Category: Nevin Manimala

Geroscience. 2025 Sep 19. doi: 10.1007/s11357-025-01855-8. Online ahead of print.

ABSTRACT

Rapamycin (RAPA) and related mTOR-inhibitors have been shown to enhance healthy aging in animal models (2-10) and to be generally safe and tolerable in older people (11-13). However, studies to assess their effects on specific age-related pathologies in humans are limited. Since improvements in cardiovascular function with RAPA treatment have been reported in preclinical studies (5, 9, 10, 14-17), we posited that RAPA could be similarly efficacious in humans. Towards this end, we performed a pilot “proof of concept” trial to examine RAPA’s effects on cardiovascular and endothelial functions that are known to decline with age (18, 19). We hypothesized that RAPA would elicit beneficial cardiovascular effects in men. A cohort of older male subjects with no known cardiac disease (ages 70-76 years) were enrolled in the open-label study and received 1 mg RAPA/day for 8 weeks. To assess cardiovascular function, cardiac MRI (CMR) was performed twice: prior to initiation of the intervention and again after 8 weeks of treatment. Endothelial function was examined using laser-Doppler flowmetry (LDF) by measuring cutaneous, endothelium-dependent, local thermal hyperemic responses pre-intervention and after 4 and 8 weeks of RAPA (1). In all 6 subjects, transmitral blood flow, peak flow rate, and maximal blood acceleration showed statistically significant improvements while endothelial function also improved over the 8-week course of RAPA treatment. Thus, cardiac and endothelial function improvements with RAPA were found and support future placebo-controlled studies in larger cohorts of healthy older persons as well as in patients with compromised diastolic and endothelial function (20, 21).

PMID:40971115 | DOI:10.1007/s11357-025-01855-8

Odontology. 2025 Sep 19. doi: 10.1007/s10266-025-01207-0. Online ahead of print.

ABSTRACT

Periodontitis, a chronic inflammatory disease influenced by host-microbiota interactions, poses a significant global health burden. Smoking exacerbates periodontitis progression and impacts treatment outcomes. Interleukin (IL)-17 and IL-35 are key mediators of inflammation, yet their roles in smoking-related periodontitis and responses to non-surgical periodontal treatment (NSPT) remain underexplored. This clinical trial aimed to evaluate the effects of NSPT on salivary and gingival crevicular fluid (GCF) levels of IL-17 and IL-35 in smokers and non-smokers with periodontitis. A total of 55 subjects were divided into three groups: smokers with periodontitis (SP), non-smokers with periodontitis (NSP), and healthy controls (C). All subjects underwent comprehensive periodontal assessments and cytokine level analyses at baseline and four weeks post-NSPT. Saliva and GCF samples were analysed for IL-17 and IL-35 using enzyme-linked immunosorbent assay (ELISA). Statistical analyses evaluated group differences and correlations. After NSPT, both SP and NSP groups exhibited significant improvements in clinical parameters (p < 0.05). Salivary IL-17 and IL-35 levels did not show significant differences between the SP, NSP, and C groups after NSPT (p > 0.05). However, in GCF, IL-17 and IL-35 concentrations significantly increased in both SP and NSP groups following NSPT (p < 0.05). The total amount of GCF IL-17 decreased significantly only in the NSP group after NSPT (p < 0.05), while the total amount of GCF IL-35 increased significantly in both SP and NSP groups (p < 0.05). Strong correlations between IL-17 and IL-35 levels in both saliva and GCF were observed. NSPT modulates inflammatory and anti-inflammatory cytokine profiles, promoting improved clinical outcomes. The impact of smoking on cytokine responses highlights the need for further research to elucidate the mechanisms underlying these cytokine modulations and their role in periodontal therapy. Trial registration ClinicalTrials.gov ( https://clinicaltrials.gov -01.01.2018-NCT05281848).

PMID:40971113 | DOI:10.1007/s10266-025-01207-0

Clin Oral Investig. 2025 Sep 19;29(10):467. doi: 10.1007/s00784-025-06563-3.

ABSTRACT

OBJECTIVES: The aim of this RCT was to clinically evaluate swelling, pain and wound healing following submucosal infiltration of injectable Platelet-Rich Fibrin (i-PRF) after extraction of impacted lower third molar.

MATERIALS AND METHODS: The study was designed as a double-blinded, parallel group, randomized controlled clinical trial. 56 patients were divided into 2 groups: in the control group the socket was left to heal spontaneously, while the test group was treated with submucosal infiltration of i-PRF. Swelling was measured with a flexible ruler using the diagonals joining Trago and Pogonion, Gonion and labial cleft. The swelling was calculated as the sum of these diagonals before surgery, on day 3 and 7. Pain was assessed by VAS scale until the 7th postoperative day. Surgical wound healing was evaluated by the Healing Index by Landry on 3, 7 ,14 and 21st day postosperatively. The relation between duration of intervention and total swelling was also evaluated.

RESULTS: 56 patients were enrolled in this study (28 for the test group and 28 for the control group). Randomization resulted in groups with similar baseline characteristics. No patients were lost during the follow-up and no adverse events were noted. On day 3 the total swelling was 12.7 ± 0.92 mm for control group and 12.1 ± 0.75 mm for test group; on day 7 it was 12.3 ± 0.88 mm for control group and 11.7 ± 0.73 mm for test group. A statistically significant difference was found on day 3 (p = 0.006) and on day 7 (p = 0.018). The relation between total swelling and duration of intervention was not statistically significant (p = 0.276). A significant reduction in pain scores was observed in the i-PRF group on days 1 and 3 (p < 0.001). Surgical wound healing also showed statistically significant improvement in the i-PRF group at all time points (days 3, 7, 14, and 21; p < 0.05).

CONCLUSIONS: Within the limit of our study, this randomized controlled clinical trial suggests that submucosal infiltration of i-PRF after the extraction of impacted lower third molars effectively reduces postoperative swelling and pain, while also promoting faster wound healing.

CLINICAL RELEVANCE: The adjunctive use of injectable platelet-rich fibrin (i‑PRF) after surgical removal of impacted mandibular third molars may contribute to improve early postoperative outcomes by attenuating soft tissue inflammation, reducing pain intensity, and accelerating wound healing. By potentially lowering the need for nonsteroidal anti-inflammatory drugs (NSAIDs) and minimizing associated adverse effects, i‑PRF represents a minimally invasive, autologous approach that could enhance patient comfort, reduce recovery time, and support faster return to daily activities.

PMID:40971054 | DOI:10.1007/s00784-025-06563-3

J Med Syst. 2025 Sep 19;49(1):116. doi: 10.1007/s10916-025-02250-8.

ABSTRACT

Mitigating clinical deterioration relies upon recognition (afferent limb) and interventions (efferent limb) by a healthcare team. Healthcare provider (HP) communication by text messaging plays a role in facilitating both limbs in the inpatient setting. We sought to quantitatively characterize healthcare provider team communications through the social network analysis (SNA) of secure text messages exchanged in the inpatient setting, and as they relate to a subgroup of patients demonstrating a deterioration during their hospitalization. Messages linked to inpatients exchanged between HPs over a 12-month period, including a cohort of messages linked to patients experiencing deterioration were analyzed using SNA. Subnetworks corresponding to individual patient encounters were constructed, including a series of subnetworks pertaining to patients with an impending clinical deterioration. Network and network participant characteristics were calculated and analyzed. From October 2022 through September 2023 there were 1,065,225 messages delivered by 3,272 HPs, associated with 4,328 inpatient hospital encounters, of which 120 hospital encounters were associated with a deterioration. SNA demonstrated significantly higher measures of eigenvector centrality among frontline providers (FLP) including advanced practice providers and housestaff, relative to attending physician (p < 0.001) and registered nurses (p < 0.001), consistent with greater influence of the FLP on information dissemination through the entire network. Within individual subnetworks associated with the care of patients experiencing a clinical deterioration, FLP participants demonstrated greater overall network influence (p = 0.032) relative to FLP counterparts in networks not associated with a deterioration, despite comparable numbers of participants and connections. Using SNA, we quantitatively characterized a text messaging network within an inpatient hospital setting, demonstrating the importance of FLPs on information dissemination, a finding demonstrated specifically within subnetworks dedicated to the care of individual deteriorating patients. Understanding characteristics of a dynamic communication network of healthcare providers may prove a valuable target in facilitating communication and in mitigating the risks of deterioration.IRB Approval: Johns Hopkins Medicine IRB (#CIR00419339).Clinical trial number: Not applicable.

PMID:40971050 | DOI:10.1007/s10916-025-02250-8

Ann Surg Oncol. 2025 Sep 19. doi: 10.1245/s10434-025-18264-y. Online ahead of print.

ABSTRACT

BACKGROUND: Low skeletal muscle mass is associated with adverse cancer outcomes and is a key diagnostic criterion for malnutrition in the Global Leadership Initiative on Malnutrition, emphasizing the importance of muscle mass assessment. This study aimed to establish sex-specific cutoff values for skeletal/psoas muscle mass index (SMI/PMI), calculated from computed tomography, in cancer patients for predicting prognosis.

METHODS: In this multicenter cohort study, preoperative SMI and PMI were analyzed in patients with gastric cancer who underwent gastrectomy without preoperative therapy between 2011 and 2016. Using 80% of the cases as a training set, sex-specific cutoffs for overall survival (OS) were determined via the optimal stratification method, adjusted for age and stage. The remaining 20% were used to validate OS differences between high and low muscle-mass groups.

RESULTS: Of 3841 registered patients from 17 hospitals, 3797 were analyzed. Spline plots showed a strong association between lower muscle mass and worse OS in males, but a weaker association in females. The SMI cutoffs were 40 cm²/m² (males) and 31 cm²/m² (females); PMI cutoffs were 3.7 cm²/m² (males) and 2.9 cm²/m² (females). In the validation set, low SMI and PMI were significantly associated with poor OS in males. In females, only PMI remained significant; body mass index better stratified prognosis than muscle indices.

CONCLUSIONS: The proposed cutoffs may facilitate the early identification of muscle loss or malnutrition, supporting timely intervention. The observed sex differences highlight the necessity to develop sex-specific strategies for nutritional and muscle mass management during cancer treatment.

PMID:40971041 | DOI:10.1245/s10434-025-18264-y

J Relig Health. 2025 Sep 19. doi: 10.1007/s10943-025-02454-9. Online ahead of print.

ABSTRACT

The objective of this study was to develop and validate the Spiritual Justice Scale (SJS) as a reliable measure of individuals’ perceptions of spiritual justice. The development of the scale was founded upon theoretical foundations and supported by rigorous statistical analyses. Exploratory factor analysis revealed a one-dimensional structure explaining 56.26% of the variance, while confirmatory factor analysis confirmed the model with acceptable fit indices. Reliability analysis demonstrated high internal consistency (Cronbach’s α = 0.95). Furthermore, a significant positive correlation was identified between the SJS and the Toronto Empathy Questionnaire (r = 0.42, p < 0.001), suggesting a close relationship between spiritual justice and compassion, as well as fairness. The findings suggest that the SJS is a psychometrically sound instrument. Its potential applications extend to research and practice in counselling, education, social work, and spirituality studies, offering a foundation for further investigations into the role of spiritual justice in psychological well-being and social functioning.

PMID:40971019 | DOI:10.1007/s10943-025-02454-9

World J Urol. 2025 Sep 19;43(1):563. doi: 10.1007/s00345-025-05946-1.

ABSTRACT

OBJECTIVES: The aim of our study was to evaluate the frequency of intervention requirements in inpatient urology consultations and the clinical and demographic factors influencing these decisions.

MATERIALS AND METHODS: We retrospectively analyzed urology consultations over a one-year period at a large tertiary regional hospital. The timing and location of consultations, indications, procedures performed, and the need for intervention were evaluated. Univariate and multivariate logistic regression analyses were conducted to identify predictors of intervention.

RESULTS: A total of 1,977 consultations were identified. The most common reasons for consultation were hematuria (18.9%), male lower urinary tract symptoms (18.3%), and obstructive uropathy (14.3%). The majority of consultations originated from the emergency department (59.5%). Urologic interventions were performed in 52.5% of the patients, with the most frequent procedures being urethral catheterization (18.2%), bladder irrigation (7.9%), and suprapubic catheterization (3%). According to the univariate analysis, refugee patients had a significantly higher intervention rate (p = 0.046). In the multivariate analysis, factors independently associated with the need for intervention included consultations initiated from the emergency department, the level of seniority of the evaluating physician, and symptom-based consultation requests (p < 0.001).

CONCLUSION: Inpatient urology consultations constitute a significant clinical workload, and a considerable proportion of those requiring intervention involve simple procedures that can be performed by nonurologist healthcare personnel. The high rate of noninterventional consultations reduces service efficiency. Improving triage systems and providing targeted training to healthcare staff may help alleviate this burden.

PMID:40971014 | DOI:10.1007/s00345-025-05946-1

Environ Monit Assess. 2025 Sep 19;197(10):1123. doi: 10.1007/s10661-025-14603-4.

ABSTRACT

Urban air quality models are essential for managing particulate matter (PM) pollution, yet their accuracy is often limited by sparse monitoring networks and outdated emission inventories. This study presents a scalable framework for improving PM10 and PM2.5 modelling through the use of high-resolution emissions inventories and enhanced validation based on calibrated low-cost sensor networks. Using Warsaw city in Poland as a representative case study, we demonstrate that incorporating high-resolution residential heating emissions from the Central Register of Emissions from Buildings (CEEB) and calibrating road dust resuspension parameters led to concentration reductions of up to 20% in urban hotspots and reduced the prediction bias for PM2.5 by 57% at key locations. Notably, the Revised scenario resolved substantial overestimations in districts where incorrect fuel classifications had previously caused overestimations. However, persistent winter overestimations and the inability to fully capture extreme PM10 peaks in dry months highlight ongoing challenges, particularly in modelling resuspension dynamics under dry conditions. Our findings reveal that low-cost sensors, when rigorously calibrated, can extend spatial coverage and improve model validation, though they may underestimate extreme pollution events. The methodological advances presented here are broadly applicable to cities worldwide, particularly those facing similar challenges of diverse emission sources and limited regulatory monitoring. This integrated approach supports more accurate forecasting and targeted mitigation strategies, offering a scalable solution for urban environments seeking to achieve international air quality standards.

PMID:40971007 | DOI:10.1007/s10661-025-14603-4

Support Care Cancer. 2025 Sep 19;33(10):864. doi: 10.1007/s00520-025-09927-3.

ABSTRACT

PURPOSE: Returning to work after cancer is a major concern, particularly in the case of head and neck cancer (HNC). As the head and neck sphere is central to communication and appearance, it can be affected to varying degrees, which can be extremely disabling. Returning to work remains a challenge for this vulnerable population.

METHODS: Using univariate and multivariate logistic regression analyses including 153 HNC survivors, we studied how different sociodemographic and clinical factors were associated with non-return to work in the VICAN national epidemiological survey set up in France. Eligible participants were aged between 18 and 60.

RESULTS: After 5 years, 48.4% of survivors had still not returned to work. Factors associated with non-return to work were age over 50 (p < 0.001), cancer recurrence (p = 0.015), lack of high school diploma (p = 0.002), pain preventing return to work (p = 0.002), and lower physical quality of life score (p = 0.031). For those under 50, older age (p < 0.001), single status (p = 0.042), recurrence (p = 0.004), manual occupation (p = 0.043), no high school diploma (p = 0.010), pain (p < 0.001), depression (p = 0.039), and impaired physical score (p = 0.009) were significantly associated with not returning to work.

CONCLUSION: Almost half of HNC survivors do not return to work following treatment. The return-to-work process is multifactorial and influenced by a wide range of medical, functional, and psychosocial variables. Our findings have identified specific patient-related risk factors, as well as key clinical and psychological determinants, which may facilitate the early identification of at-risk individuals and inform targeted interventions to optimize return-to-work outcomes.

IMPLICATIONS FOR SURVIVORS: The organization of a multidisciplinary post-treatment, “post-habilitation,” cancer strategy seems increasingly inevitable, in order to plan a return to daily life (work, sociability, married life).

PMID:40970976 | DOI:10.1007/s00520-025-09927-3

Cancer Chemother Pharmacol. 2025 Sep 19;95(1):89. doi: 10.1007/s00280-025-04808-2.

ABSTRACT

PURPOSE: Zolbetuximab, a monoclonal antibody targeting claudin 18.2 (CLDN18.2), is approved in combination with chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2-positive, unresectable, advanced or recurrent gastric cancer (in Japan) and in combination with fluoropyrimidine- and platinum-containing chemotherapy for first-line locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (in geographies including but not limited to the US, Europe, and China). Noncompartmental analysis (NCA) was previously used to evaluate the effect of zolbetuximab on pharmacokinetics (PK) of 5-fluorouracil (5-FU) and oxaliplatin; however, limitations of NCA confounded the results. This study utilized population pharmacokinetic (PopPK) analysis to address these limitations.

METHODS: In Cohort 2 of the phase 2 ILUSTRO study (NCT03505320), patients with locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive G/GEJ adenocarcinoma received zolbetuximab with modified folinic acid, 5-FU, and oxaliplatin. PopPK models were developed to evaluate the impact of zolbetuximab on PK of 5-FU and oxaliplatin (including simultaneous analysis of free and total platinum).

RESULTS: PK of 5-FU was adequately described by a 1-compartment model with zero-order input and first-order elimination. PK of free and total platinum was simultaneously described by a 3-compartment model with zero-order input, first-order elimination, and time-dependent free fraction. No impact of zolbetuximab on 5-FU PK or on systemic clearance or free fraction of oxaliplatin in plasma was observed. The effect of zolbetuximab on oxaliplatin distribution volume (12.3% decrease) was statistically significant but not considered clinically relevant.

CONCLUSION: PopPK analysis suggests no effect of zolbetuximab on 5-FU or oxaliplatin PK.

PMID:40970968 | DOI:10.1007/s00280-025-04808-2