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BACKGROUND: Physicians' recognition of end of life (EOL) has key influences on patients' 'good death'. AIM: We aimed to study physicians' attitude toward EOL, and to analyze the relationship between physicians' assessment and patients' actual survival and the trigger effect on patient's access to palliative consultation and palliative care. DESIGN: This is a multi-center retrospective cohort study in seven community hospitals in Taiwan. METHODS: Inpatients admitted between 1 March 2016 and 31 December 2020, scored ≥4 points using Taiwan version-Palliative Care Screening Tool (TW-PCST), and expired before 31 December 2020 were enrolled. Physicians answered three questions regarding these inpatients: 'surprised of mortality within 6-12 months', 'EOL' and 'in need of palliative care'. We followed up patients' actual survival and access to palliative consultation and services. RESULTS: We enrolled 10 304 cases. There was high correlation among the three questions. The median survival of patients with 'not surprised of death within 6-12 months', 'EOL', and 'needing palliative care' were 68, 60 and 58 days, respectively. Those with opposite responses were 206, 166 and 186 days, respectively. Patients' main diagnosis, TW-PCST score, physicians' palliative care qualifications and reward measures were all associated with physicians' recognition of EOL. Physicians' assessment, physicians' training, disease characteristics and TW-PSCT scores were all associated with palliative consultation and palliative care. CONCLUSIONS: Physicians are still over optimistic in recognizing inpatients' survival and palliative care needs. EOL talks can be initiated when the TW-PCST score is high. Universal palliative care training can be integrated into medical education.
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Médicos , Assistência Terminal , Humanos , Cuidados Paliativos , Pacientes Internados , Estudos Retrospectivos , Taiwan/epidemiologiaRESUMO
Objective: To compare the diagnostic performance of next-generation sequencing (NGS) detection methods in sputum samples and Mycobacterium tuberculosis strains, in order to explore the feasibility of the NGS method to detect drug resistance in sputum specimens. Methods: In this retrospective study, the sputum specimens and corresponding clinical isolates of 50 pulmonary tuberculosis patients admitted to Beijing Chest Hospital from January 2017 to December 2017 were collected. The gene mutations of katG, inhA, rpoB, embA, embB, rpsL, rrs, gyrA, gyrB and tlyA in sputum specimens and corresponding clinical isolates were detected by NGS method. The phenotypic drug susceptibility test (DST) of the strains was carried out by the proportion method. Using DST results as a reference, the sensitivity, specificity, positive predictive value and negative predictive value of the NGS method for clinical strains and sputum specimens, as well as the consistency statistic (Kappa) with phenotype DST were calculated respectively. The Chi-square test was used to compare the accuracy of the NGS testing in sputum samples and strain samples. Results: The results showed that rpoB(63.83%, 30/47) and rrs(57.45%, 27/47) were the most common mutated genes, followed by katG(46.81%, 22/47), rpsL(29.79%, 14/47), gyrA(27.66%, 13/47), embB(21.28%, 10/47), tlyA(12.77%, 6/47), gyrB(8.51%, 4/47), and inhA promoter(19.15%, 9/47), embA promoter region (12.77%, 6/47) mutation. when the NGS method was compared with the resistance phenotype of isoniazid, rifampicin, ethambutol, second-line injectable drugs (streptomycin, capreomycin, kanamycin, amikacin), levofloxacin, the sensitivity were 85.71%, 91.67%, 77.78%, 81.82%, 100.00%, 87.50%, 100.00%, 69.23%, and the specificity were 100.00%, 94.12, 87.50%, 89.47%, 97.06%, 96.97%, 94.29%, 89.29% in sputum samples, while in strain samples, the sensitivity were 92.86%, 100.00%, 81.82%, 86.96%, 88.89%, 80.00%, 100.00%, 85.71%. The specificity were 100.00%, 92.86%, 87.10%, 94.74%, 100.00%, 100.00%, 97.14%, 92.86%. Compared with the phenotypic drug susceptibility results, the NGS method has better detection performance for isoniazid, rifampicin, capreomycin, kanamycin, and amikacin in sputum specimens (Kappa≥0.75); while among the strains, the NGS method had a good detection performance for isoniazid, rifampicin, streptomycin, capreomycin, kanamycin, amikacin and levofloxacin (Kappa≥0.75). With the accuracy of the NGS method for detecting strains as a reference, there was no statistically significant difference in the accuracy of all drug resistance detected between strains and sputum specimens. Conclusions: This study showed that the NGS technology was effective in predicting the resistance of isoniazid, rifampicin, and second-line injectable drugs (capreomycin, kanamycin and amikacin) by detecting sputum samples and strain genotypes, suggesting the feasibility and potential of direct detection of sputum samples by the NGS method as an early detection method for drug resistance.
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Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Resistente a Múltiplos Medicamentos , Amicacina/farmacologia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Capreomicina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Isoniazida/farmacologia , Canamicina/farmacologia , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Rifampina/farmacologia , Escarro/microbiologia , Estreptomicina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnósticoRESUMO
Enhancing the supply of arginine (Arg), a semi-essential amino acid, has positive effects on immune function in dairy cattle experiencing metabolic stress during early lactation. Our objective was to determine the effects of Arg supplementation on biomarkers of liver damage and inflammation in cows during early lactation. Six Chinese Holstein lactating cows with similar BW (508 ± 14 kg), body condition score (3.0), parity (4.0 ± 0), milk yield (30.6 ± 1.8 kg) and days in milk (20 ± days) were randomly assigned to three treatments in a replicated 3 × 3 Latin square design balanced for carryover effects. Each period was 21 days with 7 days for infusion and 14 days for washout. Treatments were (1) Control: saline; (2) Arg group: saline + 0.216 mol/day l-Arg; and (3) Alanine (Ala) group: saline + 0.868 mol/day l-Ala (iso-nitrogenous to the Arg group). Blood and milk samples from the experimental cows were collected on the last day of each infusion period and analyzed for indices of liver damage and inflammation, and the count and composition of somatic cells in milk. Compared with the Control, the infusion of Arg led to greater concentrations of total protein, immunoglobulin M and high density lipoprotein cholesterol coupled with lower concentrations of haptoglobin and tumor necrosis factor-α, and activity of aspartate aminotransferase in serum. Infusion of Ala had no effect on those biomarkers compared with the Control. Although milk somatic cell count was not affected, the concentration of granulocytes was lower in response to Arg infusion compared with the Control or Ala group. Overall, the biomarker analyses indicated that the supplementation of Arg via the jugular vein during early lactation alleviated inflammation and metabolic stress.
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Arginina/administração & dosagem , Inflamação/veterinária , Leite/metabolismo , Animais , Biomarcadores/análise , Bovinos , Dieta/veterinária , Feminino , Saúde , Inflamação/tratamento farmacológico , Infusões Intravenosas , Lactação , Fígado/metabolismo , Paridade , Gravidez , Distribuição Aleatória , Estresse FisiológicoRESUMO
Objective: To investigate the key issues in the diagnosis and treatment of foreign body aspiration in children with tracheobronchial variations. Methods: A retrospective study was performed for 11 pediatric patients who were treated in Department of Otorhinolaryngology and Head and Neck Surgery, Henan Province People's Hospital after a diagnosis of foreign body aspiration with tracheobronchial variations between January 2015 and December 2017. There were 7 males and 4 females among the 11 cases of foreign body aspiration with tracheobronchial variations, ranging between 9 months and 11 years of age. Results: Among 11 cases, the types of variationswere tracheal bronchus in 9 cases, bridging bronchus in 1 case and simple tracheal stenosis in 1 case. All of the pediatric patients were under general anesthesia, and the foreign bodies were removed by bronchoscopy successfully with no significant complications. Conclusions: The possibility of tracheobronchial variations should be considered in children with recurrent wheezing and poor efficacy of regular treatment before foreign body aspiration. Removal of foreign body via rigid bronchoscope under general anesthesia is a safe and effective treatment. These children are needed to combine the situation oftracheobronchial variations and the location of foreign bodies to guide the operation, and strengthened the perioperative treatment.
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Corpos Estranhos/diagnóstico , Corpos Estranhos/terapia , Aspiração Respiratória/diagnóstico , Aspiração Respiratória/terapia , Doenças Respiratórias/complicações , Brônquios/anormalidades , Broncoscopia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Anormalidades do Sistema Respiratório/complicações , Estudos Retrospectivos , Traqueia/anormalidades , Estenose Traqueal/complicaçõesRESUMO
OBJECTIVE: To study the protective effect of glutamine on the intestinal tissues of septic rats by regulating the nuclear factor-κB (NF-κB) pathway. MATERIALS AND METHODS: A total of 30 rats were divided into the Sham group, Model group, and Glutamine group using a random number table. The changes in the intestinal tissues in rats were observed via hematoxylin-eosin (HE) staining, and the difference in the content of serum inflammatory factor tumor necrosis factor-α (TNF-α) was detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the apoptosis of the intestinal tissues was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the protein expression of NF-κB in intestinal tissues was detected via Western blotting. RESULTS: In the Sham group, the rats had normal activity and good mental state, and there were no evident lesions in the abdominal cavity. Compared with the rats in the Sham group, the rats in the Model group had very poor mental state and erected hair, and they trembled and barely moved. After the abdomen was opened, there were bad smell and evident bleeding in the abdominal cavity, and the cecum became black with adhesion and swelling. In the Glutamine group, the symptoms were significantly alleviated compared with the Model group. The morphological observation of the intestinal tissues revealed that in the Sham group, the intestinal villi were regularly and clearly arranged, and there was no congestion in the capillaries. Compared with the Sham group, the intestinal villi were disorderly arranged with rupture in the Model group, and the severe capillary congestion was clearly visible and accompanied by ulcer. In the Glutamine group, the intestinal villi had normal morphology and regular arrangement after treatment, the subepithelial space was significantly dilated, the capillary dilation and the congestion could be seen and the lamina propria was intact. In the Sham group, the pathological score was 0 point, and the intestinal mucosa and villi had normal structure. Compared with that in the Sham group, the pathological score of the intestinal tissues were significantly increased in the Model group (p<0.05). In the Glutamine group, the pathological score significantly declined after treatment compared with that in the Model group (p<0.05). Besides, the content of the inflammatory factor TNF-α in the intestinal tissues was the highest in the Model group (p<0.05), and it was lower in the Glutamine group than that in the Sham group (p<0.05), indicating that glutamine can effectively reduce the content of the inflammatory factor TNF-α, exerting a certain protective effect on the intestinal tissues. The number of apoptotic intestinal epithelial cells was remarkably increased in the Model group compared with that in the Sham group (p<0.05), and it was remarkably decreased in the Glutamine group compared with that in the Model group (p<0.05). The Model group had a significantly higher protein expression of NF-κB in intestinal tissues than in the Sham group and Glutamine group (p<0.05), Sham group had the lowest protein expression of NF-κB in intestinal tissues (p<0.05), and the Glutamine group had a significantly lower protein expression of NF-κB in intestinal tissues than the Model group (p<0.05). CONCLUSIONS: Glutamine inhibits the protein expression of NF-κB, thereby exerting a protective effect on intestinal tissues of sepsis rats.
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Glutamina/administração & dosagem , Mucosa Intestinal/citologia , NF-kappa B/metabolismo , Sepse/tratamento farmacológico , Animais , Apoptose , Regulação para Baixo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glutamina/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Ratos , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The objective of this study was to evaluate the effects of jugular l-Arg infusion on performance and immune function during lipopolysaccharide (LPS)-induced inflammation of lactating dairy cows. Eight Holstein cows (multiparous, 608.8 ± 31.5 kg) at mid-lactation were randomly assigned to 5-d jugular infusions of control (saline), Arg (3 g/h), LPS (0.033 µg/kg per h), and LPS + Arg (0.033 µg/kg per h of LPS and 3 g/h of Arg) in a replicated 4 × 4 Latin square design with 4 infusion periods separated by 10-d noninfusion periods. Jugular solutions of saline, Arg, LPS, and LPS + Arg were continuously infused using peristaltic pumps for approximately 6 h/d during infusion periods. Milk yield was measured on each day of the infusion period. Milk samples were obtained on the last 2 d of each infusion period, and blood samples were obtained on the last day of each infusion period before infusion (0 h) and at 3 and 6 h. We found that the jugular LPS infusion significantly increased serum concentrations of IL-1ß, IL-6, tumor necrosis factor, inducible nitric oxide synthase, and lipopolysaccharide binding protein, whereas Arg attenuated the increase in IL-6 and inducible nitric oxide synthase levels and tended to decrease the lipopolysaccharide binding protein level. Arginine alleviated the decrease in dry matter intake and milk fat yield and the increase of somatic cell count induced by LPS. Total casein in milk was decreased during the LPS-induced inflammation period, and jugular Arg infusion significantly increased the content of total casein. In contrast, lactalbumin in milk increased during the LPS-induced inflammation period, whereas jugular Arg infusion significantly decreased the content of lactalbumin. The concentrations of plasma Gly, Thr, Ile, Leu, Arg, Phe, and total free AA were significantly decreased by LPS treatment, but Arg attenuated this tendency. These results indicated that jugular Arg infusion (18 g/d) has protective effects on relieving inflammatory stress and improving immunity status triggered by LPS. In conclusion, Arg could attenuate inflammatory stress and improve milk performance of lactating dairy cows. This protective effect may be due to the ability of Arg to suppress LPS effects and improve immunity status.
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Arginina/administração & dosagem , Bovinos/imunologia , Lactação , Lipopolissacarídeos/imunologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Caseínas , Bovinos/fisiologia , Dieta/veterinária , Feminino , LeiteRESUMO
BACKGROUND AND PURPOSE: Sensory neuronopathy is a cardinal feature of cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS). Having observed that two patients with CANVAS had small median and ulnar nerves on ultrasound, we set out to examine this finding systematically in a cohort of patients with CANVAS, and compare them with both healthy controls and a cohort of patients with axonal neuropathy. We have previously reported preliminary findings in seven of these patients with CANVAS and seven healthy controls. METHODS: We compared the ultrasound cross-sectional area of median, ulnar, sural and tibial nerves of 14 patients with CANVAS with 14 healthy controls and 14 age- and gender-matched patients with acquired primarily axonal neuropathy. We also compared the individual nerve cross-sectional areas of patients with CANVAS and neuropathy with the reference values of our laboratory control population. RESULTS: The nerve cross-sectional area of patients with CANVAS was smaller than that of both the healthy controls and the neuropathy controls, with highly significant differences at most sites (P < 0.001). Conversely, the nerve cross-sectional areas in the upper limb were larger in neuropathy controls than healthy controls (P < 0.05). On individual analysis, the ultrasound abnormality was sufficiently characteristic to be detected in all but one patient with CANVAS. DISCUSSION: Small nerves in CANVAS probably reflect nerve thinning from loss of axons due to ganglion cell loss. This is distinct from the ultrasound findings in axonal neuropathy, in which nerve size was either normal or enlarged. Our findings indicate a diagnostic role for ultrasound in CANVAS sensory neuronopathy and in differentiating neuronopathy from neuropathy.
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Vestibulopatia Bilateral/diagnóstico por imagem , Ataxia Cerebelar/diagnóstico por imagem , Nervos Periféricos/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Adulto , Idoso , Anatomia Transversal , Axônios/patologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Reflexo Vestíbulo-Ocular , Transtornos de Sensação/diagnóstico por imagem , Transtornos de Sensação/etiologia , Síndrome , UltrassonografiaRESUMO
In order to avoid a fringe jump caused by high plasma density and pellet injection [Y. Zhou et al., Rev. Sci. Instrum. 87, 11E107 (2016)], a new CO2 dispersion interferometer is designed and commissioned on HL-2A for average line-density measurement and density feedback control. The second harmonic technology in this system eliminates the phase shift caused by mechanical vibration. Signals are processed by a digital phase comparator and can be monitored in real time. A series of experiments are conducted to study the characteristics of the system such as a second harmonic coefficient and long-term stability. The resolution of density measurement is less than 8 × 1017/m3, and the experiment result on HL-2A demonstrates the interferometer's capability to track plasma density evolution with rapid change. The system also shows good stability against mechanical vibrations.
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This study was undertaken to evaluate the milk protein response when cows were supplied a balanced AA profile and to determine whether a deficiency of Leucine (Leu) or Arginine (Arg) had a negative effect on milk protein. Eight mid-lactation Holstein cows were randomly assigned to 5-day continuous jugular infusions of saline (CTL), EAA mixture prepared on the profile of casein and supplied (in % of lysine (Lys)) 100% of Lys, 33.3% of methionine (Met), 110.2% of Leu, 43.6% of Arg, 50.8% of threonine (Thr), 81.6% of valine (Val), 69.7% of isoleucine (Ile), 61.4% of phenylalanine (Phe) and 34.2% of histidine (His) (Casein, 160 g/d), EAA mixture excluding Leu (-Leu, 163 g/d) or EAA mixture excluding Arg (-Arg, 158 g/d) in a duplicated 4 × 4 Latin square design with four infusion periods separated by 7-day interval period. The basal diet supplied 1.6 Mcal NEL and 94.4 g MP per 1 kg DM to meet requirements for lactation. The Casein treatment provided a balanced supply (in % of MP) of 10.3% Leu and 5.3% Arg, whereas in the two subsequent -Leu and -Arg treatments, the concentration of Leu and Arg was reduced to 8.4 and 4.6% respectively. Dry matter intake (15.4 kg/day) was not affected by treatments. The Casein treatment increased milk yield (14.9%, p < 0.001), milk protein yield (120 g, p < 0.001) and milk protein efficiency (0.03, p = 0.099) than CTL treatment. However, the -Leu treatment decreased the responses of above-measured parameters by 6.25%, 70 g, 0.05 (p < 0.06) (compared with Casein). These effects of Leu were related to decreased Leu concentration and improved concentration of Ile and Val in plasma. The -Arg treatment decreased the plasma Arg concentration than the Casein treatment, whereby resulted in the decrease of milk yield (5.7%, p = 0.073), milk protein yield (60 g, p = 0.011) and milk protein efficiency (0.04, p = 0.037). In conclusion, supply of EAA profile of casein can increase the lactation production in dairy cows, and 8.6% of Leu in MP partly limits the milk protein response when the requirements of Lys, Met and His were met. The level of Arg at 4.6% MP is not deemed to an ideal profile, as evidenced by decreased milk protein efficiency.
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Aminoácidos/administração & dosagem , Arginina/administração & dosagem , Bovinos/fisiologia , Lactação/efeitos dos fármacos , Leucina/administração & dosagem , Proteínas do Leite/metabolismo , Aminoácidos/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Arginina/farmacologia , Dieta/veterinária , Feminino , Injeções Intravenosas , Leucina/farmacologia , Leite/química , Proteínas do Leite/químicaRESUMO
There was an initial increase and a later decrease in hip fracture rates in Taiwan between 1996 and 2010 (457.9 to 390.0 fractures per 100,000 people per year). Mortality rates decreased but re-emerged later (2.26 to 1.91 deaths per 100 hip fracture admissions). The turning point for change in trends was 2003. INTRODUCTION: Fractures of the proximal femur remain a major cause of mortality and morbidity. We aimed to examine recent trends in hip fracture rates, in-hospital mortality rates, and length of hospital stay (LOS) due to hip fractures in people aged 55 and over in Taiwan. METHODS: This is a time-trend study. We used data from the National Health Insurance Research Database between 1996 and 2010 in Taiwan. Insurants aged 55 and over were included. The outcome measures were age-adjusted hip fracture rates, age-adjusted in-hospital mortality rates, and LOS due to hip fractures. We classified hip fractures into femoral neck, trochanteric, and subtrochanteric fractures. RESULTS: We identified 250,919 hospitalizations for hip fractures. The total number of hip fractures increased steadily from 12,479 to 19,841 cases. There was a trend towards initial increase and then later decrease in hip fracture rates (from 457.9 to 390.0 fractures per 100,000 people per year). LOS decreased by 46.5 % (17.53 to 9.38 days). By contrast, mortality rates for hip fractures decreased initially, but re-emerged later with a total decrement of 15.5 % (2.26 to 1.91 deaths per 100 hip fracture admissions). Women outnumbered men in all types of hip fractures, but men had higher in hospital mortality rates. LOS was similar between genders and among age groups. The turning point for change in trends was year 2003. CONCLUSIONS: While LOS shortened gradually since 1996, the absolute number of hip fractures in Taiwan continues to rise. There is still room for improvement in reducing mortality due to hip fractures.
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Fraturas do Quadril/epidemiologia , Fraturas por Osteoporose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Inquéritos Epidemiológicos , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Humanos , Incidência , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Taiwan/epidemiologiaRESUMO
With the increasing voltage of direct current transmission line, the intensity of the environmental static electric field has also increased. Thus, whether static electric fields cause biological injury is an important question. In this study, the effects of chronic exposure to environmental static electric fields on some antioxidant enzymes activities in the hepatocytes of mice were investigated. Male Institute of Cancer Research mice were exposed for 35 days to environmental static electric fields of different electric field intensities of 9.2-21.85 kV/m (experiment group I, EG-I), 2.3-15.4 kV/m (experiment group II, EG-II), and 0 kV/m (control group, CG). On days 7, 14, 21, and 35 of the exposure cycle, liver homogenates were obtained and the activities of antioxidant enzymes like superoxide dismutase, glutathione S-transferase, and glutathione peroxidase were determined, as well as the concentration of malonaldehyde. The results revealed a significant increase in superoxide dismutase activity in both EG-I and EG-II on the 7th (P < 0.05) and 35th days (P < 0.01) of the exposure cycle compared to that in the control group. However, the other test indices such as glutathione S-transferase, glutathione peroxidase, and malonaldehyde showed only minimal changes during the exposure cycle. These results revealed a weak relationship between the exposure to environmental static electric fields and hepatic oxidative stress in living organisms.
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Antioxidantes/metabolismo , Hepatócitos/enzimologia , Animais , Campos Eletromagnéticos , Meio Ambiente , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Fígado/enzimologia , Masculino , Camundongos , Oxirredução , Estresse Oxidativo/fisiologia , Eletricidade Estática , Superóxido Dismutase/metabolismoRESUMO
HOTAIR, a long non—coding RNA (lncRNA), is reported to regulate chromatin organization and promote tumor progression. However, little is known about the roles of this gene in the modulation of calcium homeostasis in human cardiomyocytes. In the present study, we demonstrated that up—regulation of HOTAIR could suppress the expression of CaV1.2 in human cardiomyocytes. However, HOTAIR knockdown promoted CaV1.2 expression in human cardiomyocytes. In addition, we found that HOTAIR overexpression significantly reduced the intracellular Ca2+ contents; while knockdown of HOTAIR enhanced the Ca2+ contents in the cardiomyocytes. Moreover, enforced expression of CaV1.2 increased the calcium level in cardiomyocytes overexpressing HOTAIR. down—regulation of HOTAIR and up—regulation of CaV1.2 further enhanced the Ca2+ contents in the cardiomyocytes Taken together, these results for the first time demonstrate that HOTAIR inhibited the intracellular Ca2+ via regulation of CaV1.2 in human cardiomyocytes.
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Canais de Cálcio Tipo L/metabolismo , Cálcio/metabolismo , RNA Longo não Codificante/metabolismo , Canais de Cálcio Tipo L/química , Linhagem Celular , Humanos , Microscopia de Fluorescência , Miócitos Cardíacos , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaRESUMO
Clostridium sp. strain Ade.TY is potentially a new biohydrogen-producing species isolated from landfill leachate sludge. Here we present the assembly and annotation of its genome, which may provide further insights into its gene interactions for efficient biohydrogen production.
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BACKGROUND AND PURPOSE: Inosine monophosphate dehydrogenases, encoded by IMPDH1 and IMPDH2, are targets for the important immunosuppressive drug, mycophenolic acid (MPA). Variation in MPA response may result, in part, from genetic variation in IMPDH1 and IMPDH2. EXPERIMENTAL APPROACH: We resequenced IMPDH1 and IMPDH2 using DNA from 288 individuals from three ethnic groups and performed functional genomic studies of the sequence variants observed. KEY RESULTS: We identified 73 single nucleotide polymorphisms (SNPs) in IMPDH1, 59 novel, and 25 SNPs, 24 novel, in IMPDH2. One novel IMPDH1 allozyme (Leu275) had 10.2% of the wild-type activity as a result of accelerated protein degradation. Decreased activity of the previously reported IMPDH2 Phe263 allozyme was primarily due to decreased protein quantity, also with accelerated degradation. These observations with regard to the functional implications of variant allozymes were supported by the IMPDH1 and IMPDH2 X-ray crystal structures. A novel IMPDH2 intron 1 SNP, G > C IVS1(93), was associated with decreased mRNA quantity, possibly because of altered transcription. CONCLUSIONS AND IMPLICATIONS: These results provide insight into the nature and extent of sequence variation in the IMPDH1 and IMPDH2 genes. They also describe the influence of gene sequence variation that alters the encoded amino acids on IMPDH function and provide a foundation for future translational studies designed to correlate sequence variation in these genes with outcomes in patients treated with MPA.
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IMP Desidrogenase/genética , Imunossupressores/farmacologia , Ácido Micofenólico/farmacologia , Polimorfismo de Nucleotídeo Único , Negro ou Afro-Americano , Animais , Asiático , Sequência de Bases , Células COS , Linhagem Celular , Chlorocebus aethiops , Humanos , IMP Desidrogenase/antagonistas & inibidores , IMP Desidrogenase/metabolismo , Isoenzimas/metabolismo , Transplante de Rim , Estados Unidos , População BrancaRESUMO
AIMS: To develop an efficient and facile expression system supply of high purity and stable activity of rFip-fve for oral administration, medicinal study and applications. METHODS AND RESULTS: A recombinant virus that contained the chimera gene, encoding a bombyxin signal peptide sequence fused to a Fip-fve-6His sequence, was constructed. The rFip-fve was purified from the supernatant of the infected Sf21 cells using a nickel-chelated affinity column, and was verified by Western blot and MALDI-MS (matrix-assisted laser desorption ionization mass spectrometry) analyses. Results showed that a glycosylated mature rFip-fve was produced and secreted into the infected cell supernatant. The immunomodulatory activity of rFip-fve was evaluated by measuring the amount of interleukin-2 released from murine splenocytes. CONCLUSIONS: A reliable scheme to express and purify active rFip-fve in a baculovirus/insect cell system for medicinal applications and genetic study is a feasible means of solving potential problems related to the production and activity of rFip-fve protein. SIGNIFICANCE AND IMPACT OF THE STUDY: The rFip-fve expressed in insect cells was processed and modified in a manner more similar to that of its native counterpart than that in bacterial cells. Therefore, the potential applications of rFip-fve that is generated in Sf21 cells can be more effectively evaluated that produced in Escherichia coli.
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Baculoviridae/fisiologia , Proteínas Fúngicas/isolamento & purificação , Fatores Imunológicos/isolamento & purificação , Microbiologia Industrial , Lectinas/isolamento & purificação , Animais , Reatores Biológicos , Linhagem Celular , Células Cultivadas , Escherichia coli , Proteínas Fúngicas/farmacologia , Fatores Imunológicos/farmacologia , Interleucina-2/biossíntese , Lectinas/farmacologia , Camundongos , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Baço/efeitos dos fármacos , Baço/imunologia , Spodoptera/virologiaAssuntos
Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , Genes Supressores de Tumor , Leiomiossarcoma/diagnóstico , Neoplasias Ureterais/diagnóstico , Neoplasias Ureterais/genética , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Diferenciação Celular , DNA de Neoplasias/genética , Diagnóstico Diferencial , Feminino , Expressão Gênica , Genes p53 , Humanos , Imuno-Histoquímica , Leiomiossarcoma/genética , Leiomiossarcoma/metabolismo , Leiomiossarcoma/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/metabolismo , Neoplasias Primárias Múltiplas/patologia , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Neoplasias Ureterais/metabolismo , Neoplasias Ureterais/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
STUDY DESIGN: Retrospective case study. OBJECTIVES: Report a rare case of cervical myelopathy induced by calcium pyrophosphate dehydrate (CPPD) deposition in multiple cervical levels. SETTING: An area teaching hospital in Taiwan. METHOD: A patient with cervical myelopathy was evaluated by computerized tomography (CT) scan and magnetic resonance (MR) image. CPPD deposition known as pseudogout was diagnosed and approved by a polarized microscope. RESULT: A prominent hypertrophy of ligmentum flavum and a retro-odontoid bulging mass induced cord compression were found in CT scan and MR image. CPPD deposition was confirmed by the histological examinations in the ligamentum flavum at the spinal levels of C3-C6. After decompression surgery of spine and comprehensive rehabilitation, the patient's neurological symptoms subsided and her neurological functions improved leading to a good prognosis. CONCLUSION: CPPD deposition in cervical spine occurring at multiple levels is rare. Image studies with CT scan and MR are complementary in the diagnosis of CPPD-induced myelopathy. Surgical decompression is always required and expected to have a good outcome.
Assuntos
Condrocalcinose/complicações , Ligamento Amarelo/patologia , Processo Odontoide/patologia , Doenças da Medula Espinal/etiologia , Doenças da Coluna Vertebral/etiologia , Idoso , Feminino , Humanos , Ligamento Amarelo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Doenças da Medula Espinal/patologia , Doenças da Coluna Vertebral/patologia , Doenças da Coluna Vertebral/radioterapia , Tomografia Computadorizada por Raios X/métodosRESUMO
2,3,5-Trisubstituted indoles are synthesized in three steps starting from resin-bound aniline 2. R1 is introduced by a palladium-mediated coupling of the aryl iodide with terminal alkynes followed by intramolecular cyclization to form the indole core. Acylation at C-3 with an acid chloride in the presence of AlCl(3) catalyst introduces R2. The indole C-5 position is then diversified either by Sonagashira or Suzuki couplings with the aryl bromide. Finally, indole N-1 can be modified by post-cleavage methylation. [reaction: see text]