Category: Nevin Manimala

J Cardiovasc Pharmacol. 2026 Jul 6. doi: 10.1097/FJC.0000000000001856. Online ahead of print.

ABSTRACT

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death globally. Cholesteryl ester transfer protein (CETP) inhibitors have been proposed as a novel strategy for cardiovascular risk reduction, yet evidence remains inconsistent. PubMed, Embase and Scopus were searched for Randomized Controlled Trials (RCTs) comparing CETP inhibitors to placebo in patients with ASCVD. Random-effects models were used to pool risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Statistical analysis was performed using R software version 4.3.3. We included 5 RCTs involving 62,565 participants, of whom 31,698 (50.7%) received CETP inhibitors. Compared to placebo, CETP inhibitors showed no significant reduction in death from coronary heart disease (RR 0.91; 95% CI: 0.82 to 1.01), unplanned coronary revascularization (RR 0.91; 95% CI: 0.79 to 1.05), non-fatal myocardial infarction (RR 0.94; 95% CI: 0.87 to 1.02) and stroke (RR 1.02; 95% CI 0.93 to 1.12). Also, no excess risk of adverse events was observed (RR 1.00; 95% CI: 0.99 to 1.02). Conversely, HDL-C (MD + 130.82%; 95% CI: 121.49 to 140.15), LDL-C (MD -32.68%; 95% CI: -40.73 to -24.63), ApoA1 (MD +45.04%; 95% CI: 40.51 to 49.57) and Apo B (MD -17.26%; 95% CI: -20.51 to -14.00) showed significant improvement. CETP inhibitors produce substantial lipid modifications but do not reduce major adverse cardiovascular events, underscoring the limitations of surrogate lipid markers and the need for outcome-based validation of lipid-modifying therapies.

PMID:42407017 | DOI:10.1097/FJC.0000000000001856

Neurology. 2026 Jul 28;107(2):e218273. doi: 10.1212/WNL.0000000000218273. Epub 2026 Jul 6.

ABSTRACT

BACKGROUND AND OBJECTIVES: The origin of fasciculation potentials (FPs) in the early stages of amyotrophic lateral sclerosis (ALS) remains a subject of debate. We investigated the role of the motor cortex in FP generation by comparing resting FP frequency in the first dorsal interosseous (FDI) muscle before and after motor cortex inhibition induced by continuous theta-burst stimulation (cTBS).

METHODS: We studied patients with early-stage ALS (G1) and a disease-control group (G2) comprising individuals with chronic lower motor neuron (LMN) disorders or benign fasciculation syndrome without upper motor neuron (UMN) involvement. Inclusion required a right FDI strength of MRC grade 4+ or 5. At baseline, we recorded FP frequency and amplitude in the right FDI (3 replicates) and the motor evoked potential (MEP) amplitude. These measures were repeated immediately after cTBS-induced corticomotor inhibition. Statistical significance was set at p < 0.05.

RESULTS: Twenty-two patients with ALS (14 men; median age 65.5 years; 72.7% spinal onset) were included, with a median disease duration of 6.4 months and a mean ALSFRS-R score of 44. The control group (G2) consisted of 11 participants. Notably, 50% of the ALS cohort showed no neurogenic features on needle EMG of the right FDI at enrollment. Baseline peripheral and cortical amplitudes and left hemisphere motor thresholds were comparable between groups. After cTBS, MEP amplitudes decreased significantly in both G1 (0.93 vs 0.50 mV, p = 0.02) and G2 (1.23 vs 0.38 mV, p = 0.02). However, a significant reduction in FP frequency (39.5%) occurred only in the ALS group (0.43 vs 0.26 Hz, p < 0.001), whereas no change was observed in G2 (0.60 vs 0.77 Hz, p = 0.14). Patients with ALS with a normal FDI EMG demonstrated an even greater reduction in FP frequency (54.5%). FP amplitudes remained stable across both groups after cTBS.

DISCUSSION: Our findings indicate that in early ALS, LMN excitability is significantly modulated by descending corticospinal input. The reduction in FP frequency after cortical inhibition suggests that FPs in early ALS are driven by a combination of both UMN and LMN hyperexcitability, distinguishing them from fasciculations in other neurogenic disorders.

PMID:42407013 | DOI:10.1212/WNL.0000000000218273

Compend Contin Educ Dent. 2026 Jan-Feb;47(1):e5-e8.

ABSTRACT

This study evaluates the accuracy and reproducibility of three centric relation (CR) recording techniques-bimanual manipulation (BM), chin-point guidance (CPG), and anterior deprogrammer (ADP)-using the OccluSense® (OS) digital occlusal analyzer. Addressing a critical gap in prosthodontic literature, the research employs a prospective, single-center, within-subjects design with 27 participants. Each underwent five CR registrations (BM, BM2, CPG, CPG2, and ADP) over 2 days. Statistical analyses (descriptive statistics, Cohen’s Kappa, and Fleiss’ Kappa) revealed that BM and CPG demonstrated substantial initial agreement with the ADP reference. However, reproducibility declined in repeated measurements. The ADP method exhibited superior consistency, reinforcing its role as the gold standard. Side-based agreement analysis highlighted operator dependency for manual techniques. The study concludes that while ADP remains the most reliable CR recording method, BM and CPG are viable alternatives when performed by skilled clinicians. Digital tools like OS enhance objectivity but do not replace clinical expertise.

PMID:42406941

Traffic Inj Prev. 2026 Jul 6:1-10. doi: 10.1080/15389588.2026.2686799. Online ahead of print.

ABSTRACT

OBJECTIVE: Motor vehicle passing speed and lateral clearance jointly determine both bicyclist injury risk and perceived safety during overtaking events. Most prior studies have examined these factors separately and/or in limited settings. Real-world evidence describing how passing speed and clearance interact across heterogeneous roadway contexts remains limited. This study evaluates high-resolution naturalistic overtaking data within a kinetic-energy injury framework to evaluate whether roadway context and bicycle infrastructure modify both passing speed and lateral clearance, and whether spatial compensation meaningfully offsets energetic exposure.

METHODS: Following institutional review board approval, naturalistic cycling data were collected from six commuter cyclists riding as normal using a sensor suite including cameras, lidar, rear-facing radar, GPS, and inertial measurement unit. Approximately 9,900 km of riding were recorded over four months. Overtaking events were detected and characterized using time-synchronized radar and lidar data, yielding 8,753 passes with reliable vehicle speed estimates after quality filtering. Overtaking events were map-matched to OpenStreetMap roadway attributes and supplemented with image-based manual coding to classify functional class, posted speed limit, lane count, centerline configuration, and bicycle infrastructure type. Ordinary least-squares regression models with participant-clustered standard errors were applied to evaluate infrastructure effects and speed-distance relationships, including interactions with driver speeding behavior.

RESULTS: Passing speed varied substantially across roadway contexts, increasing with functional class and posted speed limit. Mean passing speed ranged from approximately 10 m/s (residential roads) to nearly 15 m/s (primary and four-lane facilities). In contrast, lateral clearance varied modestly across contexts, with mean values generally between 2.2 and 3.0 m and substantial overlap among categories. After adjustment for roadway characteristics, standard painted bicycle lanes were associated with reduced passing distance (β = -0.31 m) and higher passing speed (β = +1.36 m/s) relative to roads without bicycle accommodation. Shoulders were associated with the highest passing speeds and no meaningful increase in clearance. The overall compensation slope, defined as the increase in lateral clearance with increasing speed, was small: 0.016 m per 1 m/s (∼2.8 inches per 10 mph). Modest but statistically significant compensation was observed among drivers exceeding the speed limit and on higher-speed, higher-capacity roadways.

CONCLUSIONS: Roadway context strongly influenced passing speed, whereas lateral clearance adjustments were comparatively small and inconsistent. Across various naturalistic environments, lateral clearance did not increase proportionally at higher speeds. On-road bicycle infrastructure without accompanying speed management did not reliably reduce high-speed passing and, in some contexts, was associated with closer overtaking. These findings demonstrate the need for vehicle speed reduction and improved separation of bicycles from motor vehicle traffic to reduce crash injury risk.

PMID:42406922 | DOI:10.1080/15389588.2026.2686799

Diabetes Care. 2026 Jul 6:dc260763. doi: 10.2337/dc26-0763. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the association between fear and perceived frequency of hypoglycemia and continuous glucose monitoring (CGM) metrics in adults with type 1 diabetes using diabetes technology over 12 months.

RESEARCH DESIGN AND METHODS: This retrospective explorative analysis evaluated correlations between hypoglycemia fear, perceived hypoglycemia frequency, and CGM metrics in 1,370 adults with type 1 diabetes using real-time CGM (Comparing Continuous With Flash Glucose Monitoring in Adults With Type 1 Diabetes [ALERTT1] study, n = 254) or hybrid closed-loop (The Impact Of Hybrid Closed-loop Insulin Delivery in Type 1 Diabetes On Glycemic Control And PROMs [INRANGE] studies, n = 1,116) for 12 months. Hypoglycemia fear was assessed with the Hypoglycemia Fear Survey II worry (HFS-worry) and behavior (HFS-behavior) subscales, and perceived hypoglycemia frequency with the hypoglycemia subscale of the Diabetes Treatment Satisfaction Questionnaire-status (DTSQs-hypo). Data are reported as mean ± SD.

RESULTS: At baseline (before the start of technology), mean age was 41.0 ± 13.7 years, 55.9% were women, diabetes duration was 21.6 ± 12.7 years, HbA1c was 7.6 ± 1.0% (59.0 ± 10.8 mmol/mol), and time in 3.9-10.0 mmol/L was 61.1 ± 15.5%. Over 12 months, time <3.9/<3.0 mmol/L decreased from 3.4 ± 3.5%/0.8 ± 1.4% to 2.3 ± 2.2%/0.5 ± 0.7%, while HFS-worry (21.0 ± 12.9 to 16.8 ± 12.1) and DTSQs-hypo (3.3 ± 1.5 to 2.7 ± 1.4) also decreased. HFS-worry, HFS-behavior, and DTSQs-hypo showed no clear correlations with time in hypoglycemia or other CGM metrics at baseline, at 12 months, or over 12-month change.

CONCLUSIONS: In adults using diabetes technology over 12 months, fear and perceived frequency of hypoglycemia showed no clear correlations with CGM metrics, suggesting both are influenced by more than glycemic profiles alone.

PMID:42406897 | DOI:10.2337/dc26-0763

ESC Heart Fail. 2026 Jul 6:xvag191. doi: 10.1093/eschf/xvag191. Online ahead of print.

ABSTRACT

INTRODUCTION: Acute coronary syndrome (ACS) is frequently complicated by left ventricular systolic dysfunction and heart failure. Clonal haematopoiesis of indeterminate potential (CHIP) is characterised by mutations in haematopoietic stem cells that lead to the proliferation of mutant blood cells without overt haematological disease. Whether CHIP is associated with prognosis following ACS remains uncertain.

METHODS: We conducted a systematic review and meta-analysis of observational studies that compared outcomes after ACS in patients with and without CHIP. The primary outcome was all-cause mortality. Exploratory subgroup analyses explored mutation class and study-level comorbidities.

RESULTS: Eight studies comprising diverse ACS populations, from low-risk ACS to cardiogenic shock, were included. In the primary analysis, CHIP was associated with higher all-cause mortality (pooled HR 1.61, 95% CI 1.36-1.92), with no detected statistical heterogeneity (I2 = 0%). Mutation-specific analyses were underpowered but suggested a more consistent association between TET2 mutations and adverse events. Exploratory study-level analyses suggested that differences in smoking prevalence between CHIP carriers and non-carriers may contribute to variability in association strength, but no formal interaction testing was possible.

CONCLUSIONS: CHIP is associated with increased mortality following ACS across a broad range of clinical settings, suggesting it is a marker of adverse post-ACS risk. These findings highlight the need for adequately powered prospective studies with standardised CHIP ascertainment to determine whether CHIP represents a feasible biomarker or modifiable therapeutic target.

PMID:42406895 | DOI:10.1093/eschf/xvag191

JMIR Pediatr Parent. 2026 Jul 6;9:e87452. doi: 10.2196/87452.

ABSTRACT

BACKGROUND: The gut microbiota plays a crucial role in infant nutrition through its effects on energy metabolism, nutrient absorption, and immune regulation. However, evidence from Indonesian infants remains limited.

OBJECTIVE: This study aimed to examine the association between genus-level gut microbiota abundance and weight-for-age z scores (WAZ) among 6-month-old infants in coastal Banggai District, Central Sulawesi, Indonesia.

METHODS: We conducted a nested follow-up cross-sectional observational analysis of 88 six-month-old infants, including 42 (47.7%) who were born to mothers who were assigned to receive Moringa oleifera enriched with royal jelly group and 46 (52.3%) who were assigned to receive a multiple micronutrient supplement in a previous maternal supplementation trial. Maternal and infant characteristics were collected via structured interviews and standardized anthropometric measurements. WAZ was calculated using the World Health Organization Child Growth Standards, and underweight (WAZ <-2 SD) was reported as a secondary indicator. Stool samples were analyzed using genus-specific quantitative polymerase chain reaction to quantify Bifidobacterium, Lactobacillus, Bacteroides, Clostridium, and Escherichia coli (log10 colony-forming unit/mL). Associations between bacterial abundance and WAZ were assessed using multivariable linear regression adjusted for maternal supplementation allocation and relevant maternal, environmental, and infant covariates.

RESULTS: The pooled mean WAZ was -0.47 (SD 1.09), and 8% (7/88) of the infants were underweight. The combined abundance of beneficial genera was higher than that of opportunistic bacteria (E coli and Clostridium; Wilcoxon signed-rank test; P=.002). Higher Clostridium abundance was inversely associated with WAZ (unadjusted β=-.094, 95% CI -0.173 to -0.015; P=.02; adjusted β=-.091, 95% CI -0.172 to -0.010; P=.03). No statistically significant associations were observed for Bifidobacterium (P=.13), Lactobacillus (P=.19), Bacteroides (P=.70), or E coli (P=.18) in adjusted models.

CONCLUSIONS: Among 6-month-old infants in coastal Central Sulawesi, higher genus-level Clostridium abundance was independently associated with lower WAZ. Given the cross-sectional design and genus-level quantitative polymerase chain reaction assessment, temporality and species-level mechanisms cannot be established. Longitudinal studies using more comprehensive microbiome profiling are warranted to clarify potential pathways linking gut microbiota and early-life growth.

PMID:42406892 | DOI:10.2196/87452

Epidemiology. 2026 Jul 6. doi: 10.1097/EDE.0000000000002019. Online ahead of print.

ABSTRACT

BACKGROUND: The epidemic potential of infectious diseases depends on how contacts connect individuals over time-a form of temporal connectivity that has rarely been quantified in resource-poor settings. We used the forward-reachable path (FRP)-the proportion of population reachable from an index person via direct or indirect connections-to quantify temporal connectivity in contact networks relevant for acute respiratory transmission.

METHODS: From empirical social-contact data collected in rural and urban Tamil Nadu, India, we derived contact-location-specific network statistics. These statistics were used to parameterize dynamic network models, simulate daily networks over one year, and compute FRPs.

RESULTS: In both rural and urban networks, mean FRPs rose sharply on day 1, then either increased steadily at school and work or plateaued at home and at locations included in the other layer (that is, locations other than home, school, and work). By day 365, mean FRPs followed the order: home (0.06% [rural] and 0.03% [urban]) < school (11.96% [rural] and 9.14% [urban]) < work (12.55% [rural] and 26.72% [urban]) < other (40.54% [rural] and 67.99% [urban]). The mean FRP peaked at home among those aged ≥60 years, at school among those aged 10-19 years, and at work among those aged 40-59 years.

CONCLUSIONS: Although FRP at home was bounded by household size, reachability expanded substantially through school, work, and other contacts. These findings indicate high temporal connectivity and substantial epidemic potential for acute respiratory transmission in these settings.

PMID:42406882 | DOI:10.1097/EDE.0000000000002019

Epidemiology. 2026 Jul 6. doi: 10.1097/EDE.0000000000002020. Online ahead of print.

ABSTRACT

BACKGROUND: We examined radon’s association with the complete blood count and leukocyte differential to better understand radon-related risks of stroke and myocardial infarction (MI) previously observed in the Women’s Health Initiative (WHI).

METHODS: We conducted a repeated measures analysis in this prospective cohort of post-menopausal women enrolled in 1993-1998 and examined at 5 visits over 19 years in 40 US clinical centers (n=154,630). We estimated indoor radon concentrations (pCi/L) at time-varying, geocoded addresses of participants (1993-2013) by linking them to the US Geological Survey Radon Index (1993) zoned by US Environmental Protection Agency Action Levels. We estimated covariate-adjusted, longitudinal associations of radon concentrations with complete blood count components using linear mixed-effects models. In a subset (n=6,313), we evaluated cross-sectional associations with the complete blood count differential using multivariate compositional data analysis.

RESULTS: At 2-4 and >4 pCi/L, adjusted mean (95% confidence interval) leukocytes were 48 (33, 63) and 78 (58, 98) cells/μL lower than at <2 pCi/L, while platelets, hematocrit, and hemoglobin were higher: 315 (-280, 910) and 2,033 (1,248, 2,818) cells/μL; 0.27% (0.24%, 0.30%) and 0.23% (0.19%, 0.27%); and 0.09 (0.08, 0.10) and 0.09 (0.07, 0.10) g/dL. Nonlinear spline models of the Radon Index revealed similar associations. Lymphocyte percentages were lower and other percentages were higher at higher (>4 pCi/L) vs. lower (<2 pCi/L) radon concentrations in nonlinear compositional data analysis.

CONCLUSION: The radon-related cardiovascular implications of these modest, pro-thrombotic, myeloid shifts in the complete blood count/differential among postmenopausal women in the WHI remain unknown.

PMID:42406881 | DOI:10.1097/EDE.0000000000002020

PLoS One. 2026 Jul 6;21(7):e0349441. doi: 10.1371/journal.pone.0349441. eCollection 2026.

ABSTRACT

BACKGROUND: Sickle cell disease (SCD) stands as one of the most prevalent genetic disorders in the United States (U.S.) that causes severe consequences such as organ damage and excruciating pain. Alarmingly, recent literature indicates a decline in the number of people living with SCD (PLWSCD) seeking professional care – hinting at an avoidance of the healthcare system. Therefore, this scoping review synthesizes the evidence regarding barriers and facilitators influencing healthcare utilization among PLWSCD within the U.S.

METHODS: To map the current literature on SCD management and provide a comprehensive overview of the current knowledge gaps regarding healthcare utilization for PLWSCD, a scoping review was conducted. A systematic search of articles reporting on the utilization of healthcare among PLWSCD in the U.S using seven data sources was conducted on March 24, 2023, without any restrictions on publication date and language. To capture any additional articles, the search was updated on March 4, 2024. Two reviewers independently assessed studies for inclusion, data extraction, and risk of bias (RoB).

MAIN RESULTS: A total of 708 articles were screened; 70 met the study criteria. Results indicated that the four most common barriers were social (n = 25) interpersonal (n = 23), economic (n = 15), and institutional level factors (n = 11). The top four most common facilitators were technology (n = 9), education (n = 7), autonomy (n = 6), and a positive patient-provider relationship (n = 6). The most common forms of healthcare utilization were inpatient or hospital admissions (n = 19) and emergency department (ED) visits (n = 18). Evidence-based interventions (EBI) found to decrease healthcare avoidance included individualized pain plans (IPPs) (n = 4) and quality improvement (QI) strategies (n = 3).

CONCLUSION: This scoping review identified complex multilevel barriers that impede healthcare utilization, and facilitators likely to promote healthcare utilization among PLWSCD in the U.S. Future research should prioritize developing and evaluating comprehensive, multi-level interventions that address identified barriers while leveraging facilitators to improve healthcare engagement and outcomes for this vulnerable population. Healthcare systems and health policies must urgently adopt and integrate evidence-based strategies to rebuild trust and ensure equitable, accessible care for PLWSCD.

PMID:42406873 | DOI:10.1371/journal.pone.0349441