Category: Nevin Manimala

J Clin Invest. 2025 Mar 6:e188533. doi: 10.1172/JCI188533. Online ahead of print.

ABSTRACT

BACKGROUND: Naïve cells comprise 90% of the CD4+ T-cell population in neonates and exhibit distinct age-specific capacities for proliferation and activation. We hypothesized that HIV-infected naïve CD4+ T-cell populations in children on long-term antiretroviral therapy (ART) would thus be distinct from infected memory cells.

METHODS: Peripheral blood naïve and memory CD4+ T cells from 8 children with perinatal HIV on ART initiated at age 1.7-17 months were isolated by FACS. DNA was extracted from sorted cells and HIV proviruses counted, evaluated for intactness, and subjected to integration site analysis.

RESULTS: Naïve CD4+ T cells containing HIV proviruses were detected in children with 95% statistical confidence. A median of 4.7% of LTR-containing naïve CD4+ T cells also contained HIV genetic elements consistent with intactness. Full-length proviral sequencing confirmed intactness of one provirus. In the participant with the greatest level of naïve cell infection, ISA revealed infected expanded cell clones in both naïve and memory T cells with no common HIV integration sites detected between subsets. Divergent integration site profiles reflected differential gene expression patterns of naïve and memory T cells.

CONCLUSIONS: These results demonstrate that HIV persists in both naïve and memory CD4+ T cells that undergo clonal expansion and harbor intact proviruses, suggesting that infected memory T-cell clones do not frequently arise from naïve cell differentiation in children with perinatal HIV on long-term ART.

FUNDING: Center for Cancer Research, NCI and Office of AIDS Research funding to MFK, NCI FLEX funding to JWR. Children’s and Emory JFF pilot to MM.

PMID:40048262 | DOI:10.1172/JCI188533

Exp Clin Psychopharmacol. 2025 Mar 6. doi: 10.1037/pha0000773. Online ahead of print.

ABSTRACT

Smoking prevalence in the United States has stabilized as the remaining population becomes increasingly representative of “at-risk smokers” who are unable to quit. The experience of severe fatigue may be one underrecognized but highly common problem that may help in understanding smoking maintenance and relapse. Yet, there has been no research on fatigue severity in relation to smoking behavior measured in “real time.” The purpose of the present study was to provide a pilot test of fatigue severity in the context of smoking deprivation in predicting number of puffs, puff velocity, interpuff interval, and smoking urges during an experimental relapse analogue task. Participants in the present study included 36 (Mage = 49.25 years, SD = 8.83; 54.1% male) daily cigarette smokers who reported prolonged fatigue. Results indicated that there was a statistically significant interactive effect between smoking deprivation and fatigue severity in the prediction of interpuff interval, such that those with greater fatigue severity, when smoking deprived, evinced greater time between puffs. Other analyses documented meaningful effect sizes for fatigue severity, but due to the sample size, results were generally not statistically significant. This pilot test found some empirical evidence for the continued study of fatigue severity as an individual difference factor relevant to smoking maintenance and relapse in an experimental context. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40048234 | DOI:10.1037/pha0000773

J Fam Psychol. 2025 Mar;39(2):197-207. doi: 10.1037/fam0001294. Epub 2024 Dec 30.

ABSTRACT

Grandparental involvement is a multidimensional framework of the roles grandparents play in a child’s life. However, culture-sensitive measurement of grandparental involvement, particularly in middle childhood, is underdeveloped. This study adapts and validates a self-report measure of grandparental involvement for children in Chinese migrant families. A total of 879 children completed the adapted 19-item Grandparental Involvement Inventory-Chinese version (GII-C), while their grandparents reported related information such as acceptance and rejection of the child. Our item analysis and exploratory factor analysis suggested a shortened, 16-item scale with three factors: Company and Shared Activities, Mentorship and Instrumental Assistance, and Intimacy and Closeness. This factor structure showed a good fit in confirmatory factor analysis. The GII-C showed adequate reliability and convergent validity. Grandparental involvement showed positive correlations with grandparental acceptance of the child and grandparent-grandchild attachment, as well as a negative correlation with grandparental rejection. Subgroup and regression analyses further indicated the GII-C’s known-group validity and predictive ability of child mental health outcomes. Grandparental involvement was positively associated with child resilience and psychological well-being while negatively associated with child depression, anxiety, stress, and loneliness. Our findings suggest the GII-C as a valid tool to measure Chinese grandparents’ multifaceted roles beyond childcare. Future research should replicate the GII-C in multigenerational families across cultural contexts. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40048232 | DOI:10.1037/fam0001294

J Fam Psychol. 2025 Mar;39(2):208-217. doi: 10.1037/fam0001296. Epub 2024 Dec 30.

ABSTRACT

The present study aimed to describe the level and nature of maternal sensitivity in an economically disadvantaged rural region in Peru, examining differences between measures and situations. Sixty-nine infant-mother dyads from rural Cusco, Peru, participated in this study. Maternal sensitivity was evaluated through the Ainsworth Sensitivity Scale and the Maternal Behavior Q-Sort (MBQS; regular and short version) across three naturalistic episodes, namely, free interaction, bathing, and feeding. Almost the entire range of sensitivity levels was observed for both measures. On average, these mothers showed moderate sensitivity levels, mostly regardless of the measure and situation observed. Significant associations were observed among the measures during episodes, ranging from moderate to high correlations, and differences between episodes were only found for the MBQS, with lower sensitivity scores during the feeding episode. In conclusion, all three situations and both measures have their strengths and weaknesses and can provide relevant information, particularly with samples rarely studied that we are just getting to know. However, basing the assessment only on the MBQS may not necessarily be the best choice. Selecting a more global sensitivity scale like the Ainsworth scale may be more pertinent for evaluating sensitivity cross-culturally, while the MBQS can facilitate understanding the relevance of specific predefined behaviors in particular contexts. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40048231 | DOI:10.1037/fam0001296

Psychol Methods. 2025 Mar 6. doi: 10.1037/met0000748. Online ahead of print.

ABSTRACT

Psychological and behavioral scientists develop interventions toward addressing pressing societal challenges. But such endeavors are complicated by treatments that change over time as individuals’ needs and responses evolve. For instance, students initially in a multiyear mentoring program to improve future academic outcomes may not continue with the program after interim school engagement improves. Conventional interventions bound by rigid treatment assignments cannot adapt to such time-dependent heterogeneity, thus undermining the interventions’ practical relevance and leading to inefficient implementations. Dynamic treatment regimes (DTRs) are a class of interventions that are more tailored, relevant, and efficient than conventional interventions. DTRs, an established approach in the causal inference and personalized medicine literature, are designed to address the causal query: how can individual treatment assignments in successive time points be adapted, based on time-evolving responses, to optimize the intervention’s effectiveness? This tutorial offers an accessible introduction to DTRs using a simple example from the psychology literature. We describe how, using observational data from a single naturally occurring longitudinal study, to estimate the outcomes had different DTRs been counterfactually implemented. To improve accessibility, we implement the estimation procedure in lavaan, a freely available statistical software popular in psychology and social science research. We hope this tutorial guides researchers on framing, interpreting, and testing DTRs in their investigations. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40048215 | DOI:10.1037/met0000748

Psychol Trauma. 2025 Mar 6. doi: 10.1037/tra0001887. Online ahead of print.

ABSTRACT

OBJECTIVE: Like other first responders, many firefighters show signs of posttraumatic stress disorder (PTSD) that often go undiagnosed. Developing accessible, brief, and efficient screening tools may improve identification and service utilization. The most recent adaptation of the Primary Care PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5; PC-PTSD-5 [0-20]) demonstrates promising screening performance among firefighters. Our study translated the PC-PTSD-5 [0-20] into Turkish and conducted validity and reliability analyses.

METHOD: The PC-PTSD-5 [0-20] was translated and culturally adapted into Turkish through forward translation, backward translation, and expert-led refinement. We conducted a pilot test with 30 firefighters, followed by carrying out the full study among (N = 215) firefighters from fire stations across all the districts of Istanbul. Participants in the full study completed the Turkish PC-PTSD-5 [0-20] and PCL-5, and we analyzed them for reliability, validity, and diagnostic utility.

RESULTS: The Turkish PC-PTSD-5 [0-20] demonstrated favorable psychometric properties: acceptable internal consistency (α = .61); high test-retest reliability (r = 0.88, p < .001); and strong convergent validity with PCL-5 (r = 0.81, p < .001). Receiver operating characteristic analysis revealed an area under the curve of 0.947 with an optimal cutoff score of 9 that balanced high accuracy (90.23%), sensitivity (82.86%), and specificity (91.67%), while PTSD prevalence was estimated at 16.3% in the sample.

CONCLUSIONS: The Turkish PC-PTSD-5 [0-20] demonstrates strong psychometric properties, with high accuracy at a cutoff score of 9, and excellent diagnostic utility for screening PTSD among firefighters. Future research should explore its applicability to other first responder groups and predictive validity in longitudinal studies. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40048204 | DOI:10.1037/tra0001887

Psychol Trauma. 2025 Mar 6. doi: 10.1037/tra0001842. Online ahead of print.

ABSTRACT

OBJECTIVE: The impact of cannabis use on evidence-based posttraumatic stress disorder (PTSD) treatment outcomes remains inconclusive. Further, few studies to date have examined these relationships in intensive PTSD treatment settings, with existing literature being similarly inconclusive. The present study assessed the role of cannabis use frequency prior to and concurrent with treatment on self-reported PTSD and depressive symptoms in two samples of veterans undergoing distinct (3-week and 2-week) Cognitive Processing Therapy-based intensive treatment programs (ITPs; N_3-week = 488; N_2-week = 253).

METHOD: Cannabis use frequency over the past 2 weeks was self-reported by veterans. PTSD and depression symptoms were assessed before, during, and following the ITP using the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and Patient Health Questionnaire-9, respectively. Linear mixed-effects models were used to analyze the effect of cannabis use frequency prior to and concurrent with treatment on PTSD and depressive symptom change over time.

RESULTS: Individuals in the 3- and 2-week ITPs reported low rates of cannabis use prior to and concurrent with treatment. Across models, frequency of cannabis use was not significantly related to PTSD symptoms over time. Findings surrounding the impact of cannabis use on depressive symptom severity were only found in the 2-week ITP and not replicated in the 3-week ITP.

CONCLUSION: Infrequent and/or recreational cannabis use frequency prior to or concurrent with treatment did not meaningfully impact intensive PTSD treatment outcomes. Findings associated with concurrent use need to be interpreted with caution due to the small subsample. Future research should explore whether more frequent cannabis use and the dosage differentially impact PTSD treatment outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40048203 | DOI:10.1037/tra0001842

JAMA Otolaryngol Head Neck Surg. 2025 Mar 6. doi: 10.1001/jamaoto.2024.5409. Online ahead of print.

ABSTRACT

IMPORTANCE: Up to 80% of survivors of head and neck squamous cell carcinoma (HNSCC) currently or previously smoked. Thus, tobacco use is a major modifiable risk factor for HNSCC, even in the era of human papillomavirus (HPV)-associated disease. However, how smoking underlies chromosomal and epigenetic changes that are associated with HNSCC outcomes remains unclear.

OBJECTIVE: To characterize genetic and molecular differences and associated biological pathways in patients with HNSCC based on smoking history.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients with a confirmed diagnosis of HNSCC from the Cancer Genome Atlas via cBioPortal data independent of HPV status. Data were analyzed between April 2023 and May 2024.

MAIN OUTCOMES AND MEASURES: Smoking history was defined as individuals who smoked (currently or previously) compared with nonsmokers (never smoked). Genetic and molecular differences of interest were single nucleotide variation, copy number alteration, DNA methylation, and messenger RNA (mRNA) expression. Accounting for multiple testing, we reported the false discovery rate (FDR), with a statistically significant FDR of 0.05 or less. Potential functions and pathways were investigated using the Panther classification system, and the Fisher exact test was used for overrepresentation, using the Reactome pathway dataset as a guide. Associations between smoking-related genetic alterations and overall survival were analyzed using log-rank tests.

RESULTS: Of 511 participants, 135 (26.4%) were female, and the mean (SD) age was 60.8 (11.9) years. People who smoked (389 [76.1%]) demonstrated significantly enriched copy number alterations on 9 genes located on chromosome 11q13 compared with nonsmokers (122 [23.9%]; FDR, 0.044-0.046). Two genes, FADD and CTTN, were significantly highly methylated in nonsmokers. Also, PPFIA1, FGF19, CCND1 and LTO1 were highly expressed in mRNA in those who smoked, while FADD mRNA expression was negatively correlated with FADD DNA methylation in nonsmokers (Pearson r = -0.53; 95% CI, -0.59 to -0.49) and those who smoked (Pearson r = -0.57; 95% CI, -0.63 to -0.51). People who smoked with altered FADD had higher risk of dying than those with FADD unaltered (hazard ratio, 1.40; 95% CI, 1.004-1.96). Pathway analysis showed the significant genes were collectively associated with cellular processes and biological regulations, including olfactory signaling and the PI3K/AKT network.

CONCLUSION AND RELEVANCE: The results of this cohort study suggest that there may be patterned genetic and molecular differences in patients with HNSCC based on smoking history, especially genes located on chromosome 11q13. These genomic differences due to smoking make smoking a modifiable risk factor for HNSCC outcomes.

PMID:40048195 | DOI:10.1001/jamaoto.2024.5409

JAMA Netw Open. 2025 Mar 3;8(3):e250137. doi: 10.1001/jamanetworkopen.2025.0137.

ABSTRACT

IMPORTANCE: Screening for adverse social determinants of health (SDOH) in the emergency department (ED) may help reduce health disparities in underserved populations.

OBJECTIVE: To understand barriers and facilitators to screening, documenting, and addressing adverse SDOH in a diverse sample of US EDs.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study used in-depth interviews with leaders of a purposive sample of EDs across urban, rural, academic, and community settings who self-reported screening for adverse SDOH on a prior National Emergency Department Inventory (NEDI) USA survey. EDs that completed the 2022 NEDI-USA survey and reported adverse SDOH screening were eligible for recruitment. Eligible participants were interviewed in April to September 2023. Inductive thematic analysis was conducted from September 2023 to January 2024 to identify themes and concepts.

MAIN OUTCOMES AND MEASURES: Themes and concepts related to ED practices for adverse SDOH screening and referral.

RESULTS: From 77 eligible EDs, 27 leaders agreed to be interviewed, (18 [66.7%] female; mean [range] age, 44 [30 to 63] years; mean [range] time in current role, 3.25 [<1 to 12] years). Participants worked in a variety of leadership roles (eg, chair or medical, nursing, or operations director). Findings centered around heterogeneity in ED adverse SDOH screening and documentation practices; skepticism of utility of ED adverse SDOH screening and referral; drivers of ED adverse SDOH screening, such as regulatory mandates for the expansion of adverse SDOH screening; resource, staffing, and time constraints in adverse SDOH screening and linkage to services processes; and recommendations and suggestions for improving the implementation of ED adverse SDOH screening, such as tailoring validated tools to the ED context and ED stakeholder engagement in designing the screening process. Other suggestions included having additional dedicated screening staff, particularly social workers, and strengthening relationships with existing non-ED SDOH initiatives and community resources dedicated to addressing adverse SDOH.

CONCLUSIONS AND RELEVANCE: This qualitative study of US EDs describes an overview of practices and challenges surrounding adverse SDOH screening and identified novel solutions and areas where more research is needed for the successful implementation of adverse SDOH screening in the ED setting. At the policy level, regulatory mandates instituting adverse SDOH screening should include provisions for funding to support patient needs identified by screening. Additional research on development and implementation of ED adverse SDOH screening programs is needed.

PMID:40048167 | DOI:10.1001/jamanetworkopen.2025.0137

JAMA Netw Open. 2025 Mar 3;8(3):e250160. doi: 10.1001/jamanetworkopen.2025.0160.

ABSTRACT

IMPORTANCE: Respiratory pathogen testing has been a common deimplementation focus. The COVID-19 pandemic brought new considerations for respiratory testing; recent trends in testing rates are not well understood.

OBJECTIVE: To measure trends in respiratory testing among encounters for acute respiratory infections among children and adolescents (aged <18 years) from 2016 to 2023, assess the association of COVID-19 with these trends, and describe associated cost trends.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective serial cross-sectional study included emergency department (ED) encounters and hospitalizations in US children’s hospitals among children and adolescents with a primary acute infectious respiratory illness diagnosis. Data were ascertained from the Pediatric Health Information System database from January 1, 2016, to December 31, 2023.

EXPOSURE: Respiratory pathogen testing.

MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage of encounters with respiratory testing over time. Interrupted time series models were created to assess the association of COVID-19 with testing patterns. The inflation-adjusted standardized unit cost associated with respiratory testing was also examined.

RESULTS: There were 5 090 923 eligible encounters among patients who were children or adolescents (mean [SD] age, 3.36 [4.06] years); 55.0% of the patients were male. Among these encounters, 87.5% were ED only, 77.9% involved children younger than 6 years, and 94.5% involved children without complex chronic conditions. Respiratory testing was performed in 37.2% of all encounters. The interrupted time series models demonstrated increasing prepandemic testing rates in both ED-only encounters (slope, 0.26 [95% CI, 0.21-0.30]; P < .001) and hospitalizations (slope, 0.12 [95% CI, 0.07-0.16]; P < .001). Increases in respiratory testing were seen at the onset of the COVID-19 pandemic in both ED-only encounters (level change, 33.78 [95% CI, 31.77-35.79]; P < .001) and hospitalizations (level change, 30.97 [95% CI, 29.21-32.73]; P < .001), associated initially with COVID-19-only testing. Postpandemic testing rates remained elevated relative to prepandemic levels. The percentage of encounters with respiratory testing increased from 13.6% [95% CI, 13.5%-13.7%] in 2016 to a peak of 62.2% [95% CI, 62.1%-62.3%] in 2022. While COVID-19-only testing decreased after 2020, other targeted testing and large-panel (>5 targets) testing increased. The inflation-adjusted standardized unit cost associated with respiratory testing increased from $34.2 [95% CI, $33.9-$34.6] per encounter in 2017 to $128.2 [95% CI, $127.7-$128.6] per encounter in 2022.

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that respiratory testing rates have increased over time, with large increases at the onset of the COVID-19 pandemic that have persisted. Respiratory testing rates and related costs increased significantly, supporting a need for future deimplementation efforts.

PMID:40048166 | DOI:10.1001/jamanetworkopen.2025.0160