Publications by Year: 2025

BACKGROUND: Kupffer cells (KCs) are the tissue-resident macrophages of the liver, where they serve a critical role in maintaining liver tissue homeostasis and act as a filter for circulation. The composition of hepatic macrophages changes during metabolic dysfunction-associated liver disease (MASLD), with the loss of resident KCs being a hallmark of disease progression. The mechanism(s) and consequences of KC death in metabolic liver disease have yet to be defined. Transcription factor EB (TFEB) is a master regulator of lysosome function and lipid metabolism, which has been shown to protect macrophages from lipid stress in atherosclerosis. We hypothesized that TFEB would improve KC fitness in MASLD.

METHODS: To investigate the potential beneficial effect of TFEB induction in KCs, we created a transgenic mouse in which TFEB was overexpressed specifically in KCs and evaluated its impact on disease pathogenesis in high-fat, high-sucrose (HFHS) and choline-deficient diet models of MASLD.

RESULTS: We found that TFEB induction protected KCs from cell death in both models of MASLD. KC preservation through TFEB induction reduced liver steatosis with HFHS diet via mechanisms that were dependent on macrophage lysosomal lipolysis and mitochondrial fatty acid oxidation. Fibrosis was unchanged in choline-deficient diet studies. TFEB protected KCs from cell death by diminishing oxidative stress and reducing ferroptosis through a mechanism that involved enhanced NADPH levels.

CONCLUSIONS: TFEB induction promotes KC fitness upon lipid stress during MASLD. Preservation of lipid-adapted KCs demonstrates beneficial effects against liver steatosis and protects portal filtration during MASLD.

OBJECTIVES: Lithium treatment reduces the risk of recurring episodes in bipolar disorder (BD) and probably also in major depressive disorder (MDD) and has evidence of antisuicidal effects. Study objectives were to test for effects of adding lithium treatment for one year to a year of other treatments on risks of illness recurrence, suicidal ideation, and suicide attempts.

METHODS: We compared 296 major mood disorder outpatients for 12 months with treatment that did not include lithium versus 12 months with lithium included. We considered differences in the recurrence of new episodes of illness, new suicidal ideation and suicide attempts, and estimated time to these outcomes with survival analyses.

RESULTS: With lithium treatment included, there were marked reductions in episode recurrences (3.12-fold), suicidal ideation (4.78-fold), and suicide attempts (6.54-fold) in both BD and MDD patients, with corresponding delays to these outcomes.

CONCLUSIONS: Adding lithium treatment was strongly associated with reduced risk and delay of clinical recurrence, suicidal ideation and suicide attempts in both BD and MDD outpatients.

BACKGROUND: Study-level meta-analyses have demonstrated the efficacy of cognitive-behavioural therapy for psychosis (CBTp). Limitations of conventional meta-analysis may be addressed using individual-participant-data (IPD). We aimed to determine a) whether results from IPD were consistent with study-level meta-analyses and b) whether demographic and clinical characteristics moderate treatment outcome.

METHODS: We systematically searched PubMed, Embase, PsychInfo and CENTRAL. Authors of RCTs comparing CBTp with other psychological interventions were contacted to obtain original databases. Hierarchical mixed effects models were used to examine efficacy for psychotic symptoms. Patient characteristics were investigated as moderators of symptoms at post-treatment. Sensitivity analyses were conducted for risk of bias, treatment format and study characteristics.

RESULTS: We included 14 of 23 eligible RCTs in IPD meta-analyses including 898 patients. Ten RCTs minimised risk of bias. There was no significant difference in efficacy between RCTs providing IPD and those not (p >0.05). CBTp was superior vs. other interventions for total psychotic symptoms and PANSS general symptoms. No demographic or clinical characteristics were robustly demonstrated as moderators of positive, negative, general or total psychotic symptoms at post-treatment. Sensitivity analyses demonstrated that number of sessions moderated the impact of treatment assignment (CBTp or other therapies) on total psychotic symptoms (p = 0.02).

CONCLUSIONS: IPD suggest that patient characteristics, including severity of psychotic symptoms, do not significantly influence treatment outcome in psychological interventions for psychosis while investing in sufficient dosage of CBTp is important. IPD provide roughly equivalent efficacy estimates to study-level data although significant benefit was not replicated for positive symptoms. We encourage authors to ensure IPD is accessible for future research.

OBJECTIVE: The authors explored whether a digital literacy program, Digital Outreach for Obtaining Resources and Skills (DOORS), could improve self-reported functional skills and clinical outcomes among people with serious mental illness.

METHODS: The 8-week program was offered to participants receiving treatment in community mental health centers (N=113) and an inpatient psychiatric unit (N=74). Pre- and postintervention self-report surveys were collected. Descriptive statistics and two-tailed t tests were used for analysis.

RESULTS: For patients treated in a community center, improvements were observed in 27 of the 29 self-reported functional skills that measured digital literacy. Changes in seven of these skills were statistically significant. Although these participants reported larger improvements in clinical outcomes than did inpatient participants, no statistically significant changes in symptoms were seen in either setting.

CONCLUSIONS: Digital skills training is necessary to increase access to care through technology. DOORS can improve self-reported digital literacy, but further research is necessary to determine its immediate impact on symptoms.

Knee osteoarthritis (OA) is a disease that can cause substantial pain and disability in patients. The progression of OA has been linked to inflammatory, mechanical, genetic, and metabolic factors, yet patterns of symptoms and structural damage vary considerably between knee OA patients. The heterogeneity of the disease presents a need for identifying and understanding patient subgroups to inform more personalized treatments. Identifying anatomical morphotypes, a type of classification defined by anatomical and morphological attributes, is critical for identifying subgroups of patients who are most likely to benefit from particular treatments. Cluster analysis is an unsupervised learning method that can be used to uncover subgroups in datasets without labeled outcomes to guide the analysis. In this perspective, we will review analytic challenges in identifying anatomical morphotypes using clustering methods, including finding patterns that are not clinically relevant, navigating the unique correlation structure of anatomical data, and working with high dimensional data. With the exciting applications of clustering methods to improve personalized medicine in knee OA, it is essential to consider these analytic challenges to ensure that analyses yield clinically actionable insights.

Adolescents and young adults with perinatally acquired HIV (APHIV) face elevated risk for common mental health disorders (CMD). To understand determinants of CMD among APHIV in India, we conducted a mixed methods study by screening for depression and anxiety among a cohort of APHIV in southern India. Between March-June 2023, we administered a cross-sectional survey to participants in the I'mPossible Fellowship, a peer-led mentorship program. We incorporated participatory research principles, wherein trained peer mentors (youth investigators) iteratively designed and administered focus group discussions and screening tools for depression (Patient Health Questionnaire-9: PHQ-9), anxiety (Generalized Anxiety Disorder-7: GAD-7), resilience (Child Youth Resilience Measure-Revised - CYRM-R), and an abbreviated HIV stigma Scale. We used multivariable regression to identify correlates of positive CMD screens and inductively analyzed focus group transcripts. Among 185 APHIV survey participants, mean age was 18.6 years (SD 3.5 years); 63.2% were male. Most (91.9%) had lost one or both parents, and 43.2% lived in child-care institutions (CCIs). Majority (90.4%) were virally suppressed (VL < 150 copies/mL). A high proportion screened positive (severity category of mild and above) for at least one CMD (62.7%), depression alone (25.9%), GAD alone (7%), or both (29.7%). Corresponding prevalence for moderate or severe categories were 18.9%, 14.6%, 9.7%, and 5.4%, respectively. Externalized stigma was high (74.6%), reinforcing disclosure concerns (81.1%). Loss of both parents was associated with increased odds of anxiety (aOR 2.10, 95% CI 1.07- 4.09). Exploration of anxiety and depression-related factors revealed themes that included uncertainty about transitioning to adult care, ART adherence challenges, and maladaptive coping mechanisms. Family support, disclosure fears, school pressures, stigma, and evolving societal attitudes shaped participants' mental health experiences. Our findings underscore the need to prioritize integration of mental health screening and interventions across the pediatric-to-adult HIV care continuum in India.

» Midsubstance patellar tendon repairs are rare, technically demanding surgeries that are distinct from proximal and distal avulsions due to the challenges of tendon-to-tendon healing and zone of injury tissue quality.» Primary repair using the Krackow suturing technique remains the most widely used method, often combined with patellar and tibial-based fixation.» Protective constructs such as high-strength suture configurations or cerclage wire are employed to share load with the repair site and support healing and function.» Structural and biological augmentations, including autografts, allografts, synthetic ligaments, and collagen scaffolds, are increasingly used to reinforce the injured extensor mechanism, support repair, and enhance healing, particularly in high-risk or complex patients.» Postoperative rehabilitation protocols vary but generally include a period of immobilization in extension followed by progressive flexion, isometric quadriceps activation, and return to normal activity at 9 to 12 months and return to a preinjury level at 12 to 18 months.

INTRODUCTION: Peer support has been shown to improve self-management and quality of life for adolescents and young adults (AYA) living with childhood onset chronic conditions (COCC), but little is known about the impact on AYA supporters. This review evaluates the impact of being a peer supporter with a COCC on the supporters and places those results within a theoretical context.

METHODS: Extraction and synthesis of study findings was conducted using a collaborative approach.

RESULTS: 16 articles were included. The majority of studies were qualitative and fair to good quality. Effects were categorized into 3 areas: condition-related factors, personal/professional growth, and connectedness. 4 articles described risks of serving as a peer supporter.

DISCUSSION: AYA peer supporters with COCC benefited from their role. Serving as a peer supporter may enhance skills related to becoming a successful, healthy young adult. Risks may be mitigated with training and support. Psychological theories inform the results.

IMPLICATIONS TO PRACTICE: Providers should encourage youth to engage in peer support programs as peer supporters, which may lead to improved health and related outcomes.

The growing prevalence of mental health disorders in Puerto Rico necessitates the use of efficacious mental health interventions, such as Evidence-Based Treatments (EBTs), to promote positive outcomes within this underserved population. This study aimed to describe the use of psychosocial interventions with different levels of evidence for efficacy (i.e., well-established, probably or possibly efficacious, and experimental) among mental health professionals in Puerto Rico (i.e., social workers, psychologists, counselors; N = 237). A quantitative cross-sectional design was employed to analyze data collected between October and December 2021. Chi-square tests of independence were conducted to examine differences in the self-reported use of interventions across professional disciplines and agency types. A significant portion of the sample (71.7%) reported using at least one intervention with well-established evidence. Psychologists most frequently used these well-established interventions in their practice, followed by counselors and social workers. Participants working in private agencies also endorsed higher utilization of various EBTs than those in public agencies. Logistic regression analyses were performed to assess the correlation between favorable attitudes, knowledge, and training on these practices and the self-reported use of specific interventions. Favorable attitudes towards Evidence-Based Practices (EBPs) were related to increased use of mindfulness therapy, a well-established intervention. Greater knowledge and training on EBTs were found to correlate with self-reported use of interventions with well-established and probably efficacious evidence. Findings suggest that mental health professionals in Puerto Rico use some well-established EBTs, but the modalities used varied based on a variety of factors. Our findings suggest that increasing knowledge and agency training on EBTs may be an effective way to promote the use of interventions with well-established and probably efficacious evidence. Implications for research, practice, education, and policy development in Puerto Rico are discussed.