More Than a Meal: Pilot Research Study

The national Meals on Wheels network continues to face limited funding, rising costs, unprecedented demand and need and increasing for-profit competition. That is why Meals on Wheels America set out to compare the experience and health outcomes realized by older adults who receive three different levels of service: daily traditional meal delivery, once-weekly frozen delivery and individuals on a waiting list. This study, funded by AARP Foundation and conducted by researchers at Brown University, implemented a groundbreaking approach to investigating the impact of meal service delivery on homebound seniors receiving Meals on Wheels. The study's findings validate what we've all known for decades anecdotally through firsthand experience: that Meals on Wheels does in fact deliver so much more than just a meal

Translation inhibition by rocaglates activates a species-specific cell death program in the emerging fungal pathogen Candida auris

Fungal infections are a major contributor to infectious disease-related deaths worldwide. Recently, global emergence of the fungal pathogen Candida auris has caused considerable concern because most C. auris isolates are resistant to fluconazole, the most commonly administered antifungal, and some isolates are resistant to drugs from all three major antifungal classes. To identify novel agents with bioactivity against C. auris, we screened 2,454 compounds from a diversity-oriented synthesis collection. Of the five hits identified, most shared a common rocaglate core structure and displayed fungicidal activity against C. auris These rocaglate hits inhibited translation in C. auris but not in its pathogenic relative Candida albicans Species specificity was contingent on variation at a single amino acid residue in Tif1, a fungal member of the eukaryotic initiation factor 4A (eIF4A) family of translation initiation factors known to be targeted by rocaglates. Rocaglate-mediated inhibition of translation in C. auris activated a cell death program characterized by loss of mitochondrial membrane potential, increased caspase-like activity, and disrupted vacuolar homeostasis. In a rocaglate-sensitized C. albicans mutant engineered to express translation initiation factor 1 (Tif1) with the variant amino acid that we had identified in C. auris, translation was inhibited but no programmed cell death phenotypes were observed. This surprising finding suggests divergence between these related fungal pathogens in their pathways of cellular responses to translation inhibition. From a therapeutic perspective, the chemical biology that we have uncovered reveals species-specific vulnerability in C. auris and identifies a promising target for development of new, mechanistically distinct antifungals in the battle against this emerging pathogen. IMPORTANCE Emergence of the fungal pathogen Candida auris has ignited intrigue and alarm within the medical community and the public at large. This pathogen is unusually resistant to antifungals, threatening to overwhelm current management options. By screening a library of structurally diverse molecules, we found that C. auris is surprisingly sensitive to translation inhibition by a class of compounds known as rocaglates (also known as flavaglines). Despite the high level of conservation across fungi in their protein synthesis machinery, these compounds inhibited translation initiation and activated a cell death program in C. auris but not in its relative Candida albicans Our findings highlight a surprising divergence across the cell death programs operating in Candida species and underscore the need to understand the specific biology of a pathogen in attempting to develop more-effective treatments against it.Published versio

Estimation of Excess Mortality Rates Among US Assisted Living Residents During the COVID-19 Pandemic.

The devastating effects of COVID-19 among older adults residing in long-term care settings have been well documented.1 Although much attention has been paid to COVID-19–associated mortality in nursing homes,2 less is understood about its effects on assisted living residents. Most assisted living residents are aged 80 years or older and many have multiple chronic illnesses, making them highly susceptible to poor outcomes of COVID-19.3 This study examines the excess mortality among a US cohort of assisted living residents during the COVID-19 pandemic

Optical analogues of the Newton–Schrödinger equation and boson star evolution

Many gravitational phenomena that lie at the core of our understanding of the Universe have not yet been directly observed. An example in this sense is the boson star that has been proposed as an alternative to some compact objects currently interpreted as being black holes. In the weak field limit, these stars are governed by the Newton–Schrodinger equation. Here we present an optical system that, under appropriate conditions, identically reproduces such equation in two dimensions. A rotating boson star is experimentally and numerically modelled by an optical beam propagating through a medium with a positive thermal nonlinearity and is shown to oscillate in time while also stable up to relatively high densities. For higher densities, instabilities lead to an apparent breakup of the star, yet coherence across the whole structure is maintained. These results show that optical analogues can be used to shed new light on inaccessible gravitational objects

Recommendations for Medical and Mental Health Care in Assisted Living Based on an Expert Delphi Consensus Panel A Consensus Statement

Importance Assisted living (AL) is the largest provider of residential long-term care in the US, and the morbidity of AL residents has been rising. However, AL is not a health care setting, and concern has been growing about residents’ medical and mental health needs. No guidance exists to inform this care. Objective To identify consensus recommendations for medical and mental health care in AL and determine whether they are pragmatic. Evidence Review A Delphi consensus statement study was conducted in 2021; as a separate effort, the extent to which the recommendations are reflected in practice was examined in data obtained from 2016 to 2021 (prepandemic). In the separate effort, data were from a 7-state study (Arkansas, Louisiana, New Jersey, New York, Oklahoma, Pennsylvania, Texas). The 19 Delphi panelists constituted nationally recognized experts in medical, nursing, and mental health needs of and care for older adults; dementia care; and AL and long-term care management, advocacy, regulation, and education. One invitee was unavailable and nominated an alternate. The primary outcome was identification of recommended practices based on consensus ratings of importance. Panelists rated 183 items regarding importance to care quality and feasibility. Findings Consensus identified 43 recommendations in the areas of staff and staff training, nursing and related services, resident assessment and care planning, policies and practices, and medical and mental health clinicians and care. To determine the pragmatism of the recommendations, their prevalence was examined in the 7-state study and found that most were in practice. The items reflected the tenets of AL, the role of AL in providing dementia care, the need for pragmatism due to the diversity of AL, and workforce needs

A crowdsourced intervention to promote hepatitis B and C testing among men who have sex with men in China: study protocol for a nationwide online randomized controlled trial.

BACKGROUND: The World Health Organization recommends all men who have sex with men (MSM) receive Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) testing. MSM in China are a high-risk group for HBV and HCV infection, but test uptake is low. Crowdsourcing invites a large group to solve a problem and then shares the solution with the public. This nationwide online randomized controlled trial will evaluate the effectiveness of a crowdsourced intervention to increase HBV and HCV testing among MSM in China. METHODS: Seven hundred MSM will be recruited through social media operated by MSM organizations in China. Eligible participants will be born biologically male, age 16 years or older, report previous anal sex with another man, and reside in China. After completing a baseline online survey, participants will be randomly assigned to intervention or control arms with a 1:1 allocation ratio. The intervention will include two components: (1) a multimedia component will deliver two videos and two images promoting HBV and HCV testing developed through a crowdsourcing contest in China; (2) a participatory component will invite men to submit suggestions for how to improve crowdsourced videos and images. The control arm will not view any images or videos and will not be invited to submit suggestions. All participants will be offered reimbursement for HBV and HCV testing costs. The primary outcome is HBV and HCV test uptake confirmed through electronic submission of test report photos within four weeks of enrolment. Secondary outcomes include self-reported HBV and HCV test uptake, HBV vaccination uptake, and change in stigma toward people living with HBV after four weeks. Primary and secondary outcomes will be calculated using intention to treat and as-exposed analyses and compared using two-sided 95% confidence intervals. DISCUSSION: Few previous studies have evaluated interventions to increase HBV and HCV testing in middle-income countries with a high burden of hepatitis. Delivering a crowdsourced intervention using social media is a novel approach to increasing hepatitis testing rates. HBV and HCV test uptake will be confirmed through test report photos, avoiding the limitations of self-reported testing outcomes. TRIAL REGISTRATION: NCT03482388 (29 March 2018)

Interventions to optimise the care continuum for chronic viral hepatitis: a systematic review and meta-analyses.

BACKGROUND: Advances in therapy for hepatitis B virus (HBV) and hepatitis C virus (HCV) have ushered in a new era in chronic hepatitis treatment. To maximise the effectiveness of these medicines, individuals must be engaged and retained in care. We analysed operational interventions to enhance chronic viral hepatitis testing, linkage to care, treatment uptake, adherence, and viral suppression or cure. METHODS: We did a systematic review of operational interventions, and did meta-analyses for sufficiently comparable data. We searched PubMed, Embase, WHO library, International Clinical Trials Registry Platform, PsycINFO, and CINAHL for randomised controlled trials and controlled non-randomised studies that examined operational interventions along the chronic viral hepatitis care continuum, published in English up to Dec 31, 2014. We included non-pharmaceutical intervention studies with primary or secondary outcomes of testing, linkage to care, treatment uptake, treatment adherence, treatment completion, treatment outcome, or viral endpoints. We excluded dissertations and studies of children only. Data were extracted by two independent reviewers, with disagreements resolved by a third reviewer. Studies were assessed for bias. Data from similar interventions were pooled and quality of evidence was assessed using GRADE. This study was registered in PROSPERO (42014015094). FINDINGS: We identified 7583 unduplicated studies, and included 56 studies that reported outcomes along the care continuum (41 for HCV and 18 for HBV). All studies except one were from high-income countries. Lay health worker HBV test promotion interventions increased HBV testing rates (relative risk [RR] 2·68, 95% CI 1·82-3·93). Clinician reminders to prompt HCV testing during clinical visits increased HCV testing rates (3·70, 1·81-7·57). Nurse-led educational interventions improved HCV treatment completion (1·14, 1·05-1·23) and cure (odds ratio [OR] 1·93, 95% CI 1·44-2·59). Coordinated mental health, substance misuse, and hepatitis treatment services increased HCV treatment uptake (OR 3·03, 1·24-7·37), adherence (RR 1·22, 1·05-1·41), and cure (RR 1·21, 1·07-1·38) compared with usual care. INTERPRETATION: Several simple, inexpensive operational interventions can substantially improve engagement and retention along the chronic viral hepatitis care continuum. Further operational research to inform scale-up of hepatitis services is needed in low-income and middle-income countries. FUNDING: World Health Organization and US Fulbright Program