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Proceedings of the National Academy of... Sep 2018As long-term changes in life expectancy and fertility drive the emergence of aging societies across the globe, individual countries vary widely in the development of... (Comparative Study)
Comparative Study
As long-term changes in life expectancy and fertility drive the emergence of aging societies across the globe, individual countries vary widely in the development of age-relevant policies and programs. While failure to adapt to the demographic transformation carries not only important financial risks but also social risks, most efforts to gauge countries' preparedness focus on economic indicators. Using data from the Organization for Economic Cooperation and Development (OECD) and other sources, we developed a multidimensional Aging Society Index that assesses the status of older populations across five specific domains, including productivity and engagement, well-being, equity, economic and physical security, and intergenerational cohesion. For 18 OECD countries, the results demonstrate substantial diversity in countries' progress in adapting to aging. For any given domain, there are wide differences across countries, and within most countries, there is substantial variation across domains. Overall, Norway and Sweden rank first in adaptation to aging, followed by the United States, The Netherlands, and Japan. Central and eastern European countries rank at the bottom, with huge untapped potential for successful aging. The United States ranks best in productivity and engagement, in the top half for cohesion, and in the middle in well-being, but it ranks third from the bottom in equity. Only well-being and security showed significant between-domain correlation ( = 0.59, = 0.011), strengthening the case for a multidimensional index. Examination of heterogeneity within and across domains of the index can be used to assess the need for, and effectiveness of, various programs and policies and facilitate successful adaptation to the demographic transition.
Topics: Aging; Humans; Japan; Life Expectancy; Netherlands; Social Change; Social Conditions; United States
PubMed: 30154160
DOI: 10.1073/pnas.1806260115 -
Spinal Cord Nov 2016Repeated measures, retrospective cohort study.
STUDY DESIGN
Repeated measures, retrospective cohort study.
OBJECTIVES
To classify specific causes of injury in a cohort of non-traumatic spinal cord injury (NTSCI) patients, with the aim of exploring whether there are differences in demographics or rehabilitation outcomes depending on the cause of NTSCI.
SETTING
Tertiary care, spinal cord injury rehabilitation unit.
METHODS
Patients admitted to the unit with a non-traumatic SCI between July 2008 and April 2015 were considered for this study. Demographic information and rehabilitation outcomes were obtained from the Needs Assessment Checklist (NAC). NAC1 is completed within 4 weeks post mobilisation and NAC2 upon the patient moving to the pre-discharge ward. Data were obtained for 265 patients.
RESULTS
The most common causes were vertebral column degenerative disorders, infection and vascular disorders, which together accounted for 80% of all NTSCI in this sample. Patients with vertebral column degenerative disorders were less likely to have a complete injury than patients with infections or vascular disorders. There were differences in rehabilitation outcomes on several domains of the NAC. Overall, patients with an SCI caused by an infection have the highest needs (more dependent), and patients with vertebral column degenerative disorders have the lowest needs (more independent).
CONCLUSION
The relationship between non-traumatic cause of injury and rehabilitation outcomes may be mediated by severity of injury. Individuals with infection-related NTSCI are more likely to be complete, therefore, present more significant rehab needs, and lower rehabilitation outcomes particularly in physical health, activities of daily living and bowel management domains. This supports previous findings of Kay et al. and provides a possible explanation for the differences. This further informs future interventions.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Cerebrovascular Disorders; Cohort Studies; Communicable Diseases; Demography; Female; Humans; Male; Middle Aged; Neurodegenerative Diseases; Rehabilitation Centers; Spinal Cord Injuries; Statistics, Nonparametric; Treatment Outcome; Young Adult
PubMed: 27001132
DOI: 10.1038/sc.2016.12 -
Antiviral Research Jul 2017Influenza A H7N9 virus is the latest emerging pandemic threat, and has rapidly diverged into three clades, demanding a H7N9 virus vaccine with broadened protection...
A recombinant H7N9 influenza vaccine with the H7 hemagglutinin transmembrane domain replaced by the H3 domain induces increased cross-reactive antibodies and improved interclade protection in mice.
Influenza A H7N9 virus is the latest emerging pandemic threat, and has rapidly diverged into three clades, demanding a H7N9 virus vaccine with broadened protection against unmatched strains. Hemagglutinin (HA)-based structural design approaches for stabilizing HA proteins have provided excitingly promising results. However, none of the HA-based structural design approaches has been applied to a recombinant replicative influenza virus. Here we report that our HA-based structural design approach is a first in the field to generate a recombinant replicative H7N9 virus (H7N9-53TM) showing broadened protection. The H7N9-53TM contains a replaced H3 HA transmembrane domain (TM) in its HA protein. In mice, the inactivated H7N9-53TM vaccine induced significantly higher HI titers, HA-specific IgG titers, and IFN-γ production than the corresponding H7N9-53WT inactivated virus vaccine containing wild-type HA. More excitingly, mice immunized with the H7N9-53TM showed full protection against homologous (H7N9-53) and interclade (H7N9-MCX) challenges with minimal weight loss, no detectable lung viral loads, and no apparent pulmonary lesions and inflammation, while mice immunized with the H7N9-53WT showed partial protection (only 60% against H7N9-MCX) with severe weight loss, detectable lung viral loads, and severe pulmonary lesions and inflammation. In summary, this study presents a better vaccine candidate (H7N9-53TM) against H7N9 pandemics. Furthermore, our HA-based structural design approach would be conceivably applicable to other subtype influenza viruses, especially the viruses from emerging pandemic and epidemic influenza viruses such as H5N1 and H1N1.
Topics: Amino Acid Sequence; Animals; Antibodies, Viral; Chickens; Cross Protection; Cross Reactions; Disease Models, Animal; Dogs; Female; HEK293 Cells; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Immunoglobulin G; Inflammation; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H7N9 Subtype; Influenza Vaccines; Interferon-gamma; Lung; Madin Darby Canine Kidney Cells; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Phylogeny; Protein Domains; Recombinant Proteins; Survival Rate; Vaccination; Vaccines, Inactivated; Vaccines, Synthetic; Viral Load; Weight Loss
PubMed: 28408133
DOI: 10.1016/j.antiviral.2017.03.029 -
World Journal of Surgery Dec 2023Readmission is a poor outcome for both patients and healthcare systems. The association of certain sociocultural and demographic characteristics with likelihood of...
INTRODUCTION
Readmission is a poor outcome for both patients and healthcare systems. The association of certain sociocultural and demographic characteristics with likelihood of readmission is uncertain in general surgical patients.
METHOD
A multi-centre retrospective cohort study of consecutive unique individuals who survived to discharge during general surgical admissions was conducted. Sociocultural and demographic variables were evaluated alongside clinical parameters (considered both as raw values and their proportion of change in the 1-2 days prior to admission) for their association with 7 and 30 days readmission using logistic regression.
RESULTS
There were 12,701 individuals included, with 304 (2.4%) individuals readmitted within 7 days, and 921 (7.3%) readmitted within 30 days. When incorporating absolute values of clinical parameters in the model, age was the only variable significantly associated with 7-day readmission, and primary language and presence of religion were the only variables significantly associated with 30-day readmission. When incorporating change in clinical parameters between the 1-2 days prior to discharge, primary language and religion were predictive of 30-day readmission. When controlling for changes in clinical parameters, only higher comorbidity burden (represented by higher Charlson comorbidity index score) was associated with increased likelihood of 30-day readmission.
CONCLUSIONS
Sociocultural and demographic patient factors such as primary language, presence of religion, age, and comorbidity burden predict the likelihood of 7 and 30-day hospital readmission after general surgery. These findings support early implementation a postoperative care model that integrates all biopsychosocial domains across multiple disciplines of healthcare.
Topics: Humans; Patient Readmission; Retrospective Studies; Risk Factors; Hospitalization; Demography
PubMed: 37775572
DOI: 10.1007/s00268-023-07177-0 -
The Journal of Rheumatology Nov 2010Having developed and validated a disease-specific health-related quality of life (HRQOL) measure for patients with systemic lupus erythematosus (SLE), the LupusQoL, we...
OBJECTIVE
Having developed and validated a disease-specific health-related quality of life (HRQOL) measure for patients with systemic lupus erythematosus (SLE), the LupusQoL, we determined its relationship to demographic and clinical measurements in a group of patients with SLE.
METHODS
A group of 322 outpatients completed the LupusQoL. Demographic (age, sex, marital status, ethnicity) and clinical variables (disease duration, disease activity, damage) were recorded. Associations between the 8 LupusQoL domains and age, disease duration, disease activity, and damage were explored using Spearman's correlation coefficients. Differences in LupusQoL scores were examined for sex and marital status using the Mann-Whitney U test. Ethnic groups were compared using ANOVA.
RESULTS
All domains of LupusQoL were impaired, with fatigue (56.3) being the worst affected and body image (80.0) the least. The correlations between the LupusQoL domain scores and age (r = -0.01 to -0.22) and disease duration (r = 0 to 0.16) were absent or weak. Similarly, there were no significant differences in the LupusQoL scores regarding sex, marital status, or the 3 main ethnic groups (Black-Caribbean, Asian, White). Although there were statistically significant correlations between the scores of the LupusQoL domains and some scores of the British Isles Lupus Assessment Group index (r = -0.22 to 0.09) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (r = -0.29 to 0.21), these were weak.
CONCLUSION
HRQOL was impaired in this cohort of outpatients with SLE as assessed by the validated lupus-specific LupusQoL. There were no clinically important associations between the 8 domains of the LupusQoL and clinical or demographic variables in this group of patients. Thus, the LupusQoL is a relatively independent outcome measure in patients with SLE.
Topics: Adult; Analysis of Variance; Fatigue; Female; Health Status; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Pain; Quality of Life; Severity of Illness Index; Surveys and Questionnaires
PubMed: 20810500
DOI: 10.3899/jrheum.091277 -
European Journal of Medicinal Chemistry Mar 2024The Son of Sevenless 1 (SOS1) guanine nucleotide exchange factor, prevalent across eukaryotic species, plays a pivotal role in facilitating the attachment of RAS protein... (Review)
Review
The Son of Sevenless 1 (SOS1) guanine nucleotide exchange factor, prevalent across eukaryotic species, plays a pivotal role in facilitating the attachment of RAS protein to GTP, thereby regulating the activation of intracellular RAS proteins. This regulation is part of a feedback mechanism involving SOS1, which allows both activators and inhibitors of SOS1 to exert control over downstream signaling pathways, demonstrating potential anti-tumor effects. Predominantly, small molecule modulators that target SOS1 focus on a hydrophobic pocket within the CDC25 protein domain. The effectiveness of these modulators largely depends on their ability to interact with specific amino acids, notably Phe890 and Tyr884. This interaction is crucial for influencing the protein-protein interaction (PPI) between RAS and the catalytic domain of SOS1. Currently, most small molecule modulators targeting SOS1 are in the preclinical research phase, with a few advancing to clinical trials. This progression raises safety concerns, making the assurance of drug safety a primary consideration alongside the enhancement of efficacy in the development of SOS1 modulators. This review encapsulates recent advancements in the chemical categorization of SOS1 inhibitors and activators. It delves into the evolution of small molecule modulation targeting SOS1 and offers perspectives on the design of future generations of selective SOS1 small molecule modulators.
Topics: Nuclear Family; Signal Transduction; Drug Discovery; Catalytic Domain
PubMed: 38430853
DOI: 10.1016/j.ejmech.2024.116282 -
Acta Medica Iranica 2011Over the past few decades, quality of life (QOL) has become an important concept in medical researches and treatments. Different meaningful reasons are given for this...
Over the past few decades, quality of life (QOL) has become an important concept in medical researches and treatments. Different meaningful reasons are given for this development. In the current research two standard questionnaires for evaluating of QOL were selected. First one, was a questionnaire from The World Health Organization (WHOQOL-BREF 26) and the second one, The Iranian Diabetics' Quality of Life (IRDQOL). The goal of this study is to assess the relation between different domains of these questionnaires and HbA1c in diabetics. A random sample of Iranian adult outpatient diabetics (n=76) was selected and they completed the WHOQOL and IRDQOL assessment instruments. In addition HbA1c was measured in these patients by calorimetric method. Comparisons were made between scores of "questionnaires' domains" and "HbA1c". Data analysis was carried out by the use of T-test, Spearman correlation coefficient, Pearson's correlation coefficient, and non-parametric statistical methods including Spearman correlation coefficient. Data analysis shows Psychological domain score in IRDQOL is lower than in WHOQOL and it is significant (P<0.0001). Physical domain score in IRDQOL is lower than WHOQOL and it is significant (P<0.0001). In WHOQOL questionnaire, analysis data showed when the patient's age increased, physical and psychological domain's score decreased. There is probably no relation between questionnaire domains and HbA1c in diabetics. Based on the findings in this research, there was obviously almost no difference between the two questionnaires for checking the QOL, but in IRDQOL spiritual domain is a very unreliable domain.
Topics: Adult; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Quality of Life; Surveys and Questionnaires
PubMed: 21713736
DOI: No ID Found -
PloS One 2020The environment in which a patient lives influences their health outcomes. However, the degree to which community factors are associated with readmissions is uncertain.
BACKGROUND
The environment in which a patient lives influences their health outcomes. However, the degree to which community factors are associated with readmissions is uncertain.
OBJECTIVE
To estimate the influence of community factors on the Centers for Medicare & Medicaid Services risk-standardized hospital-wide readmission measure (HWR)-a quality performance measure in the U.S.
RESEARCH DESIGN
We assessed 71 community variables in 6 domains related to health outcomes: clinical care; health behaviors; social and economic factors; the physical environment; demographics; and social capital.
SUBJECTS
Medicare fee-for-service patients eligible for the HWR measure between July 2014-June 2015 (n = 6,790,723). Patients were linked to community variables using their 5-digit zip code of residence.
METHODS
We used a random forest algorithm to rank variables for their importance in predicting HWR scores. Variables were entered into 6 domain-specific multivariable regression models in order of decreasing importance. Variables with P-values <0.10 were retained for a final model, after eliminating any that were collinear.
RESULTS
Among 71 community variables, 19 were retained in the 6 domain models and in the final model. Domains which explained the most to least variance in HWR were: physical environment (R2 = 15%); clinical care (R2 = 12%); demographics (R2 = 11%); social and economic environment (R2 = 7%); health behaviors (R2 = 9%); and social capital (R2 = 8%). In the final model, the 19 variables explained more than a quarter of the variance in readmission rates (R2 = 27%).
CONCLUSIONS
Readmissions for a wide range of clinical conditions are influenced by factors relating to the communities in which patients reside. These findings can be used to target efforts to keep patients out of the hospital.
Topics: Aged; Algorithms; Demography; Humans; Patient Readmission; Public Health; Social Environment
PubMed: 33095775
DOI: 10.1371/journal.pone.0240222 -
Neoplasia (New York, N.Y.) May 2019Glioblastoma multiforme (GBM) is a lethal brain tumor with a mean survival time of 1 year. One major reason for therapeutic failure is that GBM cells have an...
Glioblastoma multiforme (GBM) is a lethal brain tumor with a mean survival time of 1 year. One major reason for therapeutic failure is that GBM cells have an extraordinary capacity to invade normal brain tissue beyond the surgical margin, accounting for the lack of treatment efficacy. GBM cells that can infiltrate into the healthy brain possess tumor properties of stemness and invasion, and previous studies demonstrate that Musashi-1 (MSI1), a neural stem cell marker, plays an important role in the maintenance of stem cell status, cellular differentiation, and tumorigenesis in cancers. By analyzing neuronal progenitor cell markers and stemness genes, we predicted that MSI1 might be an important factor in GBM pathogenesis. Because inflammation aids in the proliferation and survival of malignant cells, the inflammatory microenvironment also promotes GBM invasion, and intercellular adhesion molecule-1 (ICAM1), a member of the immunoglobulin superfamily, is involved in inflammation. Our results indicate that the above phenomena are likely due to MSI1 upregulation, which occurred simultaneously with higher expression of ICAM1 in GBM cells. Indeed, MSI1 knockdown effectively suppressed ICAM1 expression and blocked GBM cell motility and invasion, whereas overexpressing ICAM1 reversed these effects. According to RNA immunoprecipitation assays, MSI1-mediated mRNA interactions promote ICAM1 translation. Finally, immunohistochemical analysis showed MSI1 and ICAM-1 to be coexpressed at high levels in GBM tissues. Thus, the MSI1/ICAM1 pathway plays an important role in oncogenic resistance, including increased tumor invasion, and MSI1/ICAM1 may be a target for GBM treatment.
Topics: Brain Neoplasms; Carcinogenesis; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Intercellular Adhesion Molecule-1; Nerve Tissue Proteins; Prognosis; Protein Biosynthesis; Protein Interaction Domains and Motifs; RNA Stability; RNA-Binding Proteins; Survival Rate; Tumor Cells, Cultured
PubMed: 30959276
DOI: 10.1016/j.neo.2019.02.006 -
Demography Apr 2023Today's young adults have diverse union experiences; some enter enduring marital or cohabiting unions at young ages, but many delay or dissolve their unions or remain...
Today's young adults have diverse union experiences; some enter enduring marital or cohabiting unions at young ages, but many delay or dissolve their unions or remain single. Childhood family instability-defined as parents' transitions into or out of romantic coresidential unions-offers one explanation for why some people are more likely than others to enter and exit unions. We evaluate whether this family instability hypothesis-a union-specific version of the general hypothesis that instability affects people across multiple life domains-can explain Black and White young adults' union formation and dissolution. Using data from the Panel Study of Income Dynamics' Transition into Adulthood Supplement (birth cohorts 1989-1999), we find that the marginal effects of childhood family instability on cohabitation and marriage are weaker for Black than for White youth. Further, Black-White differences in childhood family instability's prevalence are small. Consequently, novel decompositions that account for racial differences in instability's prevalence and marginal effects reveal that childhood family instability contributes little to Black-White inequality in young adults' union outcomes. Our results challenge the generalizability of the family instability hypothesis across racialized groups in the union domain. Explanations for Black-White differences in young-adult marriage and cohabitation reside beyond childhood family dynamics.
Topics: Adolescent; Young Adult; Humans; Marriage; Family Characteristics; Parents; Black People; White People
PubMed: 36811335
DOI: 10.1215/00703370-10571816