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OBJECTIVE: To investigate the outcomes of intracytoplasmic sperm injection (ICSI) in the treatment of special types of teratozoospermia such as globozoospermia, acephalic spermatozoa syndrome (ASS) and multiple morphological abnormalities of sperm flagella (MMAF). METHODS: We retrospectively analyzed the clinical data on 7 cases of globozoospermia (group A), 6 cases of ASS (group B) and 21 cases of MMAF (group C) treated by ICSI from January 2011 to January 2021, all confirmed with pathogenic or likely pathogenic gene variations. We compared the age, body mass index (BMI), sperm parameters, number of mature oocytes, and rates of fertilization, high-quality embryos, clinical pregnancy, live birth and spontaneous abortion among the three groups of patients. RESULTS: There were no statistically significant differences in the age, BMI and number of metaphase â ¡ (Mâ ¡) oocytes among the three groups (P > 0.05). Sperm concentration and motility were dramatically higher (P < 0.01) while the rates of fertilization, clinical pregnancy and live birth remarkably lower in group A than in B and C (P < 0.01). No statistically significant difference was observed in the spontaneous abortion rate among the three groups (P > 0.05). CONCLUSION: ICSI can achieve relatively satisfactory outcomes of clinical pregnancy in patients with ASS or MMAF, but only a low fertilization rate or no fertilization at all in those with globozoospermia even if treated by artificial oocyte activation.
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Aborto Espontâneo , Infertilidade Masculina , Teratozoospermia , Gravidez , Feminino , Humanos , Masculino , Injeções de Esperma Intracitoplásmicas , Teratozoospermia/genética , Infertilidade Masculina/genética , Estudos Retrospectivos , Sêmen , Espermatozoides , OócitosRESUMO
Lateral flow immunoassays (LFIs) can be used to detect intact bacteria or spores; when gold nanoparticles (AuNPs) are used as the signal reporters, the detection limits are very low. Spore-based surface display has been widely studied for enzyme immobilization and live-nontoxic oral vaccines. In this study, recombinant spores were used to improve the sensitivity of a LFI. We developed a test kit that combines streptavidin-displayed spores with a LFI assay for rapid protein detection. The recombinant spores served as a signal amplifier and AuNPs were used as the signal reporters. For detection of ß-galactosidase, which was used as the model protein, the detection limit was about 10-15 mol, while that of the conventional LFI is about 10-12 mol. In both methods, nanogold was used as the colorimetric signal and could be observed with the naked eye. This method improved LFI sensitivity without sacrificing its advantages. Furthermore, enhanced green fluorescent protein (eGFP) was also displayed on the surface of the streptavidin-displayed spores. Without AuNPs, the fluorescent recombinant spores acted as the signal, which could be detected by a fluorescence detector, such as a fluorescence microscope. The detection limit was 10-16 mol under fluorescence microscopy whose magnification was 25-fold. Therefore, in conclusion, in this proof of concept study, the detection limits of both proposed methods were far superior to those of traditional LFI assay.
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Bacillus subtilis/química , Técnicas Biossensoriais/métodos , Ouro/química , Nanopartículas Metálicas/química , Proteínas/análise , Esporos Bacterianos/química , Proteínas de Fluorescência Verde/química , Imunoensaio/métodos , Limite de Detecção , Estreptavidina/químicaRESUMO
Allium L. is one of the largest monocotyledonous genera with extensive distribution in the Northern Hemisphere. The fundamental phylogenies of Allium have been investigated using many morphological and molecular characters. However, the morphological characters may not agree with the molecular results in some Allium groups or sections (such as the Chinese Allium section Daghestanica), which may result in ambiguous species relationships and hinder further evolutionary and adaptive researches. Here, transcriptome sequences of the six Chinese endemics from Allium section Daghestanica were collected, with their single-copy genes (SCGs) were extracted. The interspecies relationships were analyzed using concatenation and coalescent methods. The branch-site model (BSM) was conducted to detect the positively selected genes (PSGs) in five highland species of this section. Based on 1644, 1281 and 1580 SCGs in flowers, leaves, and flowers-leaves combination respectively, a robust consistent and well-resolved phylogeny was generated from the concatenation method. Strong conflicts among individual gene trees were detected in the coalescent method, and morphological characters were incongruent with molecular relationships to some degree. Many PSGs were involved in responses of various stresses and stimuli (e.g. hypoxia, low temperature, aridity), DNA repair, metabolism, nutrient or energy intake, photosynthesis, and signal transduction. Our study revealed a clear interspecies relationship of Chinese endemics in Allium section Daghestanica and suggested that the discordance between morphological characters and molecular relationships might result from that the former are more susceptible to convergence compared with the latter. PSGs detected in our study may provide some insights into highland adaptation in Allium species.
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Allium/classificação , Aclimatação , Allium/anatomia & histologia , Allium/genética , China , Flores/anatomia & histologia , Flores/genética , Perfilação da Expressão Gênica , Genes de Plantas , Filogenia , Folhas de Planta/anatomia & histologia , Folhas de Planta/genéticaRESUMO
Clinical experience suggests higher occurrence of carbapenem-associated seizures in the elderly than what is reported in the available literature (range between 0.2% and 0.7%). An audit of 1345 patients with age 60 years or older, who received imipenem, ertapenem or meropenem during their acute hospitalisation found 32 (2.4%) subjects developed seizures. Subjects with more than one central nervous system disorders were 11.6 times more likely to develop seizures (odds ratio 11.61, P < 0.001) and subjects with prior history of seizures is associated with four times greater risks (odds ratio 4.02, P = 0.005). Physicians should exercise caution when prescribing carbapenems in elderly, especially those with known epilepsy and a high number of intracranial pathologies.
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Antibacterianos/efeitos adversos , Carbapenêmicos/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Ertapenem/efeitos adversos , Feminino , Hospitalização , Humanos , Imipenem/efeitos adversos , Modelos Logísticos , Masculino , Meropeném/efeitos adversos , Singapura/epidemiologia , beta-Lactamas/efeitos adversosRESUMO
UNLABELLED: Deacetylation of 7-aminocephalosporanic acid (7-ACA) at position C-3 provides valuable starting material for producing semisynthetic ß-lactam antibiotics. However, few enzymes have been characterized in this process before now. Comparative analysis of the genome of the thermophilic bacterium Alicyclobacillus tengchongensis revealed a hypothetical protein (EstD1) with typical esterase features. The EstD1 protein was functionally cloned, expressed, and purified from Escherichia coli BL21(DE3). It indeed displayed esterase activity, with optimal activity at around 65°C and pH 8.5, with a preference for esters with short-chain acyl esters (C2 to C4). Sequence alignment revealed that EstD1 is an SGNH hydrolase with the putative catalytic triad Ser15, Asp191, and His194, which belongs to carbohydrate esterase family 12. EstD1 can hydrolyze acetate at the C-3 position of 7-aminocephalosporanic acid (7-ACA) to form deacetyl-7-ACA, which is an important starting material for producing semisynthetic ß-lactam antibiotics. EstD1 retained more than 50% of its initial activity when incubated at pH values ranging from 4 to 11 at 65°C for 1 h. To the best of our knowledge, this enzyme is a new SGNH hydrolase identified from thermophiles that is able to hydrolyze 7-ACA. IMPORTANCE: Deacetyl cephalosporins are highly valuable building blocks for the industrial production of various kinds of semisynthetic ß-lactam antibiotics. These compounds are derived mainly from 7-ACA, which is obtained by chemical or enzymatic processes from cephalosporin C. Enzymatic transformation of 7-ACA is the main method because of the adverse effects chemical deacylation brought to the environment. SGNH hydrolases are widely distributed in plants. However, the tools for identifying and characterizing SGNH hydrolases from bacteria, especially from thermophiles, are rather limited. Here, our work demonstrates that EstD1 belongs to the SGNH family and can hydrolyze acetate at the C-3 position of 7-ACA. Moreover, this study can enrich our understanding of the functions of these enzymes from this family.
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Alicyclobacillus/enzimologia , Cefalosporinas/metabolismo , Esterases/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Alicyclobacillus/genética , Alicyclobacillus/metabolismo , Sequência de Aminoácidos , Clonagem Molecular , Esterases/genética , Dados de Sequência Molecular , FilogeniaRESUMO
The refractoriness of acute promyelocytic leukemia (APL) with t(11;17)(q23;q21) to all-trans retinoic acid (ATRA)-based therapy concerns clinicians and intrigues basic researchers. By using a murine leukemic model carrying both promyelocytic leukemia zinc finger/retinoic acid receptor-α (PLZF/RARα) and RARα/PLZF fusion genes, we discovered that 8-chlorophenylthio adenosine-3', 5'-cyclic monophosphate (8-CPT-cAMP) enhances cellular differentiation and improves gene trans-activation by ATRA in leukemic blasts. Mechanistically, in combination with ATRA, 8-CPT-cAMP activates PKA, causing phosphorylation of PLZF/RARα at Ser765 and resulting in increased dissociation of the silencing mediator for retinoic acid and thyroid hormone receptors/nuclear receptor corepressor from PLZF/RARα. This process results in changes of local chromatin and transcriptional reactivation of the retinoic acid pathway in leukemic cells. Meanwhile, 8-CPT-cAMP also potentiated ATRA-induced degradation of PLZF/RARα through its Ser765 phosphorylation. In vivo treatment of the t(11;17) APL mouse model demonstrated that 8-CPT-cAMP could significantly improve the therapeutic effect of ATRA by targeting a leukemia-initiating cell activity. This combined therapy, which induces enhanced differentiation and oncoprotein degradation, may benefit t(11;17) APL patients.
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Diferenciação Celular , AMP Cíclico/análogos & derivados , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteínas de Fusão Oncogênica/metabolismo , Proteólise , Tionucleotídeos/uso terapêutico , Translocação Genética , Tretinoína/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 17/genética , AMP Cíclico/farmacologia , AMP Cíclico/uso terapêutico , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Camundongos , Camundongos Endogâmicos C57BL , Correpressor 2 de Receptor Nuclear/metabolismo , Fosforilação/efeitos dos fármacos , Fosfosserina/metabolismo , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Análise de Sobrevida , Tionucleotídeos/farmacologia , Translocação Genética/efeitos dos fármacos , Tretinoína/farmacologiaRESUMO
In the past decades, diabetes, in particular type 2 diabetes (T2D)mainly characterized by global insulin resistance and pancreatic beta cell failure, had become epidemic and a severe public health threat worldwide with the development of economy and change of lifestyle.The interactions between environment factors and genetic background play vital roles in the development and progression of T2D.More recently, it had been revealed that non-coding RNA including microRNA (miRNA)and long noncoding RNA (LncRNA)are widely involved inthe regulation of glucose and lipid metabolism. So far, it had been established that deregulated miRNA and LncRNA profile in main metabolic tissues is tightly associated with T2D,and intensive studies on non-coding RNAs had shed light on understanding the pathogen-esis of T2D.The current review aimed to briefly summarize and discuss the latest findings regarding the role and mechanism of miRNAs and LncRNAs in the regulation hepatic glucose and lipid metabolism.
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Metabolismo dos Lipídeos , Diabetes Mellitus Tipo 2 , Glucose , Humanos , Resistência à Insulina , Células Secretoras de Insulina , Fígado , RNA não TraduzidoRESUMO
Enoyl coenzyme A hydratase short chain 1 (ECHS1) is an important part of the mitochondrial fatty acid ß-oxidation pathway. Altered ECHS1 expression has been implicated in cancer cell proliferation. This study assessed ECHS1 expression in human gastric cancer cell lines and investigated the effects of ECHS1 knockdown on gastric cancer cell proliferation and migration. The human gastric cancer cell lines SGC-7901, BGC-823 and MKN-28, and the immortalized human gastric epithelial mucosa GES-1 cell line were analyzed for ECHS1 protein levels using western blot. The effectiveness of ECHS1-RNA interference was also determined using western blot. Proliferation and migration of the siECHS1 cells were respectively measured with the CCK-8 and transwell assays. Phosphorylation of PKB and GSK3ß was assessed using western blot. ECHS1 protein levels were significantly higher in poorly differentiated cells than in well-differentiated cells and immortalized gastric epithelial mucosa cells. Stable expression of ECHS1 shRNA was associated with an over 41% reduction in the ECHS1 protein levels of siECHS1 cells. Constitutive knockdown of the ECHS1 gene in siECHS1 cells was associated with significantly inhibited cell proliferation and migration. We also observed decreased levels of PKB and GSK3ß phosphorylation in siECHS1 cells. ECHS1 expression is increased in human gastric cancer cells. Increased ECHS1 expression activates PKB and GSK3ß by inducing the phosphorylation of the two kinases. ECHS1 may play important roles in gastric cancer cell proliferation and migration through PKB- and GSK3ß-related signaling pathways.
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Movimento Celular , Proliferação de Células , Enoil-CoA Hidratase/genética , Diferenciação Celular , Linhagem Celular Tumoral , Enoil-CoA Hidratase/metabolismo , Expressão Gênica , Técnicas de Silenciamento de Genes , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Células HEK293 , Humanos , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias GástricasRESUMO
CONTEXT: Insulinoma is a neuroendocrine tumor derived from pancreatic ß -cells whose clinical manifestation is recurrent hypoglycemia. Insulinoma in a patient with preexisting diabetes is extraordinarily rare, and the unmasking of type 2 diabetes (T2DM) after insulinoma surgery is even rarer. CASE REPORT: This article reports a 49-year-old male patient with insulinoma that masked the diagnosis of T2DM. The patient was admitted to the hospital with symptoms of hypoglycemia, such as repeated sweating, palpitations, and asthenia for over 4 years. The patient was diagnosed with insulinoma after completing relevant examinations. The emergence of hyperglycemia after the removal of insulinoma is attributable to the coexistence of T2DM. Surprisingly, a reversible decrease in cortisol levels was observed during the diagnostic process. We searched the previously published reports of this type of case from PubMed to determine why type 2 diabetes was covered by insulinoma and why glucocorticoids decreased. CONCLUSIONS: The diagnosis of T2DM in the patient after surgery may be related to increased food intake and insulin resistance induced by hyperinsulinemia caused by long-term hypoglycemia. The reversible decrease in cortisol levels, not adrenocortical insufficiency during the diagnostic process, may be caused by a transient abnormality in glucose counterregulation.
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Diabetes Mellitus Tipo 2 , Insulinoma , Neoplasias Pancreáticas , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Insulinoma/cirurgia , Insulinoma/complicações , Insulinoma/metabolismo , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Hipoglicemia/etiologia , Hipoglicemia/diagnóstico , Glicemia/metabolismo , Hidrocortisona/sangueRESUMO
AIM: SARC-F is limited by low sensitivity for sarcopenia identification. As surrogates of muscle mass, mid-arm circumference (MAC) and/or calf circumference have been proposed as additions to SARC-F to enhance sarcopenia identification. The aim of this study was to evaluate the diagnostic performance of SARC-F, SARC-CalF, SARC-F + MAC, and SARC-CalF + MAC in sarcopenia detection, and to assess the impact of obesity on their diagnostic performance. METHODS: We studied 230 healthy non-frail community-dwelling older adults age >50 years. We performed receiver operating characteristic curve analysis for SARC-F, SARC-CalF, SARC-F + MAC and SARC-CalF + MAC against sarcopenia diagnosed by the Asian Working Group for Sarcopenia (AWGS) 2019 as the reference standard. Obesity was defined by high waist circumference (men ≥90 cm, women ≥80 cm). We performed subgroup analysis to compare between obese and non-obese groups. RESULTS: The prevalence of sarcopenia was 27.0% by AWGS 2019. SARC-CalF + MAC had the best diagnostic performance (area under the curve [AUC] 0.74, 95% confidence interval [CI] 0.67-0.81; sensitivity 66.1%; specificity 69.1%), followed by SARC-CalF (AUC 0.70, 95% CI 0.62-0.78; sensitivity 21.0%; specificity 95.8%). SARC-F (AUC 0.57, 95% CI 0.49-0.66; sensitivity 0%; specificity 100%) performed significantly worsethan its modified versions (P < 0.05). There was higher accuracy of sarcopenia identification in obese compared with non-obese groups for SARC-F + MAC (AUC 0.75, 95% CI 0.65-0.85 vs. 0.58, 95% CI 0.46-0.70) and SARC-CalF + MAC (AUC 0.75, 95% CI 0.66-0.85 vs. 0.70, 95% CI 0.59-0.81). CONCLUSIONS: The addition of arm circumference to SARC-CalF confers better diagnostic accuracy for sarcopenia identification, especially in the obese group. Thus, MAC may complement SARC-CalF for community screening of sarcopenia amongst healthy community-dwelling older adults by increasing sensitivity for the detection of sarcopenic obesity. Geriatr Gerontol Int 2024; 24: 182-188.
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Sarcopenia , Masculino , Humanos , Feminino , Idoso , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Programas de Rastreamento , Curva ROC , Perna (Membro) , Avaliação Geriátrica , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/epidemiologia , Inquéritos e QuestionáriosRESUMO
Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible lung disease with unclear pathological mechanisms. In this study, we utilized bidirectional Mendelian randomization (MR) to analyze the relationship between serum metabolites and IPF, and conducted metabolic pathway analysis. Aim: To determine the causal relationship between serum metabolites and IPF using MR analysis. Methods: A two-sample MR analysis was conducted to evaluate the causal relationship between 824 serum metabolites and IPF. The inverse variance weighted (IVW) method was used to estimate the causal relationship between exposure and results. Sensitivity analysis was conducted using MR Egger, weighted median, and maximum likelihood to eliminate pleiotropy. Additionally, metabolic pathway analysis was conducted to identify potential metabolic pathways. Results: We identified 12 serum metabolites (6 risks and 6 protective) associated with IPF from 824 metabolites. Among them, 11 were known and 1 was unknown. 1-Eicosatrienoylglycophorophospholine and 1-myristoylglycophorophospholine were bidirectional MR positive factors, with 1-myristoylglycophorophospholine being a risk factor (1.0013, 1.0097) and 1-eicosatrienoylglycophorine being a protective factor (0.9914, 0.9990). The four lipids (1-linoleoylglycerophoethanolamine*, total cholesterol in large high-density lipoprotein [HDL], cholesterol esters in very large HDL, and phospholipids in very large HDL) and one NA metabolite (degree of unsaturation) were included in the known hazardous metabolites. The known protective metabolites included three types of lipids (carnitine, 1-linoleoylglycerophoethanolamine*, and 1-eicosatrienoylglycerophophophorine), one amino acid (hypoxanthine), and two unknown metabolites (the ratio of omega-6 fatty acids to omega-3 fatty acids, and the ratio of photoshopids to total lipids ratio in chylomicrons and extremely large very low-density lipoprotein [VLDL]). Moreover, sn-Glycerol 3-phosphate and 1-Acyl-sn-glycero-3-phosphocline were found to be involved in the pathogenesis of IPF through metabolic pathways such as Glycerolide metabolism and Glycerophospholipid metabolism. Conclusion: Our study identified 6 causal risks and 6 protective serum metabolites associated with IPF. Additionally, 2 metabolites were found to be involved in the pathogenesis of IPF through metabolic pathways, providing a new perspective for further understanding the metabolic pathway and the pathogenesis of IPF.
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BACKGROUND: We compared the diagnostic performance of the short five-item and full seven-item Mini Sarcopenia Risk Assessment Questionnaire (MSRA-5 and MSRA-7) against the Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F) and SARC-F with calf circumference (SARC-CalF) scales for sarcopenia in healthy community-dwelling older adults. METHODS: We conducted a post-hoc cross-sectional secondary data analysis of a prospective cohort study, using data from 230 older adults (mean age 67.2±7.4 years, 92% Chinese, and 73% female) from the "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and Osteosarcopenic Obesity in predicting frailty and functional decline in community-dwelling Asian older adults Study" (GeriLABS-2) conducted between December 2017 and March 2019 in Singapore. We performed receiver operating characteristic curve analysis to ascertain the area under the curve (AUC) for sarcopenia diagnosis using the Asian Working Group for Sarcopenia 2019 consensus criteria. We applied the Delong method to compare the AUCs of the four instruments. RESULTS: The MSRA-5 and MSRA-7 demonstrated poor diagnostic performance (AUC of 0.511, 95% confidence interval [CI] 0.433-0.589 and AUC of 0.526, 95% CI 0.445-0.606, respectively), compared to that in SARC-CalF (AUC of 0.739, 95% CI 0.671-0.808) and SARC-F (AUC of 0.564, 95% CI 0.591-0.636). The SARC-CalF demonstrated significantly superior discriminatory ability compared to that in the SARC-F, MSRA-5, and MSRA-7 (all p<0.01). The MSRA-5 demonstrated lower sensitivity (0.464) and specificity (0.597) than in the SARC-CalF (0.661 and 0.738, respectively), whereas the MSRA-7 had higher specificity (0.887) and lower sensitivity (0.145). CONCLUSION: Conclusions: The poor diagnostic performances of the MSRA-5 and MSRA-7 in our study suggest limitations of self-reported questionnaires for assessing general and dietary risk factors for sarcopenia in healthy and culturally diverse community-dwelling older adults. Studies in different populations are needed to ascertain the utility of the MSRA for the community detection of sarcopenia.
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Avaliação Geriátrica , Sarcopenia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Avaliação Geriátrica/métodos , Estudos Prospectivos , Medição de Risco , Curva ROC , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Singapura/epidemiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Intrinsic capacity (IC) and frailty are complementary constructs that encapsulate functional capacities of older adults. Although earlier studies suggest the utility of composite IC scores in predicting risk of frailty, key gaps remain with the lack of direct comparative studies between different IC scales and lack of a composite score based on the World Health Organization Integrated Care for Older People (ICOPE) tool. We aimed to compare different IC scales, including an ICOPE-based scale, in their predictive ability for risk of frailty at 2 years in healthy community-dwelling older adults. DESIGN: Cohort study. SETTING AND PARTICIPANTS: A total of 230 participants (age: 67.2 ± 7.4 years) from the GeriLABS-2 cohort study. METHODS: We derived composite scores by summing 4 IC domains (locomotion, cognition, vitality, and psychological). We compared composite scores of 4 scales: IC1-Chew 2021, range: 0-8; IC2-Liu 2021, range: 0-4; IC3-ICOPE, range: 0-4; IC4-modified ICOPE, range: 0-8. The primary outcome was risk of frailty using the modified Fried Frailty Phenotype. We performed logistic regression to examine the association of baseline composite IC with risk of frailty. We also examined the impact of individual domains and number of impaired domains on risk of frailty. RESULTS: Among 193 (83.9%) older adults who completed 2-year follow-up, 20 (10.4%) met criteria for risk of frailty. When adjusted for covariates, 2-point per domain scales (IC1/IC4) predicted increased risk of frailty (OR, 4.31; 95% CI, 1.55-11.96; OR, 5.00; 95% CI, 1.75-14.26). When further adjusted for baseline frailty, only IC4 remained significant (OR, 4.28; 95% CI, 1.45-12.60). Among the domains, impaired locomotion and vitality were associated with risk of frailty. Greater number of impaired domains predicted increased risk of frailty (IC1/IC2: ß = 0.18-0.19, P < .05). CONCLUSIONS AND IMPLICATIONS: Baseline composite IC score using 2-point per domain scales better predicted risk of frailty at 2 years, predicated on impaired locomotion/vitality and greater number of impaired domains. For early identification of healthy older adults at risk of frailty, an ICOPE-based scale should be considered, as it is effective and accessible.
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Fragilidade , Avaliação Geriátrica , Humanos , Idoso , Masculino , Feminino , Avaliação Geriátrica/métodos , Fragilidade/diagnóstico , Medição de Risco , Estudos de Coortes , Idoso Fragilizado , Vida Independente , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , Pessoa de Meia-IdadeRESUMO
Overexpression of ECHS1 occurs in different cancers, including hepatocellular carcinoma (HCC). ECHS1 is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of ECHS1 knockdown on the regulation of HCC growth. ECHS1 shRNA suppressed the expression of ECHS1 protein in HepG2 cells compared to the negative control vector-transfected HCC cells. ECHS1 knockdown also reduced HCC cell viability and enhanced cisplatin-induced apoptosis in HCC cells. Akt activation and the expression of various cell cycle-related genes were inhibited following ECHS1 knockdown. ECHS1 shRNA suppressed hepatocellular carcinoma growth in tumor xenograft mice. These data demonstrate that ECHS1 may play a role in HCC progression, suggesting that inhibition of ECHS1 expression using ECHS1 shRNA should be further evaluated as a novel target for the control of HCC.
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Proliferação de Células , Enoil-CoA Hidratase/genética , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Animais , Apoptose , Carcinoma Hepatocelular/genética , Movimento Celular , Sobrevivência Celular , Células Cultivadas , Cisplatino , Enoil-CoA Hidratase/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Marcação In Situ das Extremidades Cortadas , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismoRESUMO
An optical technique is proposed for the accurate calibration of pulsed high magnetic fields utilizing the magnetic field dependent photoluminescence (PL) properties in an Er(3+):YVO(4) single crystal at 80 K. Bright green PL emissions are excited by a 487.5 nm laser line and can be enhanced greatly by a magnetic field at certain field values (B(c)). Since the B(c)'s under 10 T are extremely stable for a given sample at a certain temperature, and the FWHM of the enhancement peaks are less than 0.9 T, an Er(3+):YVO(4) single crystal is proven to be a good candidate for pulsed high magnetic field calibration. The detailed processes and numerous advantages of the technique are presented in this work.
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OBJECTIVE: This study aimed to (1) investigate the clinical practice for the management of sarcopenia among healthcare professionals in Asia, (2) determine the characteristics of clinical care provided by geriatricians versus by other healthcare professionals, and (3) clarify the awareness of sarcopenia. METHODS: From December 1 to 31, 2022, an online survey was completed by 1990 healthcare professionals in Asia. The survey comprises demographics and institutional characteristics, basic sarcopenia-related details, and sarcopenia-related assessment and treatment details. RESULTS: The mean respondent age was 44.2 ± 10.7 years, 36.4% of the respondents were women, and the mean years of experience in clinical practice were 19.0 ± 10.6 years. The percentages of respondents who were aware of the term "sarcopenia", its definition and the importance of its management were high, at 99.3%, 91.9%, and 97.2%, respectively. The percentages of respondents who had screened patients for, diagnosed patients with, and treated patients for sarcopenia were 42.4%, 42.9%, and 58.8%, respectively. Medical doctors had higher performance rates compared to allied health professionals (45.5% vs. 40.5% for screening, 56.8% vs. 34.5% for diagnosis, and 65.0% vs. 55.0% for treatment) (P < 0.001). Especially, among medical doctors, geriatricians had significantly higher rates compared to non-geriatricians (64.3% vs. 34.1% for screening; 76.7% vs. 44.8% for diagnosis; 82.7% vs. 54.4% for treatment, respectively) (P < 0.001). CONCLUSION: Although the importance of the concept and management of sarcopenia is well recognized, there is a gap in its detection and management in clinical practice between medical doctors and allied health professionals, and also between geriatricians and non-geriatricians. Many geriatricians collaborate with other healthcare professionals to appropriately manage sarcopenia. In the future, educating all medical staff on the proper management of sarcopenia is necessary.
Assuntos
Padrões de Prática Médica , Sarcopenia , Feminino , Humanos , Masculino , Ásia/epidemiologia , Sarcopenia/diagnóstico , Sarcopenia/terapia , Inquéritos e Questionários , Adulto , Pessoa de Meia-IdadeRESUMO
BACKGROUND: While studies have suggested the association between triglyceride-glucose (TyG) index, a reliable surrogate for insulin resistance and hypertension data are limited to the correlation of TyG and central blood pressure. This study aims to test the hypothesis that a higher TyG index is associated with elevated central systolic blood pressure (cSBP). METHODS: A total of 9249 Chinese hypertensive adults from the H-type Hypertension and Stroke Prevention and Control Project were analyzed in this study. cSBP was measured noninvasively using an A-Pulse CASPro device. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Smoothing curve and multivariate linear regression models [beta coefficient (ß) with 95% CI] were applied to analyze the association between TyG index and cSBP. Subgroup analyses were conducted to explore potential modifications to such a correlation. RESULTS: The overall mean TyG index is 8.8 ± 0.7, and the total mean cSBP is 131.3 ± 12.8 mmHg. TyG index was observed to be independently and positively associated with cSBP among the total population (ß = 0.92, 95% CI: 0.53-1.31, P < 0.001), and participants who do not use antihypertensive drugs (ß = 1.03, 95% CI: 0.46-1.60, P < 0.001), which is in accordance with the result of the smoothing curve. The association between TyG index and cSBP appears robust in all tested subgroups. CONCLUSIONS: TyG index is positively and independently associated with cSBP among hypertensive adults. Our study result suggests that TyG index might serve as an effective marker for vascular function.
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BACKGROUND: Although recommended by the Asian Working Group for Sarcopenia 2019 consensus (AWGS'19) as a screening tool for sarcopenia, there remains no consensus regarding the position (sitting, standing) or laterality (right, left) for the measurement of calf circumference (CC). This study aimed to determine the agreement between CC measurements, correlations with muscle mass and function, and diagnostic performance for sarcopenia screening. METHODS: We studied 176 healthy community-dwelling older adults (mean age, 66.8±7.1 years) from the GERILABS-2 study. CC was measured using non-elastic tape in four ways: left and right sides in the sitting and standing positions. Sarcopenia was diagnosed using the AWGS'19 criteria. We produced Bland-Altman plots to assess the agreement, partial correlations for muscle mass and function to compare convergent validity, and area under the receiver operating characteristic curve (AUC) to compare diagnostic performance. RESULTS: The prevalence rate of sarcopenia was 17.4%. Sitting CC was larger than standing regardless of laterality (right 35.31±2.95 cm vs. 34.61±2.74 cm; left 35.37±2.96 cm vs. 34.70±2.83 cm; both p<0.001), consistent with the systematic bias on Bland-Altman plots showing the overestimation of sitting over standing measurements (right bias=0.70 cm; 95% confidence interval [CI], -0.48-1.88; left bias=0.67 cm, 95% CI, -0.35-1.68). After adjusting for age and sex, CC was significantly correlated with appendicular skeletal mass, hand grip strength, knee extension, gait speed, chair stand, and short physical performance battery. Although right-sided CC measurements had better diagnostic performance (AUC=0.817), the difference was not statistically significant compared to the other positions (p>0.05). The optimal cutoff was <34 cm for all measurements, except for the left standing position (cutoff <35 cm). CONCLUSION: Standing CC measurements are recommended for sarcopenia screening in community-dwelling older adults because of their good agreement without systematic bias, convergent validity, and diagnostic performance.
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INTRODUCTION: There are limited studies exploring functional improvement in relation to characteristics of patients who, following acute hospital care, receive inpatient rehabilitation in community hospitals. We evaluated the association of acute hospital admission-related factors with functional improvement on community hospital discharge. METHODS: We conducted a retrospective cohort study among patients who were transferred to community hospitals within 14-day post-discharge from acute hospital between 2016 and 2018. Modified Barthel Index (MBI) on a 100-point ordinal scale was used to assess functional status on admission to and discharge from the community hospital. We categorised MBI into 6 bands: 0-24, 25-49, 50-74, 75-90, 91-99 and 100. Multivariable logistic regression models were constructed to determine factors associated with categorical improvement in functional status, defined as an increase in at least one MBI band between admission and discharge. RESULTS: A total of 5,641 patients (median age 77 years, interquartile range 69-84; 44.2% men) were included for analysis. After adjusting for potential confounders, factors associated with functional improvement were younger age, a higher MBI on admission, and musculoskeletal diagnosis for the acute hospital admission episode. In contrast, a history of dementia or stroke; lower estimated glomerular filtration rate; abnormal serum albumin or anaemia measured during the acute hospital episode; and diagnoses of stroke, cardiac disease, malignancy, falls or pneumonia; and other chronic respiratory diseases were associated with lower odds of functional improvement. CONCLUSION: Clinicians may want to take into account the presence of these high-risk factors in their patients when planning rehabilitation programmes, in order to maximise the likelihood of functional improvement.