40 or tau in the overall sample (p>.05 for all). However, in non-Hispanic Whites, NREM SWS negatively correlated with plasma Aβ42 (r=-0.28, p<=0.05), plasma Aβ40 (r=-0.087, p=0.72), though not significant, and plasma Tau (r=-0.153, p=0.27), though not significant. In Black/African-Americans, NREM SWS positively correlated with plasma Aβ42 (r=0.48, p=0.05), plasma Aβ40 levels (r=0.32, p=0.04), and plasma Tau levels (r=0.52, p=0.04). NREM SWS was not associated with plasma tau/Aβ42, plasma tau/Aβ40 or plasma NfL in the overall sample and across racial subgroups. Conclusion Race-specific divergent associations between NREM SWS and plasma Aβ42, Aβ40 & Tau may suggest differences in SDOH factors and mechanisms that could influence sleep and AD-risk in older-adults. Support (if any) AASMBTS#231-BS-20, NIAK23AG068534A, AARG-D- 21-848397, BFFA2022033S

An elevated neutrophil-lymphocyte ratio (NLR) has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. We explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and NYU Center for Brain Health (CBH). Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau ), as well as the trajectories of these CSF measures obtained longitudinally. A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p<0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p<0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p<0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009) (Table 1). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β = -12.193, p = 0.021), but not t-tau or p-tau . In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p<0.001), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ+ (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort (Figure 1). In both cohorts, the same associations observed in the cross-sectional analyses were observed after incoporating longitudinal CSF data (Figure 2). We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD-biomarkers may occur as part of immunosenescence.

Background An elevated neutrophil‐lymphocyte ratio (NLR) has been associated with Alzheimer’s disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Method We explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and NYU Center for Brain Health (CBH). Specifically, we examined associations between the NLR and cross‐sectional measures of amyloid‐β42 (Aβ42), total tau (t‐tau), and phosphorylated tau181 (p‐tau181), as well as the trajectories of these CSF measures obtained longitudinally. Result A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p<0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p<0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p<0.001), and a greater percentage of Aβ‐positivity (34.2% vs. 20.0%, p = 0.009) (Table 1). In the ADNI cohort, we found cross‐sectional associations between the NLR and CSF Aβ42 (β = ‐12.193, p = 0.021), but not t‐tau or p‐tau181. In the NYU cohort, we found cross‐sectional associations between the NLR and CSF t‐tau (β = 26.812, p = 0.019) and p‐tau181 (β = 3.441, p<0.001), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ+ (n = 38) displayed a stronger association between the NLR and t‐tau (β = 100.476, p = 0.037) compared to Aβ‐ subjects or the non‐stratified cohort (Figure 1). In both cohorts, the same associations observed in the cross‐sectional analyses were observed after incoporating longitudinal CSF data (Figure 2). Conclusion We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t‐tau and p‐tau181 in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD‐biomarkers may occur as part of immunosenescence.

Introduction Polysomnography (PSG) is the gold standard for sleep measurements, requiring individuals to sleep in a controlled environment. In contrast, actigraphy is more naturalistic, allowing at-home monitoring. While most studies comparing actigraphy to PSG have focused on healthy adults and individuals with sleep disorders, there has been limited research involving a well-characterized, healthy older adult population. Although actigraphy is convenient, it has been noted to differ from PSG in some aspects. Our study aims to assess the correlation between PSG and actigraphy in cognitively healthy older adults participating in NYU research on sleep, aging, and memory. Methods PSG recordings were conducted overnight at the bedside, while wrist-based data were collected on separate nights from individuals' homes. Actigraphs were worn on the non-dominant hand for seven consecutive days, validated by sleep logs. Statistical analyses, including t-tests, chi-square tests, and sensitivity-specificity assessments, were performed. Results Of the 151 subjects, 97 (64.2%) were female, 54 (35.8%) were male, 43 (28.5%) were Black/African American, and 108 (71.5%) were White. Mean age was 66 years (61-71). Mean Epworth Sleepiness Score was 5 (3-8) for women and 6 (3-9) for men. Total sleep time for PSG was 376 (332-418) with a mean difference with actigraphy of -67.4, 26, and 121 minutes (minimum, median, and maximum thresholds respectively, p< 0.0001 for all) Sleep efficiency (%) was higher in the actigraphy group (mean difference 11.2 [SD12.7]) and sleep latency was shorter in the actigraphy group (p< 0.001 for all). Sensitivity for short sleepers(< 5h) was 0.7, increasing to 0.9 in females and 0.86 in Black or African Americans. Specificity corresponded to 0.95, decreasing to 0.87 in males, and to 0.48 in whites, while increasing to 0.96 in black patients. Both sensitivity and specificity for long-sleepers(< 9h) corresponded to 0.5. Positive predictive value for short sleepers was 0.9, and 0.76 for long sleepers. Conclusion Overall, the study highlights the complexity of sleep measurements and the potential impact of conducting PSG and actigraphy on different nights. It underscores the need to consider nightly variability in sleep studies, the different diagnostic methods used, and the influence of sex and ethnicity on sleep patterns. Support (if any)

Introduction Obstructive Sleep Apnea (OSA) is as a prevalent sleep-related breathing disorder. The apnea-hypopnea index (AHI), used for the diagnosis of OSA, captures only the frequency of respiratory events and has demonstrable limitations. Measurements such as total arterial oxygen saturation < 90% (T90) and Hypoxic Burden (HB) have demonstrated utility for predicting cardiometabolic diseases, and other adverse health outcomes. Additionally, OSA has been associated with differential effects across racial/ethnic categories. In this cross-sectional study, we evaluate a community-dwelling healthy cohort of non-Hispanic Black and White older adults participating in studies on sleep, memory, and aging. Methods The study included a two-day clinical visit evaluation and one-night polysomnogram (PSG). Hypoxic burden was calculated as the area between the baseline and the SpO2 trace for any episode with >= 3% desaturation. Black and White older adults were relatively matched by age, gender, BMI and AHI4%. Multiple regression analyses with HB as the dependent variable and Age, Race, Sex, HTN, AHI4%, and BMI as the independent variables, and t-test was performed for group comparisons with a p-value < 0.05 defined as significant. Results Of the 140 subjects, 88 (62.85%) were females, 52 (37.15%) were males, 70 (50%) were non-Hispanic Black, and 70 (50%) were non-Hispanic White. The mean age was 67 (CI=63-71) years, BMI was 25 (CI=23-32) kg/m**2, and education was 16 (CI=14-18) years. Overall, male subjects had higher HB compared to females, p<.001. A significant difference in the HB was observed between blacks and whites regardless of hypertensive status, p<.008 for all. Black males and females had higher HB than white males and females, respectively, p<.0009 for all. Furthermore, age was negatively correlated with HB and this correlation was stronger in blacks compared to whites (r=-.43 vs. r=-.38, p<.05). Conclusion Hypoxic burden is a better predictor of cardio metabolic effects, compared to the AHI. Our findings indicate a more pronounced impact, particularly among blacks, with factors such as sex, hypertension, and BMI influencing this association. Future studies should examine the effects of modifiable factors, and how these may contribute to these observed sex/racial differences. Support (if any)

ADAM AND EVE covered their shame with fig leaves, which just happen to be bigger than maple leaves. But in 1906 a patriotic Canadian lady, Janet Carnochan by name, opined that \"Instead of the heterogeneous mixture of emblems on the Canadian coat-of-arms placed on the flag --\"meaning the Red Ensign, \"a single large maple leaf would be much preferable.\"

The Sustainable East Africa Research in Community Health (SEARCH) trial was a universal test-and-treat (UTT) trial in rural Uganda and Kenya, aiming to lower regional HIV-1 incidence. Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 gag and 488 pol HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections. Putative transmission clusters, with a 1.5% pairwise genetic distance threshold, were inferred from maximum likelihood phylogenies; clusters arising after the start of SEARCH were identified with Bayesian time-calibrated phylogenies. Our phylodynamic approach identified nine clusters arising after the SEARCH start date: eight pairs and one triplet, representing mostly opposite-gender linked (6/9), within-community transmissions (7/9). Two clusters contained individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, both linked to intervention communities. The identification of SEARCH-incident, within-community transmissions reveals the role of unsuppressed individuals in sustaining the epidemic in both arms of a UTT trial setting. The presence of transmitted NNRTI resistance, implying treatment failure to the efavirenz-based antiretroviral therapy (ART) used during SEARCH, highlights the need to improve delivery and adherence to up-to-date ART recommendations, to halt HIV-1 transmission.

The prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission. We present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997-2013), and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT) test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6-7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts. We conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF.