Category: Nevin Manimala

Aging Clin Exp Res. 2025 Jul 25;37(1):232. doi: 10.1007/s40520-025-03138-w.

ABSTRACT

BACKGROUND: Some observational studies have indicated that osteoarthritis (OA) is a fall risk factor. However, the causal relationship between OA and falls remains unclear.

METHODS: We conducted a two-step Mendelian randomization (MR) to investigate the causal relationships between OA, paracetamol use, and the risk of falls and to estimate the mediating effect of paracetamol use. Publicly accessible data for hip OA, knee OA, paracetamol use, and falling risk were sourced from Genome-Wide Association Studies (GWAS).

RESULT: In the forward MR analysis, the Inverse Variance Weighted (IVW) method indicated that a genetic predisposition to hip OA was significantly associated with an increased risk of falls (OR: 1.053, 95% CI: 1.014 to 1.094, P = 0.007). Consistent directions of effect were observed across other MR analysis methods. The mediated proportion of paracetamol use on the relationship between hip OA and falling risk was 21.70% (β = 0.0113, 95% CI: 5.73-37.8%, P = 0.0078). No causal relationship was observed between knee OA and falling risk, nor between knee OA and the use of paracetamol. In the reversed MR analysis, the IVW method showed that a genetic predisposition to falls may not increase the risk of developing hip and knee OA.

CONCLUSION: These results provide genetic evidence for a causal effect of hip OA on fall risk, partially mediated by paracetamol, and underscore the importance of fall prevention education and cautious paracetamol use for patients with hip OA.

PMID:40711723 | DOI:10.1007/s40520-025-03138-w

Ophthalmol Ther. 2025 Jul 25. doi: 10.1007/s40123-025-01194-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Ocular redness is common, can affect quality of life, and can be relieved by short-term use of topical adrenergic receptor (AR) agonists. Brimonidine tartrate ophthalmic solution 0.025% (LUMIFY^® 0.025%) is the first α2-AR-selective agonist approved for ocular redness. The preservative benzalkonium chloride (BAK) maintains ophthalmic solution sterility, reducing the risk of ocular infections, but may cause symptoms of ocular surface disease (OSD) in some patients. A BAK-free formulation of LUMIFY 0.025% (BTOS-PF 0.025%) could offer a solution for BAK-sensitive patients.

METHODS: This randomized, active-controlled, multicenter study aimed to establish non-inferior efficacy of BTOS-PF 0.025% to LUMIFY 0.025% and compare safety. Randomized participants received either formulation instilled as a single drop four times daily, for 4 weeks. The primary endpoint was investigator-assessed ocular redness at 5, 15, 30, 60, 90, 120, 180, and 240 min post-instillation at visit 1 (day 1). Eight hierarchical secondary endpoints included additional post-instillation timepoints at visit 1 and visits 2 and 3 (days 14 and 28), and participant-assessed redness.

RESULTS: BTOS-PF 0.025% was statistically non-inferior to LUMIFY 0.025% for ocular redness reduction across the eight timepoints at visit 1. Efficacy for both formulations was seen as early as 1 min and up to 8 h post-instillation. BTOS-PF 0.025% performed similarly to LUMIFY 0.025% after 14 and 28 days, rebound redness rates were low and similar, and total clearance of ocular redness and participant-evaluated redness were similar. The safety profile of both formulations was similar, with no severe or serious ocular events.

CONCLUSIONS: BTOS-PF 0.025% was non-inferior to LUMIFY 0.025% in reducing ocular redness in adults, was well-tolerated, and offers an alternative topical solution, without loss of efficacy or compromised safety, for patients who prefer a preservative-free formulation or are at increased risk of OSD.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05360784. Date of registration: 29 April 2022.

PMID:40711722 | DOI:10.1007/s40123-025-01194-z

Pulm Ther. 2025 Jul 25. doi: 10.1007/s41030-025-00307-0. Online ahead of print.

ABSTRACT

INTRODUCTION: A common complication of interstitial lung disease (ILD) is pulmonary hypertension (PH), which is associated with increased morbidity and mortality and worsened quality of life. In ILD, evaluating for PH is recommended prior to lung transplantation. However, this is not standardized or routinely performed in earlier stages of ILD, and guidelines lack an evidence-based approach for PH screening in this population. Furthermore, right-heart catheterization (RHC) access can be limited in many settings. The objective of PHINDER (Pulmonary Hypertension Screening in Patients with Interstitial Lung Disease for Earlier Detection) is to prospectively develop screening strategies for PH in patients with ILD.

METHODS: PHINDER is a prospective, non-interventional study that will enroll approximately 200 patients with ILD treated in a variety of settings in the United States (community centers, academic institutions, etc.). Patients must be diagnosed with ILD by high-resolution computed tomography (HRCT) and must not have a previously reported mean pulmonary arterial pressure (mPAP) > 20 mmHg. To enrich the population for PH, patients must meet additional criteria on Pulmonary Function Tests, HRCT, signs/symptoms, 6-min walk test, or echocardiography. Patients will undergo a variety of routine ILD clinical assessments. Lastly, patients receive a RHC to assess for PH, defined as mPAP > 20 mmHg with pulmonary arterial wedge pressure ≤ 15 mmHg and a pulmonary vascular resistance > 2 Wood Units. All treatment decisions are at the discretion of the provider and not influenced by study participation.

PLANNED OUTCOMES: Following study completion, statistical tools will be used to derive a practical model for a screening algorithm using the variables identified in the study as most predictive of PH in patients with ILD.

CONCLUSIONS: Using a previously developed list of clinical assessments from PH and ILD experts, the PHINDER study aims to be the first prospectively enrolled study to evaluate prognostic screening strategies that can be used to develop an algorithm to predict the risk of PH in patients with ILD.

TRAIL REGISTRATION: NCT05776225.

PMID:40711711 | DOI:10.1007/s41030-025-00307-0

Health Justice. 2025 Jul 25;13(1):46. doi: 10.1186/s40352-025-00356-2.

ABSTRACT

BACKGROUND: As the opioid overdose crisis continues to produce excessive morbidity and mortality in the United States, government agencies have applied various approaches to prevent overdoses, including law-enforcement efforts (e.g., arresting people who use drugs, interrupting drug traffickers, etc.) and treatment-based approaches (e.g., naloxone, medications for opioid use disorder, etc.). Public perception and support of these approaches are relevant for informing policy, allocating resources, and effectively implementing community interventions to prevent drug-related harms.

METHODS: Using an embedded informational survey design, we experimentally assessed whether public support for strategies to prevent overdose in South Carolina is influenced by language from federal agencies describing treatment- or enforcement-based approaches. Respondents were randomly assigned to one of three groups: (1) enforcement -based approach, (2) treatment-based approach, or (3) the control condition. Those assigned to experimental groups were presented with statistics on drug overdose deaths, followed by an informational prompt with language about overdose prevention approaches from either DEA (enforcement) or NIH (treatment), while the control group received no informational prompt.

RESULTS: Findings from a sample of 4,675 respondents indicated that those assigned the DEA prompt were significantly more likely to support enforcement-based approaches in arresting drug traffickers and people who use drugs (AME = 0.060, p < 0.001). On the other hand, those assigned to the NIH prompt were significantly more likely to agree that both law enforcement (AME = 0.065, p < 0.0001) and clinicians (AME = 0.044, p < 0.05) are capable of preventing drug overdose deaths.

CONCLUSIONS: These findings shed light on public perceptions of approaches to addressing the opioid epidemic and limited modifiability when presented with language from federal agencies. This may inform future research, practice, and/or policy aiming to maintain public safety while also providing treatment options to people who use drugs in order to reduce overdose deaths.

PMID:40711698 | DOI:10.1186/s40352-025-00356-2

Pharmacoecon Open. 2025 Jul 25. doi: 10.1007/s41669-025-00595-x. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients surviving a non-ST-elevation myocardial infarction (NSTEMI) have an elevated risk of future major adverse cardiovascular events (MACE), which can be mitigated through long-term cardiac arrhythmia monitoring. The present study evaluated the cost-effectiveness of continuous remote arrhythmia monitoring using an insertable cardiac monitor (ICM) combined with standard of care (SoC) compared with SoC alone.

METHODS: A cost-effectiveness analysis using a lifetime partitioned survival model was developed for high-risk NSTEMI patients from a UK National Health Service (NHS) perspective. Survival analysis was used to determine the transition of patients from the pre-MACE health state (where patients could experience arrhythmia, major bleeding, or systemic embolism) to the MACE health state (worsening heart failure, stroke, and acute coronary syndrome events). The survival analysis and arrhythmia diagnosis rates were informed by the BIO|GUARD-MI trial. The model captured direct costs associated with each MACE and implantation and removal of the ICM device and treatment costs following arrhythmia detection. The model captured the health implications for an ICM with SoC, compared with SoC alone, in terms of the total quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were undertaken to explore the impact of parameter uncertainty on the model results.

RESULTS: The use of ICMs plus SoC for daily remote cardiac arrhythmia monitoring is cost effective, when compared with SoC alone, in high-risk NSTEMI patients over a lifetime horizon, with an incremental cost-effectiveness ratio of £7766 per QALY gained. The ICM was associated with an additional 0.184 QALYs per patient for an additional cost of £1430. The ICM remained cost effective during the deterministic and probabilistic sensitivity analyses.

CONCLUSION: The addition of an ICM to SoC in high-risk NSTEMI patients is cost effective from the perspective of the UK NHS and would, therefore, be a further option for the management of such patients in clinical practice.

PMID:40711697 | DOI:10.1007/s41669-025-00595-x

Ann Surg Oncol. 2025 Jul 25. doi: 10.1245/s10434-025-17840-6. Online ahead of print.

ABSTRACT

BACKGROUND: Extended pelvic lymph node dissection (ePLND) plays a critical role in the accurate staging of prostate cancer; however, it is associated with increased perioperative morbidity. Refinement of the indications for ePLND through the identification of predictive factors for contralateral lymph node involvement (LNI) may contribute to minimizing overtreatment and associated complications.

PATIENTS AND METHODS: In this retrospective study, we analyzed a cohort of 223 patients with clinically unilateral prostate cancer who underwent robot-assisted radical prostatectomy combined with bilateral ePLND. Tumor laterality was defined by biopsy and magnetic resonance imaging (MRI) findings. Associations between preoperative clinical factors and contralateral LNI were assessed using statistical tests.

RESULTS: Contralateral LNI was significantly associated with PSA ≥10 ng/mL (6.3% vs. 0.7%; p = 0.047) and ≥66% positive biopsy cores in the ipsilateral lobe (8.0% vs. 0%; p = 0.0037). A risk classification model combining these two factors identified a high-risk group with 13.2% incidence of contralateral LNI, compared with 0.5% in the low-risk group (p = 0.0003).

CONCLUSIONS: PSA level at diagnosis and the proportion of positive biopsy cores in the ipsilateral lobe are useful predictors of contralateral LNI in clinically unilateral prostate cancer. A preoperative risk model incorporating these variables may support a tailored approach to ePLND, minimizing surgical burden without compromising diagnostic accuracy.

PMID:40711688 | DOI:10.1245/s10434-025-17840-6

Ann Surg Oncol. 2025 Jul 25. doi: 10.1245/s10434-025-17883-9. Online ahead of print.

NO ABSTRACT

PMID:40711687 | DOI:10.1245/s10434-025-17883-9

Elife. 2025 Jul 25;13:RP101327. doi: 10.7554/eLife.101327.

ABSTRACT

In the last decade, activity-dependent strategies for labeling multiple immediate early gene ensembles in mice have generated unprecedented insight into the mechanisms of memory encoding, storage, and retrieval. However, few strategies exist for brain-wide mapping of multiple ensembles, including their overlapping population, and none incorporate capabilities for downstream network analysis. Here, we introduce a scalable workflow to analyze traditionally coronally sectioned datasets produced by activity-dependent tagging systems. Intrinsic to this pipeline is simple multi-ensemble atlas registration and statistical testing in R (SMARTTR), an R package which wraps mapping capabilities with functions for statistical analysis and network visualization, and support for import of external datasets. We demonstrate the versatility of SMARTTR by mapping the ensembles underlying the acquisition and expression of learned helplessness (LH), a robust stress model. Applying network analysis, we find that exposure to inescapable shock (IS), compared to context training, results in decreased centrality of regions engaged in spatial and contextual processing and higher influence of regions involved in somatosensory and affective processing. During LH expression, the substantia nigra emerges as a highly influential region that shows a functional reversal following IS, indicating a possible regulatory function of motor activity during helplessness. We also report that IS results in a robust decrease in reactivation activity across a number of cortical, hippocampal, and amygdalar regions, indicating suppression of ensemble reactivation may be a neurobiological signature of LH. These results highlight the emergent insights uniquely garnered by applying our analysis approach to multiple ensemble datasets and demonstrate the strength of our workflow as a hypothesis-generating toolkit.

PMID:40709549 | DOI:10.7554/eLife.101327

J Food Sci. 2025 Jul;90(7):e70037. doi: 10.1111/1750-3841.70037.

ABSTRACT

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and behavioral changes. Emerging evidence suggests that the gut microbiota influences central nervous system function. Probiotic interventions may offer a promising therapeutic approach by modulating the gut microbiota composition and potentially improving cognitive outcomes in AD patients. This meta-analysis aimed to assess the effects of probiotic supplementation on cognitive function in AD patients by analyzing randomized controlled trials (RCTs). Following PRISMA 2020 guidelines and registered with PROSPERO (CRD42024508725), we conducted a comprehensive search across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through April 9th, 2024. Only double-blind RCTs comparing probiotic supplementation to placebo in patients aged 65 or older with clinically diagnosed AD were included. Primary outcomes were cognitive function scores from validated tools like MMSE and TYM. Our stringent inclusion criteria identified four double-blind RCTs with 251 participants aged 65 or older with clinically diagnosed AD. Statistical analysis using a random-effects model revealed significant cognitive improvement in probiotic-treated groups compared to placebo controls (Standardized Mean Difference [SMD] = 0.67; 95% CI [0.14, 1.19]; P < 0.05), though substantial heterogeneity was observed (I² = 79.16%). Subgroup analyses indicated that probiotic formulation type, dosage, and baseline AD severity may influence cognitive outcomes. While these findings suggest probiotics may offer cognitive benefits for AD patients, the high heterogeneity and limited study number necessitate additional well-designed clinical trials to confirm these promising results and establish optimal treatment protocols for clinical implementation.

PMID:40709497 | DOI:10.1111/1750-3841.70037

Pest Manag Sci. 2025 Jul 25. doi: 10.1002/ps.70096. Online ahead of print.

ABSTRACT

BACKGROUND: The removal of female mosquitoes is a critical requirement in sterile insect technique (SIT) for mosquito control. Improving the efficiency and accuracy of sex sorting is therefore vital. Previous studies have demonstrated that treating larval-pupal mixtures with a 15% sodium chloride (NaCl) solution prior to the sex sorting process reduces female contamination in Aedes mosquitoes. However, the effects of NaCl on Aedes albopictus mosquito biology and its practical application in production facilities remain insufficiently explored and warrant further investigation.

RESULTS: Exposure of larval-pupal mixtures to 15% NaCl for 60 min led to 100% larval mortality via osmotic imbalance and intestinal tissue damage, while pupae remained unaffected due to their impermeable cuticle. Males emerging from treated pupae exhibited comparable emergence, longevity, and flight ability to controls, indicating no adverse effect on male quality. NaCl pretreatment significantly improved sorting efficiency and reduced female contamination in manual sorting, achieving a 3.9-fold reduction in adult-stage contamination. Although automatic sorters increased throughput, reductions in female contamination were not statistically significant. Importantly, the sorting benefits of NaCl treatment were threshold-dependent and most evident at larger processing scales.

CONCLUSION: NaCl pretreatment is a simple, scalable, and biologically safe strategy to enhance sex separation in Ae. albopictus mass production. It is particularly advantageous under high-throughput conditions and preserves male fitness, supporting the stringent quality standards required for successful SIT-based mosquito control. © 2025 Society of Chemical Industry.

PMID:40709495 | DOI:10.1002/ps.70096