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The climacteric heralds a transition from reproductive to non-reproductive life in women, often accompanied by various clinical manifestations such as dry eye, impacting their quality of life. This study focuses on systematically developing and suitability an educational digital booklet to promote eye health practices and prevent problems among postmenopausal women. The methodological approach encompassed semi-structured interviews with women diagnosed with Dry Eye Syndrome (DES), then constructing the material integrating content, script, illustrations, and layout informed by the interview findings. Subsequent validation involved assessment by 24 health experts for content, appearance, and evaluation by a target audience of 22 women. The booklet attained high suitability scores, with a Global Content Validity Index (CVI) of 0.96, indicating superior suitability as judged by experts. Additionally, it achieved a Global CVI of 0.98 for validation by the target audience. In conclusion, the educational booklet emerges as a suitable and reliable resource for promoting eye heath among DES and non-syndrome women, offering significant potential for broader application in relevant populations.

Experimental models of Schistosoma mansoni infections in mammals have contributed greatly to our understanding of the pathology and pathogenesis of infection. We consider here hepatic and extrahepatic disease in models of acute and chronic infection. Experimental schistosome infections have also contributed more broadly to our understanding of granulomatous inflammation and our understanding of Th1 versus Th2 related inflammation and particularly to Th2-mediated fibrosis of the liver.

Chimeric antigen receptor (CAR) T cell therapy has become an important treatment for hematological cancers, and its success has spurred research into CAR T cell therapies for other diseases, including solid tumor cancers and autoimmune diseases. Notably, the development of CAR-based treatments for autoimmune diseases has shown great progress recently. Clinical trials for anti-CD19 and anti-BCMA CAR T cells in treating severe B cell-mediated autoimmune diseases, like systemic lupus erythematosus (SLE), have shown lasting remission thus far. CAR T cells targeting autoreactive T cells are beginning clinical trials for treating T cell mediated autoimmune diseases. Chimeric autoantigen receptor (CAAR) T cells specifically target and eliminate only autoreactive B cells, and they have shown promise in treating mucosal pemphigus vulgaris and MuSK myasthenia gravis. Regulatory CAR T cells have also been developed, which show potential in altering autoimmune affected areas by creating a protective barrier as well as helping decrease inflammation. These new treatments are only the beginning of potential CAR T cell applications in treating autoimmune disease. Novel CAR technologies have been developed that increase the safety, potency, specificity, and efficacy of CAR T cell therapy. Applying these novel modifications to autoimmune CARs has the potential to enhance the efficacy and applicability of CAR therapies to autoimmune disease. This review will detail several recently developed CAR technologies and discuss how their application to autoimmune disease will improve this emerging field. These include logic-gated CARs, soluble protein-secreting CARs, and modular CARs that enable CAR T cell therapies to be more specific, reach a wider span of target cells, be safer for patients, and give a more potent cytotoxic response. Applying these novel CAR technologies to the treatment of autoimmune diseases has the potential to revolutionize this growing application of CAR T cell therapies.

ABSTRACT The annual meeting for the Intermountain Branch was held in April 2024 on the campus of Brigham Young University. There were 127 branch members from Utah, Idaho, and Nevada who attended the meeting and were composed of undergraduate students, graduate or medical students, and faculty. This report highlights the diversity of, and the emerging trends in, the research conducted by American Society for Microbiology members in the Intermountain Branch.

Participant recruitment is one of the most challenging aspects of a clinical trial, directly impacting both the study’s duration and the quality of its results. Therefore, reporting successful recruitment strategies is crucial. This study aimed to document the recruitment tactics and experiences of a research team during a university-based randomized clinical trial, conducted as part of a clinical research immersion program. Recruitment took place from October 2021 to October 2022. Before the study commenced, study team members received formal training in clinical trial participant recruitment from the Principal Investigator. The recruitment strategies were integrated into initial study design, which was approved by the Institutional Review Board. A multimodal approach was employed, incorporating both direct and indirect recruitment methods. These strategies successfully met the enrollment target within the twelve-month period. Throughout the process, team members acquired valuable knowledge in recruitment design and implementation, along with transferable interpersonal and networking skills. In-person recruitment was the most efficient and cost-effective strategy, followed by personal referrals. The primary challenge was accommodating participants’ availability. Other study teams should consider these recruitment strategies during their study designs. Additionally, the knowledge and skills gained by this study team underscore the value of experiential learning in research education.

In people living with HIV (PLWH) on antiretroviral therapy (ART), virus persists in a latent form where there is minimal transcription or protein expression. Latently infected cells are a major barrier to curing HIV. Increasing HIV transcription and viral production in latently infected cells could facilitate immune recognition and reduce the pool of infected cells that persist on ART. Given that programmed cell death protein 1 (PD-1) expressing CD4+ T cells are preferentially infected with HIV in PLWH on ART, we aimed to determine whether administration of antibodies targeting PD-1 would reverse HIV latency in vivo. We therefore evaluated the impact of intravenous administration of pembrolizumab every 3 weeks on HIV latency in 32 PLWH and cancer on ART. After the first infusion of anti-PD-1, we observed a median 1.32-fold increase in unspliced HIV RNA and 1.61-fold increase in unspliced RNA:DNA ratio in sorted blood CD4+ T cells compared to baseline. We also observed a 1.65-fold increase in plasma HIV RNA. The frequency of CD4+ T cells with inducible virus evaluated using the tat/rev limiting dilution assay was higher after 6 cycles compared to baseline. Phylogenetic analyses of HIV env sequences in a participant who developed low concentrations of HIV viremia after 6 cycles of pembrolizumab did not demonstrate clonal expansion of HIV-infected cells. These data are consistent with anti-PD-1 being able to reverse HIV latency in vivo and support the rationale for combining anti-PD-1 with other interventions to reduce the HIV reservoir.

Sipuleucel-T (sip-T) is a Food and Drug Administration (FDA)-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). We hypothesized that combining sip-T with interleukin (IL)-7, a homeostatic cytokine that enhances both B and T cell development and proliferation, would augment and prolong antigen-specific immune responses against both PA2024 (the immunogen for sip-T) and prostatic acid phosphatase (PAP). Fifty-four patients with mCRPC treated with sip-T were subsequently enrolled and randomized 1:1 into observation (n=26) or IL-7 (n=28) arms of a phase II clinical trial (NCT01881867). Recombinant human (rh) IL-7 (CYT107) was given weekly×4. Immune responses were evaluated using flow cytometry, mass cytometry (CyTOF), interferon (IFN)-γ ELISpot, 3H-thymidine incorporation, and ELISA. Treatment with rhIL-7 was well tolerated. For the rhIL-7-treated, but not observation group, statistically significant lymphocyte subset expansion was found, with 2.3-2.6-fold increases in CD4+T, CD8+T, and CD56bright NK cells at week 6 compared with baseline. No significant differences in PA2024 or PAP-specific T cell responses measured by IFN-γ ELISpot assay were found between rhIL-7 and observation groups. However, antigen-specific T cell proliferative responses and humoral IgG and IgG/IgM responses significantly increased over time in the rhIL-7-treated group only. CyTOF analyses revealed pleiotropic effects of rhIL-7 on lymphocyte subsets, including increases in CD137 and intracellular IL-2 and IFN-γ expression. While not powered to detect clinical outcomes, we found that 31% of patients in the rhIL-7 group had prostate specific antigen (PSA) doubling times of >6 months, compared with 14% in the observation group. Treatment with rhIL-7 led to a significant expansion of CD4+ and CD8+ T cells, and CD56bright natural killer (NK) cells compared with observation after treatment with sip-T. The rhIL-7 treatment also led to improved antigen-specific humoral and T cell proliferative responses over time as well as to increased expression of activation markers and beneficial cytokines. This is the first study to evaluate the use of rhIL-7 after sip-T in patients with mCRPC and demonstrates encouraging results for combination approaches to augment beneficial immune responses.

BackgroundMerkel cell carcinoma (MCC) is an aggressive skin cancer associated with poor survival. Programmed cell death-1 (PD-1) pathway inhibitors have shown high rates of durable tumor regression compared with chemotherapy for MCC. The current study was undertaken to assess baseline and on-treatment factors associated with MCC regression and 3-year survival, and to explore the effects of salvage therapies in patients experiencing initial non-response or tumor progression after response or stable disease following first-line pembrolizumab therapy on Cancer Immunotherapy Trials Network-09/KEYNOTE-017.MethodsIn this multicenter phase II trial, 50 patients with advanced unresectable MCC received pembrolizumab 2 mg/kg every 3 weeks for ≤2 years. Patients were followed for a median of 31.8 months.ResultsOverall response rate to pembrolizumab was 58% (complete response 30%+partial response 28%; 95% CI 43.2 to 71.8). Among 29 responders, the median response duration was not reached (NR) at 3 years (range 1.0+ to 51.8+ months). Median progression-free survival (PFS) was 16.8 months (95% CI 4.6 to 43.4) and the 3-year PFS was 39.1%. Median OS was NR; the 3-year OS was 59.4% for all patients and 89.5% for responders. Baseline Eastern Cooperative Oncology Group performance status of 0, greater per cent tumor reduction, completion of 2 years of treatment and low neutrophil-to-lymphocyte ratio were associated with response and longer survival. Among patients with initial disease progression or those who developed progression after response or stable disease, some had extended survival with subsequent treatments including chemotherapies and immunotherapies.ConclusionsThis study represents the longest available follow-up from any first-line anti-programmed death-(ligand) 1 (anti-PD-(L)1) therapy in MCC, confirming durable PFS and OS in a proportion of patients. After initial tumor progression or relapse following response, some patients receiving salvage therapies survived. Improving the management of anti-PD-(L)1-refractory MCC remains a challenge and a high priority.Trial registration numberNCT02267603.

BackgroundThe clinical management of low-level viremia (LLV) remains unclear. The objective of this study was to investigate the association of blips and LLV with virologic failure.MethodsWe enlisted patients who newly enrolled into the HIV Research Network between 2005 and 2015, had HIV-1 RNA more than 200 copies/ml, and were either antiretroviral therapy (ART)-naive or ART-experienced and not on ART. Patients were included who achieved virologic suppression (≤50 on two consecutive viral loads) and had at least two viral loads following suppression. Blips and LLV (≥2 consecutive >51 copies/ml) were categorized separately into three categories: no blips/LLV, 51-200, 201-500. Cox proportional hazards regression was used to assess association between rates of blips/LLV and virologic failure (two consecutive >500).ResultsThe 2795 patients were mostly male (75.4%), black (50.3%), and MSM (52.9%). Median age was 38 years old (interquartile range 29-48). Most patients (88.8%) were ART-naive at study entry. Overall, 283 (10.1%) patients experienced virologic failure. A total of 152 (5.4%) patients experienced LLV to 51-200 and 110 (3.9%) patients experienced LLV to 201-500. Both LLV 51-200 [adjusted hazard ratio (aHR) 1.83 (1.10,3.04)] and LLV 201-500 [aHR 4.26 (2.65,6.86)] were associated with virologic failure. In sensitivity analysis excluding ART-experienced patients, the association between LLV 51 and 200 and virologic failure was not statistically significant.ConclusionLLV between 201 and 500 was associated with virologic failure, as was LLV between 51 and 200, particularly among ART-experienced patients. Patients with LLV below the current Department of Health and Human Services threshold for virologic failure (persistent viremia ≥200) may require more intensive monitoring because of increased risk for virologic failure.

Among 1942 persons with human immunodeficiency virus (HIV) without healthcare coverage in 2012-2015, transitioning to Medicaid (adjusted prevalence ratio, 0.95 [0.87, 1.04]) or to private health insurance (1.04 [0.95, 1.13]) was not associated with a change in consistent HIV viral suppression compared to continued reliance on the Ryan White HIV/AIDS Program.

BackgroundDespite the high prevalence of hepatitis C virus (HCV) among persons living with HIV (PWH), the prevalence of HCV screening, treatment, and sustained virologic response (SVR) is unknown. This study aims to characterize the continuum of HCV screening and treatment among PWH in HIV care.SettingAdult patients enrolled at 12 sites of the HIV Research Network located in 3 regions of the United States were included.MethodsWe examined the prevalence of HCV screening, HCV coinfection, direct-acting antiretroviral (DAA) treatment, and SVR-12 between 2014 and 2015. Multivariate logistic regression was performed to identify characteristics associated with outcomes, adjusted for site.ResultsAmong 29,071 PWH (age 18-87, 74.8% male, 44.4% black), 77.9% were screened for HCV antibodies; 94.6% of those screened had a confirmatory HCV RNA viral load test. Among those tested, 61.1% were determined to have chronic HCV. We estimate that only 23.4% of those eligible for DAA were prescribed DAA, and only 17.8% of those eligible evidenced initiating DAA treatment. Those who initiated treatment achieved SVR-12 at a rate of 95.2%. Blacks and people who inject drugs (PWID) were more likely to be screened for HCV than whites or those with heterosexual risk. Persons older than 40 years, whites, Hispanics, and PWID [adjusted odds ratio (AOR) 8.70 (7.74 to 9.78)] were more likely to be coinfected than their counterparts. When examining treatment with DAA, persons older than 50 years, on antiretroviral therapy [AOR 2.27 (1.11 to 4.64)], with HIV-1 RNA

PURPOSE:Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited. PATIENTS AND METHODS:In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RESULTS:Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus-positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1-positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death. CONCLUSION:Here, we present the longest observation to date of patients with aMCC receiving first-line anti-programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.

Objective: To investigate the feasibility, acceptability, and clinical outcome measures of a transitional care intervention for patients with traumatic brain injury (TBI) and their family caregivers. Setting: Inpatient and outpatient rehabilitation at a level I trauma center in the Southeastern United States. Participants: Patients (ages 18-75) diagnosed with moderate to severe TBI, receiving rehabilitation, and their family caregivers. Design: Quasi-experimental, single-arm, single-center feasibility study with pre- and post-test design. Participants completed a 4-month transitional care program involving monthly education and social support. Main measures: Feasibility of enrollment, data collection, intervention completion rates, and intervention acceptability. Clinical outcome measures included patient quality of life (QOL) (12-Item Short Form Health Survey (SF-12), primary outcome) and patient and caregiver self-efficacy (Self-Efficacy for Management of Chronic Conditions Scale). Results: Eleven dyads and 1 monad enrolled (N = 23, 12 patients, 11 caregivers). All completed baseline data; 91.3% (n = 21, 11 patients, 10 caregivers) completed 2-month (intervention midpoint) data; and 86% (n = 20, 11 patients, 9 caregivers) completed 4-month (intervention endpoint) data. The intervention completion rate was 91.67%. Participants engaged in a mean of 2.17 (SD = 1.34) monthly educational webinars and 2.42 (SD = 1.51) social support groups during the intervention period. Approximately 70% of participants (n = 16, 9 patients, 7 caregivers) completed acceptability data, indicating positive intervention experiences (patients: mean 9.44/10 [SD = 1.01]; caregivers: mean 9.57/10 [SD = 0.79]). Patient QOL scores did not statistically improve over time; however, patient self-efficacy scores did statistically significantly improve from baseline (mean = 7.03, SD = 1.53; P = .0197) to intervention end point (4 months) (mean = 8.35, SD = 1.71). Conclusion: Brain Injury Support To Optimize Recovering Minds (BrainSTORM) is a promising new TBI transitional care intervention that has potential to enhance care standards for patients with TBI and their family caregivers. Further research is needed to determine its efficacy. [ABSTRACT FROM AUTHOR]

Abstract Background Despite controversy over their possible health consequences, manufacturers of e-cigarettes employ a variety of marketing media to increase their popularity among adolescents. This study analyzed the relationship between adolescent e-cigarette harm perception and five types of e-cigarette advertising exposures: social media, radio, billboard, newspaper, and television. Methods This study used data from Wave 4.5 of the Population Assessment of Tobacco and Health Study (PATH). PATH collects demographic data and interview individuals about issues pertaining to tobacco use, health outcomes, attitudes, and behaviors. This study applied factor analysis to three individual PATH harm perception items to develop a composite harm perception score. Using linear regression, the study explored the relationship of harm perception and participant responses to their recalled viewing of five different types (i.e., newspaper, radio, billboard, television and social media) of advertisements within the past 30 days. A second analysis explored if adjusting for exposure to anti-tobacco messaging and environmental factors such as family approval mitigated the association of harm perception and advertisement types. Results The study sample consisted of 12,570 (weighted N = 23,993,149) individuals aged 12 to 17 years old. Unadjusted past 30-day exposure to newspaper, radio, billboard, and social media advertising all correlated with a reduced harm perception, but only the associations for newspaper and social media were statistically significant (p

The National Institutes of Health and John F. Kennedy Center for the Performing Arts convened a panel of experts to discuss the current state of research on music and the brain. The panel generated research recommendations to accelerate the study of musics effects on the brain and the implications for human health.

Chimeric antigen receptor (CAR) T cell therapy has become an important treatment for hematological cancers, and its success has spurred research into CAR T cell therapies for other diseases, including solid tumor cancers and autoimmune diseases. Notably, the development of CAR-based treatments for autoimmune diseases has shown great progress recently. Clinical trials for anti-CD19 and anti-BCMA CAR T cells in treating severe B cell-mediated autoimmune diseases, like systemic lupus erythematosus (SLE), have shown lasting remission thus far. CAR T cells targeting autoreactive T cells are beginning clinical trials for treating T cell mediated autoimmune diseases. Chimeric autoantigen receptor (CAAR) T cells specifically target and eliminate only autoreactive B cells, and they have shown promise in treating mucosal pemphigus vulgaris and MuSK myasthenia gravis. Regulatory CAR T cells have also been developed, which show potential in altering autoimmune affected areas by creating a protective barrier as well as helping decrease inflammation. These new treatments are only the beginning of potential CAR T cell applications in treating autoimmune disease. Novel CAR technologies have been developed that increase the safety, potency, specificity, and efficacy of CAR T cell therapy. Applying these novel modifications to autoimmune CARs has the potential to enhance the efficacy and applicability of CAR therapies to autoimmune disease. This review will detail several recently developed CAR technologies and discuss how their application to autoimmune disease will improve this emerging field. These include logicgated CARs, soluble protein-secreting CARs, and modular CARs that enable CAR T cell therapies to be more specific, reach a wider span of target cells, be safer for patients, and give a more potent cytotoxic response. Applying these novel CAR technologies to the treatment of autoimmune diseases has the potential to revolutionize this growing application of CAR T cell therapies. [ABSTRACT FROM AUTHOR]

This study assessed the multifaceted relations between measures of workload, psychological state, and recovery throughout an entire soccer season in female collegiate soccer athletes (19.8±1.2 yrs, 132±12.3 lbs, 63±3.2 in). A prospective longitudinal study was utilized to measure workload (GPS training load, Rate of Perceived Exertion (RPE), psychological state (mental stress, mental fatigue, and mood), and recovery (sleep duration, sleep quality, and soreness), during 90 observations (59 training sessions and 21 games). Separate linear-mixed effect models were used to assess outcomes of RPE, soreness, and sleep duration. A linear mixed-effects model explained 59% of the variance in RPE following each session. Specifically, each standard deviation increase in GPS load and mental stress in the morning prior to training increased RPE by 1.46 (SE=0.08) and 0.29 (SE=0.07), respectively, following that day's training. Furthermore, a significant interaction was found between several predictor variables and chronological day in the season while predicting RPE. Specifically, for each standard deviation increase in GPS load, RPE went up by 0.0055 per day during the season suggesting that load had a higher impact on RPE as the season progressed. In contrast, the interaction of day by mental stress, sleep duration, and soreness continued to be stronger as the season progressed. Each linear mixed-effect model predicted a larger amount of variance when accounting for individual variations in the random effects. [ABSTRACT FROM AUTHOR]

Participant recruitment is one of the most challenging aspects of a clinical trial, directly impacting both the study's duration and the quality of its results. Therefore, reporting successful recruitment strategies is crucial. This study aimed to document the recruitment tactics and experiences of a research team during a university-based randomized clinical trial, conducted as part of a clinical research immersion program. Recruitment took place from October 2021 to October 2022. Before the study commenced, study team members received formal training in clinical trial participant recruitment from the Principal Investigator. The recruitment strategies were integrated into initial study design, which was approved by the Institutional Review Board. A multimodal approach was employed, incorporating both direct and indirect recruitment methods. These strategies successfully met the enrollment target within the twelve-month period. Throughout the process, team members acquired valuable knowledge in recruitment design and implementation, along with transferable interpersonal and networking skills. In-person recruitment was the most efficient and cost-effective strategy, followed by personal referrals. The primary challenge was accommodating participants' availability. Other study teams should consider these recruitment strategies during their study designs. Additionally, the knowledge and skills gained by this study team underscore the value of experiential learning in research education. [ABSTRACT FROM AUTHOR]