Nevin Manimala

Brain Behav. 2026 Aug;16(8):e71581. doi: 10.1002/brb3.71581.

ABSTRACT

BACKGROUND: The present pilot study aimed to (1) Characterize neural markers of reward sensitivity during periods of social stress; (2) Evaluate clinical relations between neural reward markers and anhedonia; and (3) Investigate if peer victimization was associated with ventral striatum (VS) suppression and anhedonia symptoms during social stress.

METHODS: A total of 28 adolescents between the ages of 13 and 17 (M_age = 15.31; SD = 1.51; 55.2% cisgender girls) were included in analyses and completed a semi-structured interview, self-report questionnaires regarding social anxiety, stress, depression, and anhedonia, and a magnetic resonance imaging (MRI) scan while engaging in the Island Getaway task. VS BOLD signal activation estimates were then extracted during discrete phases of the task (e.g., anticipation of social feedback and outcome of social feedback) and statistically compared within-subjects.

RESULTS: Results revealed that when in the presence of social stress (defined as the potential for negative feedback), socially anxious adolescents demonstrated significantly suppressed VS activation relative to feedback anticipation. Additionally, the reduced VS activation during the outcome phase was significantly correlated with anhedonia. Moreover, relational peer victimization was associated with suppressed VS activation.

CONCLUSIONS: Findings identify novel mechanisms associated with anhedonia and blunted reward processing in socially anxious youth that could be improved via interventions that target positive-valence systems.

PMID:42518193 | DOI:10.1002/brb3.71581

Clin Implant Dent Relat Res. 2026 Aug;28(4):e70175. doi: 10.1111/cid.70175.

ABSTRACT

PURPOSE: This study aimed to compare marginal bone loss (MBL) associated with Hybrid Funnel Technique (HFT) and conventional drill osteotomy for implant site preparation when bioactive implants are used, testing the null hypothesis that no significant differences occur at 1- and 3 years.

MATERIALS AND METHODS: This prospective non-randomized controlled clinical trial included patients undergoing implant rehabilitation with bioactive-surface implants. Implants were placed using either conventional subtractive drilling (control group) or HFT (test group), which combines selective cortical preparation with medullary osteocompaction. The primary outcome was radiographic MBL at 3-year follow-up. Secondary outcomes included bleeding on probing (BoP) and plaque index (PI). Statistical analyses were performed at implant level, and linear mixed-effects models were used to account for clustering within patients and adjust for potential confounders.

RESULTS: A total of 87 implants in 43 patients were analyzed (42 control, 45 HFT). At 1-year follow-up, the test group reported significantly lower MBL (0.33 ± 0.43 mm vs. mean = 0.78 ± 0.82 mm; Mann-Whitney p-value = 0.006). At 3 years, MBL was significantly higher in the conventional site preparation group compared with the HFT group (1.34 ± 0.79 mm vs. 0.46 ± 0.69 mm; p < 0.001). In multivariate mixed-effects analysis, the implant site preparation technique was the only variable independently associated with MBL at 3 years (β = -1.10 mm, 95% CI = -1.675 to -0.527, p < 0.001), while insertion torque and other baseline variables showed no significant association. In addition, the HFT group demonstrated significantly lower BoP and PI scores, indicating more favorable peri-implant soft tissue conditions.

CONCLUSIONS: Despite the use of identical bioactive-surface implants, implant site preparation technique significantly influenced peri-implant bone remodeling. HFT demonstrated superior preservation of marginal bone over 3 years, suggesting that reduction of cortical compression during osteotomy provides a biological advantage. Implant site preparation remains a key determinant of long-term peri-implant bone stability.

PMID:42518174 | DOI:10.1111/cid.70175

Ecohealth. 2026 Jul 28. doi: 10.1007/s10393-026-01829-y. Online ahead of print.

NO ABSTRACT

PMID:42518163 | DOI:10.1007/s10393-026-01829-y

Updates Surg. 2026 Jul 28. doi: 10.1007/s13304-026-02780-x. Online ahead of print.

ABSTRACT

Adrenal tumors with unenhanced attenuation of 11-20 Hounsfield units (HU) are indeterminate on noncontrast computed tomography (CT). This interval is clinically relevant because it usually triggers additional biochemical, radiological, and multidisciplinary assessment rather than an immediate decision to operate or observe. We evaluated the pathology-confirmed histological spectrum of resected adrenal lesions across guideline-consistent attenuation categories, with particular focus on the 11-20 HU grey zone. We retrospectively reviewed 383 adults who underwent minimally invasive adrenalectomy between 2022 and 2025. Unenhanced CT attenuation values were recorded in 202 cases; two necrotised-tissue cases were excluded from the HU-based histology analysis. The final analytic cohort comprised 200 tumors classified as ≤ 10 HU, 11-20 HU, or > 20 HU. The primary outcome was final histopathology grouped as benign lesion, pheochromocytoma/paraganglioma (PPGL), metastasis, or primary malignant lesion. Clinical background was reviewed for the five non-benign 11-20 HU lesions. Exploratory multivariable logistic regression evaluated non-benign versus benign histology. The final cohort included 82 tumors with ≤ 10 HU, 44 with 11-20 HU, and 74 with > 20 HU. In the 11-20 HU group, histology was benign in 39/44 lesions (88.6%), PPGL in 3/44 (6.8%), metastasis in 1/44 (2.3%), and adrenocortical carcinoma in 1/44 (2.3%). Non-benign pathology increased from 4.9% at ≤ 10 HU to 11.4% at 11-20 HU and 33.8% at > 20 HU. In multivariable analysis, > 20 HU was associated with non-benign histology compared with ≤ 10 HU (odds ratio [OR] 10.0, 95% confidence interval [CI] 3.18-31.30), whereas 11-20 HU was not independently associated with a statistically significant increase (OR 2.81, 95% CI 0.69-11.50). Larger tumor size was also associated with non-benign histology (OR 1.30 per cm, 95% CI 1.09-1.56). Most resected adrenal tumors in the 11-20 HU grey zone were benign, but this interval still contained clinically important non-benign pathology. These findings should be interpreted as surgical-cohort data, not as prevalence estimates for true adrenal incidentalomas. Intermediate attenuation should be used as a prompt for integrated biochemical, imaging, oncological, and multidisciplinary assessment rather than as an isolated indication for adrenalectomy.

PMID:42518161 | DOI:10.1007/s13304-026-02780-x

J Racial Ethn Health Disparities. 2026 Jul 28. doi: 10.1007/s40615-026-03133-5. Online ahead of print.

ABSTRACT

OBJECTIVES: We examined if the Index of Concentration at the Extremes, a measure of neighborhood disadvantage, was associated with preterm birth (PTB) and assessed mediation by allostatic load (AL).

METHODS: We examined a subset of the Michigan Archive for Research on Child Health, a prospective ongoing cohort that began in 2016, with select biomarkers and prenatal records. We operationalized AL from the sum of eight parameters drawn from inflammatory biomarkers and prenatal records, which we dichotomized as ≥ 4 (High) or < 4 (Low). We tested for mediation of AL using Generalized Estimating Equations models clustered by zip code.

RESULTS: Of the n = 392, 46% were Black, 16% of which delivered preterm. Black pregnant people had 1.21 times higher PTB odds if they lived in a more privileged county compared to those who did not (OR = 1.21, 95% CI = 0.54, 2.73) while non-Blacks had 36% lower odds (OR = 0.64, 95% CI = 0.22, 1.85), but neither were statistically significant. Living in a more privileged county was significantly associated with 70% lower odds of high AL (OR = 0.30, 95% CI = 0.13, 0.68). Both groups had higher although not statistically significant odds of PTB if they had high AL scores (Black: OR = 1.22, 95% CI = 0.42, 3.57; Non-Black: OR = 3.24, 95% CI = 0.32, 33.11).

CONCLUSION: Although we observed trends in neighborhood disadvantage on PTB, the effects were not significant. Black pregnant people had a higher AL, but there was no evidence that AL mediated the association.

PMID:42518157 | DOI:10.1007/s40615-026-03133-5

CNS Drugs. 2026 Jul 28. doi: 10.1007/s40263-026-01319-3. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder that often requires sustained symptom control throughout the day. Although bimodal extended-release dexmethylphenidate (d-MPH XR) formulations provide initial and intermediate drug release, they may not consistently maintain therapeutic exposure into the late afternoon and evening. Trimodal formulations with an additional delayed release component may extend drug exposure later in the day, although this remains to be established. To explore differences in pharmacokinetic (PK) profiles between trimodal (CTx-1301) and bimodal delivery of d-MPH XR, a comparative bioavailability study was conducted at the highest and lowest doses for both formulations.

METHODS: In this randomized, 4-period, crossover study, adults with ADHD received single doses of CTx-1301 (50 mg and 6.25 mg) and d-MPH XR (40 mg and 5 mg). Comparative bioavailability was assessed through adjusted geometric mean ratios for exposure parameters (maximum observed plasma concentration [C_max], area under plasma concentration-time curve to last measurable concentration [AUC_last] and extrapolated to infinity [AUC_0-inf]), with a prespecified bioequivalence range of 0.80 to 1.25. Secondary endpoints included partial AUCs and safety assessments.

RESULTS: The study population (N = 45) was predominantly male (88.9%) and White (55.6%), with mean age of 29.6 ± 8.01 years. Adjusted geometric mean ratios comparing the primary exposure parameters (C_max, AUC_last, and AUC_0-inf) for CTx-1301 versus d-MPH XR were within the bioequivalence range (0.80-1.25) at both the high and low doses. The CTx-1301-to-d-MPH XR partial AUC ratios were within the bioequivalence range from 0 to 9 hours post-dose. At later intervals (AUC_9-12 and AUC_12-16), adjusted geometric mean ratios exceeded the upper bioequivalence threshold, consistent with the expected contribution of the third medication release component. Dose proportionality was observed between the two CTx-1301 doses and two d-MPH XR formulations. CTx-1301 was generally well tolerated. The most commonly reported adverse events included tachycardia, insomnia, headache, nausea, and euphoric mood. The incidence of treatment-emergent adverse events was numerically lower with CTx-1301 than with d-MPH XR; however, no statistical analysis was performed.

CONCLUSIONS: Key exposure parameters including C_max, AUC_last, and AUC_0-inf for trimodal CTx-1301 were statistically bioequivalent to bimodal d-MPH XR. Interval‑specific PK analyses demonstrated higher exposure with CTx‑1301 during later post-dose intervals (9-16 h), consistent with the formulation’s third release component. However, the clinical relevance of these PK differences requires further evaluation. CTx-1301 demonstrated dose proportionality and was well tolerated at high and low doses.

REGISTRATION: ClinicalTrials.gov, NCT04138498; 19 September 2019.

PMID:42518155 | DOI:10.1007/s40263-026-01319-3

Eur Geriatr Med. 2026 Jul 28. doi: 10.1007/s41999-026-01562-3. Online ahead of print.

ABSTRACT

PURPOSE: Cortisol dysregulation has been implicated in Alzheimer’s disease (AD), but its associations with amyloid and tau-related outcomes remain unclear. This study examined whether baseline CSF cortisol was associated with cross-sectional and baseline-adjusted 24-month multimodal AD biomarkers and cognitive outcomes.

METHODS: A total of 764 participants were included, comprising cognitively normal (CN; n = 284), individuals with mild cognitive impairment (MCI; n = 356), and patients with AD dementia (n = 124). Associations between baseline CSF cortisol, multimodal AD biomarkers, and cognitive outcomes were assessed with FDR correction.

RESULTS: CSF cortisol increased modestly from CN to MCI and AD dementia, with a small but statistically significant overall group difference after FDR correction. Cross-sectionally, in the MCI group, higher CSF cortisol was associated with higher CSF total tau and p-tau181 and a lower Aβ42/total tau ratio. In baseline-adjusted 24-month analyses, in MCI groups, higher CSF was associated with higher CSF total tau and p-tau181, greater temporal tau-PET burden, lower hippocampal volume, greater ventricular volume, and poorer cognitive outcomes. In the full cohort and MCI group, CSF-defined amyloid positivity strengthened associations of higher baseline CSF cortisol with adverse 24-month tau-related outcomes. Exploratory analyses suggested that 24-month CSF total tau and hippocampal volume partly accounted for the association between higher baseline CSF cortisol and poorer 24-month cognition in MCI; however, these findings do not establish causal mediation.

CONCLUSION: Higher CSF cortisol may be linked to tau-related pathology and poorer cognition, supporting further evaluation of its prognostic value across the AD continuum.

PMID:42518151 | DOI:10.1007/s41999-026-01562-3

Adv Ther. 2026 Jul 28. doi: 10.1007/s12325-026-03707-z. Online ahead of print.

ABSTRACT

INTRODUCTION: To date, no head-to-head comparisons of apalutamide versus darolutamide have been reported for metastatic castration-sensitive prostate cancer (mCSPC). This study compared prostate-specific antigen decline ≥ 90% (PSA90) and overall survival (OS) between apalutamide and darolutamide, both without docetaxel, among patients with mCSPC in real-world clinical practice in the USA.

METHODS: Men diagnosed with mCSPC who initiated apalutamide or darolutamide between 2022 and 2025 were identified from linked electronic medical records and insurance claims. The apalutamide and darolutamide cohorts were balanced using inverse probability of treatment weighting. PSA90 response was assessed on-treatment. The proportions of patients achieving a PSA90 response and OS through a maximum of 6 months and 24 months post-treatment initiation, respectively, were compared between the two cohorts using weighted Kaplan-Meier and weighted Cox proportional hazards models.

RESULTS: For PSA90 analyses, weighted characteristics were well balanced between the apalutamide (n = 714; mean age 73.9 years, 59.6% White, 21.2% Black, 13.7% other, 5.5% unknown race) and darolutamide cohorts (n = 145; mean age 74.3 years, 58.8% White, 21.6% Black, 15.0% other, 4.7% unknown race). PSA90 response rates through 6 months were 49% higher for apalutamide than for darolutamide (weighted hazard ratio [HR]: 1.49 [95% confidence interval (CI) 1.07, 2.07]; p = 0.017). For OS analyses, weighted characteristics were also well balanced between apalutamide (n = 1460; mean age 73.5 years, 59.6% White, 21.5% Black, 13.5% other, 5.4% unknown race) and darolutamide (n = 287; mean age 73.7 years, 60.0% White, 22.4% Black, 12.4% other, 5.2% unknown race). Apalutamide was associated with a 51% lower rate of mortality relative to darolutamide through 24 months (weighted HR: 0.49 [95% CI 0.30, 0.83]; p = 0.007).

CONCLUSION: Among patients with mCSPC treated without docetaxel, apalutamide was associated with higher PSA90 response rates and lower mortality than darolutamide. These findings indicate a potential difference in disease control and survival between the two androgen receptor-targeted agents in routine clinical practice.

PMID:42518140 | DOI:10.1007/s12325-026-03707-z

Adv Ther. 2026 Jul 28. doi: 10.1007/s12325-026-03719-9. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to evaluate the effectiveness and safety of vosoritide in Chinese children with achondroplasia (ACH) in a real-world setting.

METHODS: A total of 26 children diagnosed with ACH and treated with vosoritide were enrolled in the study. Clinical indicators such as height, sitting height, and body mass index (BMI), as well as laboratory indicators including bone age and insulin-like growth factor level, were collected and analyzed before and after treatment. Improvements in height standard deviation score (SDS), sitting height/height ratio, and BMI were evaluated. Statistical differences were analyzed across different age and sex groups. Adverse reactions during the treatment were also monitored.

RESULTS: Among the 17 patients assessed at 12 months, height SDS (based on general population growth charts) improved from – 4.7 ± 0.1 at baseline to – 4.3 ± 0.2 at 12 months (P < 0.001). With continued treatment, annual growth velocity (AGV) significantly increased, reaching 8.7 ± 1.4 cm/year in 12 patients who remained under follow-up after 18 months of treatment. Furthermore, BMI SDS exhibited a continuous decline. The sitting height/height ratio decreased during the treatment, indicating an optimization of body proportions. Additionally, growth improvement was found in both age (below five years old and above five years old) and sex (male and female) groups. Except for the total procollagen I intact N-terminal (TP1NP), which significantly increased at 12 months of treatment compared to baseline, other biochemical indicators (including insulin-like growth factor, alkaline phosphatase, and osteocalcin) showed no significant differences after the treatment.

CONCLUSION: Vosoritide exerts significant growth-promoting effects and favorable safety in Chinese children with ACH. It improves height SDS and body proportions, demonstrating consistent effectiveness across various age groups and sex groups. Early diagnosis and timely initiation of vosoritide treatment can significantly alter the growth trajectory of these children.

PMID:42518139 | DOI:10.1007/s12325-026-03719-9

Prev Sci. 2026 Jul 28. doi: 10.1007/s11121-026-01959-3. Online ahead of print.

ABSTRACT

Suicide remains a significant public health issue in corrections settings in the United States, requiring systems-focused strategies for prevention and policy. We aggregated across 37 suicide rates, structural, social, and corrections-related variables from publicly available data sources. We used Latent Profile Analysis to identify clusters by profiles of correction systems across 50 states. We analyzed descriptive statistics of state characteristics by cluster to better understand their profiles. Lastly, we conducted ANOVAs to examine differences in suicide rates between clusters. We identified four clusters of states based on their profiles of corrections variables: number of facilities, populations in prisons, jails, and private prisons, prison overcrowding, prisoner-to-staff ratios, and disparities by race/ethnicity and gender. Thirteen states showed the highest racial and gender disparities in prison populations. Twenty-eight states showed average scores across all variables. Four states showed the highest proportion of people incarcerated in privately owned facilities. Five states showed the highest incarceration rates in both prisons and jails. Significant differences in suicide rates were observed across clusters, especially within jails. Findings from this study enhance our understanding of how structural and social factors may be associated with suicide in corrections settings. The discussion includes specific, tailored prevention strategies and policy solutions aimed at systems-level intervention.

PMID:42518125 | DOI:10.1007/s11121-026-01959-3