Comprehensive safety assessment of serendipity berry sweet protein produced from Komagataella phaffii.

Serendipity berry plant (Dioscoreophyllum cumminsii (Stapf) Diels) is the source of a naturally sweet protein referred to as monellin. The safety of serendipity berry sweet protein (SBSP) containing single polypeptide monellin (MON) expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation was examined comprehensively through assessments of in vitro and in silico protein digestion, in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and 14-day and 90-day oral (dietary) toxicity studies in rats. There was no indication of allergenicity for SBSP in the in silico analyses. Results from both in vitro and in silico protein digestibility assessments indicated that SBSP is digested upon ingestion and would therefore be unlikely to pose a toxigenic or allergenic risk to consumers. SBSP was non-genotoxic in in vitro assays and showed no adverse effects in the 14-day or 90-day toxicity studies up to the highest dose tested. The 90-day toxicity study supports a NOAEL for SBSP of 1954 mg/kg bw/day, which corresponds to a NOAEL for MON of 408 mg/kg bw/day.

Depression and Anxiety in Long-Term Care Residents During the COVID-19 Pandemic: The Influence of Telehealth Availability, Cognitive Status, and Trauma History.

OBJECTIVES: The present study investigates the impact of disrupted mental health services during the COVID-19 pandemic on depression and anxiety symptoms in long-term care (LTC) residents. METHODS: The study examined clinical data from 5,645 residents who received at least two psychological services in a long-term care (LTC) or assisted living (AL) setting between March 2019 and March 2021. A series of multiple regressions were run to explore the effects of the COVID-19 shutdown on depression and anxiety symptoms while examining the effects of COVID-19-related facility closure and facility telehealth capabilities. Follow-up regression analyses explored the impact of cognitive impairment and positive trauma history on depression and anxiety symptoms. RESULTS: Post-COVID levels of anxiety and depression were higher for residents with higher levels of pre-COVID anxiety and depression. The interaction between facility closure and availability of telehealth services and trauma history predicted self-report anxiety symptoms. Clinician-observed anxiety symptoms were predicted by cognitive impairment. Residents with a history of trauma had an increase in self-reported anxiety symptoms. CONCLUSIONS: Telehealth appeared to mitigate anxiety during the pandemic for residents with higher pre-COVID anxiety. CLINICAL IMPLICATIONS: For those individuals with severe anxiety, results suggest the importance of ensuring that mental health services are available to mitigate symptoms via telehealth when infection control disrupts the usual delivery of treatment.

The role of unit cohesion and perceived resilience in substance use disorder.

Soldiers have high rates of substance use disorders (SUD), often in the aftermath of stressors experienced during military deployments. There are several factors that protect against SUD. For example, individual factors like perceived resilience and group factors such as unit cohesion may make someone less likely to abuse substances. However, there is little research on the differential influence of these resilience factors on SUD over and above deployment stressors. In this study, we examined the relative effects of perceived resilience, unit cohesion, and deployment stressors on SUD in a sample of 21,449 active duty and reserve soldiers from the U.S. Army (primarily White and male, mean age = 28.66, SD = 7.41) using structural equation modeling. We found that unit cohesion (ß = -.17) and perceived resilience (ß = -.16) had negative effects on SUD over and above deployment stressors. The study findings clarify research on resilience to SUD and have implications for addressing substance use in the military, specifically regarding the importance of building unit cohesion.

Associations of humor, morale, and unit cohesion on posttraumatic stress disorder symptoms.

Military personnel experience many stressors during deployments that can lead to symptoms of posttraumatic stress disorder (PTSD). However, not all military personnel who are exposed to deployment stressors develop PTSD symptoms. Recent research has explored factors that contribute to military personnel resilience, a multifaceted and multidetermined construct, as a means to mitigate and prevent PTSD symptoms. Much of this research has focused on the effects of individual-level factors (e.g., use of coping strategies like humor, the morale of individual unit members), with some research focusing on unit-level factors (e.g., the cohesiveness of a unit). However, there is little research exploring how these factors relate to each other in mitigating or reducing PTSD symptoms. In this study, we examined the association between deployment stressors, perceived unit cohesion, morale, humor, and PTSD symptoms in a sample of 20,901 active-duty military personnel using structural equation modeling. Results indicated that perceived unit cohesion, humor, and morale were positively associated with each other and negatively associated with PTSD symptoms over and above the effect of deployment stressors. These findings highlight the influence of resilience factors on PTSD symptoms beyond their substantial overlap and have implications for future research as well as the potential development of interventions for military personnel.

Treatment of hidradenitis suppurativa with 755-nm alexandrite laser hair removal: A randomized controlled trial.

Background: Hidradenitis supprativa is a chronic inflammatory skin disease that can respond to treatment with laser hair removal. Objective: To assess alexandrite laser hair removal laser as a treatment for hidradenitis suppurativa as measured by the Hidradenitis Supprativa Clinical Response. Materials and methods: We conducted a prospective, randomized, controlled study in adult patients with hidradenitis supprativa. Participants underwent a series of 4 monthly laser treatments to 1 side of the body, with the contralateral side serving as a control. The primary outcome was Hidradenitis Supprativa Clinical Response at week 24, 8 weeks after the final laser treatment. Results: The percent improvement across treated sites after 4 treatments was 72.73% axillary, 70% inguinal, and 100% inframammary. Across all body regions, Hidradenitis Supprativa Clinical Response was significantly higher for the sites treated with the alexandrite laser compared to the contralateral controls: 75% vs 33.33% (P = .0046, 95% CI: [0.16, 1]). Limitations: The limitations of this study include a small sample size from which the data was collected. Conclusions: The 775-nm alexandrite laser is a safe and effective treatment for hidradenitis supprativa at various anatomic sites in both resolving preexisting lesions and preventing new eruptions.

Association Between Depression Symptoms and Disability Outcomes in Older Adults at Risk of Mobility Decline.

Objective: To assess the association between depression symptoms and physical functioning and participation in daily life over 2 years in older adults at risk of mobility decline. Design: A secondary analysis of 2-year observational data from the Boston Rehabilitative Impairment Study of the Elderly. Setting: Nine primary care clinics within a single health care system. Participants: Participants (N=432; mean age ± SD, 76.6±7.0y; range, 65-96y; 67.7% women) were community-dwelling adults (>65y) at risk of mobility decline. Interventions: Not applicable. Main Outcome Measures: Secondary data analyses of the Late Life Function and Disability Instrument (primary outcome), Short Physical Performance Battery (secondary outcome), and Patient Health Questionnaire-9 (PHQ-9) (predictor). Measures were administered at baseline, 12 months, and 24 months. Participants completed a self-report survey asking about 16 medical comorbidities, and demographic information was collected at baseline. Results: Participants had an average ± SD PHQ-9 score of 1.3±3.1, ranging from 0 to 24 at baseline. Twenty-nine percent of participants reported a history of depression. Greater depression symptoms were associated with lower physical functioning (unstandardized beta [B]=-0.14, SE=0.05, P=.011) and restricted participation (frequency subscale: B=-0.21, SE=0.11, P=.001; limitation subscale: B=-0.45, SE=0.04, P<.001) cross-sectionally over 2 years. PHQ-9 was not significantly associated with the rate of change in Late Life Function and Disability Instrument score over 2 years. Conclusions: Treating depression in primary care may be an important strategy for reducing the burden of functional limitations and participation restrictions at any 1 time. Further research is needed on treatment models to cotarget depression and physical functioning among at-risk older adults.

Pangenome reconstruction in rats enhances genotype-phenotype mapping and novel variant discovery.

The HXB/BXH family of recombinant inbred rat strains is a unique genetic resource that has been extensively phenotyped over 25 years, resulting in a vast dataset of quantitative molecular and physiological phenotypes. We built a pangenome graph from 10x Genomics Linked-Read data for 31 recombinant inbred rats to study genetic variation and association mapping. The pangenome includes 0.2Gb of sequence that is not present the reference mRatBN7.2, confirming the capture of substantial additional variation. We validated variants in challenging regions, including complex structural variants resolving into multiple haplotypes. Phenome-wide association analysis of validated SNPs uncovered variants associated with glucose/insulin levels and hippocampal gene expression. We propose an interaction between Pirl1l1, chromogranin expression, TNF-α levels, and insulin regulation. This study demonstrates the utility of linked-read pangenomes for comprehensive variant detection and mapping phenotypic diversity in a widely used rat genetic reference panel.

Feasibility and Preliminary Efficacy of Virtual Rehabilitation for Middle and Older Aged Veterans With Mobility Limitations: A Pilot Study.

Objective: To evaluate the feasibility and preliminary efficacy of the transition of an outpatient center-based rehabilitation program for middle and older aged Veterans with mobility limitations to a tele-health platform. Design: Non-randomized non-controlled pilot study including 10 treatment sessions over 8 weeks and assessments at baseline, 8, 16, and 24 weeks. Setting: VA Boston Healthcare System ambulatory care between August 2020 and March 2021. Participants: Veterans aged 50 years and older (n=178) were contacted via letter to participate, and 21 enrolled in the study. Intervention: Participants had virtual intervention sessions with a physical therapist who addressed impairments linked to mobility decline and a coaching program promoting exercise adherence. Main Outcome Measures: Ambulatory Measure for Post-Acute Care (AM-PAC), Phone-FITT, and Self-Efficacy for Exercise (SEE) scale. Results: Completers (n=14, mean age 74.9 years, 86% men) averaged 9.8 out of 10 visits. Changes in the Ambulatory Measure for Post-Acute Care (AM-PAC) exceeded clinically meaningful change after 8 and 24 weeks of treatment, at 4.1 units and 4.3 units respectively. Statistically significant improvements from baseline in AM-PAC and Phone-FITT were observed after 8 weeks of treatment and at 24 weeks. No significant changes were observed in exercise self-efficacy. Conclusions: In this group of veterans, telerehab was feasible and demonstrated preliminary efficacy in both mobility and physical activity, thus justifying further investigation in a larger scale clinical trial.

The Effectiveness of Dance Interventions on Psychological and Cognitive Health Outcomes Compared with Other Forms of Physical Activity: A Systematic Review with Meta-analysis.

BACKGROUND: Physical activity is known to improve psychological and cognitive outcomes. Learning dance sequences may challenge cognition, partnered or group dance may benefit social interactions, and the artistic aspect may improve psychological wellbeing. Dance is an equally effective form of physical activity compared with other structured physical activities to improve physical health, but it is unclear how effective dance could be for psychological and cognitive outcome measures. OBJECTIVE: To systematically review the literature on the effectiveness of structured dance interventions, compared with structured exercise programmes, on psychological and cognitive outcomes across the lifespan. METHODS: Eight databases were searched from earliest records to July 2022. Studies investigating a dance intervention lasting ≥ 4 weeks, including psychological and/or cognitive health outcomes, and having a structured exercise comparison group were included. Screening and data extraction were performed by two independent reviewers at all stages. All reviewer disagreements were resolved by the primary author. Where appropriate, meta-analysis was performed, or an effect size estimate generated. RESULTS: Of 21,737 records identified, 27 studies met the inclusion criteria. Total sample size of included studies was 1392 (944 females, 418 males, 30 unreported). Dance was equally as effective as other physical activity interventions in improving quality of life for people with Parkinson's disease [mean difference 3.09; 95% confidence interval (CI) - 2.13 to 8.30; p = 0.25], reducing anxiety (standardised mean difference 2.26; 95% CI - 2.37 to 6.90; p = 0.34), and improving depressive symptoms (standardised mean difference 0.78; 95% CI - 0.92 to 2.48; p = 0.37). Preliminary evidence found dance to be superior to other physical activity interventions to improve motivation, aspects of memory, and social cognition and to reduce distress. Preliminary evidence found dance to be inferior to other physical activity interventions to improve stress, self-efficacy and language fluency. CONCLUSION: Undertaking structured dance of any genre is generally equally and occasionally more effective than other types of structured exercise for improving a range of psychological and cognitive outcomes. TRIAL REGISTRATION: PROSPERO: CRD42018099637.

Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas.

Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM.