Tag: nevin manimala

J Clin Periodontol. 2025 Sep 5. doi: 10.1111/jcpe.70032. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease driven by immune dysfunction and microbial imbalance. This study aims to identify circulating druggable proteins causally linked to the disease.

MATERIALS AND METHODS: We integrated proteomics data from deCODE genetics with periodontitis genome-wide association studies (GWAS) from the Million Veteran Program to identify proteins associated with periodontitis. Findings were replicated using GWAS data from the Gene-Lifestyle Interactions in Dental Endpoints consortium. Causal associations were validated using genetic and statistical methods, and the identified proteins were assessed for biological relevance and druggability.

RESULTS: Among the 2088 evaluated proteins, three showed robust evidence of causal association with periodontitis: FGF2 (fibroblast growth factor 2) (odds ratio [OR]: 1.06, 95% confidence interval [CI] 1.032-1.082), AZGP1 (zinc-alpha-2-glycoprotein) (OR: 1.12, 95% CI 1.058-1.189) and BTC (betacellulin) (OR: 0.86, 95% CI 0.789-0.942). Replication analysis confirmed associations for 18 proteins, with 16 showing high colocalisation. Further evaluation of drug target databases revealed indirect links between the identified proteins and approved therapies for inflammatory conditions, suggesting potential therapeutic relevance.

CONCLUSION: This study identifies three circulating proteins-FGF2, AZGP1 and BTC-as causally associated with periodontitis, highlighting their potential as therapeutic targets. These results provide a foundation for future research into targeted therapies for periodontitis.

PMID:40913361 | DOI:10.1111/jcpe.70032

Ophthalmic Physiol Opt. 2025 Sep 5. doi: 10.1111/opo.70015. Online ahead of print.

ABSTRACT

PURPOSE: To gain a better understanding of corneal Stress-Strain Index (SSI) maps in healthy eyes and to determine their changes with age.

METHOD: The eyes of 72 participants (age 43.1 ± 20.9 years, 69.5% female) were included in the analysis, considering the left and right eyes separately. Corneal biomechanics were assessed using a combination of the Pentacam and Corvis instruments, whose data enabled the production of the SSI maps. The corneas were divided into nine zones to facilitate zone-specific analysis of biomechanical behaviour. Regression analyses were conducted to evaluate the relationship between age and SSI values in each corneal zone.

RESULTS: The mean overall SSI value of the cornea for all participants was 1.075. Considering different age groups, significant differences in SSI were seen between the young and older groups in the overall map from 0.938 ± 0.067 in 20-50-year-olds to 1.143 ± 0.064 in 50-80-year-olds (ANOVA, p < 0.001). The same effect was seen for each zone separately (ANOVA, p < 0.001). The corneal central apex and peripheral zones showed higher mean SSI values (1.153 ± 0.079) and hence, higher corneal stiffness compared with paracentral zones (0.890 ± 0.057).

CONCLUSION: This paper showcases a series of maps depicting corneal elasticity and explores the differences in corneal stiffening with age across various regions of healthy corneas. The results reveal that stiffening tends to accelerate in areas that are already stiffer and decelerate in weaker regions. This deeper insight into ocular physiology could enhance clinical care by enabling more personalised treatments based on the patient’s age and the specific corneal regions being addressed.

PMID:40913331 | DOI:10.1111/opo.70015

Ophthalmic Physiol Opt. 2025 Sep 5. doi: 10.1111/opo.70013. Online ahead of print.

ABSTRACT

PURPOSE: Few studies have comprehensively investigated the effect of low dose atropine on the binocular vision system beyond accommodative amplitude. This study examined the effect of 0.05% atropine eye drops on a range of accommodation and vergence parameters across a 10-day period.

METHODS: Twenty myopic, adult participants (mean age [SD] 22.3 [1.0] years, mean spherical equivalent refraction [SD] -1.9 [1.0] D) were randomised to receive either atropine (0.05% atropine sulphate, n = 10) or control (0.9% sodium chloride, n = 10) eye drops for nightly use for nine consecutive nights. Accommodative posture, monocular and binocular accommodative amplitude (AA), positive and negative relative accommodation (PRA/NRA), binocular accommodative facility (BAF), distance and near heterophoria, positive and negative fusional vergences (PFV/NFV), near point of convergence (NPC) and gradient accommodative convergence to accommodation ratios (AC/A) were measured at baseline, day-3 and day-10.

RESULTS: By day-10, accommodative lag had increased significantly and AA, PRA and BAF had all decreased significantly in the atropine group, while there were no significant changes in any of the control group measurements. Near heterophoria shifted significantly towards esophoria and the NFV break and recovery points were decreased significantly in the atropine group by day-10. Additionally, NPC reduced by a clinically significant amount (that bordered on statistical significance), with no changes found in the control group. There was no significant change in distance heterophoria, AC/A, NRA or PFV (all p > 0.05) at day-3 or day-10 in either treatment group.

CONCLUSIONS: Atropine (0.05%) use disrupted accommodation significantly over 10 days and increased convergence at near. While near heterophoria shifted towards esophoria, participants’ ability to counteract this was also diminished by a reduction in NFV. This suggests that the near heterophoria and fusional reserves of children using 0.05% atropine for myopia control should be monitored closely.

PMID:40913324 | DOI:10.1111/opo.70013

HGG Adv. 2025 Sep 5:100501. doi: 10.1016/j.xhgg.2025.100501. Online ahead of print.

ABSTRACT

Pleiotropy, the phenomenon where a genetic region confers risk to multiple traits, is widely observed, even among seemingly unrelated traits. Knowledge of pleiotropy can improve understanding of biological mechanisms of diseases/traits, and can potentially guide identification of molecular targets or help predict side-effects in drug development. However, statistical approaches for identifying pleiotropy genome-wide are limited, particularly for two correlated traits or case-control traits with unknown sample overlap or for disease traits from family studies. We proposed PLACO+, an improved version of our pleiotropic analysis under composite null hypothesis method based on GWAS summary statistics from two traits. PLACO+ uses an inflated variance model to allow for fractions of variants to be associated with none or only one trait under the null. It is genome-wide scalable, where analytical p-value is computed as a weighted sum of extreme tail probabilities of bivariate normal product distribution. Simulations for both population-based and family-based designs demonstrate well-calibrated type I errors at stringent levels and substantially improved power of PLACO+ over conventional approaches. We illustrate PLACO+ on inflammatory bowel disease subtypes with shared controls and on correlated lipid traits with unknown sample overlap. In particular, PLACO+ revealed pleiotropic regions between triglyceride and high-density lipoprotein levels that conventional approaches missed and all of which were replicated in larger GWAS of these lipid traits. This further demonstrates the utility of PLACO+ in discovering genetic associations of traits with modest sample sizes by leveraging information from another correlated trait.

PMID:40913314 | DOI:10.1016/j.xhgg.2025.100501

Am J Health Promot. 2025 Sep 5:8901171251375977. doi: 10.1177/08901171251375977. Online ahead of print.

ABSTRACT

ObjectiveTo characterize individual- and structural-level stigma associated with government (ie, SNAP, WIC) and emergency food program (ie, food banks, pantries, cupboards, soup kitchens) utilization in the US.Data Source5 databases (PubMed, PsychINFO, Web of Science, CINAHL, Sociological Abstracts) were searched in June 2024.Study Inclusion and Exclusion CriteriaIncluded peer-reviewed articles (January 2004 – June 2024), in the US, in English, original research or systematic reviews, and report on data closely related to general food insecurity, government and emergency food program participation, and stigma manifestations among adults.Data ExtractionData on study characteristics and stigma were extracted using a structured template.Data SynthesisDescriptive statistics and thematic analysis were used.ResultsOur search yielded 99 articles. A majority studied individual-level stigma (57.4%) and used qualitative designs (62.6%). Among the 9 identified populations, food insecure adults were the most frequently studied (25.2%). Anticipated stigma (29.8%) was the most commonly reported stigma manifestation, deterring program participation.ConclusionThis review underscores the significance of addressing food insecurity-related stigma to enhance the effectiveness of food assistance programs. Given the extensive evidence of the impact of stigma on program participation, policymakers and program administrators should design, implement and test strategies to address stigma. Future research should explore intersectional stigma, develop a food insecurity-related stigma measure, and evaluate stigma-reduction interventions longitudinally and across program settings.

PMID:40913286 | DOI:10.1177/08901171251375977

J Am Heart Assoc. 2025 Sep 5:e039381. doi: 10.1161/JAHA.123.039381. Online ahead of print.

ABSTRACT

BACKGROUND: Traditional cardiovascular risk assessment entails investigator-defined exposure levels and individual risk markers in multivariable analysis. We sought to determine whether an alternative unbiased learning analysis might provide further insights into vascular risk.

METHODS: We conducted an unsupervised learning (k-means cluster) analysis in the Women’s Health Study (N=26 443) using baseline levels of triglycerides, high-sensitivity C-reactive protein, and low-density lipoprotein cholesterol to form novel exposures. We then evaluated cluster-based risk of incident coronary, cerebrovascular, and limb events using the Kaplan-Meier method and multivariable Cox models, followed by comparison with established clinical biomarker thresholds. Finally, we illustrated clinical applicability to a nonvascular outcome (type 2 diabetes).

RESULTS: Four clusters emerged and were named according to aggregate biomarker profiles: Cluster 1 (“healthy,” n=12 101), cluster 2 (“hypercholesterolemic,” n=7424), cluster 3 (“inflammatory,” n=5056), and cluster 4 (“triglyceride-rich,” n=1862). Triglyceride-rich cluster identity conferred the highest risk of future cardiovascular events (adjusted hazard ratio [HR_adj], 2.24 [95% CI, 1.93-2.60]) compared with those in the healthy cluster (reference group). Risk was intermediate in the hypercholesterolemic (predominantly elevated low-density lipoprotein cholesterol) and inflammatory (predominantly elevated high-sensitivity C-reactive protein) clusters (HR_adj, 1.44 [95% CI, 1.28-1.61]; and 1.54 [95% CI, 1.35-1.75], respectively). Clustering yielded stronger total cardiovascular disease risk associations than traditionally defined mixed dyslipidemia with modest improvement in reclassification statistics. Cluster identities also predicted incident type 2 diabetes, with the greatest risk among the triglyceride-rich cluster (HR_adj, 3.78 [95% CI, 3.29-4.35]).

CONCLUSIONS: Unsupervised learning analyses demonstrated associations that may be useful when refining cardiovascular risk and may inform atherosclerosis development in healthy individuals better than traditional classification methods.

REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT00000479.

PMID:40913283 | DOI:10.1161/JAHA.123.039381

J Am Heart Assoc. 2025 Sep 5:e040058. doi: 10.1161/JAHA.124.040058. Online ahead of print.

ABSTRACT

BACKGROUND: Supervised treadmill exercise improves walking performance in people with lower extremity peripheral artery disease, but benefits are not immediate. This study identified the time course of attaining meaningful improvement in 6-minute walk distance and patient-reported outcome measures during a 6-month supervised exercise intervention in people with peripheral artery disease.

METHODS: Participants with peripheral artery disease were randomized to supervised treadmill exercise 3 time weekly or a nonexercise control group for 6 months. Six-minute walk distance (large clinically important difference: 20 meters) and the Walking Impairment Questionnaire distance score (0-100 scale, 100 is best, clinically important difference: 5 points) were measured at the 6-week, 12-week, and 26-week follow-up using a mixed-effects model for repeated measures.

RESULTS: Of 210 randomized participants (mean age, 67.0±8.6 years, 82 [39%] women, 141 [66%] Black), 200 (95%) completed at least 1 follow-up visit. Compared with controls, supervised exercise significantly improved 6-minute walk distance by 13.0 m (P=0.049) at the 6-week, 31.8 m (P<0.001) at the 12-week, and 33.9 m (P<0.001) at the 26-week follow-up. Compared with controls, supervised exercise increased the Walking Impairment Questionnaire distance score by +2.63 (P=0.37) at the 6-week, +6.59 (P=0.049) at the 12-week, and +2.37 (P=0.49) at the 26-week follow-up.

CONCLUSIONS: In people with peripheral artery disease, >6 weeks of supervised treadmill exercise was necessary to attain a large meaningful gain in 6-minute walk, and large meaningful gains were measurable by week 12 of supervised exercise. Meaningful improvement in participant reported walking ability was first observed at the 12-week follow-up, but this statistically significant benefit was gone by the 26-week follow-up.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01408901.

PMID:40913279 | DOI:10.1161/JAHA.124.040058

J Am Heart Assoc. 2025 Sep 5:e040983. doi: 10.1161/JAHA.125.040983. Online ahead of print.

ABSTRACT

BACKGROUND: Incarcerated individuals have a disproportionate burden of cardiovascular risk factors. However, there is a paucity of data focusing on cardiovascular death and access to adequate health care among incarcerated individuals.

METHODS: We used the Mortality in Correctional Institutions database from the US Bureau of Justice Statistics to examine cardiovascular deaths in all state prisons from 2001 to 2019, health care provision, as well as differences in these measures between racial and ethnic groups.

RESULTS: From 2001 to 2019, there were a total of 18 227 (28.0% of total) cardiovascular deaths among those incarcerated in state prisons. After declining from 2001, age-standardized cardiovascular mortality rates increased since 2012, and were 128.2 per 100 000 in 2019. Most cardiovascular deaths (40.8%) occurred after ≥120 months of incarceration, with 24.4% developing the condition that caused death after incarceration. Approximately 19% of individuals were not medically evaluated, 31% did not receive any diagnostic testing, and 27% did not receive medications during their incarceration for the cardiovascular condition causing death. Compared with White counterparts, Black individuals who died while incarcerated had a higher proportion of death related to a cardiovascular cause (30.9% versus 27.8%, P<0.001) and were less likely to be medically evaluated (78.6% versus 81.9%, P<0.0001) or receive treatment during incarceration for the cardiovascular condition determined to be the cause of death (68.1% versus 72.6%, P<0.0001).

CONCLUSIONS: Cardiovascular disease is an important cause of death among individuals incarcerated in state prisons. A large number of individuals who died from cardiovascular disease, did not receive medical treatment during their incarceration, with racial disparities in carceral care provision. Strategies to ensure quality and equitable cardiovascular care for this population are needed.

PMID:40913265 | DOI:10.1161/JAHA.125.040983

J Am Acad Audiol. 2025 May 1;36(3):188-195. doi: 10.3766/jaaa.240020.

ABSTRACT

Background: Although approximately 80 percent of hearing loss cases are treatable with hearing aids (HAs), only one in four individuals who may benefit from them pursue them. Along with audiologists, physicians are integral parts of the hearing-health care team. Whether patients with hearing loss are more likely to pursue HA use based on the physician recommendation is unknown. Purpose: To investigate motivating factors and perceptions of prospective HA users, particularly the role of physician recommendations. Research Design: Patients 18 years and older who underwent an HA evaluation at our practice between January 2018 and December 2022 were identified. Patients were given a 17-question survey to assess their demographic characteristics and factors related to HA adoption via e-mail (n = 2,677) or as a physical copy (n = 487). Study Sample: Our sample (n = 321) included 182 female patients (57 percent) and 139 male patients (43 percent). Most patients identified as White/Caucasian (86 percent), followed by Black/African American (7 percent) and Hispanic/Latino (2 percent). Most patients were older adults (age 60 years and older), and 144 (45 percent) were older than 75 years. Intervention: We assessed the demographics and motivating factors related to HA adoption based on the results of the 17-question survey. Data Collection and Analysis: Data were analyzed using descriptive statistics, chi-square analyses, and multiple logistic regression. An α of 0.05 was set as the threshold of statistical significance. Results: Approximately 80 percent of participants adopted HAs after their evaluation. The most commonly selected factors that influenced their decision were cost, insurance coverage, and physician recommendation. Chi-square analyses were performed to compare these factors between patients who did and those who did not adopt HAs and yielded a significant difference (X² = 177.8; p < 0.0001). Patients’ knowledge of multiple institutional locations that offer HAs (95 percent confidence interval [CI], 0.23-0.98; p = 0.045) and the office where they were evaluated (95 percent CI, 0.12-0.85; p = 0.019) were significant predictors of HA adoption. Conclusions: Our findings align with those of previous studies of motivating factors for HA adoption; however, with the addition of physician recommendation, our study showed higher HA adoption rates. These findings provide audiologists and physicians with insights regarding factors that impact HA adoption, which can help them develop a more individualized care plan during the initial evaluation.

PMID:40913255 | DOI:10.3766/jaaa.240020

JMIR Med Inform. 2025 Sep 5;13:e69216. doi: 10.2196/69216.

ABSTRACT

BACKGROUND: Transportation insecurity is a known barrier to accessing eye care and is associated with poorer visual outcomes for patients. However, its mention is seldom captured in structured data fields in electronic health records, limiting efforts to identify and support affected patients. Free-text clinical documentation may more efficiently capture information on transportation-related challenges than structured data.

OBJECTIVE: In this study, we aimed to identify mention of transportation insecurity in free-text ophthalmology clinic notes using natural language processing (NLP).

METHODS: In this retrospective, cross-sectional study, we examined ophthalmology clinic notes of adult patients with an encounter at a tertiary academic eye center from 2016 to 2023. Demographic information and free text from clinical notes were extracted from electronic health records and deidentified for analysis. Free text was used to develop a rule-based NLP algorithm to identify transportation insecurity. The NLP algorithm was trained and validated using a gold-standard expert review, and precision, recall, and F1-scores were used to evaluate the algorithm’s performance. Logistic regression evaluated associations between demographics and transportation insecurity.

RESULTS: A total of 1,801,572 clinical notes of 118,518 unique patients were examined, and the NLP algorithm identified 726 (0.6%) patients with transportation insecurity. The algorithm’s precision, recall, and F1-score were 0.860, 0.960, and 0.778, respectively, indicating high agreement with the gold-standard expert review. Patients with identified transportation insecurity were more likely to be older (OR 3.01, 95% CI 2.38-3.78 for those aged ≥80 vs 18-60 y) and less likely to identify as Asian (OR 0.04, 95% CI 0-0.18 for Asian patients vs White patients). There was no difference by sex (OR 1.13, 95% CI 0.97-1.31) or between the Black and White races (OR 0.98, 95% CI 0.79-1.22).

CONCLUSIONS: NLP has the potential to identify patients experiencing transportation insecurity from ophthalmology clinic notes, which may help to facilitate referrals to transportation resources.

PMID:40913248 | DOI:10.2196/69216