Category: Nevin Manimala

Adv Sci (Weinh). 2025 Sep 30:e07691. doi: 10.1002/advs.202507691. Online ahead of print.

ABSTRACT

Chronic widespread pain (CWP) remains challenging due to its heterogeneous causes and complex mechanisms. A total of 2920 plasma proteins are analyzed from 29,254 UK Biobank participants. A total of 256 proteins are identified as cross-sectionally correlated with CWP. A simple (top 10 proteins) and comprehensive (all significant proteins) proteomic-based score (ProtS) is created for CWP diagnosis, both outperforming and improving the existing clinical score (area under the curve, AUC: 0.801, 0.723, and 0.791 alone, and 0.856 and 0.880 in combination). In addition, the protein score predicted 13-years risk of pain-related traits over the body, including pain onset, progression, and intensity; Moreover, it has stronger associations with nociplastic pain and fibromyalgia compared to nociceptive and neuropathic pain, implying a unique protein signature of different pain mechanisms. Finally, among 434 candidate proteins prioritized in the observational analysis, 18 are corroborated with causal relevance by Mendelian randomization, and importantly, four (CA14, DPEP1, LGALS3, and TNF) showed potential as novel drug targets repurposed for treating CWP.

PMID:41025730 | DOI:10.1002/advs.202507691

Jpn J Clin Oncol. 2025 Sep 30:hyaf152. doi: 10.1093/jjco/hyaf152. Online ahead of print.

ABSTRACT

BACKGROUND: The impact of the starting dose of tyrosine kinase inhibitors (TKIs) following combination therapy of immune checkpoint inhibitors with TKIs (i.e. IO-TKI) for advanced renal cell carcinoma (RCC) remains unclear.

METHODS: We retrospectively evaluated clinical data from 155 patients treated with first-line IO-TKI for RCC. Patients were categorized into full-dose and reduced-dose groups based on their starting dose of TKIs. Effectiveness and safety profiles were compared between groups.

RESULTS: A reduced starting dose was administered to 52 patients (34%). These patients were older (P = 0.0137) and received pembrolizumab plus axitinib more frequently, while lenvatinib plus pembrolizumab was less used (P = 0.0258) compared to the full-dose group. Progression-free survival and overall survival did not significantly differ between the full-dose and reduced-dose groups (P = 0.202 and P = 0.309, respectively). Although the objective response rate appeared higher in the full-dose group, the difference was not statistically significant after adjusting for other covariates (P = 0.0588). Safety profiles were comparable, with no significant differences in TKI dose reduction, drug interruption or discontinuation, or glucocorticoids use (P > 0.05). However, adverse events of grade ≥3 were more frequent in the full-dose group, although not statistically significant (P = 0.121).

CONCLUSION: The starting dose of TKIs did not significantly impact clinical outcomes following IO-TKI for RCC. These findings suggest a potential for the optimization of the starting dose of TKIs; however, prospective studies are warranted to confirm these findings.

PMID:41025729 | DOI:10.1093/jjco/hyaf152

J Foot Ankle Res. 2025 Dec;18(4):e70084. doi: 10.1002/jfa2.70084.

ABSTRACT

BACKGROUND: This study investigated the quality and clinical outcomes of the British Orthopaedic Foot and Ankle Society (BOFAS) registry first metatarsophalangeal joint (MTPJ) arthrodesis pathway.

METHODS: A prospective cohort study using data derived from the BOFAS registry. Adults aged ≥ 18 years with a record of undergoing first MTPJ arthrodesis in the UK from 29/08/2014 to 31/10/2019. The pre- and post-treatment pathway was evaluated by analysing Patient Reported Outcome Measures (PROMs) at baseline, 6 months and 12 months intervals. Consistency of data capture and completeness were explored using means, SD, medians and IQR for continuous variables and frequencies for categorical variables.

RESULTS: The mean age of the study population (n = 459) was 64.1 (± 12.1) years and 98.9% of the study cohort were female. Completeness of data collection was low for some items (e.g., medication 46%, surgical procedures 52%). Baseline completion of PROMs was moderate with 52.5% of participants providing MOXFQ (Manchester-Oxford Foot Questionnaire) pain and walking/standing scores at baseline. However, follow-up response rates declined substantially to 27.2% at 6 months and 15.7% at 12 months. Improvement in PROMs by 12 months following surgery was statistically and clinically significant (p < 0.001), with median scores of 10 [IQR: 0-20] for MOXFQ pain, 5.5 [0-21] for walking/standing, 0 [0-19] for social interaction, 5 [1-31] for NRS pain and 0.8 [0.7-1.0] for EQ-5D-5L.

CONCLUSION: The analysis highlights the clinical benefits of first metatarsophalangeal joint (first MTPJ) fusion surgery, with improvements in pain intensity, walking/standing ability, social interaction and quality of life. The BOFAS registry serves as a valuable tool for collecting patient-reported outcome measure (PROM) data, providing important insights into treatment effectiveness and participant well-being. Strengthening the data collection capabilities of the BOFAS registry could further enhance our understanding of the benefits of first MTPJ fusion and inform future treatment strategies.

PMID:41025702 | DOI:10.1002/jfa2.70084

Biomarkers. 2025 Sep 30:1-13. doi: 10.1080/1354750X.2025.2568858. Online ahead of print.

ABSTRACT

INTRODUCTION: High serum creatinine to total bilirubin ratio has been associated with an increased risk of developing hypertension. We evaluated the effect of biological agents on serum creatinine to total bilirubin ratio in patients with psoriasis.

METHODS: Serum creatinine and total bilirubin levels of patients were reviewed between June 2018 and October 2023.

RESULTS: This study included 302 patients, 143 (47.4%) females and 159 (52.6%) males with a mean age of 49.46 ± 13.82 years. The creatinine to total bilirubin ratio was higher in males than in females (p = 0.028), and in patients with comorbidities compared to those without (p = 0.031). Six months after biological agent treatment, serum total bilirubin levels increased (p = 0.010), while the creatinine to total bilirubin ratio significantly decreased (p = 0.038) in all patients. Serum creatinine to total bilirubin ratio decreased (p = 0.031) in patients who received IL-17 inhibitors after 6 months. Among them, patients treated with ixekizumab showed a statistically significantly decrease in creatinine to total bilirubin ratio (p = 0.015).

CONCLUSION: The decrease in creatinine to total bilirubin ratio after 6 months of treatment was statistically significant only in patients treated with IL-17 inhibitors, particularly ixekizumab. Therefore, we suggest that IL-17 inhibitors may have a protective role against hypertension in patients with psoriasis.

PMID:41025689 | DOI:10.1080/1354750X.2025.2568858

Eur J Cancer Prev. 2025 Nov 1;34(6):559-562. doi: 10.1097/CEJ.0000000000000966. Epub 2025 Oct 1.

ABSTRACT

Poor oral hygiene is a well-established risk factor for oral cavity cancer. However, the specific association between oral hygiene practices and oral cancer risk remains unclear. This study aimed to investigate the relationship between oral hygiene habits and the risk of oral cavity cancer. A case-control study was conducted involving 231 participants: 94 oral cavity cancer patients (case group) and 137 controls with other head and neck cancers. Oral health status was assessed using the Revised Oral Assessment Guide – Jönköping (ROAG-J), and a structured questionnaire was used to collect data on oral hygiene practices and lifestyle factors. The case group exhibited poorer oral hygiene practices, including lower rates of toothbrushing (68.1 vs. 90.5%) and food debris removal (38.3 vs. 63.5%), higher rates of smoking (66 vs. 11.7%) and alcohol consumption (58.5 vs. 14.6%), and poorer oral health (ROAG-J grade 2 or 3: 94.7 vs. 40.2%) compared with the control group. Multivariable logistic regression model has three independent risk factors for oral cavity cancer: smoking [odds ratio (OR): 9.77, 95% confidence interval (CI): 4.21-22.61], alcohol consumption (OR: 3.47, 95% CI: 1.48-8.10), and the presence of chronic diseases (OR: 2.90, 95% CI: 1.37-6.12), whereas food debris removal (OR: 0.25, 95% CI: 0.12-0.51) was a protective factor. Our findings highlight the importance of maintaining good oral hygiene practices in preventing oral cavity cancer. Future studies with larger sample sizes and collection of potential confounding factors are needed to confirm our findings.

PMID:41025686 | DOI:10.1097/CEJ.0000000000000966

Parasite Immunol. 2025 Oct;47(10):e70032. doi: 10.1111/pim.70032.

ABSTRACT

This study investigated whether miRNAs and cytokines could be markers of gestational and/or congenital toxoplasmosis (TX). A total of 172 clinical samples collected from women were investigated. For gestational TX, 63 plasmas from pregnant women were analysed: 44 with gestational TX (GT-PW), 11 with asymptomatic TX (AsT-PW) and 8 healthy pregnant women (H-PW). For controls, 68 plasmas: 34 healthy women (HW) and 34 with asymptomatic TX (AsT). For congenital TX, 41 amniotic fluid (AF) samples were tested: 29 with negative qPCR in AF and 12 with positive PCR. Nine miRNAs were assayed by qPCR in plasma and AF samples. IFN-γ, TNF-α and IL-10 detection in plasmas was performed by ELISA. Statistical analyses were determined by F-test and ROC curves. Among the 9 hsa-miRNAs studied, only hsa-miR-125b-5p was significantly expressed in the AsT-PW group. hsa-miR-144-3p was more expressed in the GT-PW group. In AF samples, hsa-miR-125b-5p was more expressed in 29 AF samples with Neg-qPCR and hsa-miR-144-3p in AF samples with Pos-qPCR. Pregnant women from the GT-PW group had lower IFN-γ, TNF-α, and IL-10 production than the other groups. The in silico analyses identified pathways for hsa-miR-144-3p and hsa-miR-125b-5p and were related to the pathogenesis and immune response in toxoplasmosis. These findings suggest that hsa-miR-125b-5p could be related to infection regulation and to be characterised as a potential marker for asymptomatic toxoplasmosis. On the other hand, the hsa-miR-144-3p could be related to the exacerbation of the infection since gestational and/or congenital TX groups expressed high expression of hsa-miR-144-3p and low expression of IFN-γ, TNF-α and IL-10.

PMID:41025671 | DOI:10.1111/pim.70032

Microbiol Spectr. 2025 Sep 30:e0119625. doi: 10.1128/spectrum.01196-25. Online ahead of print.

ABSTRACT

Treating multidrug-resistant (MDR) infections has become progressively dependent on limited therapeutic options, particularly polymyxins, such as colistin. This reliance has precipitated a concerning epidemiological trend: the emergence and global propagation of plasmid-mediated (mcr) as well as chromosome-mediated polymyxin resistance. Consequently, escalating resistance rates will certainly lead to diminished clinical efficacy of colistin, correlating with elevated mortality in septic patients who already face therapeutic limitations. Utilizing antimicrobial potentiators to restore the sensitivity of resistant pathogens to polymyxins represents a promising pharmacological strategy for reinvigorating the clinical utility of these agents. Here, we demonstrate that dronedarone hydrochloride (DH) exhibits significant synergistic bactericidal activity with colistin against colistin-resistant strains. DH enhances the antibacterial potency of colistin by approximately 32-fold (MIC from 8 μg/mL to 0.25 μg/mL in ExPEC ECQ001), effectively reversing resistance phenotypes. In vivo therapeutic efficacy studies demonstrated that combination therapy achieved a statistically significant reduction in bacterial burden compared to colistin therapy alone. Mechanistic studies revealed that DH has the capacity for specific molecular interactions with two critical phospholipid components: cardiolipin and phosphatidylglycerol (PG) in bacterial membranes. This binding induces membrane disruption, impairs energy production, and stimulates oxidative stress, which collectively augment the bactericidal activity of colistin. These findings position DH as a viable antibiotic adjuvant with translational potential for combination therapies against MDR pathogens. The dual targeting of membrane integrity and redox homeostasis presents a strategic advantage in circumventing conventional resistance mechanisms, thereby extending the application potential of colistin in contemporary antimicrobial regimens.IMPORTANCEColistin remains a last resort antibiotic for treating infections caused by extensively drug-resistant pathogens. However, the emergence of colistin resistance has significantly compromised its clinical utility. Our research identifies and characterizes that dronedarone hydrochloride (DH) restores bacterial sensitivity to colistin by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Mechanistic studies revealed that DH bound specifically to CL and PG, thereby enhancing membrane disruption, impairing energy production, and stimulating oxidative stress levels, which collectively augment the bactericidal activity of colistin. These findings present DH as a lead compound for combating colistin resistance, while offering novel mechanistic insights into its role as a colistin potentiator.

PMID:41025656 | DOI:10.1128/spectrum.01196-25

Dermatol Surg. 2025 Sep 30. doi: 10.1097/DSS.0000000000004881. Online ahead of print.

ABSTRACT

BACKGROUND: Skin laxity and crepiness of the arms is a cosmetic concern that before the advent of noninvasive skin tightening technologies could only be treated with surgery. Ultrasound-based technologies deliver energy to the dermis which causes neocollagenesis and neoelastogenesis to rejuvenate the skin.

OBJECTIVE: This study evaluates and compares the efficacy of a high-intensity, parallel beam ultrasound-based skin tightening (HIUS) device with microfocused ultrasound with visualization (MFU-V) for improvement of upper arm skin laxity and crepiness.

MATERIALS AND METHODS: A prospective, single-center, blinded, split-body, randomized clinical study investigated HIUS and MFU-V for improvement of upper arm skin laxity and crepiness. Subjects received a single treatment to the upper arms.

RESULTS: Fourteen female subjects completed the study. Assessments compared Day 30 and Day 90 follow-up visits with baseline. HIUS was as effective as MFU-V in improving arm laxity and crepiness. Investigators and subjects rated improved arm laxity/crepiness at Day 90. Most subjects were satisfied with the improvement of arm laxity/crepiness. There was no statistically significant difference in pain scores observed between the HIUS and MFU-V. The MFU-V treatment took more time to perform than the HIUS treatment.

CONCLUSION: High-intensity, parallel beam ultrasound-based skin tightening was effective and delivered results with high patient satisfaction for improving upper arm skin laxity/crepiness.

PMID:41025649 | DOI:10.1097/DSS.0000000000004881

Disabil Rehabil Assist Technol. 2025 Sep 30:1-14. doi: 10.1080/17483107.2025.2565405. Online ahead of print.

ABSTRACT

Using web crawling and statistical regression models based on large-scale platform data, this study examines how previous anonymous and non-anonymous donations influence subsequent contributions on charitable crowdfunding platforms, with a particular focus on health-related campaigns. Through web crawling, this study collected 1,136 projects from Qingsongchou and empirically analysed the herding effect in donation behaviour. Results indicate a significant herding effect in both anonymous and non-anonymous donations, as well as in donation amounts. This effect is stronger among non-anonymous donors compared to anonymous ones. Furthermore, this study explore moderating channels and find that social media sharing weakens the herding effect for anonymous donations but does not significantly alter the differential herding behaviour between the two groups. By distinguishing between early and late fundraising stages, this study also observe that the herding effect difference is more pronounced in the early stage. These findings enhance understanding of the economic implications of anonymous donations under information asymmetry and offer practical insights for improving anonymity mechanisms in health-oriented charitable crowdfunding.

PMID:41025637 | DOI:10.1080/17483107.2025.2565405

Int J Health Plann Manage. 2025 Sep 30. doi: 10.1002/hpm.70027. Online ahead of print.

ABSTRACT

INTRODUCTION: The Southeast Asian region of World Health Organization (SEARO) comprising 11 countries, that is Bangladesh, Bhutan, Democratic People’s Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and Timor-Leste is home to a quarter of the world’s population where severe oral health disparities persist.

AIM: This study aims to collate the oral health financing landscape, evaluate the relationship between government health expenditure and the burden of oral diseases, assess the proportionality of oral health spending relative to its share of the overall disease burden, and examine the inclusion and funding of dental care within Universal Health Coverage (UHC) benefit packages in the SEARO region.

MATERIALS AND METHODS: Data for this study were sourced from publicly available databases and relevant national health statistics repositories of SEARO countries. These datasets provided information on health financing indicators, oral health coverage, and oral disease burden. Descriptive statistics were used to summarize indicators across SEARO countries. Correlation analyses were done to examine the interrelationship between health financing indicators and oral health outcomes and oral health coverage.

RESULTS: Increased government expenditure on health was significantly and positively correlated with insurance and oral health coverage. It was inversely correlated with out-of-pocket expenses (OOPE), private health expenditure, borrowing money to cover health expenses, and ‘All cause’ DALYs (Disability Adjusted Life Years). There was no significant correlation between government health spending and ‘Oral Disorders’ DALYs. Increased private expenditure was inversely correlated with domestic general government health expenditure as a percentage of current health expenditure and oral health coverage and positively correlated with Out-of-pocket expenses and borrowing money for covering health expenses. The allocation of government spending did not correspond proportionately to the burden of oral diseases.

DISCUSSION AND CONCLUSION: The lack of correlation between government health funding and the oral disease burden and the disproportionately low government expenditure on oral health relative to the burden of oral diseases when compared to their share of the total disease burden indicates not only a significant deficiency in funding but also misplaced funding priorities. There is a need to focus on the prevention of oral diseases and direct resources towards prevention, regular training, and education of healthcare workers and the public to identify early signs and symptoms of oral disease, rather than solely on treatment.

PMID:41025615 | DOI:10.1002/hpm.70027