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Objectives: To estimate the prevalence of unmet needs for assistance among middle-aged and older adults with subjective cognitive decline (SCD) in the US and to evaluate whether unmet needs were associated with health-related quality of life (HRQOL).Design: Cross-sectional.Setting: US - 50 states, District of Columbia, and Puerto Rico.Participants: Community-dwelling adults aged 45 years and older who completed the Cognitive Decline module on the 2015--2018 Behavioral Risk Factor Surveillance System reported experiencing SCD and always, usually, or sometimes needed assistance with day-to-day activities because of SCD (n = 6,568).Measurements: We defined SCD as confusion or memory loss that was happening more often or getting worse over the past 12 months. Respondents with SCD were considered to have an unmet need for assistance if they sometimes, rarely, or never got the help they needed with day-to-day activities. We measured three domains of HRQOL: (1) mental (frequent mental distress, ≥14 days of poor mental health in the past 30 days), (2) physical (frequent physical distress, ≥14 days of poor physical health in the past 30 days), and (3) social (SCD always, usually, or sometimes interfered with the ability to work, volunteer, or engage in social activities outside the home). We used log-binomial regression models to estimate prevalence ratios (PRs). All estimates were weighted.Results: In total, 40.2% of people who needed SCD-related assistance reported an unmet need. Among respondents without depression, an unmet need was associated with a higher prevalence of frequent mental distress (PR = 1.55, 95% CI: 1.12-2.13, p = 0.007). Frequent physical distress and social limitations did not differ between people with met and unmet needs.Conclusions: Middle-aged and older adults with SCD-related needs for assistance frequently did not have those needs met, which could negatively impact their mental health. Interventions to identify and meet the unmet needs among people with SCD may improve HRQOL. [ABSTRACT FROM AUTHOR]

Mycobacterium phage Adephagia is a cluster K phage that infects Mycobacterium smegmatis and some strains of Mycobacterium pathogens. Adephagia has a siphoviral virion morphology and is temperate. Its genome is 59,646 bp long and codes for one tRNA gene and 94 predicted protein-coding genes; most genes not associated with virion structure and assembly are functionally ill-defined. Here, we determined the Adephagia gene expression patterns in lytic and lysogenic growth and used structural predictions to assign additional gene functions. We characterized 66 nonstructural genes for their toxic phenotypes when expressed in M. smegmatis , and we show that 25 of these (38%) are either toxic or strongly inhibit growth, resulting in either reduced viability or small colony sizes. Some of these genes are predicted to be involved in DNA metabolism or regulation, but others are of unknown function. We also characterize the HicAB-like toxin–antitoxin (TA) system encoded by Adephagia (gp91 and gp90, respectively) and show that the gp90 antitoxin is lysogenically expressed, abrogates gp91 toxicity, and is required for normal lytic and lysogenic growth. [ABSTRACT FROM AUTHOR]

Computational models of evolution are valuable for understanding the dynamics of sequence variation, to infer phylogenetic relationships or potential evolutionary pathways and for biomedical and industrial applications. Despite these benefits, few have validated their propensities to generate outputs with in vivo functionality, which would enhance their value as accurate and interpretable evolutionary algorithms. We demonstrate the power of epistasis inferred from natural protein families to evolve sequence variants in an algorithm we developed called sequence evolution with epistatic contributions (SEEC). Utilizing the Hamiltonian of the joint probability of sequences in the family as fitness metric, we sampled and experimentally tested for in vivo [Formula: see text]-lactamase activity in Escherichia coli TEM-1 variants. These evolved proteins can have dozens of mutations dispersed across the structure while preserving sites essential for both catalysis and interactions. Remarkably, these variants retain family-like functionality while being more active than their wild-type predecessor. We found that depending on the inference method used to generate the epistatic constraints, different parameters simulate diverse selection strengths. Under weaker selection, local Hamiltonian fluctuations reliably predict relative changes to variant fitness, recapitulating neutral evolution. SEEC has the potential to explore the dynamics of neofunctionalization, characterize viral fitness landscapes, and facilitate vaccine development., Competing Interests: Competing interests statement:The authors declare no competing interest.

Bioelectronic medicine (BEM) offers exciting opportunities to treat diseases such as movement disorders and refractory inflammatory disease. The many variations of BEM allow for noninvasive aspects of treatment that might eliminate or reduce the need for pharmaceuticals; therefore, the term "electroceuticals" may be suitable. BEM has been effective for movement disorders and improvement of prosthetic devices. Based on this implication, there is an allowance to impact many focus areas that include but are not limited to autoimmune disease, sensory motor conditions, and neurological conditions. There are a wide array of ethical issues that relate to BEM, which include informed consent, research ethics, innovation, academic-industry relationships, intellectual property, and the conundrum that needs to be addressed when altering the brain such as the issues of autonomy and free beneficence and social justice. The major goal is to heighten awareness of ethical issues and facilitate a proactive ethical approach regarding BEM research., (Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved.)