RESUMO
The particulate methane monooxygenase (pMMO) is the first enzyme in the C1 metabolic pathway in methanotrophic bacteria. As this enzyme converts methane into methanol efficiently near room temperature, it has become the paradigm for developing an understanding of this difficult C1 chemistry. pMMO is a membrane-bound protein with three subunits (PmoB, PmoA, and PmoC) and 12-14 coppers distributed among different sites. X-ray crystal structures that have revealed only three mononuclear coppers at three sites have neither disclosed the location of the active site nor the catalytic mechanism of the enzyme. Here we report a cyro-EM structure of holo-pMMO from Methylococcus capsulatus (Bath) at 2.5 Å, and develop quantitative electrostatic-potential profiling to scrutinize the nonprotein densities for signatures of the copper cofactors. Our results confirm a mononuclear CuI at the A site, resolve two CuIs at the B site, and uncover additional CuI clusters at the PmoA/PmoC interface within the membrane (D site) and in the water-exposed C-terminal subdomain of the PmoB (E clusters). These findings complete the minimal set of copper factors required for catalytic turnover of pMMO, offering a glimpse of the catalytic machinery for methane oxidation according to the chemical principles underlying the mechanism proposed earlier.
Assuntos
Cobre/química , Metano/química , Oxigenases/metabolismo , Catálise , Domínio Catalítico , Cobre/metabolismo , Microscopia Crioeletrônica , Metanol/química , Methylococcus capsulatus/química , Oxirredução , Ligação Proteica , Conformação Proteica , ÁguaRESUMO
BACKGROUND AND PURPOSE: Various clinical and neuroimaging predictive factors have been identified for the recovery of upper extremity (UE) motor function after stroke. However, few studies have addressed factors related to the recovery of lower extremity (LE) motor function after stroke or performed direct comparisons of UE and LE motor recovery in the same set of patients. In this study, predictive factors for UE and LE motor recovery after stroke were investigated using clinical and neuroimaging characteristics. METHODS: Forty-two subacute ischaemic stroke patients underwent structural and functional magnetic resonance imaging data acquisition and cognitive/behavioral assessments using the Fugl-Meyer assessment, the National Institutes of Health Stroke Scale (NIHSS) and the Mini-Mental State Examination (MMSE) 2 weeks after stroke onset. Neuroimaging factors, including corticospinal tract (CST) fractional anisotropy, lesion volume, CST lesion load and interhemispheric homotopic functional connectivity, were extracted. The outcome of motor function was assessed by Fugl-Meyer assessment scores 3 months after onset. RESULTS: Early clinical and neuroimaging factors for predicting motor recovery were noticeably different for UE and LE. UE motor function recovery was related to age, NIHSS, MMSE, CST lesion load, lesion volume, ipsilesional CST integrity and interhemispheric homotopic functional connectivity. In contrast, LE motor recovery was related to ipsilesional and contralesional CST integrity and MMSE. Specifically, LE recovery showed a strong relationship to the preservation of cognitive function compared with motor impairment. CONCLUSIONS: Our results indicate that different mechanisms underlie UE and LE motor recovery after stroke. LE motor recovery seems to be more intensively modulated by cognitive functions than UE.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Humanos , Extremidade Inferior/diagnóstico por imagem , Tratos Piramidais , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico por imagem , Extremidade SuperiorRESUMO
According to Ministry of Health and Welfare of Taiwan, cancer has been one of the major causes of death in Taiwan since 1982. The Intensive-Modulated Radiation Therapy (IMRT) is one of the most important radiotherapies of cancers, especially for Nasopharyngeal cancers, Digestive system cancers and Cervical cancers. For patients, if they can receive the treatment at the earliest possibility while diagnosed with cancers, their survival rate increases. However, the discussion of effective patient scheduling models of IMRT to reduce patients' waiting time is still limited in literature. This study proposed a mathematical model to improve the efficiency of patient scheduling. The research was composed of two stages. In the first stage, the online stochastic algorithm was proposed to improve the performance of present scheduling system. In the second stage the impact of future treatment to reduce patients' waiting time was considered. A genetic algorithm (GA) was then proposed to solve the online stochastic scheduling problem. This research collected data from a practical medical institute and the proposed model was validated with real data. It contributes to both theory and practice by proposing a practical model to assist the medical institute in implementing patient scheduling in a more efficient manner.
Assuntos
Radioterapia de Intensidade Modulada , Algoritmos , Agendamento de Consultas , Humanos , Modelos Teóricos , Planejamento da Radioterapia Assistida por Computador , TaiwanRESUMO
ß-Casomorphin is an opioid-like bioactive peptide derived from ß-casein of milk that plays a crucial role in modulating animal's feed intake, growth, nutrient utilization and immunity. However, the effect of ß-casomorphin on lipid metabolism in chickens and its mechanism remain unclear. The aim of this study was to investigate the effects of ß-casomorphin on fat deposition in broiler chickens and explore its mechanism of action. A total of 120 21-day-old Arbor Acres male broilers (747.94±8.85 g) was chosen and randomly divided into four groups with six replicates of five birds per replicate. Three groups of broilers were injected with 0.1, 0.5 or 1.0 mg/kg BW of ß-casomorphin in 1 ml saline for 7 days, whereas the control group received 1 ml saline only. The results showed that subcutaneous administration of ß-casomorphin to broiler chickens increased average daily gain, average daily feed intake and fat deposition, and decreased feed : gain ratio (P<0.05). The activity of malate dehydrogenase in the pectoral muscle, liver and abdominal adipose tissue was also increased along with the concentrations of insulin, very-low-density lipoprotein and triglyceride in the plasma (P<0.05). The activity of hormone-sensitive lipase in the liver and abdominal adipose tissue and the concentration of glucagon in the plasma were decreased by injection with ß-casomorphin (P<0.05). Affymetrix gene chip analysis revealed that administering 1.0 mg/kg BW ß-casomorphin caused differential expression of 168 genes in the liver with a minimum of fourfold difference. Of those, 37 genes are directly involved in lipid metabolism with 18 up-regulated genes such as very low density lipoprotein receptor gene and fatty acid synthase gene, and 19 down-regulated genes such as lipoprotein lipase gene and low density lipoprotein receptor gene. In conclusion, ß-casomorphin increased growth performance and fat deposition of broilers. Regulation of fat deposition by ß-casomorphin appears to take place through changes in hormone secretion and enzyme activities by controlling the gene expression of lipid metabolism and feed intake, increasing fat synthesis and deposition.
Assuntos
Gordura Abdominal/fisiologia , Galinhas , Endorfinas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Gordura Abdominal/efeitos dos fármacos , Ração Animal , Animais , Endorfinas/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/metabolismo , Fígado/enzimologia , Malato Desidrogenase/metabolismo , Masculino , Distribuição Aleatória , Triglicerídeos/metabolismoRESUMO
This study was to investigate the effect of oxidized wheat gluten (OG) on growth performance, gut morphology and its oxidative states of broilers. One hundred and eighty-day-old male broilers (10 chicks/pen) were randomly allocated into three dietary treatments: control diet (CON), diet with 8% wheat gluten (WG) and diet with 8% OG with six pens/treatment. Body weight (BW) (21 and 35 days) and average daily gain (ADG) (1-21 days and 22-35 days) decreased (p < .05) and feed conversion ratio (FCR) (1-21 days and 22-35 days) increased (p < .05) in OG treatment. Feed intake (FI) decreased (p < .05) in WG and OG treatments during 22-35 days. However, FI was not influenced by dietary treatments during 1-21 days (p > .05). The OG-fed broilers had a lower faecal pH value (p < .05) and higher faecal moisture content (p < 05) at 14, 21, 28 and 35 days. Villus height, crypt depth and V/C value were not different (p > .05) among treatments at 21 and 35 days. Lipid peroxidation (LPO) (21 and 35 days) and malondialdehyde (MDA) (35 days) content in crop of OG treatment increased (p < .05). Oxidized glutathione (GSSG) (21 days), LPO (21 and 35 days) and MDA (21 and 35 days) content in ileum of OG treatment increased (p < .05). The reduced glutathione/oxidized glutathione (GSH/GSSG) (21 days) and (GSH) (35 days) in ileum of OG treatment decreased (p < .05). The present findings indicate that OG might be a stressor for broiler gut, which could induce oxidative stress both in crop and in ileum, and the diarrhoea as well. The growth performance of broiler was consequently depressed.
Assuntos
Galinhas , Glutens/toxicidade , Íleo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Triticum/química , Animais , Papo das Aves , Fezes/química , Glutens/química , Concentração de Íons de Hidrogênio , Masculino , Oxirredução , Água/químicaRESUMO
Objectives: To analyze and understand the risk factors related to HIV new infections among men who have sex with men (MSM). Methods: A longitudinal observational study among MSM was conducted to collect information on HIV related behaviors and sero-conversion. Univariate and multivariate generalized estimating equations (GEE) were used to discuss the risk factors for HIV new infection. Results: A total number of 4 305 MSM were followed during 2013-2015. Among those self-reported MSM who are seeking partners on the Interner tended to have higher proportion on receptive anal intercourse and consistent condom use during anal intercourse than the subgroups seeking their partners in gay bars or bathrooms. HIV incidence among followed MSM during the study period appeared as 4.3/100 person years, with adjusted RR (aRR) of HIV infection for receptive anal intercourse as group 2.20 (95% CI: 1.49-3.24) times than that of insertion anal intercourse group. Those who used rush-poppers (aRR=1.55, 95% CI: 1.10-2.17), unprotected anal intercourse (aRR=2.24, 95%CI: 1.62-3.08), and those with syphilis infection (aRR=2.95, 95%CI: 2.00-4.35) were also risk factors for HIV new infections. After controlling other factors, the relationship between the ways of seeking partners and HIV new infection was not statistical significant. Conclusion: Risk factors for HIV new infection among MSM appeared complex and interactive, suggesting that further studies are needed to generate tailored strategies for the prevention of HIV epidemic among MSM population.
Assuntos
Infecções por HIV/diagnóstico , Homossexualidade Masculina , Assunção de Riscos , Parceiros Sexuais , Sexo sem Proteção , Adulto , Estudos de Coortes , Humanos , Incidência , Masculino , Fatores de Risco , Comportamento Sexual , Minorias Sexuais e de Gênero , Inquéritos e QuestionáriosRESUMO
A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.
Assuntos
Família , Predisposição Genética para Doença , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , Adulto , Feminino , Humanos , Masculino , TaiwanRESUMO
BACKGROUND AND PURPOSE: Brain connectivity analysis has been widely used to investigate brain plasticity and recovery-related indicators of patients with stroke. However, results remain controversial because of interindividual variability of initial impairment and subsequent recovery of function. In this study, we aimed to investigate the differences in network plasticity and motor recovery-related indicators according to initial severity. METHODS: We divided participants (16 males and 14 females, aged 54.2 ± 12.0 years) into groups of different severity by Fugl-Mayer Assessment score, i.e. moderate (50-84), severe (20-49) and extremely severe (<20) impairment groups. Longitudinal resting-state functional magnetic resonance imaging data were acquired at 2 weeks and 3 months after onset. The differences in network plasticity and recovery-related indicators between groups were investigated using network distance and graph measurements. RESULTS: As the level of impairment increased, the network balance was more disrupted. Network balance, interhemispheric connectivity and network efficiency were recovered at 3 months only in the moderate impairment group. However, this was not the case in the extremely severe impairment group. A single connection strength between the ipsilesional primary motor cortex and ventral premotor cortex was implicated in the recovery of motor function for the extremely severe impairment group. The connections of the ipsilesional primary motor cortex-ventral premotor cortex were positively associated with motor recovery as the patients were more severely impaired. CONCLUSIONS: Differences in plasticity and recovery-related indicators of motor networks were noted according to impairment severity. Our results may suggest meaningful implications for recovery prediction and treatment strategies in future stroke research.
Assuntos
Encéfalo/fisiopatologia , Córtex Motor/fisiopatologia , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico por imagemRESUMO
Objective: To investigate the current status of HIV infection and the related factors in HIV antibody positive clients of female sex workers (FSWs) recently reported in Shaanxi province. Methods: The HIV/AIDS cases newly diagnosed in males living in Shaanxi from January 1th of 2013 to June 30th of 2014 were selected and those infected through " commercial heterosexual behavior" were identified. The information about their demographic characteristics, previous unprotected heterosexual sex and the sample sources were collected, and serum or plasma samples were collected from them and tested with BED-CEIA. The proportion of recent HIV infections and associated factors were investigated. Results: The proportion of recent HIV infection and HIV-antibody detection rate in 212 HIV antibody positive male clients of FSWs were 25.5% and 6.6% respectively. The cases who had the educational level of junior middle school or high middle school were wore likely to have long term HIV infections than those with lower educational level (aOR=0.28, 95% CI: 0.08-0.93). Compared with patients identified by hospitals or sexually transmitted diseases clinics, recent HIV infections were more likely to be found through preoperative test or blood transfusion test (aOR=3.14, 95% CI: 1.06-9.30) and blood donation test (aOR=4.19, 95% CI:1.01-17.42). Compared with the cases who had commercial sex only in Xi' an or other province or both in Xi' an and other province, the cases who had commercial sex in other cities in Shaanxi were more likely to be infected recently (aOR=0.19, 95%CI: 0.07-0.57). Compared with the cases had temporary heterosexual sex partner, those who had no temporary sex partners were more likely to be infected recently (aOR=9.03, 95% CI: 3.00-27.18) (P<0.05). Conclusions: The proportion of recent HIV infections among HIV antibody positive clients of FSWs was high and the HIV-antibody detection rate among them was low. The educational level, sample source, geographic area and temporary heterosexual partner were related factors for recent HIV infection. The HIV infection in the clients of FSWs, especially those with lower educational level, was serious in Shaanxi. It is necessary to strengthen behavior intervention and improve HIV defection according to the characteristics of this population.
Assuntos
Infecções por HIV/diagnóstico , Trabalho Sexual/estatística & dados numéricos , Profissionais do Sexo/estatística & dados numéricos , Parceiros Sexuais , Sexo sem Proteção/estatística & dados numéricos , Adulto , Terapia Comportamental , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/epidemiologia , Heterossexualidade , Humanos , Masculino , Fatores de RiscoRESUMO
Objective: To compare the prevalence of HIV/STD and related health care seeking behaviors among male STD clinic attendees between Xi'an and Xianyang cities. Methods: During June and July 2016, 206 male STD clinic attendees were studied in Xi'an city, with another 221 male STD clinic attendees in Xianyang city. Cross-sectional questionnaire survey was used to collect attendees'behavioral information. Blood samples were collected via HIV/HCV/Syphilis testing. Results: The prevalence rate of HIV infection was 2.4% (5/206) in Xi'an and 0.9% (2/221) in Xianyang, with no statistical significant difference between the two cities. The prevalence rate of syphilis was 4.9% (10/206) in Xi'an, which was significantly lower than 13.6% (30/221) in Xianyang. The proportion of respondents, diagnosed with other sexually transmitted diseases, in Xi'an was higher than that of Xianyang. The proportions of commercial heterosexual sex and sex with temporary sexual partners in the past 3 months were 18.0% (37/206) and 15.5% (32/206) in Xi'an, lower than 46.6% (103/221) and 15.8% (35/221) in Xianyang (χ(2)=39.70, Ð <0.01; χ(2)=0.01, P=0.93) . The proportions of condom use with commercial sex workers or temporary sexual partners in the past 3 months among Xi'an were 37.8% (14/37) and 6.3% (2/32) , lower than 93.1% (95/102) and 57.1% (20/35) in Xianyang (χ(2)=49.06, Ð <0.01; χ(2)=19.63, Ð <0.01) . Conclusion: Differences were noticed between Xi'an and Xianyang city in terms of STD and HIV prevalences, behaviors related to commercial sex and use of condoms among the male STD clinic attendees that calling for targeted actions in control of high risk behavlors in both HIV/AIDS and STDs transmission.
Assuntos
Infecções por HIV/epidemiologia , Comportamentos Relacionados com a Saúde , Trabalho Sexual , Comportamento Sexual , Infecções Sexualmente Transmissíveis/epidemiologia , Adulto , Instituições de Assistência Ambulatorial , Cidades , Preservativos , Estudos Transversais , Infecções por HIV/psicologia , Heterossexualidade , Humanos , Masculino , Prevalência , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/psicologia , Sífilis/epidemiologia , Sorodiagnóstico da SífilisRESUMO
BACKGROUND AND PURPOSE: We investigated the effect of stress hyperglycemia on the functional outcomes of non-diabetic hemorrhagic stroke. In addition, we investigated the usefulness of intensive rehabilitation for improving functional outcomes in patients with stress hyperglycemia. METHODS: Non-diabetic hemorrhagic stroke patients were recruited and divided into two groups: intracerebral hemorrhage (ICH) (n = 165) and subarachnoid hemorrhage (SAH) (n = 156). Each group was divided into non-diabetics with or without stress hyperglycemia. Functional assessments were performed at 7 days and 3, 6 and 12 months after stroke onset. The non-diabetic with stress hyperglycemia groups were again divided into two groups who either received or did not receive intensive rehabilitation treatment. Serial functional outcome was compared between groups. RESULTS: For the ICH group, patients with stress hyperglycemia had worse modified Rankin Scale, National Institutes of Health Stroke Scale, Functional Ambulatory Category and Korean Mini-Mental State Examination scores than patients without stress hyperglycemia. For the SAH group, patients with stress hyperglycemia had worse scores on all functional assessments than patients without stress hyperglycemia at all time-points. After intensive rehabilitation treatment of patients with stress hyperglycemia, the ICH group had better scores on Functional Ambulatory Category and the SAH group had better scores on all functional assessments than patients without intensive rehabilitation treatment. CONCLUSIONS: Stress hyperglycemia affects the long-term prognosis of non-diabetic hemorrhagic stroke patients. Among stress hyperglycemia patients, intensive rehabilitation can enhance functional improvement after stroke.
Assuntos
Hiperglicemia/complicações , Hemorragias Intracranianas/reabilitação , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/complicações , Hemorragia Subaracnóidea/reabilitação , Idoso , Estudos de Coortes , Feminino , Humanos , Hiperglicemia/sangue , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Acidente Vascular Cerebral/sangue , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/complicações , Resultado do TratamentoRESUMO
HLJ1 (DNAJB4), a DNAJ/Hsp40 chaperone, has emerged as a novel prognostic marker in lung cancers; however, the molecular contribution and functionality in neoplastic diseases remain to be established. This study demonstrated that HLJ1 inhibits epithelial-mesenchymal transition in vitro and reduces lung cancer metastasis in vivo. Using shRNA silencing and ectopic expression of HLJ1, we found that HLJ1 not only suppresses catalytic activity of Src but also downregulates the formation of oncogenic complexes associated with the EGFR, FAK and STAT3 signaling pathways. A screen of specimens from HLJ1-knockout mice and lung cancer patients validated that HLJ1 expression is inversely correlated with Src activity. Mechanistically, HLJ1 protein directly bound to catalytic and protein-binding domains of Src through its amino acid Y172 and the P301/P304 motif. Following Src-induced HLJ1 phosphorylation at Y172, HLJ1-Src interaction was elevated, resulting in Src inhibition and malignancy suppression. Interestingly, both Src-binding regions also occurred in other DNAJB family members and contributed to anti-invasive activities of DNAJB proteins. We conclude that HLJ1 is an endogenous Src inhibitor that can suppress cancer metastasis through complex interacting mechanisms. This HLJ1-Src complex might provide a promising molecular model for developing new anticancer strategies.
Assuntos
Proteínas de Choque Térmico HSP40/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Quinases da Família src/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Modelos Animais de Doenças , Progressão da Doença , Ativação Enzimática , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico HSP40/química , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/farmacologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Knockout , Modelos Biológicos , Modelos Moleculares , Mutação , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/genética , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Interferência de RNA , RNA Interferente Pequeno/genética , Domínios de Homologia de src , Quinases da Família src/química , Quinases da Família src/metabolismoRESUMO
BACKGROUND AND PURPOSE: A common single nucleotide polymorphism, Val66Met, in the human brain-derived neurotrophic factor (BDNF) gene has a potential role in the pathogenesis and treatment of stroke. The relevance of the BDNF Val66Met polymorphism to long-term stroke outcomes was examined, specifically with respect to changes in corticospinal integrity. METHODS: Thirty-five stroke patients with unilateral motor weakness were genotyped within 2 weeks after onset (T1), and changes in the integrity of the ipsilesional corticospinal tract (CST) as well as alterations in motor function at 1 month (T2) and 3 months after onset (T3) were tracked. RESULTS: On the basis of the Fugl-Meyer assessment upper extremity score, carriers of the Met allele (Val/Met and Met/Met) showed poorer motor outcomes at T2 and T3 compared to carriers of only the Val allele (Val/Val). For both BDNF allele types, patients exhibited characteristic degeneration of the CST compared to healthy controls. There were no differences between the two genotypes with respect to time-dependent changes in diffusion-tensor-imaging-derived parameters of the CST. However, the two groups showed different relationships between motor outcomes and directional diffusivities according to the elapsed time after onset. Poorer motor function was associated with lower axial diffusivity values for the Val/Val genotype group in the sub-acute phase (T1 and T2) but with higher radial diffusivity values for the Val/Met and Met/Met genotype group in the early chronic phase (T3). CONCLUSIONS: Motor recovery in stroke patients may be affected by the BDNF Val66Met polymorphism, possibly through its effects on distinct pathological processes underlying corticospinal degeneration.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Tratos Piramidais/patologia , Recuperação de Função Fisiológica/genética , Acidente Vascular Cerebral/genética , Adulto , Idoso , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologiaRESUMO
The rs1076560 polymorphism of DRD2 (encoding dopamine receptor D2) is associated with alternative splicing and cognitive functioning; however, a mechanistic relationship to schizophrenia has not been shown. Here, we demonstrate that rs1076560(T) imparts a small but reliable risk for schizophrenia in a sample of 616 affected families and five independent replication samples totaling 4017 affected and 4704 unaffected individuals (odds ratio=1.1; P=0.004). rs1076560(T) was associated with impaired verbal fluency and comprehension in schizophrenia but improved performance among healthy comparison subjects. rs1076560(T) also associated with lower D2 short isoform expression in postmortem brain. rs1076560(T) disrupted a binding site for the splicing factor ZRANB2, diminished binding affinity between DRD2 pre-mRNA and ZRANB2 and abolished the ability of ZRANB2 to modulate short:long isoform-expression ratios of DRD2 minigenes in cell culture. Collectively, this work implicates rs1076560(T) as one possible risk factor for schizophrenia in the Han Chinese population, and suggests molecular mechanisms by which it may exert such influence.
Assuntos
Receptores de Dopamina D2/genética , Esquizofrenia/genética , Adulto , Alelos , Processamento Alternativo/genética , Encéfalo/metabolismo , China , Cognição/fisiologia , Etnicidade/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Precursores de RNA/metabolismo , Splicing de RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Receptores de Dopamina D2/metabolismo , Fatores de Risco , Esquizofrenia/metabolismoRESUMO
BACKGROUND: Use of polysomnography (PSG) is the gold standard of diagnosis and measurement of treatment effectiveness for paediatric obstructive sleep apnoea (OSA). Although adenotonsillectomy (T&A) is effective in diminishing the apnoea-hypopnoea index (AHI), a meta-analysis of postoperative changes for all other PSG parameters and outcome comparisons between obese and non-obese children following T&A have never been conducted. OBJECTIVE OF REVIEW: To comprehensively review polysomnographic findings after surgery for obese and non-obese children with OSA. SEARCH STRATEGY: Study protocol was registered on PROSPERO (CRD42013004737). Two authors independently searched databases including PubMed, MEDLINE, EMBASE and Cochrane Review from January 1997 to July 2014. The keywords used included the following: sleep apnea, OSA, sleep apnea syndromes, tonsillectomy, adenoidectomy, infant, child, adolescent, and Humans. EVALUATION METHOD: A comprehensive systematic review and meta-analysis for literature for OSA children treated by T&A with polysomnography data. Random-effects model was applied to determine postoperative sleep parameter changes and the surgical success rate between obese and non-obese groups. The quality of studies was assessed using the Newcastle-Ottawa Scale. RESULTS: In total, 51 studies with 3413 subjects were enrolled. After surgery, sleep architecture was altered by a significant decrease in sleep stage 1, and an increase in slow-wave sleep and the rapid eye movement stage, and enhanced sleep efficiency. The mean difference between pre- and postoperative was a significant reduction of 12.4 event/h in AHI, along with a reduction of obstructive index, hypopnoea index, central index and arousal index. Mean and minimum oxygen saturation increased significantly after surgery. The overall success rate was 51% for postoperative AHI <1 (obese versus non-obese versus combined, 34% versus 49% versus 56%), and 81% for AHI <5 (obese versus non-obese versus combined, 61% versus 87% versus 84%). Meta-regression analyses demonstrate that postoperative AHI was positively correlated with AHI and body mass index z score before surgery. CONCLUSIONS: Meta-analysis of current literature shows T&A offers prominent improvement in a variety of sleep parameters. Improvements in non-obese children exceeded those for obese children. Postoperative residual OSA remained in roughly half of the children, especially those with severe disease and obesity, making additional treatment strategies and/or long-term follow-up highly desirable.
Assuntos
Adenoidectomia , Obesidade Infantil/complicações , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia , Criança , Humanos , Polissonografia , Resultado do TratamentoRESUMO
The objective of this study was to evaluate the effects of different levels of flavones of sea buckthorn fruits (FSBF) on growth performance, carcass quality, fat deposition, and lipometabolism for broilers. 240 one-day-old Arbor Acres male broilers were randomly allotted to 4 dietary treatments (0, 0.05%, 0.10%, and 0.15% FSBF) with 6 replicates of 10 birds. Broilers were reared for 42 d. Results showed FSBF quadratically improved average daily feed intake (ADFI), average daily gain (ADG), and final body weight (BW) (P = 0.002, P = 0.019 and P = 0.018, respectively). The abdominal fat percentage in 0.05%, 0.10%, and 0.15% FSBF supplementation groups was decreased by 21.08%, 19.12%, and 19.61% with respect to the control group, respectively (P < 0.05). The intramuscular fat (IMF) content in the breast muscle of the broilers was increased by 7.21%, 23.42% and 6.30% in 0.05%, 0.10% and 0.15% FSBF groups, and that in the thigh meat was raised by 4.43%, 24.63% and 12.32%, compared with the control group, respectively (P < 0.05). FSBF had a quadratic effect on the abdominal fat percentage and IMF in the breast muscle (P < 0.05). Dietary FSBF also modified fatty acids of muscular tissues, resulting in a higher ratio of unsaturated to saturated fatty acids (P < 0.05). Supplementing FSBF in the diet greatly decreased the levels of triglyceride, cholesterol, and low-density lipoprotein cholesterol (P < 0.05). Moreover, the quadratic responses were also observed in the levels of insulin and adiponectin in serum (P = 0.020 and P = 0.037, respectively). Abdominal fat percentage was correlated negatively with insulin and positively with adiponectin (P < 0.05). IMF content in the breast and thigh muscles were correlated positively with insulin, and negatively with adiponectin (P < 0.05). A positive correlation existed between breast muscle, IMF, and leptin (P < 0.05). In conclusion, adding FSBF into the diets affected growth performance and fat deposition of broilers by regulating lipometabolism. Fat deposition and distribution of broilers were closely associated with concentrations of insulin and adiponectin. The optimal level of FSBF supplemented in diet was 0.05 to 0.10% in this study.
Assuntos
Tecido Adiposo/metabolismo , Composição Corporal/efeitos dos fármacos , Galinhas/fisiologia , Dieta/veterinária , Flavonas/farmacologia , Carne/análise , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Galinhas/crescimento & desenvolvimento , Suplementos Nutricionais/análise , Flavonas/administração & dosagem , Masculino , Distribuição AleatóriaRESUMO
BACKGROUND: A cross-sectional retrospective study suggested a link between allergic diseases and Parkinson's disease. However, the temporal association between asthma and Parkinson's disease remains unknown. METHODS: From the Taiwan National Health Insurance Research Database, 10 455 patients who were diagnosed with asthma between 1998 and 2008 and aged ≥45 years and 41 820 age- and sex-matched controls were selected for our study and observed until the end of 2011. Those who developed Parkinson's disease during the follow-up period were identified. We also examined the asthma severity, as indicated by the frequency of admission (times per year) for asthma exacerbation, and the risk of subsequent Parkinson's disease. RESULTS: Patients with asthma had an increased risk of developing Parkinson's disease (hazard ratio [HR]: 3.10, 95% confidence interval [CI]: 2.20-4.36) after we adjusted for demographic data, health system use, medical comorbidities, and medication use. Sensitivity tests yielded consistent findings after we excluded observations on the first year (HR: 2.90, 95% CI: 2.04-4.13) and first 3 years (HR: 2.46, 95% CI: 1.64-3.69). Patients with asthma who had more frequent admissions (times per year) during the follow-up period exhibited a greater risk of subsequent Parkinson's disease (>2: HR: 16.42, 95% CI: 5.88-45.91; 1-2: 12.69, 95% CI: 5.03-31.71; 0-1: HR: 2.92, 95% CI: 1.91-4.49). CONCLUSION: Patients with asthma had an elevated risk of developing Parkinson's disease later in life, and we observed a dose-dependent relationship between greater asthma severity and a higher risk of subsequent Parkinson's disease.
Assuntos
Asma/epidemiologia , Doença de Parkinson/epidemiologia , Idoso , Comorbidade , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de RiscoRESUMO
This study was conducted to investigate the effects of stress on the absorption of glycylsarcosine in the jejunum of broilers, as well as the underlying mechanisms. A glucocorticoid analogue, dexamethasone (DEX), was chosen to simulate the effects of endogenous glucocorticoids. Two hundred 21-day-old male Arbor Acre broilers were randomly allotted to 4 groups with 5 replicates in each group and 10 birds per replicate by a completely randomized assignment involving a single factorial arrangement of injection dose DEX. The broilers were injected with 1-mL DEX (0.1-, 0.5-, and 2.5-mg/kg BW) or saline subcutaneously in the abdomen 1×/d for 7 d. The broilers were weighed, killed, and sampled at 28 days old. The results showed that DEX dose-dependently reduced growth and endogenous corticosterone content in the plasma of the broilers (P<0.05). DEX decreased absorption of glycylsarcosine by jejunum brush border membrane vesicles and gut sacs (P<0.05). DEX treatment increased the crypt depth of the jejunum, decreased the villus height, absorption area, and ratio of villus height to crypt depth (P<0.05). Effect of dexamethasone on villus width was not obvious (P>0.05). It was concluded that DEX reduced the absorption of glycylsarcosine in the jejunum of broilers.
Assuntos
Galinhas/metabolismo , Dexametasona/metabolismo , Dipeptídeos/metabolismo , Glucocorticoides/metabolismo , Jejuno/fisiologia , Estresse Fisiológico , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Jejuno/efeitos dos fármacos , Masculino , Distribuição AleatóriaRESUMO
We demonstrated a unique CMOS approach for the production of a high-performance germanium (Ge) quantum dot (QD) metal-oxide-semiconductor phototransistor. In the darkness, low off-state leakage (Ioff â¼ 0.27 pA µm(-2)), a high on-off current ratio (Ion/Ioff â¼ 10(6)), and good switching behaviors (subthreshold swing of 175 mV/dec) were measured on our Ge-QD phototransistor at 300 K, indicating good hetero-interfacial quality of the Ge-on-Si. Illumination makes a significant enhancement in the drain current of Ge QD phototransistors when biased at both the on- and off-states, which is a great benefit from Ge QD-mediated photoconductive and photovoltaic effects. The measured photocurrent-to-dark-current ratio (Iphoto/Idark) and the photoresponsivities from the Ge QD phototransistor are as high as 4.1 × 10(6) and 1.7 A W(-1), respectively, under an incident power of 0.9 mW at 850 nm illumination. A superior external quantum efficiency of 240% and a very fast temporal response time of 1.4 ns suggest that our Ge QD MOS phototransistor offers great promise as optical switches and transducers for Si-based optical interconnects.
RESUMO
To explore regulation of inosinic acid content in chicken meat as a result of feed additives, 576 one-day-old male Arbor Acres broilers were randomly allotted into 8 dietary treatments including control, purine nucleotide (P), betaine (B), soybean isoflavone (S), purine nucleotide + betaine (PB), purine nucleotide + soybean isoflavone (PS), betaine +soybean isoflavone (BS), and purine nucleotide + betaine + soybean isoflavone (PBS) by a 2 × 2 × 2 factorial arrangement. At d 42 of age, broilers were slaughtered, and growth performance, carcass characteristics, inosinic acid content, and activities of enzyme closely related to inosinic acid metabolism of broilers were measured. The results revealed that these feed additives did not affect ADG and ADFI of the broilers (P > 0.05). However, supplementing purine nucleotides lowered feed/gain of broilers in PS and PBS groups (P < 0.05). There was a significant interaction on feed/gain of broilers between purine nucleotides and soybean isoflavone (P < 0.05). The abdominal fat percentages in groups B, S, BS, and PBS were lower than the control group, respectively (P < 0.05). The thigh muscle percentages of groups P and B were higher than that of group PB (P < 0.05). There were certain interactions on the percentage of thigh muscle (P = 0.05) and abdominal fat (P < 0.05) between P, B, and S groups. Compared with the control group, inosinic acid content in broiler breast meat was improved by using feed additives (P < 0.05). Supplementing purine nucleotides, betaine, soybean isoflavone, and their combinations increased alkaline phosphatase activity in breast meat of broilers (P < 0.05). Purine nucleotides improved the activity of adenosine deaminase, but decreased the activity of 5'-nucleotidase. Soybean isoflavone lowered the activity of alkaline phosphatase. There were no significant interactions on activities of creatine kinase, adenosine deaminase, alkaline phosphatase, and 5'-nucleotidase between these additives (P > 0.05). The umami rating of broiler breast meat increased in conjunction with supplementing these additives. In conclusion, supplementing standard feed with the additives investigated in this study could improve inosinic acid content in chicken meat by increasing synthase activity or inhibiting degradation enzyme activity without inferior growth performance and carcass quality.