Meeting the Health Needs of Society Through Curricular Innovation in Physical Therapist Education: Examples From 3 Entry-Level Programs.

BACKGROUND AND PURPOSE: Entry-level physical therapist (PT) education programs play a critical role in inspiring future leaders to become moral change agents, capable of understanding and addressing evolving societal health needs. Social reconstructionism represents an educational philosophy focused on alleviating pervasive inequities and improving the health of society; however, its application in PT education is not well understood. The purpose of this article is to describe the approach 3 entry-level PT programs used to manifest social reconstructionism within their curricula to foster social consciousness and strengthen moral agency. METHOD/MODEL DESCRIPTION AND EVALUATION: The Framework for Educating Health Professionals to Address the Social Determinants of Health informed the development of a conceptual framework that illustrates the role of PT education programs in creating transformative learning environments and preparing learners to meet societal health needs. Concepts within this framework were operationalized according to 5 domains put forth by Jensen et al. and related competencies put forth by the Association of American Medical Colleges. OUTCOMES: Narratives from each program demonstrate how the design and implementation of curricula, grounded in social reconstructionism, can be accomplished through 1) ongoing modifications, 2) thoughtful reconstruction, and 3) initial design. Sample learning activities, objectives, and assessment strategies are provided. DISCUSSION AND CONCLUSION: The proposed method was effective in guiding meaningful objectives, learning activities, and assessment strategies grounded in social reconstructionism. Such findings can inform the design of curricula that inspire the next generation of transformative leaders who work to alleviate pervasive inequities and improve the health of society.

Coercive Control in 2SLGBTQQIA+ Relationships: A Scoping Review.

Existing measures and theories of intimate partner coercive control largely evaluate men's coercion of women. The extent of knowledge pertaining to intimate relationships among other genders and sexual identities is unclear. Guided by a theoretical framework of intersectionality, we examined and synthesized original studies on coercive control by (perpetration) or against (victimization) Two Spirit, lesbian, gay, bisexual, trans, queer, questioning, intersex, and asexual individuals within intimate partner relationships. We searched eight academic databases for records from 2014 through 2022 and hand-searched review articles' reference lists, supplemented with gray literature and website searches. Using duplicate screening, we identified 1,774 unique documents; 526 met preliminary eligibility criteria and 277 were retained for data extraction in duplicate. Coercive control was more common among minority individuals and was related to mental health challenges. Few studies reported on gender- or sexual-identity specific forms of coercive control, and an intersectional focus was uncommon. This review revealed a lack of agreed definition of coercive control or accepted standard of measurement, and a gap in research with individuals who identify as gender diverse, gender fluid or intersex, or those identifying their sexuality as asexual, pansexual, or sexually diverse.

Bridging Gaps in Care Following Hospitalization for Suicidal Adolescents: As Safe As Possible (ASAP) and BRITE App.

OBJECTIVE: We present results from a 2-site, randomized clinical trial to assess the efficacy of a brief intervention (As Safe As Possible [ASAP]), a safety plan phone application (BRITE), and their combination on suicide attempts, suicidal ideation, non-suicidal self-injury, re-hospitalizations. and suicidal events among adolescents. METHOD: Adolescents (n= 240; 12-17 years of age) who were hospitalized for suicidal ideation with plan and/or intent, and/or suicide attempt, were assigned to 1 of 4 treatment conditions in a 2 by 2 design: ASAP+BRITE app+treatment as usual (TAU); (2) BRITE+TAU; (3) ASAP+TAU; and (4) TAU alone. Independent evaluators assessed suicidal ideation and behavior at 4, 12, and 24 weeks using the Columbia-Suicide Severity Rating Scale (C-SSRS) and re-hospitalization using the Child and Adolescent Services Assessment (CASA). RESULTS: No group differences were found on primary outcomes, except that ASAP participants were less likely to be re-hospitalized over 6 months (15.6%, vs 26.5%, p = .046). Participants hospitalized for an attempt and assigned to BRITE had a lower rate of subsequent attempts (odds ratio [OR] = 0.16, p = .01) and a greater time to attempt (hazard ratio [HR] = 0.20, p = .02). ASAP+BRITE, albeit not statistically significant, was most consistently associated with a reduction (60% reduction) in suicide attempts. CONCLUSION: ASAP, BRITE, and their combination are equally effective at decreasing risk for suicidal events 6 months post hospital discharge among suicidal adolescents; the ASAP intervention (with or without BRITE) was associated with lower rates of re-hospitalization. The BRITE app in youth hospitalized for suicide attempt had promising outcomes in regard to future attempts. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. The research was performed with permission from the University of Pittsburgh Institutional Review Board and the University of Texas Institutional Review Board. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. CLINICAL TRIALS REGISTRATION INFORMATION: Establishing Efficacy of an Inpatient Intervention and Phone App to Reduce Suicidal Risk (ASAP+BRITE); https://clinicaltrials.gov/study/; NCT03825588.

Estimates of late Early Cretaceous atmospheric CO2 from Mongolia based on stomatal and isotopic analysis of Pseudotorellia.

PREMISE: The Aptian-Albian (121.4-100.5 Ma) was a greenhouse period with global temperatures estimated as 10-15°C warmer than pre-industrial conditions, so it is surprising that the most reliable CO2 estimates from this time are <1400 ppm. This low CO2 during a warm period implies a very high Earth-system sensitivity in the range of 6 to 9°C per CO2 doubling between the Aptian-Albian and today. METHODS: We applied a well-vetted paleo-CO2 proxy based on leaf gas-exchange principles (Franks model) to two Pseudotorellia species from three stratigraphically similar samples at the Tevshiin Govi lignite mine in central Mongolia (~119.7-100.5 Ma). RESULTS: Our median estimated CO2 concentration from the three respective samples was 2132, 2405, and 2770 ppm. The primary reason for the high estimated CO2 but with relatively large uncertainties is the very low stomatal density in both species, where small variations propagate to large changes in estimated CO2. Indeed, we found that at least 15 leaves are required before the aggregate estimated CO2 approaches that of the full data set. CONCLUSIONS: Our three CO2 estimates all exceeded 2000 ppm, translating to an Earth-system sensitivity (~3-5°C/CO2 doubling) that is more in keeping with the current understanding of the long-term climate system. Because of our large sample size, the directly measured inputs did not contribute much to the overall uncertainty in estimated CO2; instead, the inferred inputs were responsible for most of the overall uncertainty and thus should be scrutinized for their value choices.

Behaviours of farmed saltwater crocodiles (Crocodylus porosus) housed individually or in groups.

Saltwater crocodiles (Crocodylus porosus) are farmed in Australia primarily for their skins and meat. Commercially, they are raised in group pens as hatchlings and grower crocodiles and then moved to unitised (individual) pens for the final finishing stage when they are several years old. They will exhibit aggressive behaviour towards each other in captivity. Unitised pens can prevent animal injury and teeth marks on the skins but may result in other social restrictions. Research into behavioural housing preferences could assist the industry and inform the process of guideline development for optimal crocodile management and welfare. This study assessed the impacts of two housing systems, unitised or group pens, in 20 commercial finishing crocodiles through measuring behavioural profiles of individuals from video recordings, including housing preference when given a choice. Both pens included water and an above-water shelf, but the crocodiles in unitised pens could also access underneath the shelf. A threat perception test was applied to assess anxiety when housed individually or in groups. However, it was difficult to apply a standardised stimulus to all animals that reliably elicited a behavioural response. Further work would be needed to validate this test for commercial reptiles as the outcomes were not robust. The behavioural observation results showed clear differences in where the crocodiles spent their time across the day and in their activity levels between the pen types. However, interpretation of this variation was confounded by the physical and social differences between the pen types given the inconsistency in shelf access. Behaviours exhibited also differed given there were social opportunities in the group pens where individuals were observed engaged in both aggressive and non-aggressive contact interactions. In the free choice environment, crocodiles spent similar amounts of time in both unitised and group pens, suggesting there were features of both pen types that were attractive to the animals. However, skins were damaged from teeth marks highlighting the physical and economical risks of group housing. Further work could validate behavioural tests to quantify affective state impacts in different housing environments and whether social interactions do provide benefits for improving crocodile welfare.

Identifying Person-Specific Drivers of Depression in Adolescents: Protocol for a Smartphone-Based Ecological Momentary Assessment and Passive Sensing Study.

BACKGROUND: Adolescence is marked by an increasing risk of depression and is an optimal window for prevention and early intervention. Personalizing interventions may be one way to maximize therapeutic benefit, especially given the marked heterogeneity in depressive presentations. However, empirical evidence that can guide personalized intervention for youth is lacking. Identifying person-specific symptom drivers during adolescence could improve outcomes by accounting for both developmental and individual differences. OBJECTIVE: This study leverages adolescents' everyday smartphone use to investigate person-specific drivers of depression and validate smartphone-based mobile sensing data against established ambulatory methods. We describe the methods of this study and provide an update on its status. After data collection is completed, we will address three specific aims: (1) identify idiographic drivers of dynamic variability in depressive symptoms, (2) test the validity of mobile sensing against ecological momentary assessment (EMA) and actigraphy for identifying these drivers, and (3) explore adolescent baseline characteristics as predictors of these drivers. METHODS: A total of 50 adolescents with elevated symptoms of depression will participate in 28 days of (1) smartphone-based EMA assessing depressive symptoms, processes, affect, and sleep; (2) mobile sensing of mobility, physical activity, sleep, natural language use in typed interpersonal communication, screen-on time, and call frequency and duration using the Effortless Assessment of Risk States smartphone app; and (3) wrist actigraphy of physical activity and sleep. Adolescents and caregivers will complete developmental and clinical measures at baseline, as well as user feedback interviews at follow-up. Idiographic, within-subject networks of EMA symptoms will be modeled to identify each adolescent's person-specific drivers of depression. Correlations among EMA, mobile sensor, and actigraph measures of sleep, physical, and social activity will be used to assess the validity of mobile sensing for identifying person-specific drivers. Data-driven analyses of mobile sensor variables predicting core depressive symptoms (self-reported mood and anhedonia) will also be used to assess the validity of mobile sensing for identifying drivers. Finally, between-subject baseline characteristics will be explored as predictors of person-specific drivers. RESULTS: As of October 2023, 84 families were screened as eligible, of whom 70% (n=59) provided informed consent and 46% (n=39) met all inclusion criteria after completing baseline assessment. Of the 39 included families, 85% (n=33) completed the 28-day smartphone and actigraph data collection period and follow-up study visit. CONCLUSIONS: This study leverages depressed adolescents' everyday smartphone use to identify person-specific drivers of adolescent depression and to assess the validity of mobile sensing for identifying these drivers. The findings are expected to offer novel insights into the structure and dynamics of depressive symptomatology during a sensitive period of development and to inform future development of a scalable, low-burden smartphone-based tool that can guide personalized treatment decisions for depressed adolescents. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43931.

The Food Addiction Clinical Treatment (FACT) Manual: A Harm Reduction Treatment Approach.

While the construct of food addiction has been controversial, there is growing evidence that certain foods can activate biobehavioral and neurological mechanisms consistent with addiction to other substances. Despite increased evidence and acceptance of certain foods as addictive substances amongst the scientific community, there is a paucity of interventions available that are uniquely suited for the treatment of this condition. Further, many of the addiction and disordered eating treatment models currently utilized for food addiction are seemingly at odds, with the former often recommending complete abstinence from trigger foods and the latter promoting intake of all foods in moderation. The Food Addiction Clinical Treatment (FACT) manual was created as an alternative using an empirically supported harm-reduction model specifically targeted to treat the addiction and disordered eating features of food addiction. The purpose of the current article is to expose readers to the key tenets of the FACT manual, demonstrate the feasibility of this intervention with a sample of participants with severe food addiction, and discuss future directions for the treatment of food addiction. Positive outcomes from this intervention provide preliminary evidence for the efficacy of FACT for the treatment of food addiction with minimal negative adverse effects. Future research using randomized control trials and longer follow-up is needed to validate the FACT manual as an empirically supported treatment for food addiction.

Post-discharge complications and hospital readmissions are associated with nutritional risk and malnutrition status in a cohort of Canadian pediatric patients.

BACKGROUND: This study constitutes a secondary analysis of a prospective cohort aiming to evaluate the potential correlation between nutritional risk and status at admission with the occurrence of post-discharge complications and hospital readmissions in children receiving care at high resource Centres. METHODS: Data was collected from 5 Canadian tertiary pediatric Centers between 2012 and 2016. Nutritional risk and status were evaluated at hospital admission with validated tools (STRONGkids and Subjective Global Nutrition Assessment [SGNA]) and anthropometric measurements. Thirty days after discharge, occurrence of post-discharge complications and hospital readmission were documented. RESULTS: A total of 360 participants were included in the study (median age, 6.1 years; median length of stay, 5 days). Following discharge, 24.1% experienced complications and 19.5% were readmitted to the hospital. The odds of experiencing complications were nearly tripled for participants with a high nutritional risk compared to a low risk (OR = 2.85; 95% CI [1.08-7.54]; P = 0.035) and those whose caregivers reported having a poor compared to a good appetite (OR = 2.96; 95% CI [1.59-5.50]; P < 0.001). According to SGNA, patients identified as malnourished had significantly higher odds of complications (OR, 1.92; 95% CI, 1.15-3.20; P = 0.013) and hospital readmission (OR, 1.95; 95% CI, 1.12-3.39; P = 0.017) than to those well-nourished. CONCLUSIONS: This study showed that complications and readmission post-discharge are common, and these are more likely to occur in malnourished children compared to their well-nourished counterparts. Enhancing nutritional care during admission, at discharge and in the community may be an area for future outcome optimization.

Dystrophin deficiency impairs cell junction formation during embryonic myogenesis from pluripotent stem cells.

Mutations in the DMD gene lead to Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder affecting young boys as they acquire motor functions. DMD is typically diagnosed at 2-4 years of age, but the absence of dystrophin has negative impacts on skeletal muscles before overt symptoms appear in patients, which poses a serious challenge in current standards of care. Here, we investigated the consequences of dystrophin deficiency during skeletal muscle development. We used single-cell transcriptome profiling to characterize the myogenic trajectory of human pluripotent stem cells and showed that DMD cells bifurcate to an alternative branch when they reach the somite stage. Dystrophin deficiency was linked to marked dysregulations of cell junction proteins involved in the cell state transitions characteristic of embryonic somitogenesis. Altogether, this work demonstrates that in vitro, dystrophin deficiency has deleterious effects on cell-cell communication during myogenic development, which should be considered in future therapeutic strategies for DMD.

Knowledge, attitudes, and practices and long-term immune response after rVSVΔG-ZEBOV-GP Ebola vaccination in healthcare workers in high-risk districts in Uganda.

BACKGROUND: The rVSVΔG-ZEBOV-GP Ebola vaccine (rVSV-ZEBOV) has been used in response to Ebola disease outbreaks caused by Ebola virus (EBOV). Understanding Ebola knowledge, attitudes, and practices (KAP) and the long-term immune response following rVSV-ZEBOV are critical to inform recommendations on future use. METHODS: We administered surveys and collected blood samples from healthcare workers (HCWs) from seven Ugandan healthcare facilities. Questionnaires collected information on demographic characteristics and KAP related to Ebola and vaccination. IgG ELISA, virus neutralization, and interferon gamma ELISpot measured immunological responses against EBOV glycoprotein (GP). RESULTS: Overall, 37 % (210/565) of HCWs reported receiving any Ebola vaccination. Knowledge that rVSV-ZEBOV only protects against EBOV was low among vaccinated (32 %; 62/192) and unvaccinated (7 %; 14/200) HCWs. Most vaccinated (91 %; 192/210) and unvaccinated (92 %; 326/355) HCWs wanted to receive a booster or initial dose of rVSV-ZEBOV, respectively. Median time from rVSV-ZEBOV vaccination to sample collection was 37.7 months (IQR: 30.5, 38.3). IgG antibodies against EBOV GP were detected in 95 % (61/64) of HCWs with vaccination cards and in 84 % (162/194) of HCWs who reported receiving a vaccination. Geometric mean titer among seropositive vaccinees was 0.066 IU/mL (95 % CI: 0.058-0.076). CONCLUSION: As Uganda has experienced outbreaks of Sudan virus and Bundibugyo virus, for which rVSV-ZEBOV does not protect against, our findings underscore the importance of continued education and risk communication to HCWs on Ebola and other viral hemorrhagic fevers. IgG antibodies against EBOV GP were detected in most vaccinated HCWs in Uganda 2─4 years after vaccination; however, the duration and correlates of protection warrant further investigation.

Coercive control in a national U.S. self-report survey: Prediction of repeated intimate partner violence.

Coercive, controlling behavior toward intimate partners correlates with physical intimate partner violence (IPV). We examined whether it also predicts subsequent IPV or other aggression. We conducted a secondary analysis of self-reports by 1,039 women and 509 men who participated in the first two waves of the Interpersonal Conflict and Resolution Study (Mumford et al., 2019). We defined coercive control as any reported perpetration at Wave 1 of threat to physically harm, threat to use information to control, or put down or disrespect their partner. The participants also reported perpetration of verbal abuse and physical or sexual aggression against intimate partners. We tested correlations of these behaviors with similar acts toward nonintimates (friends or unfamiliar persons) in Wave 1 and the prediction of physical violence in Wave 2, approximately 5 months later. Coercive control (14% of men, 26% of women) was correlated with physical or sexual IPV (8% of men, 15% of women) in both women and men and with physical violence and coercive control to nonintimates. In logistic regressions entering Wave 1 physical IPV on the first step, Wave 1 coercive control was a significant independent predictor of Wave 2 physical IPV overall, and for men but not women. Coercive control did not independently predict nonintimate physical violence. Coercive control toward an intimate partner is a unique predictor of physical IPV among men. Future research should use improved measures of coercive control and further examine coercive control as an indicator of general antisociality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

How pharmacists would design and implement a community pharmacy-based colorectal cancer screening program.

Background: Distributing CRC screening through pharmacies, a highly accessible health service, may create opportunities for more equitable access to CRC screening. However, providing CRC screening in a new context introduces a substantial implementation challenge. Methods: We conducted 23 semi-structured interviews with community pharmacists practicing in Washington state and North Carolina about distributing fecal immunochemical tests (FIT) to patients in the pharmacy. The Consolidated Framework for Implementation Research (CFIR) was used to guide analysis. Results: Pharmacists believed that delivering FITs was highly compatible with their environment, workflow, and scope of practice. While knowledge about FIT eligibility criteria varied, pharmacists felt comfortable screening patients. They identified standardized eligibility criteria, patient-facing educational materials, and continuing education as essential design features. Pharmacists proposed adapting existing pharmacy electronic health record systems for patient reminders/prompts to facilitate FIT completion. While pharmacists felt confident that they could discuss test results with patients, they also expressed a need for stronger communication and care coordination with primary care providers. Discussion: When designing a pharmacy-based CRC screening program, pharmacists desired programmatic procedures to fit their current knowledge and context. Findings indicate that if proper attention is given to multi-level factors, FIT delivery can be extended to pharmacies.

Discovery of genomic loci for liver health and steatosis reveals overlap with glutathione redox genetics.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in the United States, encompassing a wide spectrum of liver pathologies including steatosis, steatohepatitis, fibrosis, and cirrhosis. Despite its high prevalence, there are no medications currently approved by the Food and Drug Administration for the treatment of NAFLD. Recent work has suggested that NAFLD has a strong genetic component and identifying causative genes will improve our understanding of the molecular mechanisms contributing to NAFLD and yield targets for future therapeutic investigations. Oxidative stress is known to play an important role in NAFLD pathogenesis, yet the underlying mechanisms accounting for disturbances in redox status are not entirely understood. To better understand the relationship between the glutathione redox system and signs of NAFLD in a genetically-diverse population, we measured liver weight, serum biomarkers aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and graded liver pathology in a large cohort of Diversity Outbred mice. We compared hepatic endpoints to those of the glutathione redox system previously measured in the livers and kidneys of the same mice, and we screened for statistical and genetic associations using the R/qtl2 software. We discovered several novel genetic loci associated with markers of liver health, including loci that were associated with both liver steatosis and glutathione redox status. Candidate genes within each locus point to possible new mechanisms underlying the complex relationship between NAFLD and the glutathione redox system, which could have translational implications for future studies targeting NAFLD pathology.

Early Parental Knowledge and Parent-Child Conversations Promote Preschool Language Skills: A Randomized Controlled Trial.

OBJECTIVE: This randomized controlled trial examined the long-term impact of the 3Ts-HV intervention on preschool-aged children's language skills through promoting parental knowledge and parent-child conversational turns during toddlerhood among families from low-socioeconomic status backgrounds, controlling for parental education level, parental language skills, and child's age. METHODS: Ninety two parent-toddler dyads of low socioeconomic status were randomized to receive either the 3Ts-HV intervention (n = 46) or Healthy Lifestyle control (n = 46) curriculum from 14 to 20 months. Parental language skills were assessed at 14 months; parental knowledge was assessed at 14 and 26 months; parent-child conversational turn count was assessed at 14 and 38 months; children's language skills were assessed at 50 months. RESULTS: A significant serial mediation effect (ß = 0.05, 95% CI [0.002; 0.13]) revealed that the 3Ts-HV intervention increased parental knowledge at 26 months, contributed to more frequent parent-child conversational turns at 38 months, and in turn promoted children's language skills at 50 months. CONCLUSIONS: The present study provides empirical evidence illustrating the underlying longitudinal processes from increasing parental knowledge and enriching parent-child linguistic interactions during toddlerhood, to promoting children's language development at preschool age. These findings point to a significant path to supporting families who face socioeconomic challenges early in life to promote equity in children's early language experiences and narrow disparities in children's developmental outcomes.

Hippocampal subfield volume in older adults with and without mild cognitive impairment: Effects of worry and cognitive reappraisal.

Studies have confirmed that anxiety, especially worry and rumination, are associated with increased risk for cognitive decline, including Alzheimer's disease and related dementias (ADRD). Hippocampal atrophy is a hallmark of ADRD. We investigated the association between hippocampus and its subfield volumes and late-life global anxiety, worry, and rumination, and emotion regulation strategies. We recruited 110 participants with varying worry severity who underwent magnetic resonance imaging and clinical interviews. We conducted cross-sectional regression analysis between each subfield and anxiety, worry, rumination, reappraisal, and suppression while adjusting for age, sex, race, education, cumulative illness burden, stress, neuroticism, and intracranial volume. We imputed missing data and corrected for multiple comparisons across regions. Greater worry was associated with smaller subiculum volume, whereas greater use of reappraisal was associated with larger subiculum and CA1 volume. Greater worry may be detrimental to the hippocampus and to subfields involved in early ADRD pathology. Use of reappraisal appears protective of hippocampal structure. Worry and reappraisal may be modifiable targets for ADRD prevention.

Race-Related Differences in Sipuleucel-T Response among Men with Metastatic Castrate-Resistant Prostate Cancer.

Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T in men with mCRPC were explored. Patients' blood samples were obtained to assess serum cytokines, humoral responses, and cellular immunity markers before and after treatment. Baseline cumulative product parameters (total nucleated and CD54+ cell counts and CD54 upregulation) were evaluated. IgM titers against the immunogen PA2024, the target antigen PAP, prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) were quantified by ELISA. Cytotoxic T-lymphocyte activity was determined by ELISpots, and cytokine and chemokine concentrations were determined by Luminex.Twenty-nine African American (AA) men and 28 non-African American (non-AA) men with mCRPC received sipuleucel-T. Baseline total nucleated cell count, CD54+ cell count, CD54 expression, and cumulative product parameters were higher in non-AA men. Although PSA baseline levels were higher in AA men, there were no racial differences in IgM antibody and IFNγ ELISpots responses against PA2024, PAP, PSA, and PSMA before and after treatment. Expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells, and the levels of Th1 cytokine granulocyte-macrophage colony-stimulating factor and chemokines CCL4 and CCL5, were significantly higher in AA men before and/or after treatment. Despite no difference in the overall survival, PSA changes from baseline were significantly different between the two races. The data suggest that immune correlates in blood differ in AA and non-AA men with mCRPC pre- and post-sipuleucel-T. SIGNIFICANCE: Our novel findings of higher expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells in African American patients with metastatic castrate-resistant prostate cancer (mCRPC) prior and post-sipuleucel-T suggest activation of CD4+ and CD8+ T cells. The data indicate that racial differences observed in these and other immune correlates before and after sipuleucel-T warrant additional investigation to further our understanding of the immune system in African American men and other men with mCRPC.

The role of reoperation in pediatric cerebellar pilocytic astrocytoma.

OBJECTIVE: Cerebellar pilocytic astrocytomas (cPAs) in childhood have long been recognized to have a good prognosis after total resection, but the outcome after incomplete resective surgery remains largely unpredictable, with the incidence of radiological progressive disease ranging from 18% to 100%. It has been traditionally thought that gross-total resection was required for long-term survival, and small residuals were classically resected in a subsequent operation. METHODS: The authors analyzed their pediatric low-grade glioma (PLGG) database for cases treated between 1985 and 2020 and filtered for intracranial PAs, to determine what clinical or radiological factors precipitated revisional resective surgery in their single quaternary care center cohort. RESULTS: Using the pediatric low-grade glioma database, 283 patients were identified to have a histopathological diagnosis of intracranial PA between 1985 and 2020, of which 200 lesions were within the cerebellum (70.7%). The majority of patients with cPA were between 1 and 10 years of age (n = 145, 72.5%) without gender predominance (M/F = 99:101), usually presenting with 1 lesion (n = 197, 98.5%). Gross-total resection was achieved in 74.5% (n = 149) of initial surgeries for cPA. In patients with subtotal resection, the mean largest diameter of the postoperative residual tumor was 1.06 cm (range 0-2.95 cm). Seven patients with subtotal resection did not require a second resective intervention. In 31 patients the neuro-oncology multidisciplinary team recommended a second resection at a mean time interval of 22.9 months (range 0.13-81.6 months) from the initial surgery. Proportionally, the children who underwent multiple resections were also more likely to receive adjuvant chemo/radiotherapy. Functionally, the children in the multiple operation cohort experienced more complications of therapy including ongoing endocrinopathy, treatment-associated hearing deficit, and neurocognitive deficits. CONCLUSIONS: Residual disease in cPA should be maintained under clinicocoradiological surveillance postoperatively with adoption of a more conservative approach when residual disease is not significantly changing over time.

Interferon-signaling pathways are upregulated in people with HIV with abnormal pulmonary diffusing capacity (DL CO ).

OBJECTIVE: People with HIV (PWH) are at greater risk of developing lung diseases even when they are antiretroviral therapy (ART)-adherent and virally suppressed. The most common pulmonary function abnormality in PWH is that of impaired diffusing capacity of the lungs for carbon monoxide (DL CO ), which is an independent risk factor for increased mortality in PWH. Earlier work has identified several plasma biomarkers of inflammation and immune activation to be associated with decreased DL CO . However, the underpinning molecular mechanisms of HIV-associated impaired DL CO are largely unknown. DESIGN: Cross-sectional pilot study with PWH with normal DL CO (values greater than or equal to the lower limit of normal, DL CO  ≥ LLN, N = 9) or abnormal DL CO (DL CO  < LLN, N = 9). METHODS: We compared the gene expression levels of over 900 inflammation and immune exhaustion genes in PBMCs from PWH with normal vs. abnormal DL CO using the NanoString technology. RESULTS: We found that 26 genes were differentially expressed in the impaired DL CO group. These genes belong to 4 categories: 1. Nine genes in inflammation and immune activation pathways, 2. seven upregulated genes that are direct targets of the interferon signaling pathway, 3. seven B-cell specific genes that are downregulated, and 4. three miscellaneous genes. These results were corroborated using the bioinformatics tools DAVID (Database for Annotation, Visualization and Integrated Discovery) and GSEA (Gene Sets Enrichment Analysis). CONCLUSION: The data provides preliminary evidence for the involvement of sustained interferon signaling as a molecular mechanism for impaired DL CO in PWH.