We present fine mapping of a cis-acting nucleotide sequence found in the 5 region of yellow fever virus genomic RNA that is required for RNA replication. There is evidence that this sequence interacts with a complementary sequence in the 3 region of the genome to cyclize the RNA. Replicons were constructed that had various deletions in the 5 region encoding the capsid protein and were tested for their ability to replicate. We found that a sequence of 18 nucleotides (residues 146 to 163 of the yellow fever virus genome, which encode amino acids 9 to 14 of the capsid protein) is essential for replication of the yellow fever virus replicon and that a slightly longer sequence of 21 nucleotides (residues 146 to 166, encoding amino acids 9 to 15) is required for full replication. This region is larger than the core sequence of 8 nucleotides conserved among all mosquitoborne flaviviruses and contains instead the entire sequence previously proposed to be involved in cyclization of yellow fever virus RNA.Flaviviruses are small enveloped viruses. The virion contains a positive-strand RNA genome of about 10.7 kb encapsidated by 180 copies of the capsid (C) protein in a nucleocapsid core, which is enveloped by a lipid bilayer in which 180 copies of each of two transmembrane proteins, envelope (E) and membrane (M), are anchored (2, 9). The flaviviruses include a large number of serious human pathogens such as yellow fever virus (YFV), four serotypes of dengue virus (DENV), Japanese encephalitis virus, West Nile virus, and tick-borne encephalitis virus. Although good vaccines have been developed against some flaviviruses (YFV, Japanese encephalitis virus, and tickborne encephalitis virus), they remain a serious health risk around the world.The flavivirus RNA contains one large open reading frame flanked by 5Ј and 3Ј nontranslated regions that are required for replication and translation of the RNA (11). Analysis of the sequences of several flavivirus RNAs showed that short sequences close to the 5Ј and 3Ј ends are complementary, and we proposed that these sequences might function to cyclize the RNA during replication (5). The cyclization sequence at the 5Ј end is located within the region encoding the N-terminal region of the capsid protein. Its 3Ј counterpart is located in the 3Ј nontranslated region. A core region of 8 nucleotides within the cyclization domain is conserved among all mosquito-borne flaviviruses (5). Khromykh et al. (7,8) examined the importance of the cyclization sequences by analyzing the ability of truncated and mutated Kunjin virus (KUNV) RNA molecules to replicate in transfected cells. They found that deletion mutants lacking the sequence encoding the first 20 amino acids of KUNV capsid protein are unable to replicate (8). They further showed that a mutant RNA that had five changes within the 8-nucleotide core conserved sequence was unable to replicate. Compensating changes in the 3Ј region that restored the complementarity of the cyclization sequence restored the ability of the RNA to replicate, althoug...

Associations between rurality and obesity varied by degree of rurality, socioeconomic status, and geography. Therefore, traditional "one-size-fits-all" approaches to reducing rural-urban health disparities in older adults may be more effective if tailored to the area-specific rural-urban gradients in health.

These results suggest that rural-urban status is both a continuum and multidimensional. Distinct elements of rural-urban status may influence health in nuanced ways that require additional exploration in future studies.

BackgroundOver 50 million informal caregivers in the United States provide care to an aging adult, saving the economy hundreds of billions of dollars annually from costly hospitalization or institutionalization. Despite the benefits associated with caregiving, caregiver stress can lead to negative physical and mental health consequences, or “caregiver burden”. Given these potential negative consequences of caregiver burden, it is important not only to understand the multidimensional components of burden but to also understand the experience from the perspective of the caregiver themselves. Therefore, the objectives of our study are to use exploratory factor analysis to obtain a set of latent factors among a subset of caregiver burden questions identified in previous studies and assess their reliability.MethodsAll data was obtained from the 2011 National Study of Caregiving (NSOC). Exploratory factor analysis (EFA) was performed to identify a set of latent factors assessing four domains of caregiver burden in “child caregivers”: those informal caregivers who provide care to a parent or stepparent. Sensitivity analysis was also conducted by repeating the EFA on demographic subsets of caregivers.ResultsAfter multiple factor analyses, four consistent caregiver burden factors emerged from the 23 questions analyzed: Negative emotional, positive emotional, social, and financial. Reliability of each factor varied, and was strongest for the positive emotional domain for caregiver burden. These domains were generally consistent across demographic subsets of informal caregivers.ConclusionThese results provide researchers a more comprehensive understanding of caregiver burden to target interventions to protect caregiver health and maintain this vital component of the US health care system.

Informal caregiving is an integral component of the health care system, saving the national economy more than $522 billion annually. The current study examined how the association between caregiving intensity and caregiver quality of life varies by sociodemographic factors through a secondary analysis of the National Study of Caregiving. Generalized linear models assessed the associations among four aspects of caregiving intensity, three aspects of caregiver quality of life, and key sociodemographic factors. Compared to White individuals, Black individuals had higher levels of overall caregiving intensity (β = 0.293, 95% confidence interval [CI] [0.140, 0.447]), number of instrumental activities of daily living performed (β = 0.060, 95% CI [0.030, 0.090]), and hours spent caregiving per month (β = 0.025, 95% CI [0.002, 0.049]), yet experienced significantly fewer negative impacts on quality of life. Understanding how informal caregiving affects caregiver quality of life is critical to inform public health policies and programs designed to support caregivers and protect this critical component of the U.S. health care system. [Journal of Gerontological Nursing, 43(6), 17-24.].