Precarious Work and Housing for Michigan Farmworkers During the COVID-19 Pandemic and Beyond.

OBJECTIVES: Farmworkers in Michigan face precarious and exploitative labor conditions that affect their access to affordable, fair, and quality housing, which are key social determinants of health. We sought to assess the health, working conditions, and housing access, affordability, and quality of farmworkers living in and outside of employer-provided housing during the COVID-19 pandemic. METHODS: We conducted a mixed methods cross-sectional study in collaboration with community partners from the Michigan Farmworker Project and the Michigan Department of Civil Rights. We assessed housing, labor conditions, and general health through in-depth phone interviews with seasonal, migrant, and H-2A farmworkers (n = 63) during the height of the COVID-19 pandemic (2020-2021) in Michigan. Descriptive analyses of these data included comparisons by type of farmworker and type of housing (employer-provided or other). RESULTS: The majority of farmworkers interviewed were women and seasonal farmworkers and spoke primarily Spanish. A significant share of farmworker participants reported living in poverty (38.3%) and had low or very low food security (27.0%). Nearly half of farmworkers (47.6%) rated their health as "fair" or "poor" during the year prior to the interview, and more than a third reported 3 or more chronic conditions (39.6%) and lack of health insurance coverage (38.7%). Among the 43 workers tested, 25.6% reported testing positive for COVID-19. Farmworkers reported experiences of objectification and dehumanization. Three-quarters of workers reported feeling that they were treated as less than human by supervisors and one-third reported verbal abuse. Farmworkers also experienced challenges exacerbated by their social vulnerability that impeded them from finding affordable, quality housing. Regarding housing quality, the majority of workers (80.6%) reported one or more environmental hazards around their residence, and about a third reported not having air conditioning (33.%) and lacking a functioning washing machine (33.9%). Concerns about the quality of drinking water accessible to workers and exposure to chemicals were shared by participants. CONCLUSION: This study adds valuable knowledge to the understanding of the systemic barriers to housing and work conditions for female and male seasonal, migrant, and H-2A farmworkers in Michigan. Shortcomings in the regulatory and policy environment result in precarious housing and work conditions, including exploitative labor practices. These conditions negate equality, fairness, and health equity, important tenants for public health.

A classification algorithm based on dynamic ensemble selection to predict mutational patterns of the envelope protein in HIV-infected patients.

BACKGROUND: Therapeutics against the envelope (Env) proteins of human immunodeficiency virus type 1 (HIV-1) effectively reduce viral loads in patients. However, due to mutations, new therapy-resistant Env variants frequently emerge. The sites of mutations on Env that appear in each patient are considered random and unpredictable. Here we developed an algorithm to estimate for each patient the mutational state of each position based on the mutational state of adjacent positions on the three-dimensional structure of the protein. METHODS: We developed a dynamic ensemble selection algorithm designated k-best classifiers. It identifies the best classifiers within the neighborhood of a new observation and applies them to predict the variability state of each observation. To evaluate the algorithm, we applied amino acid sequences of Envs from 300 HIV-1-infected individuals (at least six sequences per patient). For each patient, amino acid variability values at all Env positions were mapped onto the three-dimensional structure of the protein. Then, the variability state of each position was estimated by the variability at adjacent positions of the protein. RESULTS: The proposed algorithm showed higher performance than the base learner and a panel of classification algorithms. The mutational state of positions in the high-mannose patch and CD4-binding site of Env, which are targeted by multiple therapeutics, was predicted well. Importantly, the algorithm outperformed other classification techniques for predicting the variability state at multi-position footprints of therapeutics on Env. CONCLUSIONS: The proposed algorithm applies a dynamic classifier-scoring approach that increases its performance relative to other classification methods. Better understanding of the spatiotemporal patterns of variability across Env may lead to new treatment strategies that are tailored to the unique mutational patterns of each patient. More generally, we propose the algorithm as a new high-performance dynamic ensemble selection technique.

Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels.

HIV-1 group M was transmitted to humans nearly one century ago. The virus has since evolved to form distinct clades, which spread to different regions of the world. The envelope glycoproteins (Envs) of HIV-1 have rapidly diversified in all infected populations. We examined whether key antigenic sites of Env and signatures of vaccine efficacy are evolving toward similar or distinct structural forms in different populations worldwide. Patterns of amino acid variants that emerged at each position of Env were compared between diverse HIV-1 clades and isolates from different geographic regions. Interestingly, at each Env position, the amino acid in the clade ancestral or regional-founder virus was replaced by a unique frequency distribution (FD) of amino acids. FDs are highly conserved in populations from different regions worldwide and in paraphyletic and monophyletic subclade groups. Remarkably, founder effects of Env mutations at the clade and regional levels have gradually decreased during the pandemic by evolution of each site toward the unique combination of variants. Therefore, HIV-1 Env is evolving at a population level toward well-defined "target" states; these states are not specific amino acids but rather specific distributions of amino acid frequencies. Our findings reveal the powerful nature of the forces that guide evolution of Env and their conservation across different populations. Such forces have caused a gradual decrease in the interpopulation diversity of Env despite an increasing intrapopulation diversity.IMPORTANCE The Env protein of HIV-1 is the primary target in AIDS vaccine design. Frequent mutations in the virus increase the number of Env forms in each population, limiting the efficacy of AIDS vaccines. Comparison of newly emerging forms in different populations showed that each position of Env is evolving toward a specific combination of amino acids. Similar changes are occurring in different HIV-1 subtypes and geographic regions toward the same position-specific combinations of amino acids, often from distinct ancestral sequences. The predictable nature of HIV-1 Env evolution, as shown here, provides a new framework for designing vaccines that are tailored to the unique combination of variants expected to emerge in each virus subtype and geographic region.

Treatment with Uric Acid Reduces Infarct and Improves Neurologic Function in Female Mice After Transient Cerebral Ischemia.

BACKGROUND: Exogenous administration of uric acid, a naturally occurring antioxidant that scavenges reactive oxygen species in vasculature, has shown protective efficacy in both rodent models of stroke and human stroke patients in Spain as an adjuvant treatment to mechanical thrombectomy. Before clinical trials can be initiated in the United States, however, confirmation of efficacy in alternative preclinical models is required in accordance with stroke therapy academic industry roundtable-RIGOR criteria. To date, preclinical efficacy has only been established in the acute setting in male rodents. METHODS: To address this need, we subjected 7- to 9-week old ovariectomized female mice to filament-induced right middle cerebral artery ischemia and reperfusion, an established preclinical model of mechanical thrombectomy. Fidelity of the procedure was monitored by laser Doppler flowmetry. A separate lab randomly assigned animals to vehicle versus uric acid infusion, which was initiated immediately after 45 minutes of reperfusion. Poststroke analysis of infarction size and neurologic function were conducted by investigators blind to treatment group, with a 7-day primary endpoint and a 3-day intermediary analysis at 1and. RESULTS: Infarct size and neurologic function at 7 days poststroke were significantly improved in uric acid-treated animals, relative to vehicle. CONCLUSION: Efficacy of uric acid in preclinical models of stroke is now expanded to include female mice analyzed at a later time point than has been investigated previously. These results support stroke therapy academic industry roundtable-RIGOR driven determination of the suitability of acute administration of uric acid as an adjuvant to mechanical thrombectomy in clinical trials for patients with stroke.