Isolation and loneliness as pathways to heavy drinking early in the pandemic.

INTRODUCTION: social isolation and forced quarantines during the early phases of the COVID-19 pandemic coincided with a steep and persistent rise in alcohol consumption among US adults. While the association between loneliness and drinking is well established, less is known about the impact of social isolation (a known correlate of loneliness) and the interplay between these two variables in relation to drinking. METHODS: we recruited US adults using the MTurk platform for an online survey in early April 2020. The initial survey was followed up with a second wave, 30 days later in mid to late May. Data from the current analyses focus on this second wave of data collection. RESULTS: we found significant direct effects on heavy drinking for both social isolation (c' = 0.495; P < .01) and loneliness (b = 0.071; P < .05). We also found a significant indirect path from social isolation to heavy drinking through social isolation's impact on elevating loneliness (a = 0.919; P < .001). The indirect effect of social isolation on the composite measure of heavy drinking was 0.0652 (0.919 × 0.071) and was significant at the 0.05 level after bootstrapping estimates of the variance were constructed. CONCLUSIONS: those most isolated early in the pandemic were at increased risk for heavy drinking, in part because their social isolation led to increased loneliness. Post-pandemic research is needed to explore whether the relationships that stemmed from social isolation during the pandemic led to a persistent pattern of behavioral risk that maintained high rates of heavy drinking.

Expanding the scope of methylation-sensitive restriction enzyme (MSRE) PCR for forensic identification of body fluids through the novel use of methylation-dependent restriction enzymes (MDRE) and the combination of autosomal and Y-chromosomal markers.

Methylation-sensitive/-dependent restriction enzyme (MSRE/MDRE) PCR can be performed to detect hypomethylated or hypermethylated CpG sites. With the combined use of different tissue-specific CpG markers, MSRE/MDRE-PCR leads to tissue-specific methylation patterns (TSMPs), enabling the correlation of DNA samples to their source tissue. MSRE/MDRE assays can use the same platform as forensic STR typing and offer many advantages in the field of forensic body fluid detection. In the present study, we aimed to establish MSRE assays for the detection of blood, saliva, vaginal secretion, and semen, using markers from literature and from our own database search. We designed two different MSRE test-sets, which include two novel Y-chromosomal non-semen markers, and enable differentiation between female and male non-semen samples. Furthermore, we established an MSRE/MDRE semen approach, which includes only Y-chromosomal non-semen and semen markers. This Y-semen multiplex PCR utilizes the novel combination of the methylation-sensitive enzyme SmaI and the methylation-dependent enzyme GlaI, which enables more sensitive detection of male body fluids within male/female DNA mixtures. Our validation tests confirmed that MSRE/MDRE assays exhibit high sensitivity, similar to that of STR typing.

High Doses of Exogenous Glucagon Stimulate Insulin Secretion and Reduce Insulin Clearance in Healthy Humans.

Glucagon is generally defined as a counterregulatory hormone with a primary role to raise blood glucose concentrations by increasing endogenous glucose production (EGP) in response to hypoglycemia. However, glucagon has long been known to stimulate insulin release, and recent preclinical findings have supported a paracrine action of glucagon directly on islet ß-cells that augments their secretion. In mice, the insulinotropic effect of glucagon is glucose dependent and not present during basal euglycemia. To test the hypothesis that the relative effects of glucagon on hepatic and islet function also vary with blood glucose, a group of healthy subjects received glucagon (100 ng/kg) during fasting glycemia or experimental hyperglycemia (∼150 mg/dL) on 2 separate days. During fasting euglycemia, administration of glucagon caused blood glucose to rise due to increased EGP, with a delayed increase of insulin secretion. When given during experimental hyperglycemia, glucagon caused a rapid, threefold increase in insulin secretion, as well as a more gradual increase in EGP. Under both conditions, insulin clearance was decreased in response to glucagon infusion. The insulinotropic action of glucagon, which is proportional to the degree of blood glucose elevation, suggests distinct physiologic roles in the fasting and prandial states.

COVID-19-Related Outcomes Among Group Home Residents with Serious Mental Illness in Massachusetts in the First Year of the Pandemic.

This study examined COVID-19 infection and hospitalizations among people with serious mental illness who resided in residential care group homes in Massachusetts during the first year of the COVID-19 pandemic. The authors analyzed data on 2261 group home residents and COVID-19 data from the Massachusetts Department of Public Health. Outcomes included positive COVID-19 tests and COVID-19 hospitalizations March 1, 2020-June 30, 2020 (wave 1) and July 1, 2020-March 31, 2021 (wave 2). Associations between hazard of outcomes and resident and group home characteristics were estimated using multi-level Cox frailty models including home- and city-level frailties. Between March 2020 and March 2021, 182 (8%) residents tested positive for COVID-19, and 51 (2%) had a COVID-19 hospitalization. Compared with the Massachusetts population, group home residents had age-adjusted rate ratios of 3.0 (4.86 vs. 1.60 per 100) for COVID infection and 13.5 (1.99 vs. 0.15 per 100) for COVID hospitalizations during wave 1; during wave 2, the rate ratios were 0.5 (4.55 vs. 8.48 per 100) and 1.7 (0.69 vs. 0.40 per 100). In Cox models, residents in homes with more beds, higher staff-to-resident ratios, recent infections among staff and other residents, and in cities with high community transmission risk had greater hazard of COVID-19 infection. Policies and interventions that target group home-specific risks are needed to mitigate adverse communicable disease outcomes in this population.Clinical Trial Registration Number This study provides baseline (i.e., pre-randomization) data from a clinical trial study NCT04726371.

De novo design of high-affinity binders of bioactive helical peptides.

Many peptide hormones form an α-helix on binding their receptors1-4, and sensitive methods for their detection could contribute to better clinical management of disease5. De novo protein design can now generate binders with high affinity and specificity to structured proteins6,7. However, the design of interactions between proteins and short peptides with helical propensity is an unmet challenge. Here we describe parametric generation and deep learning-based methods for designing proteins to address this challenge. We show that by extending RFdiffusion8 to enable binder design to flexible targets, and to refining input structure models by successive noising and denoising (partial diffusion), picomolar-affinity binders can be generated to helical peptide targets by either refining designs generated with other methods, or completely de novo starting from random noise distributions without any subsequent experimental optimization. The RFdiffusion designs enable the enrichment and subsequent detection of parathyroid hormone and glucagon by mass spectrometry, and the construction of bioluminescence-based protein biosensors. The ability to design binders to conformationally variable targets, and to optimize by partial diffusion both natural and designed proteins, should be broadly useful.

Group Home Staff Experiences With Work and Health in the COVID-19 Pandemic in Massachusetts.

Importance: Direct reports of the experiences of staff working in group homes for people with serious mental illness (SMI) and/or intellectual or developmental disabilities (ID/DD) are rarely reported. Hearing from workers about their experiences in the COVID-19 pandemic may inform future workforce and public policy. Objective: To gather baseline data on worker experience with the perceived effects of COVID-19 on health and work in the pandemic prior to initiating an intervention to mitigate the spread of COVID-19 and to measure differences in worker experience by gender, race, ethnicity, education, and resident population served (persons with SMI and/or IDD/DD). Design, Setting, and Participants: This mixed-mode, cross-sectional survey study was conducted using online then paper-based self-administration from May to September 2021 at the end of the first year of the pandemic. Staff working in 415 group homes that provided care within 6 Massachusetts organizations serving adults aged 18 years or older with SMI and/or ID/DD were surveyed. The eligible survey population included a census of staff who were currently employed in participating group homes during the study period. A total of 1468 staff completed or partially completed surveys. The overall survey response rate was 44% (range by organization, 20% to 52%). Main Outcomes and Measures: Self-reported experiential outcomes were measured in work, health, and vaccine completion. Bivariate and multivariate analyses explore experiences by gender, race, ethnicity, education, trust in experts and employers, and population served. Results: The study population included 1468 group home staff (864 [58.9%] women; 818 [55.7%] non-Hispanic Black; 98 [6.7%] Hispanic or Latino). A total of 331 (22.5%) group home staff members reported very serious perceived effects on health; 438 (29.8%) reported very serious perceived effects on mental health; 471 (32.1%) reported very serious perceived effects on health of family and friends; and 414 reported very serious perceived effects (28.2%) on access to health services, with statistically significant differences observed by race and ethnicity. Vaccine acceptance was higher among persons with higher educational attainment and trust in scientific expertise and lower among persons who self-reported as Black or Hispanic/Latino. A total of 392 (26.7%) respondents reported needing support for health needs, and 290 (19.8%) respondents reported needing support for loneliness or isolation. Conclusions and Relevance: In this survey study, approximately one-third of group home workers reported serious personal health and access to health care barriers during the first year of the COVID-19 pandemic in Massachusetts. Addressing unmet health needs and access to health and mental health services, including inequities and disparities by race, ethnicity, and education, should benefit staff health and safety, as well as that of the individuals with disabilities who rely on them for support and care.

A distributable LC-MS/MS method for the measurement of serum thyroglobulin.

Background: Despite its clear advantages over immunoassay-based testing, the measurement of serum thyroglobulin by mass spectrometry remains limited to a handful of institutions. Slow adoption by clinical laboratories could reflect limited accessibility to existing methods that have sensitivity comparable to modern immunoassays, as well as a lack of tools for calibration and assay harmonization. Methods: We developed and validated a liquid chromatography-tandem mass spectrometry-based assay for the quantification of serum thyroglobulin. The protocol combined peptide immunoaffinity purification using a commercially available, well-characterized monoclonal antibody and mobile phase modification with dimethylsulfoxide (DMSO) for enhanced sensitivity. To facilitate harmonization with other laboratories, we developed a novel, serum-based 5-point distributable reference material (Husky Ref). Results: The assay demonstrated a lower limit of quantification of 0.15 ng/mL (<20 %CV). Mobile phase DMSO increased signal intensity of the target peptide at least 3-fold, improving quantification at low concentrations. Calibration traceable to Husky Ref enabled harmonization between laboratories in an interlaboratory study. Conclusions: Sensitive mass spectrometry-based thyroglobulin measurement can be achieved using a monoclonal antibody during peptide immunoaffinity purification and the addition of mobile phase DMSO. Laboratories interested in deploying this assay can utilize the provided standard operating procedure and freely-available Husky Ref reference material.

A Targeted Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification of Peptides from the Carboxyl-terminal Region of Type III Procollagen, Biomarkers of Collagen Turnover.

BACKGROUND: The development of analytical approaches to help reduce the risk of growth hormone (GH) doping is important to fair competition and the health of athletes. However, the reliable detection of GH use remains challenging. The identification of novel biomarkers of GH administration could lead to a better understanding of the physiological response to GH, more sensitive detection of the illicit use of GH in sport, and better management of patients treated for GH disorders. METHODS: We developed a targeted liquid chromatography-tandem mass spectrometry method to simultaneously quantify the carboxyl-terminal propeptide of type III procollagen (P-III-CP) and type III collagen degradation products in human serum. Following proteolysis, we instituted a simple acid precipitation step to reduce digested sample complexity before peptide immunoenrichment, which improved the recovery of one target peptide from serum. We evaluated the concentration of each biomarker at different age ranges and after GH administration in healthy participants. RESULTS: The assay was linear over an estimated concentration range of 0.3 to1.0 nM and 0.1 to 0.4 nM for each surrogate peptide of P-III-CP and collagen fragments, respectively. Intra-day and inter-day coefficients of variation were ≤15%. Biomarker concentrations appeared to vary with age and to reflect age-specific collagen turnover. Moreover, their concentrations changed after GH administration. CONCLUSIONS: Our method quantifies the proteins belonging to the family of P-III-CP and type III collagen degradation products in human serum, which could be used to detect GH administration in athletes and better understand diseases involving GH therapy or altered type III collagen turnover.

Epigenetic Mechanisms of ART-Related Imprinting Disorders: Lessons From iPSC and Mouse Models.

The rising frequency of ART-conceived births is accompanied by the need for an improved understanding of the implications of ART on gametes and embryos. Increasing evidence from mouse models and human epidemiological data suggests that ART procedures may play a role in the pathophysiology of certain imprinting disorders (IDs), including Beckwith-Wiedemann syndrome, Silver-Russell syndrome, Prader-Willi syndrome, and Angelman syndrome. The underlying molecular basis of this association, however, requires further elucidation. In this review, we discuss the epigenetic and imprinting alterations of in vivo mouse models and human iPSC models of ART. Mouse models have demonstrated aberrant regulation of imprinted genes involved with ART-related IDs. In the past decade, iPSC technology has provided a platform for patient-specific cellular models of culture-associated perturbed imprinting. However, despite ongoing efforts, a deeper understanding of the susceptibility of iPSCs to epigenetic perturbation is required if they are to be reliably used for modelling ART-associated IDs. Comparing the patterns of susceptibility of imprinted genes in mouse models and IPSCs in culture improves the current understanding of the underlying mechanisms of ART-linked IDs with implications for our understanding of the influence of environmental factors such as culture and hormone treatments on epigenetically important regions of the genome such as imprints.

Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy.

The antitumor efficacy of cancer immunotherapy can correlate with the presence of certain bacterial species within the gut microbiome. However, many of the molecular mechanisms that influence host response to immunotherapy remain elusive. In this study, we show that members of the bacterial genus Enterococcus improve checkpoint inhibitor immunotherapy in mouse tumor models. Active enterococci express and secrete orthologs of the NlpC/p60 peptidoglycan hydrolase SagA that generate immune-active muropeptides. Expression of SagA in nonprotective E. faecalis was sufficient to promote immunotherapy response, and its activity required the peptidoglycan sensor NOD2. Notably, SagA-engineered probiotics or synthetic muropeptides also augmented anti-PD-L1 antitumor efficacy. Taken together, our data suggest that microbiota species with specialized peptidoglycan remodeling activity and muropeptide-based therapeutics may enhance cancer immunotherapy and could be leveraged as next-generation adjuvants.

The Vitamin D Metabolite Ratio Is Associated With Changes in Bone Density and Fracture Risk in Older Adults.

Recent studies have suggested that 25-hydroxyvitamin D (25(OH)D) may be a poor biomarker of bone health, in part because measured levels incorporate both protein-bound and free vitamin D. The ratio of its catabolic product (24,25-dihydroxyvitamin D [24,25(OH)2 D]) to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide more information on sufficient vitamin D stores and is not influenced by vitamin D-binding protein concentrations. We evaluated whether the VMR or 25(OH)D are more strongly associated with bone loss and fracture risk in older adults. We performed a retrospective cohort study of 786 community-dwelling adults aged 70 to 79 years who participated in the Health Aging and Body Composition study. Our primary outcomes were annual changes in bone density and incident fracture. The mean age of these participants was 75 ± 3 years, 49% were female, 42% were Black, and 23% had an estimated glomerular filtration rate (eGFR) <60 mL/mL/1.73m2 . In fully adjusted models, a 50% lower VMR was associated with 0.3% (0.2%, 0.6%) more rapid decline in total hip bone mineral density (BMD). We found similar relationships with thoracic and lumbar spine BMD. In contrast, 25(OH)D3 concentrations were not associated with longitudinal change in BMD. There were 178 fractures during a mean follow-up of 10 years. Each 50% lower VMR was associated with a 49% (95% confidence interval [CI] 1.06, 2.08) greater fracture risk, whereas lower 25(OH)D3 concentrations were not significantly associated with fracture risk (hazard ratio [HR] per 50% lower 1.07 [0.80, 1.43]). In conclusion, among a diverse cohort of community-dwelling older adults, a lower VMR was more strongly associated with both loss of BMD and fracture risk compared with 25(OH)D3 . Trials are needed to evaluate the VMR as a therapeutic target in persons at risk for worsening BMD and fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.

SPTBN1 encodes ßII-spectrin, the ubiquitously expressed ß-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal ßII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect ßII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of ßII-spectrin in the central nervous system.

Variably methylated retrotransposons are refractory to a range of environmental perturbations.

The agouti viable yellow (Avy) allele is an insertional mutation in the mouse genome caused by a variably methylated intracisternal A particle (VM-IAP) retrotransposon. Avy expressivity is sensitive to a range of early-life chemical exposures and nutritional interventions, suggesting that environmental perturbations can have long-lasting effects on the methylome. However, the extent to which VM-IAP elements are environmentally labile with phenotypic implications is unknown. Using a recently identified repertoire of VM-IAPs, we assessed the epigenetic effects of different environmental contexts. A longitudinal aging analysis indicated that VM-IAPs are stable across the murine lifespan, with only small increases in DNA methylation detected for a subset of loci. No significant effects were observed after maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation. A genetic mouse model of abnormal folate metabolism exhibited shifted VM-IAP methylation levels and altered VM-IAP-associated gene expression, yet these effects are likely largely driven by differential targeting by polymorphic KRAB zinc finger proteins. We conclude that epigenetic variability at retrotransposons is not predictive of environmental susceptibility.

Psychological resilience early in the COVID-19 pandemic: Stressors, resources, and coping strategies in a national sample of Americans.

Spreading rapidly across the United States beginning in the spring of 2020, the coronavirus disease 2019 (COVID-19) pandemic radically disrupted Americans' lives. Previous studies of community-wide disasters suggested people are fairly resilient and identified resources and strategies that promote that resilience. Yet, the COVID-19 pandemic is in some ways unique, with high levels of uncertainty, evolving implications and restrictions, and varied and uneven impacts. How resilient were Americans as the pandemic progressed? What psychosocial resources and coping strategies facilitated adjustment as the country moved into a summer of uneven reopenings and reclosures? Data from a national sample of 674 Americans were gathered at the height of early lockdowns and peaking infections in mid-April, 2020, and again, 5 and 10 weeks later. The study aimed to determine levels and sources of distress and to identify the resources and coping efforts that promoted or impeded resilience. Early levels of distress diminished to some extent over subsequent months while levels of wellbeing were comparable with usual norms, suggesting a largely resilient response. COVID-19-related stress exposure also decreased gradually over time. Older age, higher levels of mindfulness and social support, and meaning focused coping predicted better adjustment, reflecting resilience, while avoidance coping was particularly unhelpful. In models predicting change over time, approach-oriented coping (i.e., active coping, meaning-focused coping, and seeking social support) was minimally predictive of subsequent adjustment. Given the unique and ongoing circumstances presented by COVID-19, specific interventions targeting psychosocial resources and coping identified here may help to promote resilience as the pandemic continues to unfold. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Combining 68Ga-PSMA-PET/CT-Directed and Elective Radiation Therapy Improves Outcome in Oligorecurrent Prostate Cancer: A Retrospective Multicenter Study.

BACKGROUND: In case of oligo-recurrent prostate cancer (PC) following prostatectomy, 68Ga-PSMA-PET/CT can be used to detect a specific site of recurrence and to initiate metastasis-directed radiation therapy (MDT). However, large heterogeneities exist concerning doses, treatment fields and radiation techniques, with some studies reporting focal radiotherapy (RT) to PSMA-PET/CT positive lesions only and other studies using elective RT strategies. We aimed to compare oncological outcomes and toxicity between PET/CT-directed RT (PDRT) and PDRT plus elective RT (eRT; i.e. prostate bed, pelvic or paraaortal nodes) in a large retrospective multicenter study. METHODS: Data of 394 patients with oligo-recurrent 68Ga-PSMA-PET/CT-positive PC treated between 04/2013 and 01/2018 in six different academic institutions were evaluated. Primary endpoint was biochemical-recurrence-free survival (bRFS). bRFS was analyzed using Kaplan-Meier survival curves and log rank testing. Uni- and multivariate analyses were performed to determine influence of treatment parameters. RESULTS: In 204 patients (51.8%) RT was directed only to lesions seen on 68Ga-PSMA-PET/CT (PDRT), 190 patients (48.2%) received PDRT plus eRT. PDRT plus eRT was associated with a significantly improved 3-year bRFS compared to PDRT alone (53 vs. 37%; p = 0.001) and remained an independent factor in multivariate analysis (p = 0.006, HR 0.29, 95% CI 0.12-0.68). This effect was more pronounced in the subgroup of patients who were treated with PDRT and elective prostate bed radiotherapy (ePBRT) with a 3-year bRFS of 61% versus 22% (p <0.001). Acute and late toxicity grade ≥3 was 0.8% and 3% after PDRT plus eRT versus no toxicity grade ≥3 after PDRT alone. CONCLUSIONS: In this large cohort of patients with oligo-recurrent prostate cancer, elective irradiation of the pelvic lymphatics and the prostatic bed significantly improved bRFS when added to 68Ga-PSMA-PET/CT-guided focal radiotherapy. These findings need to be evaluated in a randomized controlled trial.

Associations of alcohol, marijuana, and polysubstance use with non-adherence to COVID-19 public health guidelines in a US sample.

Background: We sought to understand the association between heavy alcohol and frequent drug use and non-adherence to recommended social distancing and personal hygiene guidelines for preventing the spread of COVID-19 early in the US pandemic. Methods: A survey was offered on the crowdsourcing platform, Amazon Mechanical Turk (MTurk) during April 2020 (the early days of strict, social distancing restrictions). The study included 1,521 adults ages 18 years and older who resided in the US and were enrolled as MTurk workers, i.e., workers who are qualified by Amazon to complete a range of human interaction tasks, including surveys through the MTurk worker platform. Main predictors included measures of heavy drinking, marijuana, and polysubstance use. The dependent measures were measures of social distancing and personal hygiene, based on guidelines recommended at the time of the survey by the US Centers for Disease Control to prevent the spread of COVID-19. Results: We found consistent negative associations between heavy drinking and drug use and adherence to social distancing and personal hygiene. Additionally, three control variables, age, gender, and race/ethnicity, were significant correlates of adherence to these measures. Conclusions: The findings here are consistent with previous research exploring links between substance use and other adverse health behaviors. Further, the negative association between heavy drinking (five or more drinks in one sitting) and adherence underscore the public health risks entailed with the unrestricted reopening of public drinking establishments.

Treatment Retention in Opioid Dependent Clients Receiving Medication-Assisted Treatment: Six-Month Rate and Baseline Correlates.

BACKGROUND: In the current opioid overdose epidemic, treatment retention among clients receiving medication-assisted treatment (MAT) for opioid dependence is a significant and growing concern among treatment providers, policymakers, and researchers. Methods: We examined a sample of clients enrolled in a federally funded MAT expansion program implemented in four sites in Connecticut. Program participants received MAT for their opioid use disorders (OUDs). All program sites utilized a person in recovery from OUD (a recovery support coach, RSC) as part of the treatment team. By performing bivariate analyses and multivariate logistic regression models, we evaluated the association of 6-month retention and program site, gender, age, race/ethnicity, and past month substance use. Results: At 6-month follow-up, 58.9% of participants were classified as "retained." Multivariate logistic regression analysis revealed that participants who were older, reported no past month cocaine/crack use, or reported any illegal drug use other than cocaine/crack, were significantly more likely to be retained in treatment at follow-up. Conclusions: Retention rates were relatively high in these Connecticut sites compared to those examined in previous literature. Findings suggest that efforts for enhancing retention and successful treatment outcomes need to consider and potentially address the unique needs, problems, and risks of younger clients and clients with crack/cocaine involvement. The importance of drug use screening for those entering MAT is underscored. Future research needs to explore how levels of client involvement in adjunctive therapies may impact their retention.

Americans' distress early in the COVID-19 pandemic: Protective resources and coping strategies.

OBJECTIVE: The rapid emergence of the coronavirus disease 2019 (COVID-19) pandemic in the United States has dramatically altered daily life and taken a toll on Americans' physical, mental, social, and financial well-being. Based on previous widespread disasters, future high prevalence of short- and long-term adverse mental health consequences are anticipated. Studies of COVID-19 outside the United States indicated moderately high levels of distress, but we have little information regarding Americans' distress nor the factors associated with relative distress or adjustment during this unprecedented time. This study represents the first national view of Americans' distress during the massive disruption of COVID-19 and identifies levels of stress exposure, protective psychosocial resources, and coping strategies. METHOD: Data were collected April 7-9, 2020 from an online platform, using best practices for ensuring high-quality data; 1,015 completed respondents are included ([53.9%] women; average age = 38.9 years; mostly White [82.4%] and non-Hispanic [91.5%]). Respondents' locations ranged across the United States, from 18.5% in the Northeast to 37.8% in the South. RESULTS: Fairly high levels of stress exposure and peritraumatic and general distress (depression, anxiety, and stress) were reported. Emotion regulation skills along with active and distraction coping emerged as the strongest predictors of lower distress levels. CONCLUSIONS: These results identify potential targets for online mental health interventions-focusing on engaging in adaptive emotion regulation and coping (e.g., through telehealth mental health first aid)-during the pandemic to offset the likely rise in distress over the months ahead. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Oligorecurrent Prostate Cancer Treated with Metastases-directed Radiotherapy: Role of Addition and Duration of Androgen Deprivation.

BACKGROUND: Approximately 40-70% of biochemically recurrent prostate cancer (PCa) is oligorecurrent after prostate-specific membrane antigen (PSMA) positron emission tomography (PET) staging. Metastasis-directed radiotherapy (MDT) of PSMA-positive oligorecurrence is now frequently used, but the role of concurrent androgen deprivation therapy (ADT) remains unclear. OBJECTIVE: To determine the effect of concurrent ADT with PSMA PET-directed MDT on biochemical progression-free survival (bRFS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multicenter study of 305 patients with biochemical recurrence and PSMA PET-positive oligorecurrence following initial curative treatment between April 2013 and January 2018. INTERVENTION: MDT with fractionated or stereotactic body radiotherapy for all PSMA-positive metastatic sites; 37.8% received concurrent ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was bRFS, which was measured using Kaplan-Meier curves and log-rank testing. Secondary outcomes were ADT-free survival, overall survival (OS), and toxicity was analyzed using the Common Terminology Criteria for Adverse Events v4.03. Univariate and multivariate analyses were performed to determine independent clinicopathological factors. RESULTS AND LIMITATIONS: The median follow-up was 16 mo (interquartile range 9-27). Some 96% of the patients initially had high-risk PCa. A median of one (range 0-19) nodal metastases and one (range 0-5) distant metastases were treated. MDT+ADT significantly improved bRFS and remained an independent factor (hazard ratio 0.28, 95% confidence interval 0.16-0.51; p<0.0001). bRFS was not significantly different between MDT+≤6 mo of ADT and MDT alone (p=0.121). Patients receiving MDT had 1- and 2-yr ADT-free survival of 93% and 83%, respectively. New therapies, most frequently MDT (23%), were required more frequently after MDT (85% vs 29%; p<0.001). Grade ≥3 acute toxicity was observed in 0.9% of patients and late toxicity in 2.3%. CONCLUSIONS: In this cohort of patients with oligorecurrent PCa, concurrent ADT with MDT improved bRFS significantly, but a large number of patients treated with MDT were spared from ADT for 2yr, although a greater need for other salvage therapies was observed. PATIENT SUMMARY: The role of concurrent androgen deprivation therapy (ADT) with radiotherapy for prostate cancer oligorecurrence identified on prostate-specific membrane antigen positron emission tomography was studied. We concluded that radiotherapy alone could prolong the time to start of ADT. However, the risk of disease progression and consequently the need for further treatments is higher after local radiotherapy alone without immediate ADT.