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1.
Small ; : e2005357, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33615728

RESUMO

Despite numerous inherent merits of metal-organic frameworks (MOFs), structural fragility has imposed great restrictions on their wider involvement in many applications, such as in catalysis. Herein, a strategy for enhancing stability and enabling functionality in a labile Zr(IV)-MOF has been proposed by in situ porphyrin substitution. A size- and geometry-matched robust linear porphyrin ligand 4,4'-(porphyrin-5,15-diyl)dibenzolate (DCPP2- ) is selected to replace the 4,4'-(1,3,6,8-tetraoxobenzo[lmn][3,8]phenanthroline-2,7(1H,3H,6H,8H)-diyl)dibenzoate (NDIDB2- ) ligand in the synthesis of BUT-109(Zr), affording BUT-110 with varied porphyrin contents. Compared to BUT-109(Zr), the chemical stability of BUT-110 series is greatly improved. Metalloporphyrin incorporation endows BUT-110 MOFs with high catalytic activity in the photoreduction of CO2 , in the absence of photosensitizers. By tuning the metal species and porphyrin contents in BUT-110, the resulting BUT-110-50%-Co is demonstrated to be a good photocatalyst for selective CO2 -to-CO reduction, via balancing the chemical stability, photocatalytic efficiency, and synthetic cost. This work highlights the advantages of in situ ligand substitution for MOF modification, by which uniform distribution and high content of the incoming ligand are accessible in the resulting MOFs. More importantly, it provides a promising approach to convert unstable MOFs, which mainly constitute the vast MOF database but have always been neglected, into robust functional materials.

2.
Transl Res ; 227: 30-41, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32554072

RESUMO

The purinergic P2X3 receptor in the carotid body (CB) is considered a new target for treating hypertension, although approaches for targeted regulating P2X3 receptor expression are lacking. Here, we explored the feasibility of targeted P2X3 receptor down-regulation in CBs by localized low-intensity focused ultrasound (LIFU)-mediated gene delivery to reduce the blood pressure. Thirty-two Kunming canines were randomly assigned to the treatment group (n = 14), negative control group (n = 10), LIFU + cationic microbubbles group (n = 4), and LIFU-only group (n = 4). Plasmid-loaded cationic microbubbles were injected and bilateral CBs were irradiated with a LIFU-based transducer. Flow cytometry showed that 33.15% of transfected cells expressed the green fluorescent protein reporter gene. T7 endonuclease I assays showed an insertion-deletion rate of 8.30%. The P2X3 receptor mRNA- and protein-expression levels in CBs decreased by 56.31% and 45.10%, respectively, in the treatment group. Mean systolic (152.5 ± 3.0 vs 138.0 ± 2.9 mm Hg, P = 0.003) and diastolic (97.8 ± 1.5 vs 87.2 ± 2.3 mm Hg, P= 0.002) blood pressures reduced on day 14 in the treatment group, compared with the baseline values, whereas no effects were observed with LIFU treatment or cationic microbubbles injection alone. Canines treated with this strategy exhibited no local or systemic adverse events. Thus, LIFU-mediated gene delivery to CBs successfully modulated CB function and reduced blood pressure in a canine model, suggesting a new possibility for treating hypertension and further clinical translation.


Assuntos
Pressão Sanguínea/fisiologia , Regulação para Baixo , Técnicas de Transferência de Genes , Hipertensão/terapia , Receptores Purinérgicos P2X3/fisiologia , Acústica , Animais , Modelos Animais de Doenças , Cães , Terapia Genética , Humanos
3.
Chin J Integr Med ; 26(12): 890-896, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33259021

RESUMO

OBJECTIVE: To investigate the application status of Chinese medicine (CM) in cancer rehabilitation, so as to provide references for improving the level of CM cancer rehabilitation. METHODS: A survey questionnaire regarding "application status of CM rehabilitation in cancer patients" for oncologists (doctor version) and cancer patients (patient version) were developed, respectively. From September 2014 to November 2016, a total of 1,000 doctors from oncology department in 48 hospitals and 2,000 cancer patients from CM oncology department from 8 hospitals in China were recruited in this survey. The psychological, nutrition and exercise rehabilitation guidance for cancer patients provided by doctors, their mastery conditions regarding cancer staging treatment and CM syndrome differentiation, and recommendation from doctors on CM rehabilitation were investigated. Cancer patients' awareness on the importance of psychological, nutrition and exercise rehabilitation, as well as their knowledge and needs for rehabilitation were also analyzed. The impact of gender, age, professional title, hospitals grades of physicians on their knowledge of cancer staging treatment and CM syndrome differentiation, and the relationship between gender, age, education level and economic conditions and patient's knowledge along with the needs of CM rehabilitation were further analyzed. RESULTS: Totally 1,000 questionnaires were issued to doctors and 963 questionnaires returned, among which 948 were valid representing a response rate of 94.80%. A total of 2,000 questionnaires were issued to patients and 1,705 valid data finally returned with a response rate of 85.25%. The survey showed that cancer patients generally paid much attention to psychological, nutritional and sports rehabilitation, and had a strong demand for CM rehabilitation. Knowledge of CM rehabilitation was not well provided by oncologists, and the rehabilitation guidance as well as CM rehabilitation measures were obviously insufficient in cancer patients. Educational and economic levels were positively correlated with cognition level of CM rehabilitation knowledge among cancer patients (Kendall-tau_b correlation coefficients=0.130, 0.057, respectively; P<0.05). Gender and education level were positively correlated with the patients' willingness for taking CM measures (Kendall-tau_b correlation coefficient=0.057, 0.105, respectively; P<0.05). Age was negatively correlated with intention of applying CM measures (kendall-taub correlation coefficient=-0.105, P<0.05). CONCLUSIONS: Health education and professional training for both cancer patients and oncologists should be strengthened and CM rehabilitation knowledge among cancer patients and oncologists should be improved, so as to give full play to CM in cancer rehabilitation.

4.
J Appl Gerontol ; : 733464820975551, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267710

RESUMO

The Community Aging in Place-Advancing Better Living for Elders (CAPABLE) program reduces disability in low-income older adults. In this study, we used CAPABLE baseline and 5-month data to examine whether its effects in reducing activities of daily living (ADLs) and instrumental ADLs (IADLs) difficulties differed by participants' financial strain status. At baseline, participants with financial strain were more likely to report higher scores on depression (p < .001), have low energy (p < .001), and usually feel tired (p = .004) compared with participants without financial strain, but did not differ in ADL/IADL scores. Participants with financial strain benefited from the program in reducing ADL (relative risk [RR]: 0.61, 95% confidence interval [CI]: 0.43, 0.86) and IADL disabilities (RR: 0.69, 95% CI: 0.54, 0.87), compared with those with financial strain receiving attention control. Individuals with financial strain benefited more from a home-based intervention on measures of disability than those without financial strain. Interventions that improve disability may be beneficial for financially strained older adults.

5.
Neural Plast ; 2020: 8842110, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299396

RESUMO

Musculoskeletal pain (MSP) is one of the most severe complaints in women undergoing menopause. The prevalence of MSP varied when taking the menopausal state and age factor into consideration. This study investigated the prevalence of MSP in perimenopausal women and its association with menopausal state. The MEDLINE, Embase, Web of Science, and PubMed databases were searched from inception to July 2020, and 16 studies were retrieved for the current meta-analysis. The primary outcome measure was the MSP Odds Ratio (OR). The estimated overall prevalence of MSP among perimenopausal women was 71% (4144 out of 5836, 95% confidence interval (CI): 64%-78%). Perimenopausal women demonstrated a higher risk for MSP than premenopausal ones (OR: 1.63, 95% CI: 1.35-1.96, P = 0.008, I 2 = 59.7%), but similar to that in postmenopausal ones (OR: 1.07, 95% CI: 0.95-1.20, P = 0.316, I 2 = 13.4%). The postmenopausal women were at a higher risk of moderate/severe MSP than the premenopausal ones (OR: 1.45, 95% CI: 1.21-1.75, P = 0.302, I 2 = 16.5%) or the perimenopausal ones (OR: 1.40, 95% CI: 1.09-1.79, P = 0.106, I 2 = 55.4%). In conclusion, the perimenopause is a state during which women are particularly predisposed to develop MSP. As to moderate to severe degrees of MSP, the odds increase linearly with age, from premenopause to peri- and then to postmenopause.

6.
Helicobacter ; : e12771, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33368906

RESUMO

BACKGROUND: Although many studies have focused on the protective function of H pylori in some allergic diseases, it remains unknown as whether H pylori infection exerts a similar protective effect on atopic dermatitis(AD). Thus, the aim of this study was to evaluate the association between H pylori infection and AD. MATERIALS AND METHODS: An animal model of H pylori infection-AD was established by epicutaneous sensitization with calcipotriol after infection with H pylori by gavage. The Treg cells were analyzed by flow cytometry and immunohistochemistry. The expression of key inflammatory cytokines in dermal tissues was investigated at the mRNA level by real-time PCR. RESULTS: Compared with that in the H pylori-negative AD group, the severity of skin lesions, such as hyperemia, erythema, and swelling, was lower in the H pylori-positive AD group, while the serum IgE level decreased significantly in the H pylori-positive AD group. The percentage of CD4+ CD25+ Foxp3+ Treg cells in the peripheral blood and the number of Foxp3+ cells in dermal tissues increased significantly in the H pylori-positive AD group. The expression of IL-10 and TGF-ß was upregulated, while the expression of IL-4 mRNA was downregulated in dermal tissues in the H pylori-positive AD group. The adoptive transfer assay showed that the number of CFSE+ Treg cells in the cervical lymph nodes of AD mice was significantly higher than that in normal mice, indicating the Tregs in H pylori-positive mice had a tendency to migrate to the skin tissue. It was also found that H pylori infection induced CCR4+ Treg cells expansion synchronously in gastric lymph nodes, spleen, blood, mesenteric lymph node (MLN), and cervical lymph nodes by the time of H pylori infection. CONCLUSIONS: H pylori infection alleviated calcipotriol-inducing AD manifestations by inducing the amplification of CD4+ CD25+ Foxp3+ Treg cells in the peripheral blood. H pylori showed possible protection against atopic dermatitis, suggesting an immune dialogue between gastrointestinal tract and skin.

7.
J Am Geriatr Soc ; 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33368158

RESUMO

OBJECTIVES: To investigate the rate and patterns of accumulation of frailty manifestations in relationship to all-cause mortality and whether there is a point in the progression of frailty beyond which the process becomes irreversible and death becomes imminent (a.k.a. point of no return). DESIGN: Longitudinal observational study. SETTING: Community or a non-nursing home residential care setting. PARTICIPANTS: Two thousand five hundred and fifty seven robust older adults identified at baseline in 2011 with follow-up for all-cause mortality between 2011 and 2018. MEASUREMENTS: Frailty was measured by the physical frailty phenotype. Cox models were used to study the relationships of the number of frailty criteria (0-5) at each point in time and its accumulation patterns with all-cause mortality. Markov state-transition models were used to study annual transitions between health states (i.e., frailty, recovery, and death) after becoming frail among those with frailty onset (n = 373). RESULTS: There was a nonlinear association between greater number of frailty criteria and increasing risk of mortality, with a notable risk acceleration after having accumulated all five criteria (hazard ratio (HR) = 32.6 vs none, 95% confidence interval (CI) = 15.7-67.5). In addition, the risk of one-year mortality tripled, and the likelihood of recovery (i.e., reverting to be robust or pre-frail) halved among those with five frailty criteria compared to those with three or four criteria. A 50% increase in mortality risk was also associated with frailty onset without (vs with) a prior history of pre-frailty (HR = 1.51, 95% CI = 1.20-1.90). CONCLUSION: Both the number and rate of accumulation of frailty criteria were associated with mortality risk. Although there was insufficient evidence to declare a point of no return, having all five-frailty criteria signals the beginning of a transition toward a point of no return. Ongoing monitoring of frailty progression could aid clinical and personal decision-making regarding timing of intervention and eventual transition from curative to palliative care.

8.
Mol Divers ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200293

RESUMO

Here, two series of novel ursolic acid-based 1,2,4-triazolo[1,5-a]pyrimidines derivatives were synthesized and screened for their anti-inflammatory activity by evaluating their inhibition effect of using LPS-induced inflammatory response in RAW 264.7 macrophages in vitro; the effects of different concentrations of the compounds on the secretion of nitric oxide (NO) and inflammatory cytokines including TNF-α and IL-6 were evaluated. Their toxicity was also assessed in vitro. Results showed that the most prominent compound 3 could significantly decrease production of the above inflammatory factors. Docking study was performed for the representative compounds 3, UA, and Celecoxib to explain their interaction with cyclooxygenase-2 (COX-2) receptor active site. In vitro enzyme study implied that compound 3 exerted its anti-inflammatory activity through COX-2 inhibition.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33216872

RESUMO

BACKGROUND: Increasingly, lifestyle factors in mid-life are reported to impact health and functional status in old age. This work examines associations between dietary trajectories in middle-age and subsequent impairments in physical function. METHODS: Data are from 851 participants (61% men, mean age at first dietary assessment = 47 years, range 30-59 years) from the Baltimore Longitudinal Study of Aging. We used latent class analysis to derive dietary trajectories based on adherence to the Alternative Healthy Eating Index-2010 (AHEI), and further classified them based on tertiles, as poor (score <39.3), intermediate (39.3-48.9) or good (>48.9). Physical function was assessed with the Short Physical Performance Battery (SPPB). Random effects tobit regression models were used to examine associations between dietary trajectories and later physical function. RESULTS: Two latent classes of AHEI scores were generated and labeled "greatly improved" or "moderately improved". In the greatly improved class, participants showed a trend in overall AHEI score from poor/intermediate to good diet categories across dietary assessments with age, over time. In the moderately improved class, the overall AHEI score shifted from poor to intermediate diet categories over time, and the prevalence of the good diet category remained low. Mean AHEI score between ages 30-59 years was higher in the greatly, than moderately, improved class. The moderately improved class had 1.6 points lower SPPB score (indicating poorer physical function) at older age than the greatly improved class (P=.022). CONCLUSIONS: Findings suggest that improving diet quality in middle age may contribute to better physical function in older age.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33152217

RESUMO

Objective: Inbreeding depression of reproduction is a major concern in the conservation of native chicken genetic resources. Here, based on the successful development of strongly inbred (Sinb) and weakly inbred (Winb) Langshan chickens, we aimed to evaluate inbreeding effects on reproductive traits and identify candidate genes involved in inbreeding depression of reproduction in Langshan chickens. Methods: A two-sample t-test was performed to estimate the differences in phenotypic values of reproductive traits between Sinb and Winb chicken groups. Three healthy chickens with reproductive trait values around the group mean values were selected from each of the groups. Differences in ovarian and hypothalamus transcriptomes between the two groups of chickens were analyzed by RNA sequencing (RNA-Seq). Results: The Sinb chicken group showed an obvious inbreeding depression in reproduction, especially for traits of age at the first egg and egg number at 300 days (P < 0.01). Furthermore, 68 and 618 differentially expressed genes (DEGs) were obtained in the hypothalamus and ovary between the two chicken groups, respectively. In the hypothalamus, DEGs were mainly enriched in the pathways related to vitamin metabolism, signal transduction and development of the reproductive system, such as the riboflavin metabolism, Wnt signaling pathway, ECM-receptor interaction and focal adhesion pathways, including STRA6, SERPINF1, SFRP2, WNT6 and FZD4 genes. In the ovary, DEGs were significantly enriched in pathways associated with basic metabolism, including amino acid metabolism, oxidative phosphorylation, and glycosaminoglycan degradation. A series of key DEGs involved in folate biosynthesis (GGH, GCH1), oocyte meiosis and ovarian function (CPEB1, SMC1B, and SPDYA), spermatogenesis and male fertility (PTGDS, MOV10L1, and DEUP1) were identified, and these may play important roles in inbreeding depression in reproduction. Conclusion: The results improve our understanding of the regulatory mechanisms underlying inbreeding depression in chicken reproduction and provide a theoretical basis for the conservation of species resources.

11.
BMC Cardiovasc Disord ; 20(1): 473, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33143646

RESUMO

BACKGROUND: Ruptured sinus of Valsalva aneurysm (SVA) is a rare cardiovascular disease in which some patients exhibit aortic valve insufficiency. SVA repair and valve replacement are usually required for treatment. Here, we report 5 cases of ruptured SVA with severe post-anaesthesia aortic regurgitation (AR). To the best of our knowledge, this is the first report of ruptured SVA with severe post-anaesthesia AR. CASE PRESENTATION: From 2018 to 2020, there were 5 cases of ruptured SVA with severe AR after anaesthesia in our hospital. The main symptoms were palpitation and shortness of breath. Transthoracic echocardiography (TTE) with colour-flow Doppler showed ruptured aortic sinus aneurysms without AR. Post-anaesthesia echocardiography showed severe AR. Direct patch closure of the ruptured aneurysm resolved the left-to-right shunt and AR, and the aortic valve was not replaced. CONCLUSIONS: Post-anaesthesia AR without obvious structural defects may occur in patients with ruptured SVAs. Valve replacement may not be necessary.

12.
Exp Gerontol ; 142: 111136, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33164891

RESUMO

Resiliency is the ability to respond to, adapt to and recover from stressors. Deterioration of resiliency in older adults has been hypothesized to be regulated by age-related changes in stress response systems, including the Hypothalamic Pituitary Adrenal (HPA) axis and the innate immune system response. Although age-related chronic inflammation is strongly related to lack of resiliency, the impact of chronic inflammation on acute stress response is unclear. Here we describe the impact of a five-hour exposure to cold temperature acute stressor, on immune and corticosterone response using older and younger IL-10tm/tm mice, a mouse model with chronic inflammatory pathway activation, and age and gender matched C57/Bl6 background control (WT) mice. Overall, mice exposed to 4 °C for 5 h had significantly higher plasma corticosterone levels compared to those that remained at room temperature (25 °C), with the exception of the WT females. Cold stressed mice had lower plasma tumor necrosis factor receptor 1 (TNFR1) levels with varying significance, in all ages and phenotypes, with the exception of the old female WT mice. In contrast, the effects of cold stress on pro-inflammatory cytokine interleukin 6 (IL-6) levels were inconsistent and not significant, with the exception of the female IL-10tm/tm mice. In conclusion, these findings demonstrate that sex, age and chronic inflammatory pathway activation all influence corticosterone secretion and inflammatory processes in the face of acute cold stress.

13.
Am J Med ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33242482

RESUMO

BACKGROUND: Frailty, a clinical state of vulnerability, is associated with subsequent adverse geriatric syndromes in the general population. We examined the long-term impact of frailty on geriatric outcomes among older patients with coronary heart disease. METHODS: We used the National Health and Aging Trends Study, a prospective cohort study linked to a Medicare sample. Coronary heart disease was identified by self-report and/or ICD codes one-year prior to the baseline visit. Frailty was measured using the Fried physical frailty phenotype. Geriatric outcomes were assessed annually during a six-year follow-up. RESULTS: Of the 4,656 participants, 1,213 (26%) had a history of coronary heart disease one-year prior to their baseline visit. Compared to those without frailty, subjects with frailty were older (Age ≥75: 80.9% vs. 68.9%, p<0.001), more likely to be female, and belong to an ethnic minority. The prevalence of hypertension, stroke, falls, disability, anxiety/depression, and multimorbidity were much higher in the frail, than non-frail, participants. In a discrete time survival model, the incidence of geriatric syndromes during six year follow-up including (1) dementia, (2) loss of independence, (3) activities of daily living disability, (4) instrumental activities of daily living disability, (5) and mobility disability were significantly higher in the frail than in the non-frail coronary heart disease older patients. CONCLUSION: In patients with coronary heart disease, frailty is a risk factor for the accelerated development of geriatric outcomes. Efforts to identify frailty in the context of coronary heart disease are needed, as well as interventions to limit or reverse frailty status for older coronary heart disease patients.

14.
BMC Med ; 18(1): 333, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33092582
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1683-1688, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067974

RESUMO

OBJECTIVE: To compare the clinical efficacy between frontline haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) and salvage haplo-HSCT for patients with severe aplastic anemia (SAA). METHODS: A total of 39 patients with severe aplastic anemia or very severe aplastic anemia from May 1st, 2013 to December 31st, 2018 were analyzed retrospectively. All of them underwent bone marrow + peripheral blood hemopoietic stem cell transplantation. There were 20 cases who accepted frontline haplo-HSCT for a median course of 1 (1-3) month, and 19 cases who accepted salvage haplo-HSCT for a median course of 72 (6-168) months. Conditioning regimen: 22 cases received Flu/Cy+ATG, and 17 cases received Bu/Cy+ATG. RESULTS: The time of hematopoietic reconstitution, infection rate, and grade I-Ⅱ and Ⅲ-Ⅳ acute/chronic graft versus host disease showed no statistically significance between the frontline haplo-HSCT group and the salvage haplo-HSCT group. In the frontline haplo-HSCT group, 1 case (5%) failed in second engraftment, in the salvage haplo-HSCT group 2 cases (10.5%) failed in primary engraftment and 4 cases (21.1%) in second engraftment. The incidence of engraftment failure was higher in the salvage haplo-HSCT group than that in the frontline haplo-HSCT group (P=0.04). The median time of follow-up after allo-HSCT was 45 months (ranging from 3 to 92). The mortality was 10% (2/20) in the frontline haplo-HSCT group, and 42.1% (8/19) in the salvage haplo-HSCT group. The estimated 5-year failure-free survival rate (FFS) of the frontline haplo-HSCT group was higher than that of the salvage haplo-HSCT group (90% vs 57.4%) (P=0.02). CONCLUSION: The frontline haplo-HSCT is an effective and safe approach for the patients with severe aplastic anemia who lack a HLA-matched sibling donor.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Humanos , Estudos Retrospectivos , Condicionamento Pré-Transplante
16.
Artigo em Inglês | MEDLINE | ID: mdl-33057609

RESUMO

BACKGROUND: Frailty (physical frailty phenotype, PFP) and its criteria (slow gait, weakness, weight loss, low activity, and exhaustion) are each associated with cognitive dysfunction. The extent to which the PFP is associated with cognition beyond that expected from its component parts remains uncertain. METHODS: We used the National Health and Aging Trends Study to quantify associations between PFP criteria and cognitive performance (level/change) using adjusted mixed effects models. We tested whether frailty was associated with excess cognitive vulnerability (synergistic/excess effects, Cohen's d) beyond criteria contributions by assessing interactions between each criterion and frailty. RESULTS: Among 7,439 community-dwelling older adults (mean age=75.2years) followed for a mean of 3.2years(SE=0.03), 14.1% were frail. The PFP and PFP criteria were all associated with lower baseline cognitive performance, among which slow gait (-0.31SD,SE=0.02) and frailty (-0.23SD,SE=0.02) were strongest. Only slow gait (-0.03SD/year,SE=0.01), frailty (-0.02SD/year,SE=0.01), weight loss (-0.02SD/year,SE=0.01), and weakness (-0.02SD/year,SE=0.01) were associated with cognitive decline. Frailty was associated with cognitive performance above and beyond each criterion (excess effects ranging from -0.07SD(SE=-0.05) for slow gait to -0.23SD(SE=0.03) for weakness); the same was not true for cognitive decline. Slow gait was the only criterion associated with cognitive change among both frail and non-frail participants (frail:Cohen's d/year=-0.03,SE= 0.01; non-frail:Cohen's d/year=-0.02,SE= 0.01). CONCLUSIONS: PFP is an important frailty measure that is cross-sectionally associated with lower cognitive performance, but not with subsequent cognitive decline, above and beyond its criteria contributions. Further research into the construct of frailty as a "syndrome" correlated with cognition and other adverse outcomes is needed.

17.
Small ; 16(41): e1906564, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32964611

RESUMO

The exploration of efficient electrocatalysts is the central issue for boosting the overall efficiency of water splitting. Herein, pertinently creating active sites and improving conductivity for metal-organic frameworks (MOFs) is proposed to tailor electrocatalytic properties for overall water splitting. An Ni(II)-MOF nanosheet array is presented as an ideal material model and a facile alkali-etched strategy is developed to break its NiO bonds accompanied with the introduction of extra-framework K cations, which contribute to creating highly active open metal sites and largely improving the electrical conductivity. As a result, the assembled defect-Ni-MOF||defect-Ni-MOF electrolyte cell delivers a lower and stable voltage of 1.50 V at 10 mA cm-2 in alkaline medium for overall water splitting, comparable to the combination of iridium and platinum as benchmark catalysts.

18.
J Card Fail ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32956817

RESUMO

BACKGROUND: We reported 3 novel nonsynonymous single nucleotide variants of Bcl2-associated athanogene 3 (BAG3) in African Americans with heart failure (HF) that are associated with a 2-fold increase in cardiac events (HF hospitalization, heart transplantation, or death). METHODS AND RESULTS: We expressed BAG3 variants (P63A, P380S, and A479V) via adenovirus-mediated gene transfer in adult left ventricular myocytes isolated from either wild-type (WT) or cardiac-specific BAG3 haploinsufficient (cBAG3+/-) mice: the latter to simulate the clinical situation in which BAG3 variants are only found on 1 allele. Compared with WT myocytes, cBAG3+/- myocytes expressed approximately 50% of endogenous BAG3 levels and exhibited decreased [Ca2+]i and contraction amplitudes after isoproterenol owing to decreased L-type Ca2+ current. BAG3 repletion with WT BAG3 but not P380S, A479V, or P63A/P380S variants restored contraction amplitudes in cBAG3+/- myocytes to those measured in WT myocytes, suggesting excitation-contraction abnormalities partly account for HF in patients harboring these mutants. Because P63A is near the WW domain (residues 21-55) and A479V is in the BAG domain (residues 420-499), we expressed BAG3 deletion mutants (Δ1-61 and Δ421-575) in WT myocytes and demonstrated that the BAG but not the WW domain was involved in enhancement of excitation-contraction by isoproterenol. CONCLUSIONS: The BAG3 variants contribute to HF in African American patients partly by decreasing myocyte excitation-contraction under stress, and that both the BAG and PXXP domains are involved in mediating ß-adrenergic responsiveness in myocytes.

19.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(9): 936-941, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32933622

RESUMO

OBJECTIVE: To investigate whether there is a difference in cerebellar development between appropriate -for-gestational-age (AGA) infants and small-for-gestational-age (SGA) infants. METHODS: A total of 165 AGA infants and 105 SGA infants, with a gestational age of 26-40+6 weeks, were enrolled in this study. Within 24-48 hours after birth, ultrasound examination was performed to measure the transverse diameter of the cerebellum, the height of the vermis, the area of the vermis, the perimeter of the vermis, and the area and perimeter of the cerebellum on transverse section. A Pearson correlation analysis was used to investigate the correlation between cerebellar measurements and gestational age. RESULTS: In both AGA and SGA infants, all cerebellar measurements were positively correlated with gestational age (r=0.50-0.81, P<0.05). In AGA and SGA infants, there were no significant differences in the measurements between the 25-27+6 weeks, 28-30+6 weeks, and 31-33+6 weeks of gestational age subgroups (P>0.05), while in the 34-36+6 weeks and 37-40+6 weeks subgroups, the SGA infants had significantly lower measurements than the AGA infants (P<0.05). CONCLUSIONS: The SGA infants with a gestational age of <34 weeks have intrauterine cerebellar development similar to AGA infants, but those with a gestational age of ≥34 weeks have poorer intrauterine cerebellar development than AGA infants.


Assuntos
Cerebelo , Recém-Nascido Pequeno para a Idade Gestacional , Idade Gestacional , Humanos , Lactente , Ultrassonografia
20.
JCI Insight ; 5(20)2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32941181

RESUMO

BACKGROUNDPhysical frailty in older individuals is characterized by subjective symptoms of fatigue and exercise intolerance (EI). Objective abnormalities in skeletal muscle (SM) mitochondrial high-energy phosphate (HEP) metabolism contribute to EI in inherited myopathies; however, their presence or link to EI in the frail older adult is unknown.METHODSHere, we studied 3 groups of ambulatory, community-dwelling adults with no history of significant coronary disease: frail older (FO) individuals (81 ± 2.7 years, mean ± SEM), nonfrail older (NFO) individuals (79 ± 2.0 years), and healthy middle-aged individuals, who served as controls (CONT, 51 ± 2.1 years). Lower extremity SM HEP levels and mitochondrial function were measured with 31P magnetic resonance (MR) techniques during graded multistage plantar flexion exercise (PFE). EI was quantified by a 6-minute walk (6MW) and peak oxygen consumption during cardiopulmonary testing (peak VO2).RESULTSDuring graded exercise, FO, NFO, and CONT individuals all fatigued at similar SM HEP levels, as measured by 31P-MR. However, FO individuals fatigued fastest, with several-fold higher rates of PFE-induced HEP decline that correlated closely with shorter exercise duration in the MR scanner and with 6MW distance and lower peak oxygen consumption on cardiopulmonary testing (P < 0.001 for all). SM mitochondrial oxidative capacity was lower in older individuals and correlated with rapid HEP decline but less closely with EI.CONCLUSIONSeveral-fold faster SM energetic decline during exercise occurs in FO individuals and correlates closely with multiple measures of EI. Rapid energetic decline represents an objective, functional measure of SM metabolic changes and a potential new target for mitigating frailty-associated physical limitations.FUNDINGThis work was supported by NIH R21 AG045634, R01 AG063661, R01 HL61912, the Johns Hopkins University Claude D. Pepper Older Americans Independence Center P30AG021334, and the Clarence Doodeman Endowment in Cardiology at Johns Hopkins.

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