Tobacco use among adults with disabilities in nine countries-Demographic and Health Survey, 2016-2021.

Few studies have investigated tobacco use among people with disabilities living in low- and middle-income countries (LMICs). We aimed to examine current tobacco use among men and women with disabilities using Demographic and Health Survey (DHS) data from 9 LMICs. We considered a respondent currently use tobacco products if they reported current use of any combustible/smoked tobacco products or smokeless tobacco products. We performed secondary analyses of DHS data from 2016-2021 collected in Haiti, Mali, Mauritania, Nigeria, Pakistan, Rwanda, South Africa, Timor-Leste, and Uganda. We examined marginal effects in logistic regression to calculate the adjusted prevalence and adjusted prevalence differences of tobacco use by disability status, controlling for selected sociodemographic characteristics. The adjusted prevalence of current use of tobacco products among women with a moderate/severe disability, mild disability, and no disability varied across countries, with medians of 1.9% (range = 0.1% [Mali] to 11.3% [Pakistan]), 3.2% (range = 0.9% [Nigeria] to 13.3% [South Africa]), and 2.3% (range = 0.5% [Nigeria] to 8.9% [South Africa]), respectively. For men with moderate/severe disability, the median adjusted prevalence for current use of tobacco products was 18.8% (range = 8.9% [Rwanda] to 55.0% [Timor-Leste]). The median prevalences of current use of tobacco products for men with mild disability and no disability were similar to those with moderate/severe disability, at 16.5% and 15.9%, respectively. Current tobacco product use among people with disabilities varied for countries included in our study; however, with few exceptions, current tobacco product use was similar across disability status groups. Additional research is warranted to determine whether our findings extend beyond the nine countries assessed here. It is important to consider the needs of people with disabilities in tobacco prevention, control, and cessation efforts so that this substantial population can benefit equitably from such programs, interventions, or policies.

County-Level Geographic Disparities in Disabilities Among US Adults, 2018.

INTRODUCTION: Local data are increasingly needed for public health practice. County-level data on disabilities can be a valuable complement to existing estimates of disabilities. The objective of this study was to describe the county-level prevalence of disabilities among US adults and identify geographic clusters of counties with a higher or lower prevalence of disabilities. METHODS: We applied a multilevel logistic regression and poststratification approach to geocoded 2018 Behavioral Risk Factor Surveillance System data, Census 2018 county-level population estimates, and American Community Survey 2014-2018 poverty estimates to generate county-level estimates for 6 functional disabilities and any disability type. We used cluster-outlier spatial statistical methods to identify clustered counties. RESULTS: Among 3,142 counties, median estimated prevalence was 29.5% for any disability and differed by type: hearing (8.0%), vision (4.9%), cognition (11.5%), mobility (14.9%), self-care (3.7%), and independent living (7.2%). The spatial autocorrelation statistic, Moran's I, was 0.70 for any disability and 0.60 or greater for all 6 types of disability, indicating that disabilities were highly clustered at the county level. We observed similar spatial cluster patterns in all disability types except hearing disability. CONCLUSION: The results suggest substantial differences in disability prevalence across US counties. These data, heretofore unavailable from a health survey, may help with planning programs at the county level to improve the quality of life for people with disabilities.

Post-COVID conditions and healthcare utilization among adults with and without disabilities-2021 Porter Novelli FallStyles survey.

BACKGROUND: Adults with disabilities are at increased risk for SARS-CoV-2 infection and severe disease; whether adults with disabilities are at an increased risk for ongoing symptoms after acute SARS-CoV-2 infection is unknown. OBJECTIVES: To estimate the frequency and duration of long-term symptoms (>4 weeks) and health care utilization among adults with and without disabilities who self-report positive or negative SARS-CoV-2 test results. METHODS: Data from a nationwide survey of 4510 U.S. adults administered from September 24, 2021-October 7, 2021, were analyzed for 3251 (79%) participants who self-reported disability status, symptom(s), and SARS-CoV-2 test results (a positive test or only negative tests). Multivariable models were used to estimate the odds of having ≥1 COVID-19-like symptom(s) lasting >4 weeks by test result and disability status, weighted and adjusted for socio-demographics. RESULTS: Respondents who tested positive for SARS-CoV-2 had higher odds of reporting ≥1 long-term symptom (with disability: aOR = 4.50 [95% CI: 2.37, 8.54] and without disability: aOR = 9.88 [95% CI: 7.13, 13.71]) compared to respondents testing negative. Among respondents who tested positive, those with disabilities were not significantly more likely to experience long-term symptoms compared to respondents without disabilities (aOR = 1.65 [95% CI: 0.78, 3.50]). Health care utilization for reported symptoms was higher among respondents with disabilities who tested positive (40%) than among respondents without disabilities who tested positive (18%). CONCLUSIONS: Ongoing symptoms among adults with and without disabilities who also test positive for SARS-CoV-2 are common; however, the frequency of health care utilization for ongoing symptoms is two-fold among adults with disabilities.

Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus.

OBJECTIVE: Evaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care. METHODS: Active SLE patients (SLE Disease Activity Index 2000 (SLEDAI-2K) ≥6 during screening and SLEDAI-2K ≥4 for clinical features at week 0) despite receiving oral glucocorticoids, antimalarials, or immunomodulatory drugs were randomised (3:2) to receive ustekinumab (intravenous infusion ~6 mg/kg at week 0, followed by subcutaneous injections of ustekinumab 90 mg at week 8 and every 8 weeks) or placebo through week 48. The primary endpoint was SLE Responder Index (SRI)-4 at week 52, and major secondary endpoints included time to flare through week 52 and SRI-4 at week 24. RESULTS: At baseline, 516 patients were randomised to placebo (n=208) or ustekinumab (n=308). Following the planned interim analysis, the sponsor discontinued the study due to lack of efficacy but no safety concerns. Efficacy analyses included 289 patients (placebo, n=116; ustekinumab, n=173) who completed or would have had a week 52 visit at study discontinuation. At week 52, 44% of ustekinumab patients and 56% of placebo patients had an SRI-4 response; there were no appreciable differences between the treatment groups in the major secondary endpoints. Through week 52, 28% of ustekinumab patients and 32% of placebo patients had a British Isles Lupus Assessment Group flare, with a mean time to first flare of 204.7 and 200.4 days, respectively. Through week 52, 70% of ustekinumab patients and 74% of placebo patients had ≥1 adverse event. CONCLUSIONS: Ustekinumab did not demonstrate superiority over placebo in this population of adults with active SLE; adverse events were consistent with the known safety profile of ustekinumab. TRIAL REGISTRATION NUMBER: NCT03517722.

Therapy-related myeloid neoplasms with normal karyotype show distinct genomic and clinical characteristics compared to their counterparts with abnormal karyotype.

Therapy-related myeloid neoplasms (t-MNs) are a complication of treatment with cytotoxic chemotherapy and/or radiation therapy. The majority of t-MNs show chromosomal abnormalities associated with myelodysplastic syndrome (MDS) or KMT2A rearrangements and are characterized by poor clinical outcomes. A small but substantial subset of patients have normal karyotype (NK) and their clinical characteristics and mutational profiles are not well studied. We retrospectively studied patients diagnosed with t-MN at three institutions and compared the mutational profile and survival data between t-MNs with NK and t-MNs with abnormal karyotype (AK). A total of 204 patients with t-MN were identified including 158 with AK and 46 with NK. NK t-MNs, compared to AK, were enriched for mutations in TET2 (p < 0.0001), NPM1 (p < 0.0001), ASXL1 (p = 0.0003), SRSF2 (p < 0.0001), RUNX1 (p = 0.0336) and STAG2 (p = 0.0099) and showed a significantly lower frequency of TP53 mutations (p < 0.0001). Overall survival (OS) was significantly lower in AK t-MNs as compared to NK cases (p = 0.0094). In our study, NK t-MNs showed a significantly better OS, a higher prevalence of MN-associated mutations and a lower frequency of TP53 mutations compared to their AK counterparts. The distinct clinical and mutational profile of NK t-MNs merits a separate classification.

State-specific prevalence of current e-cigarette use by disability status and disability type-United States, BRFSS 2016-2018.

BACKGROUND: Cigarette smoking is the leading cause of preventable disease and death in the United States. The tobacco product landscape has diversified to include electronic cigarettes (e-cigarettes). Adults with disabilities are more likely than adults without disabilities to smoke cigarettes, but within the current body of literature, there is limited information on the use of e-cigarettes among adults with disabilities. OBJECTIVE: To assess overall and state-specific prevalence of current e-cigarette use among adults by disability status, disability type, sex, and age. METHODS: Disability was defined as having serious difficulty with vision, hearing, mobility, cognition, or any difficulty with self-care or independent living. The Behavioral Risk Factor Surveillance System cross-sectional survey data (2016-2018; n = 1,150,775) were used to estimate state and District of Columbia prevalence of current e-cigarette use among adults (aged ≥18 years) with and without disabilities, overall and by disability type, sex, and age group. RESULTS: Median prevalence of current e-cigarette use was higher among adults with than without disabilities (6.5% vs. 4.3%, P < 0.05). Among adults with disabilities, use varied from 2.5% in DC to 10.0% in Colorado; median use was highest among those with cognitive disabilities (10.0%) and those aged 18-24 years (18.7%). CONCLUSIONS: Prevalence of current e-cigarette use was higher among adults with than without disabilities and varied across states by disability status, type, and age group. The findings underscore the need to monitor e-cigarette use among adults with disabilities and specifically include them in tobacco control policies and programs addressing e-cigarette use.

Guselkumab, an inhibitor of the IL-23p19 subunit, provides sustained improvement in signs and symptoms of active psoriatic arthritis: 1 year results of a phase III randomised study of patients who were biologic-naïve or TNFα inhibitor-experienced.

OBJECTIVE: Evaluation of the efficacy and safety of guselkumab, a human monoclonal antibody targeting the interleukin-23p19 subunit, in patients with psoriatic arthritis (PsA) through 1 year. METHODS: Adults who met ClASsification criteria for Psoriatic ARthritis, with active disease (≥3 swollen and ≥3 tender joints; C reactive protein ≥0.3 mg/dL) despite standard treatment (31% previously received ≤2 tumour necrosis factor inhibitors (TNFi)), were randomised (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week0, Week4, then Q8W; or placebo with cross-over to guselkumab 100 mg Q4W at Week24 (PBO→Q4W) through Week48. Clinical efficacy through Week52 (employing non-responder imputation) and adverse events (AEs) through Week60 were evaluated. RESULTS: Of 381 treated patients, 90% completed the study. Numerical increases in the proportions of patients achieving ≥20% improvement in ACR criteria (ACR20) were observed post-Week24, reaching 73% (94/128) and 60% (76/127) for Q4W-randomised and Q8W-randomised patients, respectively, by Week52. Proportions of patients achieving ACR50/ACR70/skin responses and minimal/very low disease activity were maintained, as were improvements in physical function and health-related quality of life, through Week52 in guselkumab-randomised patients. Response to guselkumab was maintained in both TNFi-naïve and TNFi-experienced patients. Serious AEs and serious infections occurred in similar proportions of guselkumab Q4W-randomised (3% and 0%) and Q8W-randomised (6% and 2%) patients through Week60, with no new safety concerns versus observations through Week24. No guselkumab-treated patient and two patients receiving placebo died; no study participant developed opportunistic infection or inflammatory bowel disease. CONCLUSION: Guselkumab provided sustained improvement across multiple clinical manifestations of PsA, maintaining a favourable benefit-risk profile, through 1 year regardless of prior TNFi exposure.

Chromatin regulatory dynamics of early human small intestinal development using a directed differentiation model.

The establishment of the small intestinal (SI) lineage during human embryogenesis ensures functional integrity of the intestine after birth. The chromatin dynamics that drive SI lineage formation and regional patterning in humans are essentially unknown. To fill this knowledge void, we apply a cutting-edge genomic technology to a state-of-the-art human model of early SI development. Specifically, we leverage chromatin run-on sequencing (ChRO-seq) to define the landscape of active promoters, enhancers and gene bodies across distinct stages of directed differentiation of human pluripotent stem cells into SI spheroids with regional specification. Through comprehensive ChRO-seq analysis we identify candidate stage-specific chromatin activity states, novel markers and enhancer hotspots during the directed differentiation. Moreover, we propose a detailed transcriptional network associated with SI lineage formation or regional patterning. Our ChRO-seq analyses uncover a previously undescribed pattern of enhancer activity and transcription at HOX gene loci underlying SI regional patterning. We also validated this unique HOX dynamics by the analysis of single cell RNA-seq data from human fetal SI. Overall, the results lead to a new proposed working model for the regulatory underpinnings of human SI development, thereby adding a novel dimension to the literature that has relied almost exclusively on non-human models.

Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by regulating intestinal microbiota and the IL-6/STAT3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Baitouweng (BTW) decoction, a Chinese traditional medicine prescription, has been used to treat ulcerative colitis (UC) over hundreds of years. In this study, we investigated the anti-inflammatory effects of BTW and intestinal flora of dextran sulfate sodium (DSS)-induced UC mice, and we investigated the mechanism of BTW in the preliminary treatment of UC. AIM OF STUDY: The aim of this study was to elucidate the mechanism of BTW in treating UC through molecular biology and high-throughput sequencing. METHODS: DSS-induced UC mice were established and randomly divided into the following four groups: control group, DSS group, BTW group and sulfasalazine (SASP) group. Except for the control group, 3% DSS drinking water was given to each group for 7 days, and the other two groups were intragastrically administered with BTW and SASP. Mice were sacrificed after gavage for 10 days. Body weight loss, disease activity index (DAI), colon length, colon histopathology and the expression of inflammatory cytokines were measured. Intestinal content samples were collected, and intestinal flora differences were analyzed by 16 S rDNA sequencing. RESULTS: BTW effectively reduced the symptoms and histopathological score of UC mice, and it reduced the production of IL-6, IL-1ß and TNF-α. Activation of the IL-6/STAT3 pathway was also suppressed by BTW treatment. Moreover, 16 S rDNA sequencing showed that the intestinal flora of mice in the DSS group was disordered compared to the control group. After treatment with BTW, the diversity of intestinal flora was significantly improved. At the phylum level, the proportion of Firmicutes to Bacteroidetes was decreased, and the ratio of Proteobacteria was decreased. At the genus level, the relative abundance of Escherichia-Shigella was decreased, but that of Lactobacillus and Akkermansia were increased. CONCLUSION: BTW significantly improved the inflammatory symptoms of mice with acute colitis, and the latent mechanism of BTW may be related to various signaling pathways, including the modulation of intestinal microflora and inflammatory signaling pathways, such as IL-6/STAT3.

A vertebrate model to reveal neural substrates underlying the transitions between conscious and unconscious states.

The field of neuropharmacology has not yet achieved a full understanding of how the brain transitions between states of consciousness and drug-induced unconsciousness, or anesthesia. Many small molecules are used to alter human consciousness, but the repertoire of underlying molecular targets, and thereby the genes, are incompletely understood. Here we describe a robust larval zebrafish model of anesthetic action, from sedation to general anesthesia. We use loss of movement under three different conditions, spontaneous movement, electrical stimulation or a tap, as a surrogate for sedation and general anesthesia, respectively. Using these behavioral patterns, we find that larval zebrafish respond to inhalational and IV anesthetics at concentrations similar to mammals. Additionally, known sedative drugs cause loss of spontaneous larval movement but not to the tap response. This robust, highly tractable vertebrate model can be used in the detection of genes and neural substrates involved in the transition from consciousness to unconsciousness.

Physical activity types among US adults with mobility disability, Behavioral Risk Factor Surveillance System, 2017.

BACKGROUND: The Physical Activity Guidelines for Americans, second edition, recommend that all adults participate in moderate-intensity equivalent aerobic physical activity at least 150-300 min/week for substantial health benefits and muscle-strengthening activities involving all major muscle groups 2 or more days a week. The prevalence of the general population meeting the Guidelines and the types of physical activity in which they engage have been described elsewhere. Similar descriptions are lacking for individuals with mobility disability whose physical activity profiles may differ from the general population. OBJECTIVE: This study examined patterns of aerobic and muscle-strengthening physical activity among US adults with mobility disability. METHODS: We used 2017 Behavioral Risk Factor Surveillance System data from 66,635 adults with mobility disability. We estimated the percentage who engaged in any aerobic physical activity, met the aerobic and/or muscle-strengthening guidelines, and who participated in specific activities. RESULTS: Less than half (45.2%) of US adults with mobility disability reported engaging in aerobic physical activity, and 39.5% met one or both components of the physical activity guidelines. Walking was the most commonly reported activity type (34.0%). CONCLUSIONS: Walking is a common activity type among adults with mobility disability. Efforts to make walking or wheelchair rolling a safe, viable option are important to helping decrease barriers that may limit the ability of those with mobility disability to engage in walking or other physical activity types.

[Preliminary evaluation and mechanism of adipose-derived stem cell transplantation from allogenic diabetic rats in the treatment of diabetic rat wounds].

Objective: To investigate whether adipose-derived stem cells (ASCs) from allogeneic diabetic rats can promote wound healing in diabetic rats or not and the mechanism. Methods: (1) Fifty-six male Wistar rats aged 12-16 weeks were divided into diabetic group and healthy group according to the random number table (the same grouping method below), with 28 rats in each group. Rats in healthy group were not treated with any treatment. Rats in diabetic group were injected with 10 g/L streptozotocin 60 mg/kg intraperitoneally in one time to establish the diabetic model. Four rats in diabetic group and 4 rats in healthy group were selected according to the random number table, and the adipose tissue in the inguinal region was taken to culture and purify ASCs, so as to obtain healthy rat-derived ASCs (hereinafter referred to as nASCs) and diabetic rat-derived ASCs (hereinafter referred to as dASCs). The third passage of nASCs (n=3) and dASCs (n=3) were taken, and the positive expression rates of cell surface differentiation antigens CD105, CD31, CD34, and CD44 were detected with flow cytometer for defining ASCs purity. (2) The rest 24 rats in healthy group and 24 rats in diabetic group were used to make three round full-thickness skin defect wounds with a diameter of 12 mm on the back of each rat. Immediately after injury, phosphate buffer saline (PBS), nASCs of 2×10(7)/mL, and dASCs of 2×10(7)/mL each in the volume of 0.5 mL were subcutaneously injected into three wounds and their margins of each rat, respectively. On post injury day (PID) 1, 3, 7, and 12, 6 rats in each group were selected according to the random number table to calculate the wound area, and the wound tissue was stained with hematoxylin-eosin to observe the histological morphology of the wound. (3) Human ASCs (hASCs) were subcultured, and the 4th to 7th passage of cells were used for the subsequent experiments. The hASCs were divided into 7 groups, with 12 samples in each group. Cells in blank control group were cultured with mesenchymal stem cell culture medium, and cells in simple advanced glycation end products (AGEs) group, simple protein group, simple high glucose group, simple high osmotic pressure group, AGEs-high glucose combination group, and protein-high osmotic pressure combination group were cultured with mesenchymal stem cell culture medium containing a final mass concentration of 100 mg/L AGEs, 100 mg/L bovine serum albumin (BSA), 28 mmol/L D-glucose, 28 mmol/L mannitol, 100 mg/L AGEs+ 28 mmol/L D-glucose, 100 mg/L BSA+ 28 mmol/L mannitol, respectively. Cell proliferation was detected by cell counting kit 8 at post culture hour (PCH) 2 and on post culture day (PCD) 2, 4 and 6. (4) The hASCs were divided into blank control group, simple AGE group, simple high glucose group, and AGE-high glucose combination group, with 12 samples in each group, which were treated the same as corresponding groups in experiment (3). On PCD 0, 2, 4, and 6, the positive expression rates of cell surface differentiation antigens CD105, CD44, and CD45 were detected by flow cytometer to estimate their homeostasis. (5) The hASCs were divided into AGE-high glucose combination group and protein-high osmotic pressure combination group, with 9 samples in each group, which were treated the same as corresponding groups in experiment (3). On PCD 2, 4, and 6, the expression of intracellular protein was detected by cyanine 3-streptavidin double-antibody sandwich technique. Data were processed with analysis of variance for factorial design, least significant difference test, and Bonferroni correction. Results: (1) The positive expression rates of CD44 in nASCs and dASCs were both higher than 96%, the positive expression rates of CD31 and CD34 were low, and the positive expression rates of CD105 were about 40%, which basically met the purity requirements. (2) The areas of wounds treated by three methods in rats of healthy group and diabetic group were similar on PID 1 (P>0.05). In healthy group, compared with (0.682 1±0.078 9), (0.314 3±0.113 7), and (0.064 3±0.002 1) cm(2) of the PBS-treated wounds in rats, the area of nASCs-treated wounds in rats decreased significantly on PID 3, 7, and 12 [(0.464 1±0.092 6), (0.223 9±0.072 7), and (0.034 3±0.012 5) cm(2), P<0.05], the area of dASCs-treated wounds in rats decreased significantly on PID 3 and 12 [(0.514 1±0.124 1) and (0.043 7±0.032 8) cm(2), P<0.05] but was not obviously changed on PID 7 [(0.274 2±0.062 5) cm(2), P>0.05]. Compared with those of the dASCs-treated wounds of rats within the same group, the area of the nASCs-treated wounds of rats in healthy group decreased significantly on PID 3 and 7 (P<0.05) but was not obviously changed on PID 12 (P>0.05). In diabetic group, compared with (0.853 5±0.204 8), (0.670 5±0.164 8), and (0.131 4±0.074 4) cm(2) of the PBS-treated wounds in rats, the area of nASCs-treated wounds in rats decreased significantly on PID 3, 7, and 12 [(0.633 4±0.132 5), (0.331 8±0.023 5), and (0.074 2±0.003 8) cm(2), P<0.05], the area of dASCs-treated wounds in rats decreased significantly on PID 3 [(0.773 6±0.182 2) cm(2), P<0.05] but was not obviously changed on PID 7 and 12 [(0.510 6±0.192 2) and (0.114 4±0.003 1) cm(2), P>0.05]. Compared with the dASCs-treated wounds of rats within the same group, the area of the nASCs-treated wounds of rats in diabetic group was not obviously changed on PID 3 and 7 (P>0.05) but decreased significantly on PID 12 (P<0.05). There was no obvious difference in histological morphology of the wounds treated with three methods in rats of each group on PID 1. On PID 3, a small amount of microvessels were formed in the wounds treated with nASCs and dASCs of rats in both groups, but microvessel formation was almost undetected in the PBS-treated wounds. On PID 7, more small blood vessels and fibroblasts (Fbs) were observed in the wounds treated with nASCs and dASCs of rats in both groups, but the small blood vessels and Fbs were slightly less in the PBS-treated wounds. On PID 12, the wounds treated with nASCs and dASCs of rats in the two groups were covered by epithelial tissue, the granulation tissue in the PBS-treated wounds of rats in healthy group was not obvious, and the PBS-treated wounds of rats in diabetic group were not completely epithelialized. (3) Compared with those of blank control group, the cell number of hASCs in simple AGEs group decreased significantly on PCD 2, 4, and 6 (P<0.05), which increased significantly on PCD 2 and 4 in simple high glucose group (P<0.05), and that in AGEs-high glucose combination group decreased significantly on PCD 4 and 6 (P<0.05). (4) Compared with that on PCD 4 within the same group, the positive expression rate of CD105 in hASCs decreased significantly in blank control group, simple AGEs group, and AGEs-high glucose combination group on PCD 6 (P<0.05). The positive expression rate of CD44 was higher than 95%, and that of CD45 was less than 2% in hASCs of each group at each time point. (5) Detection values of 7 proteins were located in the confidence interval. The expression levels of basic fibroblast growth factor and tissue inhibitor of metalloproteinase-1 in hASCs of AGEs-high glucose combination group and protein-high osmotic pressure combination group showed increasing trend with the prolongation of culture time. The expression level of human monocyte chemoattractant protein 1 (MCP-1) in hASCs of AGEs-high glucose combination group showed increasing trend with the prolongation of culture time, while the expression level of growth-regulated oncogene (GRO) on PCD 6 was significantly higher than that on PCD 4 within the same group (P<0.05); the expression levels of MCP-1 and GRO in hASCs of protein-high osmotic pressure combination group showed decreasing trend with the prolongation of culture time. The expression level of follistatin in hASCs of protein-high osmotic pressure combination group decreased obviously on PCD 4, while that in hASCs of AGEs-high glucose combination group was significantly lower on PCD 6 than that on PCD 4 (P<0.05). The expression level of vascular endothelial growth factor (VEGF) in hASCs of protein-high osmotic pressure combination group decreased gradually with the prolongation of culture time, while that in hASCs of AGEs-high glucose combination group on PCD 4 decreased significantly as compared with that on PCD 2 (P<0.05). The expression level of urokinase-type plasminogen activator receptor in hASCs of protein-high osmotic pressure combination group on PCD 6 was significantly higher than that on PCD 4 within the same group (P<0.05) and that of AGEs-high glucose combination group on PCD 6 (P<0.05). Conclusions: Both nASCs and dASCs can promote wound healing in rats with simple defect injury, but dASCs have no significant effect on wound healing in rats with diabetes mellitus, which may be related to the inhibition of ASCs proliferation and the influence of high glucose and AGEs intervention on their homeostasis and secretory function.

Survival outcomes of diffuse large B-cell lymphoma by association with concurrent or antecedent follicular lymphoma and double hit status.

Diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL) (tDLBCL) has been traditionally associated with an aggressive course, but more recent studies have shown longer survivals. The clinical significance of concurrent FL at the time of diagnosis of DLBCL (cDLBCL/FL) is less clear. We compared outcomes of tDLBCL, cDLBCL/FL, and de novo DLBCL (dDLBCL) and then evaluated the impact of double hit (DH) rearrangements (MYC with BCL2 and/or BCL6) in these subgroups' outcomes. The progression free survival (PFS) and overall survival (OS) were not significantly different among the three groups (dDLBCL, tDLBCL, and cDLBCL/FL). The effect of DH on survival was then analyzed in two subgroups: (1) dDLBCL and (2) tDLBCL + cDLBCL/FL. PFS and OS were significantly shorter in lymphomas with DH in each of these two subgroups. We conclude that DH status drives outcomes in all DLBCLs, regardless of their transformation status.

[Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China].

The correct thoughts and principles of diagnosis and treatment of chronic refractory wounds need to be formulated. Through the relevant domestic and international consensus and based on clinical experience, the Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China is proposed. It is considered that in the diagnosis and treatment of chronic refractory wounds, in the case of fully understanding the patient's medical history, the following thoughts and principles should be complied in order. (1) Pay attention to the cleanliness of the wound after being cleaned. (2) Reasonably perform debridement to avoid being " excessive" or " not thorough". (3) Reasonably perform examination, diagnosis, and differential diagnosis of pathogenic factors. (4) Treat according to etiology. (5) Find comorbidities and prevent adverse outcomes. (6) Select the correct wound treatment method reasonably and timely. When the conservative wound care treatment is considered, pay attention to embodying the concept of etiological treatment, treat the wound according to the principles of safety, phase, selectivity, and effectiveness, and make a reasonable choice of continuing conservative treatment or surgical treatment in time after completing the preparation of the wound bed. When surgical treatment is considered, pay attention to the selection of reasonable surgical method and donor site, pay attention to the healing rate of surgical wound site and the outcome of donor site, and give reasonable protection to the wound site after surgery. (7) Carry out rehabilitation treatment after wound healing and related health education.

Identification of circular RNAs hsa_circ_0044235 in peripheral blood as novel biomarkers for rheumatoid arthritis.

Circular RNAs (circRNAs) are a new class of RNAs that can be used as biomarkers in clinical blood samples. However, little is known about circRNAs' diagnostic values for rheumatoid arthritis (RA). In this study, the hsa_circ_0054189, hsa_circ_0008675, hsa_circ_0082689, hsa_circ_0082688, hsa_circ_0010932, hsa_circ_0002473 and hsa_circ_0044235 in peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). For hsa_circ_0044235, only one abnormal expression circRNAs in peripheral blood was selected as a targeted circRNA to explore the diagnostic value for RA. Our work demonstrated that the hsa_circ_0044235 in peripheral blood was decreased significantly in RA patients. The hsa_circ_0044235 in peripheral blood from RA patients did not correlate with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) or disease activity score 28 (DAS28). Receiver operating characteristic (ROC) curve analysis suggested that the hsa_circ_0044235 in peripheral blood has significant value in the diagnosis of RA. The risk score based on hsa_circ_0044235 in peripheral blood also distinguished significantly the patients with RA from systemic lupus erythematosus (SLE). This study suggests that the hsa_circ_0044235 in peripheral blood may be a potential biomarker of patients with RA.

Development and validation of brain target controlled infusion of propofol in mice.

Mechanisms through which anesthetics disrupt neuronal activity are incompletely understood. In order to study anesthetic mechanisms in the intact brain, tight control over anesthetic pharmacology in a genetically and neurophysiologically accessible animal model is essential. Here, we developed a pharmacokinetic model that quantitatively describes propofol distribution into and elimination out of the brain. To develop the model, we used jugular venous catheters to infuse propofol in mice and measured propofol concentration in serial timed brain and blood samples using high performance liquid chromatography (HPLC). We then used adaptive fitting procedures to find parameters of a three compartment pharmacokinetic model such that all measurements collected in the blood and in the brain across different infusion schemes are fit by a single model. The purpose of the model was to develop target controlled infusion (TCI) capable of maintaining constant brain propofol concentration at the desired level. We validated the model for two different targeted concentrations in independent cohorts of experiments not used for model fitting. The predictions made by the model were unbiased, and the measured brain concentration was indistinguishable from the targeted concentration. We also verified that at the targeted concentration, state of anesthesia evidenced by slowing of the electroencephalogram and behavioral unresponsiveness was attained. Thus, we developed a useful tool for performing experiments necessitating use of anesthetics and for the investigation of mechanisms of action of propofol in mice.

Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease.

BACKGROUND: Therapeutic options for the treatment of anemia secondary to chronic kidney disease (CKD) remain limited. Vadadustat (AKB-6548) is an oral hypoxia-inducible factor prolyl-hydroxylase domain (HIF-PHD) inhibitor that is being investigated for the treatment of anemia secondary to CKD. METHODS: A phase 2a, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial (NCT01381094) was undertaken in adults with anemia secondary to CKD stage 3 or 4. Eligible subjects were evenly randomized to 5 groups: 240, 370, 500, or 630 mg of once-daily oral vadadustat or placebo for 6 weeks. All subjects received low-dose supplemental oral iron (50 mg daily). The primary endpoint was the mean absolute change in hemoglobin (Hb) from baseline to the end of treatment. Secondary endpoints included iron indices, safety, and tolerability. RESULTS: Ninety-three subjects were randomized. Compared with placebo, vadadustat significantly increased Hb after 6 weeks in a dose-dependent manner (analysis of variance; p < 0.0001). Vadadustat increased the total iron-binding capacity and decreased concentrations of ferritin and hepcidin. The proportion of subjects with at least 1 treatment-emergent adverse event was similar between vadadustat- and placebo-treated groups. No significant changes in blood pressure, vascular endothelial growth factor, C-reactive protein, or total cholesterol were observed. Limitations of this study included its small sample size and short treatment duration. CONCLUSIONS: Vadadustat increased Hb levels and improved biomarkers of iron mobilization and utilization in patients with anemia secondary to stage 3 or 4 CKD. Global multicenter, randomized phase 3 trials are ongoing in non-dialysis-dependent and dialysis-dependent patients.

Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros.

The ability to generate hematopoietic stem cells from human pluripotent cells would enable many biomedical applications. We find that hematopoietic CD34+ cells in spin embryoid bodies derived from human embryonic stem cells (hESCs) lack HOXA expression compared with repopulation-competent human cord blood CD34+ cells, indicating incorrect mesoderm patterning. Using reporter hESC lines to track the endothelial (SOX17) to hematopoietic (RUNX1C) transition that occurs in development, we show that simultaneous modulation of WNT and ACTIVIN signaling yields CD34+ hematopoietic cells with HOXA expression that more closely resembles that of cord blood. The cultures generate a network of aorta-like SOX17+ vessels from which RUNX1C+ blood cells emerge, similar to hematopoiesis in the aorta-gonad-mesonephros (AGM). Nascent CD34+ hematopoietic cells and corresponding cells sorted from human AGM show similar expression of cell surface receptors, signaling molecules and transcription factors. Our findings provide an approach to mimic in vitro a key early stage in human hematopoiesis for the generation of AGM-derived hematopoietic lineages from hESCs.

Adults with One or More Functional Disabilities - United States, 2011-2014.

Nearly 40 million persons in the United States have a disability, as defined by responses to six questions recommended by the U.S. Department of Health and Human Services as the national standard for identifying disabilities in population-based health surveys (1). Although these questions have been used to estimate prevalence of functional disabilities overall, as well as types of functional disabilities (disability type), no study has yet investigated the characteristics of U.S. adults by number of disability types. Knowing the characteristics of persons living with multiple disability types is important for understanding the overall functional status of these persons. CDC analyzed data from the family component of the National Health Interview Survey (NHIS) for the years 2011-2014 to estimate the percentage of adults aged 18-64 years with one, two, three, or four or more disability types, by selected demographic and socioeconomic characteristics. Overall, 22.6 million (11.9%) working-age adults were found to have any disability, and in this population, most (12.8 million) persons had only one disability type. A generally consistent pattern between increasing indicators of low socioeconomic status and the number of disability types was observed. Understanding the demographic and socioeconomic characteristics of working-age adults with disabilities, including those with multiple disability types, might help to further the inclusion of persons with disabilities in public health programs and policies.