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Clinical Immunology (Orlando, Fla.) Oct 2017JAK3 is a tyrosine kinase essential for signaling downstream of the common gamma chain subunit shared by multiple cytokine receptors. JAK3 deficiency results in TBNK...
JAK3 is a tyrosine kinase essential for signaling downstream of the common gamma chain subunit shared by multiple cytokine receptors. JAK3 deficiency results in TBNK severe combined immune deficiency (SCID). We report a patient with SCID due to a novel mutation in the JAK3 JH4 domain. The function of the JH4 domain remains unknown. This is the first report of a missense mutation in the JAK3 JH4 domain, thereby demonstrating the importance of the JH4 domain of JAK3 in host immunity.
Topics: Fatal Outcome; Female; Humans; Infant; Janus Kinase 3; Mutation; Osteomyelitis; Protein Domains; Severe Combined Immunodeficiency; Spine
PubMed: 28917720
DOI: 10.1016/j.clim.2017.09.007 -
International Journal For Quality in... Feb 2016To describe the associations between demographics and health-related quality of life for chronic non-malignant pain patients.
OBJECTIVE
To describe the associations between demographics and health-related quality of life for chronic non-malignant pain patients.
DESIGN
A cohort study.
SETTING
A multidisciplinary Danish pain centre.
STUDY PARTICIPANTS
All patients treated at the centre between 2007 and 2013.
MAIN OUTCOME MEASURES
Levels of pain, anxiety and depression, and physical and mental status. The Hospital Anxiety and Depression Scale and the Medical Outcomes Study Short-Form Health Survey (SF-36) were used.
RESULTS
A total of 1176 patients were included. The majority were women (64%), the mean age was 46.7 ± 14.4 (range 18-89), and 21% were able to work full or part time. On a Numeric Rating Scale from 0 to 10, median pain-intensity was 8 (interquartile range 7-8) and pain-discomfort 8 (interquartile range 7-9) at time of referral. More than half of the patients had symptoms of anxiety and depression. Most of the individual SF-36 domains had median scores between 0 and 40 (Scale from 0 to 100). Patients younger than 50 years of age as well as patients on sick leave/disability pension had significantly lower SF-36 scores. Level of pain, anxiety and depression decreased and SF-36-scores increased significantly after a course of treatment which in most cases consisted of both medical, physiotherapeutic and psychological treatment as well as health-oriented education. The chi-square test, Mann-Whitney U-test, the Kruskal-Wallis and Wilcoxon Signed-rank test were used for analyses.
CONCLUSIONS
In order to improve treatment at a multidisciplinary pain centre, it may be of value to target treatments to different patient subgroups based on, amongst other things, age and employment status.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anxiety; Chronic Pain; Demography; Denmark; Depression; Female; Humans; Male; Middle Aged; Pain Clinics; Pain Measurement; Quality of Life
PubMed: 26678805
DOI: 10.1093/intqhc/mzv108 -
Evaluation & the Health Professions Dec 2015To understand what circumstances lend groups to be recognized as hardly reached by health services and research, we systematically reviewed studies that identified their... (Review)
Review
To understand what circumstances lend groups to be recognized as hardly reached by health services and research, we systematically reviewed studies that identified their priority populations as hard to reach. We classified attributes of hardly reached groups into cultural/environmental, individual, and demographic domains. Of the 334 identified studies, 78.74% used attributes that were classified into the cultural/environmental, 74.85% the individual, and 50% the demographic domain to identify those hardly reached. Of all possible combinations of domains, the most common was the use of all three domains (28.74%). Overall, papers were more likely to use attributes to identify their hardly reached population that fell into more than one domain (74.85%) compared to only one domain (25.15%; χ(2), p < .0001). Through this review, we identified the attributes of those who have been identified as hardly reached in published research. No single attribute is used to identify those who are hardly reached. This reflects a socioecological perspective, emphasizing that both intrapersonal and external elements may cause interventions to fail to reach those intended. Moreover, the focus not on populations hardly reached but on the attributes of those hardly reached suggests objectives for interventions to reach them better.
Topics: Age Factors; Cognition; Environment; Ethnicity; Health Promotion; Humans; Residence Characteristics; Sex Factors; Sexual Behavior; Social Support; Socioeconomic Factors; Stereotyping; Substance-Related Disorders
PubMed: 26405265
DOI: 10.1177/0163278715605883 -
Clinical Therapeutics Jun 2003Anemia is a reduction in the oxygen-carrying capacity of red blood cells that results in a variety of symptoms, including dyspnea, headaches, light-headedness, and... (Review)
Review
BACKGROUND
Anemia is a reduction in the oxygen-carrying capacity of red blood cells that results in a variety of symptoms, including dyspnea, headaches, light-headedness, and fatigue. Although anemia has been associated with reduced health-related quality of life (HRQoL), its treatment has not yet been consistently shown to improve HRQoL.
OBJECTIVE
This systematic review of the literature was conducted to determine whether the treatment of anemia improves HRQoL domains, regardless of the type of underlying disease.
METHODS
Data for this review were drawn from the clinical trial databases from 2 previous systematic literature reviews of erythropoiesis-stimulating protein treatment for renal insufficiency- and cancer-related anemia, both spanning the period January 1, 1980, through December 31, 2001. MEDLINE, Cancerlit, and Current Contents/Clinical Medicine were searched using the combined terms erythropoietin, kidney failure, neoplasms, and anemia. The reference lists of all identified articles were searched manually for additional relevant papers. The review included prospective studies that reported both HRQoL and hematocrit (Hct) in patients with cancer or renal insufficiency who received treatment for anemia with an erythropoiesis-stimulating protein. HRQoL was categorized by domain (overall, energy/fatigue, physical, activity); changes in HRQoL domains were expressed as effect sizes and meta-analyzed, as were correlation coefficients. The effects on HRQoL of dropout rate, study duration, baseline Hct, and change in Hct were examined in meta-regression analyses.
RESULTS
Sixteen studies each were identified in patients with renal insufficiency (N = 2253) and patients with cancer (N = 10,695). The treated groups included 11,710 patients, and the control groups included 1238 patients. The baseline Hct in all treated groups averaged 26.0%: 28.3% in the group with cancer and 24.4% in the group with renal insufficiency. The mean improvement in Hct from baseline to the end of treatment was 8.3% (range, 1.0%-16.5%) in treated patients and 1.0% (range, 0.0%-3.3%) in controls. The Hct changes were similar in treated patients with cancer and treated patients with renal insufficiency, as was the HRQoL effect size (0.43). Dropout rate and study duration were not significant predictors of HRQoL changes, but change in Hct was a significant predictor in both conditions. Meta-analysis of the correlation coefficients, adjusting for HRQoL domains, showed a consistent and significant positive correlation between change in Hct and change in HRQoL (P < 0.001).
CONCLUSION
The consistency in both direction and magnitude of effect across many studies and thousands of patients supports the hypothesis that treatment of anemia with erythropoiesis-stimulating protein improves selected HRQoL domains in patients with renal insufficiency- or cancer-related anemia.
Topics: Anemia; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Renal Insufficiency; Treatment Outcome
PubMed: 12860499
DOI: 10.1016/s0149-2918(03)80170-4 -
Journal of Cystic Fibrosis : Official... May 2022There is no data exclusively on the relationship between health-related quality-of-life (HRQOL) and lung disease severity in early school-aged children with cystic...
BACKGROUND
There is no data exclusively on the relationship between health-related quality-of-life (HRQOL) and lung disease severity in early school-aged children with cystic fibrosis (CF). Using data from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) we assessed the relationships between HRQOL, lung function and structure.
METHODS
125 children aged 6.5-10 years enrolled in the AREST CF program were included from CF clinics at Royal Children's Hospital (RCH), Melbourne (n = 66) and Perth Children's Hospital (PCH), Perth (n = 59), Australia. Demographics, HRQOL measured by Cystic Fibrosis Questionnaire-Revised (CFQ-R), spirometry, multiple-breath washout (MBW) and chest CT were collected across two years. Correlation between CFQ-R scores and lung structure/function parameters and agreement between parent-proxy and child-reported HRQOL were evaluated.
RESULTS
No correlation was observed between most CFQ-R domain scores and FEV1 z-scores, excepting weak-positive correlation with parent CFQ-R Physical (rho = 0.21, CI 0.02-0.37), and Weight (rho = 0.21, CI 0.03-0.38) domain and child Body domain (rho = 0.26, CI 0.00-0.48). No correlation between most CFQ-R domain scores and LCI values was noted excepting weak-negative correlation with parent Respiratory (rho = -0.23, CI 0.41-0.05), Emotional (rho = -0.24, CI 0.43-0.04), and Physical (-0.21, CI 0.39-0.02) domains. Furthermore, structural lung disease on CT data demonstrated little to no association with CFQ-R parent and child domain scores. Additionally, no agreement between child self-report and parent-proxy CFQ-R scores was observed across the majority of domains and visits.
CONCLUSION
HRQOL correlated poorly with lung function and structure in early school-aged children with CF, hence clinical trials should consider these outcomes independently when determining study end-points.
Topics: Australia; Child; Cystic Fibrosis; Health Status; Humans; Lung; Quality of Life; Severity of Illness Index
PubMed: 34801433
DOI: 10.1016/j.jcf.2021.11.005 -
Cancer Medicine Apr 2020Recent studies have demonstrated that various long non-coding RNAs (lncRNAs) participate in the gastric cancer (GC) development and metastasis. Some lncRNAs exert their...
Recent studies have demonstrated that various long non-coding RNAs (lncRNAs) participate in the gastric cancer (GC) development and metastasis. Some lncRNAs exert their regulatory function by interacting with microRNAs. Here we identified a novel lncRNA RP11-81H3.2 that was highly expressed in the GC tissue and cell lines. RP11-81H3.2 knockdown significantly inhibited the proliferation, migration, and invasion of GC cells. Mechanistically, we demonstrated that RP11-81H3.2 directly interacted with miR-339 while miR-339 regulated the HNRNPA1 expression by targeting HRRNPA1 3'-UTR. RP11-81H3.2-miR-339-HNRNPA1 interaction network regulated the GC cell proliferation, migration, and invasion. Moreover, our results confirmed that RP11-81H3.2 knockdown suppressed the tumor growth of GC in a xenograft model in vivo. In summary, the results suggest that RP11-81H3.2 functions as an oncogene in GC and could be utilized as a promising diagnosis and therapeutic marker for GC treatment.
Topics: Animals; Apoptosis; Biomarkers, Tumor; Cell Movement; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Heterogeneous Nuclear Ribonucleoprotein A1; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Middle Aged; Prognosis; Protein Interaction Domains and Motifs; RNA, Long Noncoding; Stomach Neoplasms; Survival Rate; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
PubMed: 32052594
DOI: 10.1002/cam4.2867 -
Demography Aug 2012The financial viability of Social Security, the single largest U.S. government program, depends on accurate forecasts of the solvency of its intergenerational trust...
The financial viability of Social Security, the single largest U.S. government program, depends on accurate forecasts of the solvency of its intergenerational trust fund. We begin by detailing information necessary for replicating the Social Security Administration's (SSA's) forecasting procedures, which until now has been unavailable in the public domain. We then offer a way to improve the quality of these procedures via age- and sex-specific mortality forecasts. The most recent SSA mortality forecasts were based on the best available technology at the time, which was a combination of linear extrapolation and qualitative judgments. Unfortunately, linear extrapolation excludes known risk factors and is inconsistent with long-standing demographic patterns, such as the smoothness of age profiles. Modern statistical methods typically outperform even the best qualitative judgments in these contexts. We show how to use such methods, enabling researchers to forecast using far more information, such as the known risk factors of smoking and obesity and known demographic patterns. Including this extra information makes a substantial difference. For example, by improving only mortality forecasting methods, we predict three fewer years of net surplus, $730 billion less in Social Security Trust Funds, and program costs that are 0.66% greater for projected taxable payroll by 2031 compared with SSA projections. More important than specific numerical estimates are the advantages of transparency, replicability, reduction of uncertainty, and what may be the resulting lower vulnerability to the politicization of program forecasts. In addition, by offering with this article software and detailed replication information, we hope to marshal the efforts of the research community to include ever more informative inputs and to continue to reduce uncertainties in Social Security forecasts.
Topics: Age Distribution; Forecasting; Humans; Models, Statistical; Mortality; Risk Factors; Sex Distribution; Social Security; Socioeconomic Factors; Statistics as Topic; United States; United States Social Security Administration
PubMed: 22592944
DOI: 10.1007/s13524-012-0106-z -
Medicine Jun 2024This study aimed to investigate the different impacts of sensorial and mobility frailty on overall and domain-specific cognitive function. Further, the independent... (Observational Study)
Observational Study
This study aimed to investigate the different impacts of sensorial and mobility frailty on overall and domain-specific cognitive function. Further, the independent associations between other intricate capacity (IC) dimensions, including vitality and psychological dimensions, and overall and domain-specific cognitive function were investigated. A total of 429 participants (mean age, 72.91 ± 7.014 years; 57.30% female) underwent IC capacity assessment. Other covariates, such as demographics, health-related variables were also assessed. Overall or domain-specific cognitive impairment was used as a dependent variable in logistic regression analyses adjusted for demographic, health-related, and psychosocial confounders. After adjustment for demographic, health-related, and psychosocial confounders, individuals with sensorial frailty (odds ratio [OR] = 0.435; 95% confidence interval [CI] = 0.236-0.801; P = .008) had a significantly lower risk of mild cognitive impairment (MCI), marginally low delayed memory impairment (OR = 0.601, 95% CI = 0.347-1.040; P = .069), and language impairment (OR = 0.534, 95% CI = 0.305-0.936; OR = 0.318, P = .029; OR = 0.318,95% CI = 0.173-0.586; P < .001) by Boston naming and animal fluency tests than did those with both sensorial and mobility frailty or mobility frailty only. Depressive symptoms had a significant negative influence on executive function. Cardiovascular disease and non-skin malignancy were independent determinants of MCI, and diabetes mellitus was independently associated with processing speed, attention, and executive function. Sensorial and mobility frailty were independent risk factors for cognitive impairment. Mobility frailty had a greater negative influence on the overall cognitive function and memory and language function than did sensorial frailty. The reserve decline in the psychological dimension of IC and chronic diseases also had a significant adverse influence on overall and domain-specific cognition function.
Topics: Humans; Female; Male; Aged; Cognitive Dysfunction; Independent Living; China; Cognition; Frailty; Frail Elderly; Aged, 80 and over; Geriatric Assessment; Cross-Sectional Studies; Mobility Limitation; East Asian People
PubMed: 38847667
DOI: 10.1097/MD.0000000000038500 -
Nature Communications Jun 2018To date, the molecular mechanism underlying constitutive signal transducer and activator of transcription 3 (STAT3) activation in gliomas is largely unclear. In this...
To date, the molecular mechanism underlying constitutive signal transducer and activator of transcription 3 (STAT3) activation in gliomas is largely unclear. In this study, we report that Smad6 is overexpressed in nuclei of glioma cells, which correlates with poor patient survival and regulates STAT3 activity via negatively regulating the Protein Inhibitors of Activated STAT3 (PIAS3). Mechanically, Smad6 interacts directly with PIAS3, and this interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and the Ring domain of PIAS3. Smad6 recruits Smurf1 to facilitate PIAS3 ubiquitination and degradation, which also depends on the MH2 domain and the PY motif of Smad6. Consequently, Smad6 reduces PIAS3-mediated STAT3 inhibition and promotes glioma cell growth and stem-like cell initiation. Moreover, the Smad6 MH2 transducible protein restores PIAS3 expression and subsequently reduces gliomagenesis. Collectively, we conclude that nuclear-Smad6 enhances glioma development by inducing PIAS3 degradation and subsequent STAT3 activity upregulation.
Topics: Adult; Aged; Aged, 80 and over; Animals; Brain; Brain Neoplasms; Carcinogenesis; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Cohort Studies; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Glioma; HEK293 Cells; Humans; Infant; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Molecular Chaperones; Protein Domains; Protein Inhibitors of Activated STAT; Proteolysis; STAT3 Transcription Factor; Signal Transduction; Smad6 Protein; Survival Rate; Ubiquitin-Protein Ligases; Ubiquitination; Up-Regulation; Xenograft Model Antitumor Assays; Young Adult
PubMed: 29950561
DOI: 10.1038/s41467-018-04936-9 -
Molecular Neurobiology Mar 2021LDL receptor-related protein (LRP) 10 was recently identified as a Parkinson's disease gene through genome-wide linkage and sequencing analysis, but its role in...
LDL receptor-related protein (LRP) 10 was recently identified as a Parkinson's disease gene through genome-wide linkage and sequencing analysis, but its role in Parkinson's disease in various populations is still unclear. The aim of this study was to determine the frequency and spectrum of LRP10 mutations in a cohort of Parkinson's disease patients from mainland China. All LRP10 exons and their flanking intron regions were screened by direct sequencing in 567 unrelated Parkinson's disease patients and 600 unrelated controls. We detected 29 exonic or splicing variants in 79 patients with Parkinson's disease. Five variants (c.A181C:p.I61L, c.C652T:p.Q218X, c.C833T:p.T278I, c.T1592G:p.I531S, c.T1697C:p.L566P) were predicted to be disease-causing or damaging by multiple in silico tools. Our study provides genetic evidence that LRP10 defects may correlate with sporadic Parkinson's disease.
Topics: Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Asian People; China; Ethnicity; Female; Genetic Predisposition to Disease; Humans; LDL-Receptor Related Proteins; Male; Middle Aged; Mutation; Parkinson Disease; Protein Domains; Young Adult
PubMed: 33118139
DOI: 10.1007/s12035-020-02186-9