Epistasis reduces fitness costs of influenza A virus escape from stem-binding antibodies.

The hemagglutinin (HA) stem region is a major target of universal influenza vaccine efforts owing to the presence of highly conserved epitopes across multiple influenza A virus (IAV) strains and subtypes. To explore the potential impact of vaccine-induced immunity targeting the HA stem, we examined the fitness effects of viral escape from stem-binding broadly neutralizing antibodies (stem-bnAbs). Recombinant viruses containing each individual antibody escape substitution showed diminished replication compared to wild-type virus, indicating that stem-bnAb escape incurred fitness costs. A second-site mutation in the HA head domain (N129D; H1 numbering) reduced the fitness effects observed in primary cell cultures and likely enabled the selection of escape mutations. Functionally, this putative permissive mutation increased HA avidity for its receptor. These results suggest a mechanism of epistasis in IAV, wherein modulating the efficiency of attachment eases evolutionary constraints imposed by the requirement for membrane fusion. Taken together, the data indicate that viral escape from stem-bnAbs is costly but highlights the potential for epistatic interactions to enable evolution within the functionally constrained HA stem domain.

Investigating Relationships Between Preparedness for Practice, Grade Point Average, and Demographic Correlates Among Prelicensure Nursing Students.

ABSTRACT: Understanding the factors contributing to the clinical preparedness of nursing students provides essential information for their successful transition into the workforce. The aims of this study were to examine preparedness for practice with demographic factors, grade point average, and taking care of multiple patient caseloads. This study used a correlational design with 185 prelicensure nursing students in the midwestern United States. The results showed that self-reported clinical preparedness was associated with program type and externship experience. The findings contribute to nursing education by bringing new information that contributes to the understanding of students' preparedness for practice.

Predictors of Preventive Health Practices, Chronic Disease Burden and Health Status Among Underserved Bangladeshi Americans in Michigan.

The Bangladeshi American community in Michigan is growing rapidly. Little is known about the correlates of health status and preventive health services among Bangladeshi Americans. The purpose of this study was to examine the relationships between demographic factors, preventive health practices, chronic conditions and health status of this population. Data were collected through self-administered surveys during community events in Hamtramck, Michigan and analyzed using descriptive statistics and multiple linear regression. The surveys were completed by 166 Bangladeshi Americans. A majority reported not having an up-to-date physical/dental exams, colorectal, cervical, or breast cancer screening. The length of U.S. residency was associated with cancer screening utilization while employment status was correlated with self-reported health status. Our results demonstrate a need for development and implementation of language-appropriate and cultural interventions to address the unique healthcare needs of this growing population.

The Patient Protection and Affordable Care Act and Utilization of Preventive Health Care Services Among Asian Americans in Michigan during Pre- and Post-Affordable Care Act Implementation.

Since the implementation of the Patient Protection and Affordable Care Act (ACA), significant increases in the percent of insured United States residents has steadily increased. Studies have shown that there is an increase in preventative services usage and a decrease in chronic disease burden with increased access to insurance. However, very little has been studied about how the implementation of ACA has impacted utilization of health services and health status among Asian Americans. In this study, we recruited 427 Asian Americans who attended health fairs and examined (1) changes in health care coverage and utilization of preventive health services before and after ACA, (2) health status on chronic disease risk factors, (3) comparing health services utilization by insurance status and types of insurance, and (4) identifying relationships between health care utilization and demographic factors. Study results indicate that even though the percentage of insured Asian Americans in Michigan increased significantly over study periods, health care utilization and chronic disease burden did not change significantly. The insured tended to utilize preventive health services more than the uninsured, but the types of insurance did not affect health care utilization. Gender and having a primary care physician were significant predictors in determining health care utilization. There is a need in this population for language-appropriate and culturally-sensitive education about the importance and availability of preventive services, which could improve adherence to preventive health services, thereby reducing health disparities.

Risk assessment of a highly pathogenic H5N1 influenza virus from mink.

Outbreaks of highly pathogenic H5N1 clade 2.3.4.4b viruses in farmed mink and seals combined with isolated human infections suggest these viruses pose a pandemic threat. To assess this threat, using the ferret model, we show an H5N1 isolate derived from mink transmits by direct contact to 75% of exposed ferrets and, in airborne transmission studies, the virus transmits to 37.5% of contacts. Sequence analyses show no mutations were associated with transmission. The H5N1 virus also has a low infectious dose and remains virulent at low doses. This isolate carries the adaptive mutation, PB2 T271A, and reversing this mutation reduces mortality and airborne transmission. This is the first report of a H5N1 clade 2.3.4.4b virus exhibiting direct contact and airborne transmissibility in ferrets. These data indicate heightened pandemic potential of the panzootic H5N1 viruses and emphasize the need for continued efforts to control outbreaks and monitor viral evolution.

Parental Perceptions and Perceived Environmental Influences on Active Transport to School in U.S. Inner-City Neighborhoods: Through the Lens of Health Equity.

Physical inactivity remains high amongst Asian American (AA) children. The Safe Routes to School (SRTS) Program is a viable approach for increasing levels of physical activity by encouraging active transport to school (ATS). The objective of this study was to investigate the factors that affect ATS among Asian American children in inner-city schools. An adapted version of the national SRTS survey that measures socio-demographics, environmental factors, and parental perceptions toward school routes and transportation modes were administered in eight public schools in Hamtramck, Michigan. Multinominal logistic regression results indicated that the age of children, distance to school, perceived school encouragement, and parents' perceptions on safety were the predominant factors associated with Asian American children participating in ATS. The study is among the first to investigate underserved environmental and access factors that influence Asian American children's ATS patterns. Particularly, these findings showed that the safety perceptions of parents play a key role in affecting their decisions about ATS and should be considered in future interventions and programming designs to promote ATS.

The Role of Gut Barrier Dysfunction and Microbiome Dysbiosis in Colorectal Cancer Development.

Accumulating evidence indicates that breakdown of the+ protective mucosal barrier of the gut plays a role in colorectal cancer (CRC) development. Inflammation and oxidative stress in the colonic epithelium are thought to be involved in colorectal carcinogenesis and the breakdown of the integrity of the colonic barrier may increase the exposure of colonocytes to toxins from the colonic milieu, enhancing inflammatory processes and release of Reactive Oxygen Species (ROS). The aetiological importance of the gut microbiome and its composition - influenced by consumption of processed meats, red meats and alcoholic drinks, smoking, physical inactivity, obesity - in CRC development is also increasingly being recognized. The gut microbiome has diverse roles, such as in nutrient metabolism and immune modulation. However, microbial encroachment towards the colonic epithelium may promote inflammation and oxidative stress and even translocation of species across the colonic lumen. Recent research suggests that factors that modify the above mechanisms, e.g., obesity and Western diet, also alter gut microbiota, degrade the integrity of the gut protective barrier, and expose colonocytes to toxins. However, it remains unclear how obesity, lifestyle and metabolic factors contribute to gut-barrier integrity, leading to metabolic disturbance, colonocyte damage, and potentially to CRC development. This review will discuss the interactive roles of gut-barrier dysfunction, microbiome dysbiosis, and exposure to endogenous toxins as another mechanism in CRC development, and how biomarkers of colonic mucosal barrier function may provide avenues for disease, prevention and detection.