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BACKGROUND: Although culture remains the standard for TB diagnosis, 15-20% of patients diagnosed and treated for TB are culture-negative. We explored clinical characteristics, risk factors and treatment outcomes for culture-negative TB in a Peruvian cohort.METHODS: We recruited 4,500 index TB patients and 10,160 household contacts in Lima, Peru, and enrolled 692 secondary patients diagnosed with TB during follow-up of household contacts. We analyzed smear and culture status, sociodemographic factors, clinical characteristics and TB treatment outcomes to compare culture-negative and positive patients.RESULTS: Of the 4,880 adult patients, 915 (18.8%) were culture-negative. Culture-negative patients were less likely to report symptoms of TB disease and disease of longer duration. A multivariate analysis showed no statistically significant difference in loss to follow-up, treatment failure or recurrence between the culture-negative and -positive groups but a higher rate of death among culture-negative patients with an adjusted OR of 1.65 (95% CI 1.05-2.60). In a multivariate analysis of determinants of culture negativity, older age, substance use and being a secondary case were associated with culture status.CONCLUSIONS: More recognition and awareness of culture-negative TB is key for early and correct diagnosis to reduce transmission and improve treatment outcomes.
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Tuberculose Pulmonar , Adulto , Humanos , Tuberculose Pulmonar/diagnóstico , Fatores de Risco , Resultado do Tratamento , Peru/epidemiologia , Falha de TratamentoRESUMO
Monolayers of transition metal dichalcogenides (TMD) are promising materials for optoelectronics devices. However, one of the challenges is to fabricate large-scale growth of high quality TMD monolayers with the desired properties in order to expand their use in potential applications. Here, we demonstrate large-scale tungsten disulfide (WS2) monolayers grown by van der Waals Epitaxy (VdWE). We show that, in addition to the large structural uniformity and homogeneity of these samples, their optical properties are very sensitive to laser irradiation. We observe a time instability in the photoluminescence (PL) emission at low temperatures in the scale of seconds to minutes. Interestingly, this change of the PL spectra with time, which is due to laser induced carrier doping, is employed to successfully distinguish the emission of two negatively charged bright excitons. Furthermore, we also detect blinking sharp bound exciton emissions which are usually attractive for single photon sources. Our findings contribute to a deeper understanding of this complex carrier dynamics induced by laser irradiation which is very important for future optoelectronic devices based on large scale TMD monolayers.
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Levels of hydrogen sulfide (H2S), a gaseous signaling molecule, are reduced in the serum of individuals who smoke. We hypothesized that tobacco smoke influenced smooth muscle relaxation by decreasing H2S levels and this effect could also influence expression of cystathionine γ-lyase (CSE) and sulfonylurea receptor-2 (SUR-2). The aim of this study was to explore the effect of tobacco smoke on H2S-mediated rat thoracic aorta relaxation and its possible mechanism. Thirty-two Sprague-Dawley rats were divided into four groups: control (C) group, short-term smoker (SS) group, mid-term smoker (MS) group, and long-term smoker (LS) group. H2S concentrations in serum, action of H2S on rat aortic vascular relaxation, and expression of CSE and SUR-2 in thoracic aortic smooth muscle were measured. Although there was no significant difference in H2S between the C and the SS groups, concentration of H2S was significantly reduced in both the LS and MS groups compared to control (P<0.01). Furthermore, H2S was significantly lower in the LS than in the MS group (P<0.05). Rat aortic vascular relaxation was lower in all three treatment groups compared to the control, with the most significant decrease observed in the LS group (P<0.05 compared to the MS group). Expression of CSE and SUR-2 was reduced in the LS and MS groups compared to control (P<0.05), with the lowest levels observed in the LS group (P<0.05). Therefore, tobacco smoke reduced expression of CSE and SUR-2 in rat thoracic aorta, which may inhibit H2S production and vascular dilation.
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Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Sulfeto de Hidrogênio , Poluição por Fumaça de Tabaco , Animais , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Axillary branching is controlled by a very complex mechanism involving various endogenous and environmental factors. Previous studies have shown that Tb1/BRC1 is the point of integration in the network of molecular mechanisms regulating axillary branching in plants. In this study, we cloned the Tb1/BRC1 ortholog, NtBRC1, from Nicotiana tabacum and functionally analyzed its role in the control of axillary branching in tobacco. Overexpression of NtBRC1 resulted in significant retardation of axillary branching, and downregulation of this gene resulted in significant acceleration of axillary branching after decapitation. This indicates a negative role for this gene in the regulation of axillary branching. In-line with previous reports, NtBRC1 was found to be expressed predominantly in axillary buds. Additionally, as expected, expression was decreased 8 h following decapitation, which further confirms its role in the suppression of axillary branching. Furthermore, the expression of NtBRC1 was significantly downregulated by cytokinin, but was not affected by GR24, a synthetic strigolactone. Based on the data collected in the present study, we demonstrate that NtBRC1 negatively regulates axillary branching in tobacco after decapitation and functions downstream of the cytokinin signaling pathway inside axillary buds.
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Nicotiana/fisiologia , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Clonagem Molecular , Citocininas/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Lactonas/farmacologia , Nicotiana/genéticaRESUMO
Despite sharing a similar genetic abnormality, patients with core binding factor acute myeloid leukemia (CBF-AML), which is characterized by the presence of t(8;21) or inv(16)/t(16;16), show heterogeneous survival. Other molecular or cytogenetic factors are supposed to have an impact on the prognosis. We enrolled 24 CBF-AML patients to determine the impact of cytogenetic abnormality, and c-KIT, FLT3, NPM1, and CEBPA mutations on the prognosis. Only three patients had the c-KIT mutation (3/24, 12.5%) and one had the FLT3 mutation. However, over half of the patients (14/24) harbored additional cytogenetic changes, including ten with loss of sexual chromosomes (LOS) [all in the t(8;21) group], and six had additional abnormalities (two cases had both LOS and additional abnormalities). From this small-number study, no association was found between c-KIT mutation and survival and relapse rate. However, additional chromosome abnormalities had a significant association with relapse of the disease (P = 0.027). Stem cell transplant had a trend of benefitting patients after relapse (P = 0.065). This implies that chromosome abnormalities occur in CBF-AML and might take part in the heterogeneous nature of CBF-AML.
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Aberrações Cromossômicas , Fatores de Ligação ao Core/genética , Leucemia Mieloide Aguda/genética , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Adulto JovemRESUMO
Several case-control studies have been conducted to investigate the association between the tumor necrosis factor-α (TNF-α)-308G/A polymorphism and vitiligo risk. However, the results of these studies are inconsistent; therefore, we attempted to comprehensively evaluate the association between TNF-α-308G/A polymorphism and vitiligo risk via a meta-analysis. Studies reporting the association between TNF-α-308G/A polymorphism and vitiligo risk were retrieved from PubMed and EmBase databases. Data were extracted from these studies and the pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association. Six case-control studies including 1391 vitiligo cases and 2455 control subjects were included in this meta-analysis. The overall results showed the lack of a significant difference in TNF-α-308G/A genotype distribution between the patients and controls when the G allele and GG, GG + GA, GG, and GG genotypes were compared against the A allele and the GA + AA, AA, AA, and GA genotypes, respectively (ORs = 0.65, 0.53, 0.63, 0.41, 0.55; 95%CI = 0.35-1.23, 0.24-1.18, 0.10-4.09, 0.08-1.97, 0.25-1.21; P = 0.188, 0.121, 0.627, 0.264, 0.135, respectively). This meta-analysis suggests that the TNF-α-308G/A polymorphism may not be associated with vitiligo risk. As few studies are available in this field and current evidence remains limited, these results must be corroborated with well-designed and larger studies in the future.
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Alelos , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Vitiligo/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Genótipo , Humanos , Razão de Chances , Viés de Publicação , Risco , Vitiligo/epidemiologiaRESUMO
Osteopontin (OPN) plays an important role in the metastasis and recurrence of tumors after resection of hepatocellular carcinoma (HCC). In this study, the down-regulation effect on OPN expression in HCC cells of RNA interference (RNAi) molecules designed to target different segments of OPN was investigated to identify a more effective site for OPN knockdown. Specific small interfering RNAs (siRNAs A, B, and C) of OPN were synthesized and transfected into an HCC cell line (HEP-G2; representing the OPNi-A, OPNi-B, and OPNi-C groups). Fluorescent quantitative polymerase chain reaction and immunohistochemical methods were used to detect the mRNA and protein expression of OPN before and after RNAi. Results showed that after transfection, the fluorescence intensity of the OPNi-A group was greater than those of the OPNi-B and OPNi-C groups. After 48 h of transfection, the ΔCT values of OPN mRNA expression in the OPNi-A-C groups increased from 8.31 ± 1.58, 8.78 ± 1.49, and 8.25 ± 1.51 to 12.14 ± 1.43, 10.22 ± 1.97, and 10.48 ± 1.88, respectively (P < 0.05), and the OPN protein levels (immunohistochemistry scores) decreased from 6.44 ± 1.67, 5.43 ± 2.05, and 5.45 ± 2.52 to 2.84 ± 1.52, 4.43 ± 1.65, and 3.95 ± 1.43 points, respectively. These results indicated that RNAi based on different segments of the OPN gene had different down-regulatory effects on OPN expression. Synthesis of targeted siRNA aimed at specific OPN segments might have important significance for dealing with the invasiveness and metastasis of HCC cells.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/genética , Osteopontina/biossíntese , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/patologia , Invasividade Neoplásica/genética , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Osteopontina/genética , Interferência de RNARESUMO
Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.
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Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Apolipoproteína A-I/sangue , Apolipoproteínas/sangue , Transtorno Bipolar/sangue , Anidrase Carbônica I/sangue , Transtornos do Metabolismo dos Lipídeos/metabolismo , Lipoproteínas HDL/sangue , Proteômica , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Bases de Dados de Proteínas , Diagnóstico Diferencial , Progressão da Doença , Regulação para Baixo , Transtorno Depressivo Maior/diagnóstico , Eletroforese em Gel Bidimensional , Immunoblotting , Imunoprecipitação , Transtornos do Metabolismo dos Lipídeos/complicações , Espectrometria de Massas/métodosRESUMO
We evaluated changes in BAX and BCL2 expression levels after spinal cord ischemia/reperfusion injury (SCII) and hypothermia during operations in rats. Eighty rats were divided into four groups: Group A (N = 20, 18°C); Group B (N = 20, 28°C); Group C (N = 20, room temperature); and Group D (N = 20, sham operation control). Spinal cord ischemia was induced for 90 min. Hypothermia was induced 15 min before, and maintained during ischemia, followed by heating to normothermia for 30 min after reperfusion. Motor function of the lower limbs was evaluated according to the Tarlov score at 72 and 168 h. For each rat, spinal cord samples were taken at 6, 24, 72 h, and 1 week to evaluate the histopathological changes, neuronal apoptosis, and BAX and BCL2 expression levels. Compared with normothermia, hypothermia significantly improved hind limb function; Group B achieved a higher score than Group A. Group D showed no neurologic deficiency, while the other groups showed various degrees. Group C exhibited greater neuronal apoptosis, higher BAX expression, but lower BCL2 expression than the other groups. Compared with Group A, BAX was expressed less and BCL2 more in Group B, and there was less apoptosis in Group B. Hypothermia preserves hind limb motor function and reduces neuronal death, thereby protecting rats from SCII. The spinal cord may be protected from SCII by inhibition of BAX and activation of BCL2. However, deep hypothermia may inhibit the expression of BCL2, resulting in a worse outcome than mild hypothermia.
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Proteínas Proto-Oncogênicas c-bcl-2/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Isquemia do Cordão Espinal/genética , Medula Espinal/metabolismo , Proteína X Associada a bcl-2/genética , Animais , Apoptose/genética , Temperatura Baixa , Regulação da Expressão Gênica , Membro Posterior/irrigação sanguínea , Membro Posterior/fisiopatologia , Masculino , Atividade Motora/fisiologia , Neurônios/metabolismo , Neurônios/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Medula Espinal/patologia , Isquemia do Cordão Espinal/metabolismo , Isquemia do Cordão Espinal/patologia , Isquemia do Cordão Espinal/fisiopatologia , Proteína X Associada a bcl-2/metabolismoRESUMO
Pathological scar tissues and normal skin tissues were differentiated by screening for differentially expressed genes in pathologic scar tissues via gene expression microarray. The differentially expressed gene data was analyzed by gene ontology and pathway analyses. There were 5001 up- or down-regulated genes in 2-fold differentially expressed genes, 956 up- or down-regulated genes in 5-fold differentially expressed genes, and 114 up- or down-regulated genes in 20-fold differentially expressed genes. Therefore, significant differences were observed in the gene expression in pathological scar tissues and normal foreskin tissues. The development of pathological scar tissues has been correlated to changes in multiple genes and pathways, which are believed to form a dynamic network connection.