Citations

Objective To evaluate the safety and efficacy of Grayson's presurgical nasoalveolar molding (PNAM) technique on nasal and alveolar morphology in infants with unilateral cleft lip and palate (UCLP). Design Systematic review and meta-analysis. Setting : Multicenter international literature across clinical and academic institutions. Patients, Participants Infants with UCLP reported in 21 eligible studies (n = 534), of whom 368 received PNAM. Interventions Presurgical nasoalveolar molding (PNAM) according to the Grayson protocol. Main Outcome Measure(s) : Changes in nasal symmetry (nostril width ratio, columellar angle) and alveolar morphology (alveolar gap dimensions, intertuberosity distance). Results PNAM was performed for an average duration of 96 days with 11 adjustments per patient. Pooled analyses demonstrated significant improvements in nasal symmetry: nostril width ratio decreased from 2.4 (95% CI, 1.7–3.1; I² = 98%) to 1.8 (95% CI, 0.9–2.6; I² = 97%), and the columellar angle increased from 52° (95% CI, 42.0–62.8; I² = 100%) to 70° (95% CI, 59.1–80.6; I² = 98%). Alveolar gap narrowed from 10.7 mm (95% CI, 9.5–11.9; I² = 92%) to 3.9 mm (95% CI, 3.1–4.8; I² = 93%). Intertuberosity distance increased slightly, from 31.3 mm (95% CI, 29.3–33.3; I² = 95%) to 31.8 mm (95% CI, 28.9–34.8; I² = 98%). Conclusions Grayson's PNAM appears to improve nasal and alveolar morphology in infants with UCLP prior to definitive surgery. Standardized outcome measures and long-term prospective studies are needed to confirm these findings and refine clinical protocols.

Importance The ideal duration of androgen deprivation therapy (ADT) for treating localized prostate cancer is unknown due to variable adherence and treatment durations tested in clinical trials. Objective To determine the ideal duration of ADT for patients with prostate cancer treated with radiotherapy. Data Sources This individual patient data meta-analysis of 13 randomized phase 3 clinical trials evaluated the use of radiotherapy alone or with ADT. It included patients with a median follow-up of 11.3 (IQR, 9.5-14.5) years and ADT duration of 0 to 36 months. Most patients (7392 [72%]) included had National Comprehensive Cancer Network high-risk or very high-risk disease. Study Selection For this meta-analysis, a systematic literature search from 1980 to 2020 was performed in trial registries (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov), MEDLINE (1966-2020), Embase (1982-2020), Web of Science, and Scopus to identify trials. Data Extraction and Synthesis Intention-to-treat and as-treated analyses were performed. The number needed to treat to prevent 1 distant metastasis at 10 years was calculated based on prognostic risk group. The analyses were conducted from January 5 to August 15, 2023. Main Outcomes and Measures The primary end point for this study was overall survival, defined as time to death or last follow-up from randomization. Secondary end points included biochemical recurrence, distant metastasis (DM), prostate cancer–specific mortality, and other-cause mortality. Results The median (IQR) age among the 10 266 male patients was 70 (65-74) years. Longer durations of ADT were associated with nonlinear improvement in relative benefits of DM, prostate cancer–specific mortality, and overall survival, with reduced estimated benefits beyond 9 to 12 months of ADT based on the end point. There was a near-linear increase in other-cause mortality associated with long-term ADT use (hazard ratio, 1.28; 95% CI, 1.09-1.50; P = .002 for 28 vs 0 months of ADT). The optimal ADT duration based on 10-year DM was 0, 6, 12 months, and undefined for patients with 1 intermediate-risk factor, 2 or more intermediate-risk factors, and National Comprehensive Cancer Network high-risk and very high-risk disease, respectively. Conclusions and Relevance The results of this meta-analysis suggest that, for men with localized prostate cancer treated with definitive radiotherapy and ADT, there are relative and absolute benefits from increasing durations of ADT that help provide individualized risk estimates.

Greater degrees of aerobic fitness are associated with greater insulin-mediated muscle glucose uptake. Insulin regulates adipose tissue lipolysis, whether aerobic fitness affects insulin’s ability to regulate lipolysis is unknown. We found that greater fitness is associated with improved adipose tissue insulin responsiveness independent of age, sex, BMI, visceral adipose tissue, body fat (kg), percent body fat, and adipocyte size. This suggests that exercise, if it improves fitness, may improve both adipose tissue and muscle function.

Abstract Twohey, E, Dobbs, WC, Malone, CM, Fields, JB, Jones, MT, and Jagim, AR. The use of a consumer-grade bioelectrical impedance analysis device for weight certification in collegiate wrestling: Implications for minimal wrestling weight determination. J Strength Cond Res 39(12): 1321–1326, 2025—Wrestlers are required to complete a preseason weight certification assessment, which includes a weigh-in, a hydration test, and a body fat percentage (BF%) measurement. This information is then used to establish their minimal wrestling weight (MWW) and minimal weight class. Skinfold (SKF) is the primary method used for determining body fat for collegiate wrestling, yet impedance devices are being considered for use in the future. The purpose of this study was to examine differences in body fat and the resulting MWW values derived from SKF and a consumer-grade multifrequency bioelectrical impedance analysis (MFBIA) device. Thirty-one collegiate male wrestlers produced a urine sample for urine specific gravity assessment to ensure adequate hydration status. Subjects then completed a weigh-in, followed by 2 body composition assessments using a (a) MFBIA device and (b) skinfold calipers to determine body density and BF%. No significant differences were observed for estimates of BF% (SKF: 13.4 ± 2.8% vs. MFBIA: 14.0 ± 3.3%; p = 0.198) or computed MWW values (SKF: 69.8 ± 8.7 kg vs. MFBIA: 69.4 ± 9.7 kg; p = 0.348) between devices. When determining the minimal weight class for each device, there were discrepancies in 11 of the 31 wrestlers (35%). Although the current MFBIA device can provide an acceptable estimate of BF% and similar resulting MWW value at the group level, the methods cannot be used interchangeably.

Aging plays a major role in the development of numerous chronic diseases, one of which is a marked decline in skeletal health. Beyond diminishing bone mass and strength, mammals of advanced age experience a decline in skeletal mechanotransduction—that is, the ability of the skeleton to respond adaptively to mechanical perturbation. One possibility for the loss of mechanotransduction in bone with aging is an age-associated increase in the population density of senescent cells—those cells that have undergone irreversible cell cycle arrest, resistance to apoptosis, and production of a modified secretome (the SASP) that has damaging effects to nearby healthy (non-senescent) cells. We investigated whether the presence of senescent cells might drive some of the diminished mechanical response observed in aged bone, by testing the hypothesis that the clearance of senescent cells via intermittent senolytic treatment promotes mechanical responsiveness in an aged skeleton. C57BL/6 mice aged 6 months and 22 months were treated weekly with the senolytic cocktail Dasatinib and Quercetin (D + Q) for 1 month, then subjected to low level in vivo mechanical loading of the ulna for 1 week. The 6-month-old mice exhibited a doubling of load-induced ulnar periosteal bone formation when treated with D + Q, compared to vehicle-treated mice, but the periosteal response to loading was not significantly altered by D + Q in the aged (22-month) mice. We further probed the efficacy of D + Q in mechanotransduction by switching to an endocortical model—the axial tibia loading system. Here, the 22-month-old mice had nearly double the load-induced endocortical bone formation compared to vehicle-treated mice. We further assayed the cortical bone gene expression profile in loaded and control tibias from treatment-naïve 6-month and 22-month mice, to determine whether there is significant overlap between mechanically induced signaling genes and SASP genes. We found significant load-induced changes among several SASP genes, suggesting that inhibition of the SASP (i.e., senomorphics) might interfere with mechanical signaling from otherwise healthy cells. In summary, clearance of senescent cells via intermittent D + Q treatment is effective at improving endocortical mechanical responsiveness in the aged skeleton, which is commonly diminished throughout the course of aging.

Objective The effects of deep brain stimulation (DBS) manifest across multiple timescales, spanning seconds to months, and involve direct electrical effects, neuroplasticity, and network reorganization. In epilepsy, the delayed impact of DBS on seizures presents challenges for optimization. Single‐pulse stimulation and resulting brain stimulation evoked potentials (BSEPs) provide a means to assess effective connectivity and network excitability. This study integrates BSEPs and short trials of DBS during stereoelectroencephalography (sEEG) to map seizure network engagement, modulate network dynamics, and monitor excitability and interictal abnormalities for biomarker informed neuromodulation. Methods Ten individuals with drug resistant epilepsy undergoing clinical sEEG were enrolled in this retrospective cohort study of epilepsy neuromodulation biomarkers. Each patient underwent a trial of high frequency (145Hz) thalamic DBS. BSEPs were acquired before and after DBS trials. Baseline BSEP amplitude assessed seizure network engagement, and modulation of amplitude (pre vs post DBS) assessed change in network excitability. Interictal epileptiform discharges were tracked by an automated classifier. Results Baseline BSEPs delineated distinct patterns of network engagement between thalamic subfields with maximal frontotemporal engagement achieved with stimulation of the anterior nucleus of the thalamus‐ventral anterior nucleus junction. DBS delivered for >1.5 hours reduced BSEP amplitudes compared to baseline, and the degree of modulation correlated with baseline connectivity strength. Shorter DBS trials did not induce reliable BSEP amplitude suppression, but did immediately suppress interictal epileptiform discharge rates in well‐connected seizure networks. Interpretation BSEPs and trials of DBS during sEEG provide novel network biomarkers to evaluate the modulation of large‐scale networks across multiple timescales, advancing biomarker informed neuromodulation. ANN NEUROL 2026;99:748–760

Abstract Candida auris is an emerging fungal pathogen with high rates of multidrug resistance, posing a significant global health threat. Immunosuppressed patients are particularly vulnerable to multidrug-resistant (MDR) C. auris infections. This systematic review and meta-analysis (SR-MA) aimed to assess the global prevalence of MDR-C. auris isolates in humans and their resistance to antifungal drugs, primarily fluconazole (FLZ), voriconazole (VOR), and amphotericin B (AmB). A comprehensive search was conducted in PubMed, Scopus, and ScienceDirect databases on published studies regarding clinical C. auris isolates and the use of antifungal susceptibility testing assay from 17 March 2015 to 1 February 2024. Meta-analysis was conducted using random-effects models to determine the estimated pooled prevalence of MDR-C. auris isolates and their antifungal resistance profiles from immunosuppressed humans. A total of 81 research studies were included in the final analysis, with the overall pooled prevalence of the three most important antifungal drugs; FLZ (92.5% | 95% CI: 89.5–94.7), VOR (49.0% | 95% CI: 37.6–60.4), and AmB (51.0% | 95% CI: 42.3–59.7). According to the subgroup analyses, FLZ-resistant C. auris was the most prevalent isolate observed in the five continents reporting compared to the VOR- and AmB-resistant C. auris having lower pooled prevalence. Further, higher pooled prevalence of MDR-C. auris isolates were observed from males (68.2%, n = 578) compared to females (37.1%, n = 283). Finally, the global pooled prevalence for mortality in immunosuppressed patients with MDR-C. auris from 13 research studies was 41.5% (95% CI: 29.9–54.2). This SR-MA study establishes the variation of MDR-C. auris resistance patterns observed from different continents and the importance to conduct further research studies using potent antifungal drugs. Accordingly, it is imperative to establish stringent surveillance on the increasing prevalence of antifungal resistance particularly in low-income regions with limited research resources to prevent increasing prevalence of MDR-C. auris.