Prevalence and risk factors for hypertension and diabetes among those screened in a refugee settlement in Uganda.

BACKGROUND: Diabetes and hypertension are increasingly prevalent in low and middle income countries, but they are not well documented in refugee settlements in these settings. We sought to estimate the prevalence and associated characteristics of diabetes and hypertension among adults presenting for clinic-based HIV testing in Nakivale Refugee Settlement in Uganda. METHODS: HIV-negative adults presenting to outpatient clinics for HIV testing at three health centers in Nakivale Refugee Settlement were enrolled from January 2019 through January 2020. Multi-lingual research assistants administered questionnaires aloud to ascertain medical history and sociodemographic information. The research assistants used standardized procedures to measure participants' blood pressure to detect hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg), and conduct a point-of-care blood glucose test for diabetes (random blood glucose ≥11.1 mmol/L with self-reported frequent urination or thirst, or fasting blood glucose ≥7.0 mmol/L regardless of symptoms), as per Uganda Ministry of Health guidelines. We used χ-square or Fisher's exact test to test for differences in disease prevalence by refugee status and log-binomial or Poisson regression models to estimate associations of immigration status and country of origin, respectively, with hypertension and diabetes while controlling for age, sex, education level, and body mass index. RESULTS: Among 2127 participants, 1379 (65%) were refugees or asylum seekers and 748 (35%) were Ugandan nationals. Overall, 32 participants met criteria for diabetes (1.5%, 95% CI 1.1-2.1%) and the period prevalence was 2.3% (95% CI 1.7-3.0). There were 1067 (50%, 95% CI 48.0-52.2%) who met the criteria for pre-hypertension and 189 (9%, 95% CI 7.7-10.1%) for hypertension. These proportions did not vary by immigration status or country of origin in univariate tests or multivariable regression models. CONCLUSIONS: Hypertension was common and diabetes was uncommon among those screened in a Ugandan refugee settlement. Routine blood pressure screening should be considered in this setting. Additional research could develop diabetes screening criteria to help identify at risk individuals in this limited resource setting.

Overcoming Ethical Challenges to Engaging Men Who Have Sex with Women in HIV Research.

Men who have sex with women are understudied in HIV research despite the extent to which they experience HIV-related mortality and contribute to the epidemic among women. During our experience of developing and piloting an HIV prevention intervention for men living with HIV in South Africa, and planning to have a child with an HIV-negative woman, ethical questions were posed regarding implementation of a male-centered intervention that did not require female partner participation. Two overarching ethical issues were the potential for (1) compromising women's reproductive and sexual autonomy and (2) increasing HIV-acquisition risks for the woman because the intervention efficacy was unknown. We describe here how these concerns were addressed to facilitate development of a male-centered HIV-prevention intervention. We hope this process manuscript will support researchers, clinicians, and reviewers to engage men who have sex with women in HIV prevention and care.

Federal requirements for nursing homes to include certified nursing assistants in resident care planning and interdisciplinary teams: A policy analysis.

Starting in 2016, Centers for Medicare and Medicaid Services implemented the first phase of a 3-year multi-phase plan revising the manner in which nursing homes are regulated. In this revision, attention was placed on the importance of certified nursing assistants (CNAs) to resident care and the need to empower these frontline workers. Phase II mandates that CNAs be included as members of the nursing home interdisciplinary team that develops care plans for the resident that are person-centered and comprehensive and reviews and revises these care plans after each resident assessment. While these efforts are laudable, there are no direct guidelines for how to integrate CNAs in the interdisciplinary team. We recommend the inclusion of direct guidelines, in which this policy revision clarifies the expected contributions from CNAs, their responsibilities, their role as members of the interdisciplinary team, and the expected patterns of communication between CNAs and other members of the interdisciplinary team.

Corrigendum: The Effects of Framework Mutations at the Variable Domain Interface on Antibody Affinity Maturation in an HIV-1 Broadly Neutralizing Antibody Lineage.

[This corrects the article DOI: 10.3389/fimmu.2020.01529.].

The Effects of Framework Mutations at the Variable Domain Interface on Antibody Affinity Maturation in an HIV-1 Broadly Neutralizing Antibody Lineage.

Understanding affinity maturation of antibodies that can target many variants of HIV-1 is important for vaccine development. While the antigen-binding site of antibodies is known to mutate throughout the co-evolution of antibodies and viruses in infected individuals, the roles of the mutations in the antibody framework region are not well understood. Throughout affinity maturation, the CH103 broadly neutralizing antibody lineage, from an individual designated CH505, altered the orientation of one of its antibody variable domains. The change in orientation was a response to insertions in the variable loop 5 (V5) of the HIV envelope. In this study, we generated CH103 lineage antibody variants in which residues in the variable domain interface were mutated, and measured the binding to both autologous and heterologous HIV-1 envelopes. Our data show that very few mutations in an early intermediate antibody of the lineage can improve binding toward both autologous and heterologous HIV-1 envelopes. We also crystallized an antibody mutant to show that framework mutations alone can result in a shift in relative orientations of the variable domains. Taken together, our results demonstrate the functional importance of residues located outside the antigen-binding site in affinity maturation.

An Improved Method for Measuring Chromatin-binding Dynamics Using Time-dependent Formaldehyde Crosslinking.

Formaldehyde crosslinking is widely used in combination with chromatin immunoprecipitation (ChIP) to measure the locations along DNA and relative levels of transcription factor (TF)-DNA interactions in vivo. However, the measurements that are typically made do not provide unambiguous information about the dynamic properties of these interactions. We have developed a method to estimate binding kinetic parameters from time-dependent formaldehyde crosslinking data, called crosslinking kinetics (CLK) analysis. Cultures of yeast cells are crosslinked with formaldehyde for various periods of time, yielding the relative ChIP signal at particular loci. We fit the data using the mass-action CLK model to extract kinetic parameters of the TF-chromatin interaction, including the on- and off-rates and crosslinking rate. From the on- and off-rate we obtain the occupancy and residence time. The following protocol is the second iteration of this method, CLKv2, updated with improved crosslinking and quenching conditions, more information about crosslinking rates, and systematic procedures for modeling the observed kinetic regimes. CLKv2 analysis has been applied to investigate the binding behavior of the TATA-binding protein (TBP), and a selected subset of other TFs. The protocol was developed using yeast cells, but may be applicable to cells from other organisms as well.

Second-generation method for analysis of chromatin binding with formaldehyde-cross-linking kinetics.

Formaldehyde-cross-linking underpins many of the most commonly used experimental approaches in the chromatin field, especially in capturing site-specific protein-DNA interactions. Extending such assays to assess the stability and binding kinetics of protein-DNA interactions is more challenging, requiring absolute measurements with a relatively high degree of physical precision. We previously described an experimental framework called the cross-linking kinetics (CLK) assay, which uses time-dependent formaldehyde-cross-linking data to extract kinetic parameters of chromatin binding. Many aspects of formaldehyde behavior in cells are unknown or undocumented, however, and could potentially affect CLK data analyses. Here, we report biochemical results that better define the properties of formaldehyde-cross-linking in budding yeast cells. These results have the potential to inform interpretations of "standard" chromatin assays, including chromatin immunoprecipitation. Moreover, the chemical complexity we uncovered resulted in the development of an improved method for measuring binding kinetics with the CLK approach. Optimum conditions included an increased formaldehyde concentration and more robust glycine-quench conditions. Notably, we observed that formaldehyde-cross-linking rates can vary dramatically for different protein-DNA interactions in vivo Some interactions were cross-linked much faster than the in vivo macromolecular interactions, making them suitable for kinetic analysis. For other interactions, we found the cross-linking reaction occurred on the same time scale or slower than binding dynamics; for these interactions, it was sometimes possible to compute the in vivo equilibrium-binding constant but not binding on- and off-rates. This improved method yields more accurate in vivo binding kinetics estimates on the minute time scale.

RNA synthesis is associated with multiple TBP-chromatin binding events.

Competition ChIP is an experimental method that allows transcription factor (TF) chromatin turnover dynamics to be measured across a genome. We develop and apply a physical model of TF-chromatin competitive binding using chemical reaction rate theory and are able to derive the physical half-life or residence time for TATA-binding protein (TBP) across the yeast genome from competition ChIP data. Using our physical modeling approach where we explicitly include the induction profile of the competitor in the model, we are able to estimate yeast TBP-chromatin residence times as short as 1.3 minutes, demonstrating that competition ChIP is a relatively high temporal-resolution approach. Strikingly, we find a median value of ~5 TBP-chromatin binding events associated with the synthesis of one RNA molecule across Pol II genes, suggesting multiple rounds of pre-initiation complex assembly and disassembly before productive elongation of Pol II is achieved at most genes in the yeast genome.

Beating the one-half limit of ancilla-free linear optics Bell measurements.

We show that optically encoded two-qubit Bell states can be unambiguously discriminated with a success probability of more than 50% in both single-rail and dual-rail encodings by using active linear-optical resources that include Gaussian squeezing operations. These results are in contrast to the well-known upper bound of 50% for unambiguous discrimination of dual-rail Bell states using passive, static linear optics and arbitrarily many vacuum modes. We present experimentally feasible schemes that improve the success probability to 64.3% in dual-rail and to 62.5% in single-rail for a uniform random distribution of Bell states. Conceptually, this demonstrates that neither interactions that induce nonlinear mode transformations (such as Kerr interactions) nor auxiliary entangled photons are required to go beyond the one-half limit. We discuss the optimality of our single-rail scheme and talk about an application of our dual-rail scheme in quantum communication.