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Background: The majority of older adults prefer to remain in their homes, or to "age-in-place." To accomplish this goal, many older adults will rely upon home- and community-based services (HCBS) for support. However, the availability and accessibility of HCBS may differ based on whether the older adult lives in the community or in a senior housing apartment facility. Methods: This paper reports findings from the Pathways to Life Quality study of residential change and stability among seniors in upstate New York. Data were analyzed from 663 older adults living in one of three housing types: service-rich facilities, service-poor facilities, and community-dwelling in single-family homes. A multinomial logistic regression model was used to examine factors associated with residence type. A linear regression model was fitted to examine factors associated with HCBS utilization. Results: When compared to community-dwelling older adults, those residing in service-rich and service-poor facilities were more likely to be older, report more activity limitations, and provide less instrumental assistance to others. Those in service-poor facilities were more likely to have poorer mental health and lower perceived purpose in life. The three leading HCBS utilized were senior centers (20%), homemaker services (19%), and transportation services (18%). More HCBS utilization was associated with participants who resided in service-poor housing, were older, were female, and had more activity limitations. More HCBS utilization was also associated with those who received instrumental support, had higher perceived purpose in life, and poorer mental health. Conclusions: Findings suggest that older adults' residential environment is associated with their health status and HCBS utilization. Building upon the Person-Environment Fit theories, dedicated efforts are needed to introduce and expand upon existing HCBS available to facility residents to address physical and mental health needs as well as facilitate aging-in-place.
Background Relatively greater increases in hypertension prevalence among US rural residents may contribute to geographic disparities in recurrent stroke. There is limited US information on poststroke antihypertensive medication use by rural/urban residence. We assessed antihypertensive use and lifestyle characteristics for US rural compared with urban stroke survivors and residence-based trends in use between 2005 and 2019. Methods and Results US stroke survivors with hypertension were identified in the 2005 to 2019 national Behavioral Risk Factor Surveillance System surveys. We ascertained the survey-weighted prevalence of reported antihypertensive use and lifestyle characteristics (ie, physical activity, diabetes, cholesterol, body mass index, and smoking) among respondents with hypertension in odd years over this period by rural/urban residence. Separate trend analyses were used to detect changes in use over time. Survey-weighted logistic regression was used to calculate unadjusted and adjusted (sociodemographic and lifestyle factors) odds ratios for antihypertensive use by year. Our study included 82 175 individuals (36.4% rural residents). Lifestyle characteristics were similar between rural and urban residents except for higher smoking prevalence among rural residents. Antihypertensive use was similar between rural and urban stroke survivors in unadjusted and adjusted analyses (>90% in both populations). Trend analyses showed a small but significant increase in antihypertensive use over time among urban (P=0.033) but not rural stroke survivors (P=0.587). Conclusions Our findings indicate that poststroke antihypertensive use is comparable in rural and urban residents with a reported history of hypertension, but additional work is merited to identify reasons for a trend for increased use of these drugs among urban residents.
Aneurysm hemodynamics play an important role in aneurysm growth and subsequent rupture. Within the available hemodynamic characteristics, particle residence time (PRT) is relatively unexplored. However, some studies have shown that PRT is related to thrombus formation and inflammation. The goal of this study is to evaluate the association between PRT and aneurysm rupture and morphology.
Dermal fillers are gel-type substances for nonsurgical medical-device use to achieve facial rejuvenation. Currently, the most widely used skin fillers are hyaluronic-acid-based dermal fillers. This study aimed to explain the change in the volume of injected dermal fillers by developing a mathematical kinetic model for various dermal fillers. The kinetics of the injected fillers were separated by a biphasic phenomenon. We attributed an increase in filler volume to the hydration of hyaluronic acid molecules and injection-site reaction and a decrease in volume to enzyme-mediated degradation. To explain these in vivo characteristics of dermal fillers, we proposed a two-compartment model, divided into a depot compartment (where the filler was injected) and a subcutaneous compartment (an observation compartment where the fillers swell and degrade), assuming that the swelling and degradation occurred in accordance with the swelling and degradation rate constants, respectively. The model was developed using five hyaluronic-acid-based dermal fillers and NONMEM. We determined that the rate-limiting step for the complete degradation of the dermal fillers in vivo was the swelling phase, as described by the swelling rate constant (Kswell). This study could enable scientists developing novel dermal fillers to predict the in vivo behavior of fillers.
Cancer disparities in rural and frontier communities are an important issue in Utah because much of Utah is sparsely populated. The aims of this study were to investigate whether there are differences in the cancer incidence and 5-year survival rates in Utah by metropolitan/rural residence and to investigate disparities in distributions of cancer risk factors. We used cancer registry records to identify patients diagnosed with a first primary cancer in Utah between 2004 and 2008. We estimated 5-year survival and incidence rates. The Cox proportional hazards model was used to estimate hazard ratios (HRs) for the risk of death. There were 32,498 (86.9%) patients with cancer who lived in metropolitan counties and 4906 (13.1%) patients with cancer who lived in rural counties at the time of cancer diagnosis. Patients with cancer from rural counties were more likely to be older, American Indian/Alaskan Native, non-Hispanic, male, and diagnosed at higher stage. Rural residents had a five-year relative survival that was 5.2% lower than metropolitan residents and a 10% increase in risk of death (HR = 1.10, 95% CI = 1.03, 1.18) after adjustment for multiple factors. Overall, the cancer incidence rates in rural counties were lower by 11.9 per 100,000 per year (449.2 in rural counties vs. 461.1 in metropolitan counties). Cancer patients living in rural counties of Utah had different demographic characteristics as well as differences in incidence and survival rates. Further studies with individual-level data are necessary to investigate the reasons behind these differences in cancer incidence and survival to reduce disparities.
The therapeutic action of drugs is predicated on their physical engagement with cellular targets. Here we describe a broadly applicable method using bioluminescence resonance energy transfer (BRET) to reveal the binding characteristics of a drug with selected targets within intact cells. Cell-permeable fluorescent tracers are used in a competitive binding format to quantify drug engagement with the target proteins fused to Nanoluc luciferase. The approach enabled us to profile isozyme-specific engagement and binding kinetics for a panel of histone deacetylase (HDAC) inhibitors. Our analysis was directed particularly to the clinically approved prodrug FK228 (Istodax/Romidepsin) because of its unique and largely unexplained mechanism of sustained intracellular action. Analysis of the binding kinetics by BRET revealed remarkably long intracellular residence times for FK228 at HDAC1, explaining the protracted intracellular behaviour of this prodrug. Our results demonstrate a novel application of BRET for assessing target engagement within the complex milieu of the intracellular environment.
A transient inline spiking system is a promising tool for evaluating the performance of a virus filter in continuous operation. For better implementation of the system, we performed a systematic analysis to understand the residence time distribution (RTD) of inert tracers in the system. We aimed to understand the RTD of a salt spike, not retained onto or within the membrane pore, to focus on its mixing and spreading within the processing units. A concentrated NaCl solution was spiked into a feed stream as the spiking duration (tspike) was varied from 1 to 40 min. A static mixer was employed to mix the salt spike with the feed stream, which then passed through a single-layered nylon membrane inserted in a filter holder. The RTD curve was obtained by measuring the conductivity of the collected samples. An analytical model, the PFR-2CSTR model, was employed to predict the outlet concentration from the system. The slope and peak of the RTD curves were well-aligned with the experimental findings when τPFR = 4.3 min, τCSTR1 = 4.1 min, and τCSTR2 = 1.0 min. CFD simulations were performed to describe the flow and transport of the inert tracers through the static mixer and the membrane filter. The RTD curve spanned more than 30 min, much longer than tspike, since solutes were dispersed within processing units. The flow characteristics in each processing unit correlated with the RTD curves. Our detailed analysis of the transient inline spiking system would be helpful for implementing this protocol in continuous bioprocessing.
Most drugs are used in the clinic and drug candidate target multiple proteins, and thus detailed characterization of their efficacy targets is required. While current methods rely on quantitative measurements at thermodynamic equilibrium, kinetic parameters such as the residence time of a drug on its target provide a better proxy for efficacy in vivo. Here, we present a residence time proteome integral solubility alteration (ResT-PISA) assay, which facilitates monitoring temporal protein solubility profiles after drug removal ("off-curve") in cell lysates or intact cells, quantifying the lifetime of drug-target interaction. A compressed version of the assay measures the integral under the off-curve enabling the multiplexing of binding affinity and residence time assessments into a single proteomic analysis. We introduce a combined scoring system for three parametric dimensions to improve prioritization of targets. By providing complementary information to other characteristics of drug-target interaction, the ResT-PISA approach will be useful in drug development and precision medicine.
University students have changed their behaviour due to the COVID-19 pandemic. In this paper, we describe the characteristics of PCR+ and PCR- nodes, analyse the structure, and relate the structure of student leaders to pandemic contagion as determined by PCR+ in 93 residential university students. Leadership comes from the male students of social science degrees who have PCR +, with an eigenvector centrality structure, β-centrality, and who are part of the bow-tie structure. There was a significant difference in β-centrality between leaders and non-leaders and in β-centrality between PCR+ and non-leaders. Leading nodes were part of the bow-tie structure. MR-QAP results show how residence and scientific branch were the most important factors in network formation. Therefore, university leaders should consider influential leaders, as they are vectors for disseminating both positive and negative outcomes.
Species gain membership of regional assemblages by passing through multiple ecological and environmental filters. To capture the potential trajectory of structural changes in regional meta-communities driven by biological invasions, one can categorize species pools into assemblages of different residence times. Older assemblages, having passed through more environmental filters, should become more functionally ordered and structured. Here we calculate the level of compartmentalization (modularity) for three different-aged assemblages (neophytes, introduced after 1500 AD; archaeophytes, introduced before 1500 AD, and natives), including 2,054 species of vascular plants in 302 reserves in central Europe. Older assemblages are more compartmentalized than younger ones, with species composition, phylogenetic structure and habitat characteristics of the modules becoming increasingly distinctive. This sheds light on two mechanisms of how alien species are functionally incorporated into regional species pools: the settling-down hypothesis of diminishing stochasticity with residence time, and the niche-mosaic hypothesis of inlaid neutral modules in regional meta-communities.
Loneliness among older people has now become a serious public health issue. There have been few previous studies conducted among Chinese populations on the correlations between loneliness, self-rated health, and instrumental activities of daily living (IADL), and their association with demographic characteristics. In this study, data were collected using quota sampling through survey interviews. Older people living in representative districts were recruited. Of the participants, 60.1% rated their health as average and 58.1% showed a high level of loneliness. IADL and self-rated health (SRH) were found to be moderately positively correlated, with r = 0.357, p < 0.001. A low negative correlation was found between the level of loneliness and IADL, with r = -0.276; and SRH, with r = -0.288, p < 0.05. Ordinal Regression results showed that subjects with higher IADL scores (OR: 0.64, 95% CI: 0.39-1.05) were less lonely, while those with a less desirable economic status (OR: 3.34, 95% CI: 1.40-7.96) and living in the central business district were more likely to have a higher loneliness score (OR: 21.33, 95% CI: 4.81-95.41). It is essential to screen for loneliness, and interventions should be focused on improving social connections and support for older people to overcome their feelings of loneliness.
Transition metal sulfide (TMS) holds great potential in cancer photothermal therapy (PTT) because of the high absorbance in the near-infrared (NIR) region. The short blood circulation time and limited tumor accumulation of TMS-based photothermal agents, however, limit their applications. Herein, we design a novel TMS-based PTT agent, ruthenium sulfide-based nanoclusters (NCs), to overcome the current limitations. We firstly develop a simple method to prepare oleic acid coated ruthenium sulfide nanodots (OA-RuS1.7 NDs) and assemble them into water-soluble NCs via sequentially coating with denatured bovine serum albumin (dBSA) and poly(ethylene glycol) (PEG). The obtained PEG-dBSA-RuS1.7 NCs possess excellent photothermal conversion ability. More significantly, they exhibit enhanced blood circulation time and tumor-targeting efficiency in vivo compared with other TMS-based PTT nanoagents, which may be attributed to their appropriate hydrodynamic diameter (~70 nm) and an ideal charge (~0 mV). These characteristics help the PEG-dBSA-RuS1.7 NCs to escape the removal by the reticuloendothelial system (RES) and kidney. All these advantages enable the PEG-dBSA-RuS1.7 NCs to selectively concentrate in tumor sites and effectively ablate the cancer cells upon NIR irradiation.
Approximately 32,000 people take their own lives every year in the United States. In Kentucky, suicide mortality rates have been steadily increasing since 1999. Few studies in the United States have assessed spatial clustering of suicides. The purpose of this study was to identify high-risk clusters of suicide at the county level in Kentucky and assess the characteristics of those suicide cases within the clusters.
Induction of memory CD8 T cells residing in peripheral tissues is of interest for T cell-based vaccines as these cells are located at mucosal and barrier sites and can immediately exert effector functions, thus providing protection in case of local pathogen encounter. Different memory CD8 T cell subsets patrol peripheral tissues, but it is unclear which subset is superior in providing protection upon secondary infections. We used influenza virus to induce predominantly tissue resident memory T cells or cytomegalovirus to elicit a large pool of effector-like memory cells in the lungs and determined their early protective capacity and mechanism of reactivation. Both memory CD8 T cell pools have unique characteristics with respect to their phenotype, localization, and maintenance. However, these distinct features do not translate into different capacities to control a respiratory vaccinia virus challenge in an antigen-specific manner, although differential activation mechanisms are utilized. While influenza-induced memory CD8 T cells respond to antigen by local proliferation, MCMV-induced memory CD8 T cells relocate from the vasculature into the tissue in an antigen-independent and partially chemokine-driven manner. Together these results bear relevance for the development of vaccines aimed at eliciting a protective memory CD8 T cell pool at mucosal sites.
There has been a growing interest in how the built environment affects health and well-being. Housing characteristics are associated with human health while environmental chemicals could have mediated the effects. However, it is unclear if and how residence duration might have a role in health and well-being. Therefore, the aim of the present study was to investigate the associations among residence duration, common chronic diseases, and cognitive function in older adults in a national and population-based setting. Data were extracted from the US National Health and Nutrition Examination Survey, 2001-2002, with assessment information on demographics, lifestyle factors, housing characteristics, self-reported common chronic diseases, and cognitive function by using the digit symbol substitution test from the Wechsler Adult Intelligence Scale (a measurement of attention and psychomotor speed). Statistical analyses including the chi-square test, t test, and survey-weighted general linear modeling and logistic regression modeling were performed. Residence duration was significantly associated with risk of asthma but not with other chronic disease, showing a longer stay in the same housing leading to lower risk of asthma (OR 0.43, 95%CI 0.27-0.69, P = 0.002) among the American older adults. However, having asthma was not associated with cognitive function decline. In conclusion, residence duration was found to be associated with risk of asthma but not cognitive function. Future research examining the relationship of residence duration and cognitive tests by other domains of cognitive function following asthma episodes would be suggested. For practice and policy implications, familiarity with the housing environment might help with lessening respiratory symptoms.
Even though several studies have examined various risk factors for hypertension, residential influence is poorly explored especially in the low-income countries. We aim to investigate the association between residential characteristics and hypertension in resource limited and transitional settings like Nepal. A total of 14,652 individuals aged 15 and above were selected from 2016-Nepal Demographic and Health Survey. Individuals with blood pressure ≥140/90 mmHg or a history of hypertension (as identified by physicians/health professionals) or under antihypertensive medication were defined as hypertensive. Residential characteristics were represented by area level deprivation index, with a higher score representing higher level of deprivation. Association was explored using a two-level logistic regression. We also assessed if residential area modifies the association between individual socio-economic status and hypertension. Area deprivation had a significant inverse association with the risk of hypertension. Individuals from the least deprived areas had higher odds of hypertension compared to highly deprived areas 1.59 (95% CI 1.30, 1.89). Additionally, the association between literacy a proxy of socio-economic status and hypertension varied with a place of residence. Literate individuals from highly deprived areas were likely to have a higher odds of hypertension compared to those with no formal education. In contrast, literate from the least deprived areas had lower odds of hypertension. These results identify counterintuitive patterns of associations between residential characteristics and hypertension in Nepal, as compared with most of the epidemiological data from high-income countries. Differential stages of demographic and nutritional transitions between and within the countries might explain these associations.
The activation loop (A-loop) plays a key role in regulating the catalytic activity of protein kinases. Phosphorylation in this region enhances the phosphoryl transfer rate of the kinase domain and increases its affinity for ATP. Furthermore, the A-loop possesses autoinhibitory functions in some kinases, where it collapses onto the protein surface and blocks substrate binding when unphosphorylated. Due to its flexible nature, the A-loop is usually disordered and untraceable in kinase domain crystal structures. The resulting lack of structural information is regrettable as it impedes the design of drug A-loop contacts, which have proven favourable in multiple cases. Here, we characterize the binding with A-loop engagement between type 1.5 kinase inhibitor 'example 172' (EX172) and Mer tyrosine kinase (MerTK). With the help of crystal structures and binding kinetics, we portray how the recruitment of the A-loop elicits a two-step binding mechanism which results in a drug-target complex characterized by high affinity and long residence time. In addition, the type 1.5 compound possesses excellent kinome selectivity and a remarkable preference for the phosphorylated over the dephosphorylated form of MerTK. We discuss these unique characteristics in the context of known type 1 and type 2 inhibitors and highlight opportunities for future kinase inhibitor design.
According to the World Health Organization, optimal adherence to Antiretroviral Therapy (ART) improves quality of life. Patients who use ART have varying characteristics in terms of where they live. The effect of place of residence on ART adherence is unclear in Ethiopia. Therefore, the aim of this systematic review and meta-analysis was to estimate the pooled association between place of residence and adherence to ART.
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