RESUMO
OBJECTIVES: To assess the prevalence, all-cause mortality and determinants of advanced HIV disease (AHD) or severe immunosuppression (SIS) in the rural-urban communities of Southwestern China. STUDY DESIGN: Retrospective cohort study. METHOD: Data on HIV/AIDS cases reported in 2005-20 were collected from Case Report System. A binary logistic regression model assessed the risk factors of AHD/SIS prevalence. Survival curves across rural-urban regions were compared using Kaplan-Meier estimates and log-rank tests. Determinants of all-cause mortality were identified using the Cox proportional hazard model. RESULTS: Among 14,533 newly diagnosed HIV/AIDS patients, 7497 (51.6%) presented with AHD and 2564 (17.6%) with SIS. Compared with urban patients, rural patients had a higher prevalence of AHD (56.7% vs 40.7%) and SIS (20.1% vs 12.4%), all-cause mortality (AHD 12.3 vs 5.6, SIS 16.3 vs 5.5, per 100 person-years). Their 5-year survival probability (AHD 59.5% vs 77.1%; SIS 54.4% vs 76.3%) and mean survival time (AHD 106.5 vs 140.6 months, SIS 95.3 vs 144.2 months, p < 0.0001) were lower. Rural patients had an increased risk of SIS prevalence (adjusted odds ratios 1.45, 95% confidence interval [CI] 1.28-1.64; p < 0.0001) and mortality of the total cohort (adjusted hazard ratios 1.41, 95% CI 1.29-1.55; p < 0.0001), AHD cohort (1.38, 1.24-1.54; p < 0.0001), and SIS cohort (1.49, 1.23-1.81; p < 0.0001). CONCLUSIONS: A high prevalence of AHD/SIS was a severe phenomenon that caused high mortality in rural areas. A regional point-of-care strategy targeting AHD/SIS detection and management is essential for reducing the mortality risk.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Estudos Retrospectivos , Infecções por HIV/epidemiologia , Infecções por HIV/diagnóstico , Fatores de Risco , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Asthma was identified as the most common comorbidity in hospitalized patients during the 2009 H1N1 influenza pandemic. We determined using a murine model of allergic asthma whether these mice experienced increased morbidity from pandemic H1N1 (pH1N1) viral infection and whether blockade of interleukin-4 receptor α (IL-4Rα), a critical mediator of Th2 signalling, improved their outcomes. METHODS: Male BALB/c mice were intranasally sensitized with house dust mite antigen (Der p 1) for 2 weeks; the mice were then inoculated intranasally with a single dose of pandemic H1N1 (pH1N1). The mice were administered intraperitoneally anti-IL-4Rα through either a prophylactic or a therapeutic treatment strategy. RESULTS: Infection with pH1N1 of mice sensitized to house dust mite (HDM) led to a 24% loss in weight by day 7 of infection (versus 14% in non-sensitized mice; p < .05). This was accompanied by increased viral load in the airways and a dampened anti-viral host responses to the infection. Treatment of HDM sensitized mice with a monoclonal antibody against IL-4Rα prior to or following pH1N1 infection prevented the excess weight loss, reduced the viral load in the lungs and ameliorated airway eosinophilia and systemic inflammation related to the pH1N1 infection. CONCLUSION: Together, these data implicate allergic asthma as a significant risk factor for H1N1-related morbidity and reveal a potential therapeutic role for IL-4Rα signalling blockade in reducing the severity of influenza infection in those with allergic airway disease.
Assuntos
Asma/metabolismo , Hipersensibilidade/metabolismo , Influenza Humana/metabolismo , Pyroglyphidae/metabolismo , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/metabolismo , Animais , Anticorpos Monoclonais/administração & dosagem , Asma/induzido quimicamente , Asma/tratamento farmacológico , Modelos Animais de Doenças , Humanos , Hipersensibilidade/tratamento farmacológico , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
AIM: To evaluate the performance of T2 mapping histograms at the extraocular muscles (EOMs) in predicting the response to glucocorticoid therapy in the patients with active and moderate-severe thyroid-associated ophthalmopathy (TAO). MATERIALS AND METHODS: Thirty active and moderate-severe TAO patients (responsive group, n=20; unresponsive group, n=10) were enrolled, and evaluated using T2 mapping before treatment. Histogram parameters (mean, median, max, min, 10th, 90th percentiles, skewness, and kurtosis) of T2 relaxation time (T2RT) at the EOMs for each orbit, and clinical variables (age, sex, disease duration, anti-thyroid treatment, smoking habit, pre-treatment thyroid function, thyrotrophin receptor antibody, diplopia presence, activity and severity scores) were collected and compared between groups. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to assess the predictive value of identified independent variables for treatment response. RESULTS: The responsive group showed significantly shorter disease duration (p=0.003), while higher T2RTmin than unresponsive group (p<0.001). Multivariate analysis showed that T2RTmin and disease duration were independent predictors for responsive TAOs. ROC curve analyses indicated that setting a cut-off value of ≥54.3 for T2RTmin demonstrated the optimal predicting specificity for responsive TAOs (100%), while a combination of T2RTmin ≥54.3 and disease duration ≤4.5 showed optimal predicting efficiency and sensitivity (area under the curve, 0.820; sensitivity, 65%). CONCLUSIONS: Histogram analysis can help to exhibit the heterogeneity of T2RT at the EOMs. T2RTmin, together with disease duration may be the promising marker for predicting response to glucocorticoid therapy in the patients with active and moderate-severe TAO.
Assuntos
Glucocorticoides/uso terapêutico , Oftalmopatia de Graves/diagnóstico por imagem , Oftalmopatia de Graves/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIM: To evaluate the postoperative magnetic resonance imaging (MRI) findings of intracranial foreign body granulomas (FBGs) and true recurrent tumours (RTs) and thus lead to a basis for management decision-making. MATERIALS AND METHODS: Twenty-two patients with previous brain tumour surgery were diagnosed clinically with RT and underwent surgery. Re-operative pathology revealed FBG in eight patients and RT in 14 patients. MRI findings before the initial operation were compared to those before the re-operation. RESULTS: Features of FBGs versus RTs on MRI were as follows: (1) mean lesion size: 1.3 ± 0.7 (0.5-2.6) versus 3.2 ± 1.7 (1.1-6.3) cm (p=0.001, odds ratio [OR] = 4.18); (2) hypointensity on T2-weighted imaging (WI): 6/8 (75%) versus 0/14 (0%; p<0.001, OR=75.4); (3) non-restricted diffusion on diffusion-WI (DWI): 6/8 (75%) versus 2/14 (14.3%; p=0.008, OR=18); and (4) "ring and bubble" appearance on contrast-enhanced T1WI: 7/8 (87.5%) versus 2/14 (14.3%; p=0.001, OR=42). In comparison with their original tumours, the FBGs in the FBG group showed significantly lower T2 signal intensity, lower signal on DWI, and more cases of non-restricted diffusion on DWI (p=0.04, 0.04, 0.04, respectively). CONCLUSION: On brain MRI, FBGs can be differentiated from RTs by their relatively smaller size, hypointensity on T2WI, lack of restricted diffusion on DWI, and "ring and bubble" appearance on contrast-enhanced T1WI. Comparing the MRI findings of the focal lesion in the tumour bed with those of the original tumour is suggested to enhance diagnostic confidence.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Granuloma de Corpo Estranho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Tomada de Decisão Clínica , Diagnóstico Diferencial , Feminino , Seguimentos , Granuloma de Corpo Estranho/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/patologia , Reoperação , Adulto JovemRESUMO
BACKGROUND: The stability of proteins in the collecting tubes after blood draw is critical to the measured concentrations of the proteins. Although the guidelines issued by the Clinical and Laboratory Standards Institute (CLSI) suggest centrifugation should take place within 2 h of drawing blood, it is very difficult to follow these guidelines in hospitals or clinics. It is necessary to study the effect of times to blood processing on the stability of the proteins of interest. METHODS: In this work, the plasma proteins of interest were those relevant to dementia, such as amyloid ß 1-40 (Aß1-40), Aß1-42, Tau protein (Tau), and α-synuclein. The times to blood processing after blood draw ranged from 0.5 to 8 h. The storage temperatures of blood were room temperature (approx. 25°C) and 30°C. After storage, blood samples were centrifuged at room temperature to obtain plasma samples. Ultrasensitive immunomagnetic reduction was applied to assay these proteins in the plasma. RESULTS: The levels of plasma Aß1-40, Tau, and α-synuclein did not significantly change until 8 h after blood draw when stored at room temperature. Plasma Aß1-42 levels did not change significantly after 8 h of storage at room temperature before blood processing. Higher storage temperatures, such as 30°C, for blood samples accelerated the significant variations in the measured concentrations of Aß1-40, Tau, and α-synuclein in plasma. CONCLUSION: According to these results, for clinical practice, it is suggested that blood samples be stored at room temperature for no longer than 4.5 h after blood draw until centrifugation for the assay of dementia biomarkers in plasma.
Assuntos
Peptídeos beta-Amiloides/sangue , Coleta de Amostras Sanguíneas , Centrifugação , Demência , alfa-Sinucleína/sangue , Proteínas tau/sangue , Biomarcadores/sangue , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Centrifugação/métodos , Centrifugação/normas , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Demência/sangue , Demência/diagnóstico , Precisão da Medição Dimensional , Humanos , Temperatura , Fatores de TempoRESUMO
PURPOSE: To explore the morphological and microstructural changes of grey and white matter in the patients of thyroid-associated ophthalmopathy (TAO). METHODS: Twenty-five TAO patients and 25 well-matched healthy controls were recruited. Structural T1- and diffusion-weighted magnetic resonance imaging data were analyzed using voxel-based morphometry and voxel-based analysis of diffusion tensor imaging. RESULTS: Compared with healthy controls, TAO group showed significantly decreased grey matter volume in the brain region of the right middle frontal gyrus. Meanwhile, TAO group showed significantly decreased fractional anisotropy (FA), but increased mean, axial and radial diffusivities in the brain regions of the right superior occipital gyrus, middle occipital gyrus and cuneus in TAO group. In addition, the FA value in significant brain regions showed a positive correlation with visual acuity (r = 0.456, P = 0.025) and a negative correlation with disease duration (r = - 0.609, P = 0.003). CONCLUSION: Significant morphological and microstructural abnormalities in areas corresponding to known functional deficits of vision and cognition could be found in TAO patients. These results extended our understanding of neural relationships with TAO.
Assuntos
Encéfalo/patologia , Encéfalo/ultraestrutura , Oftalmopatia de Graves/patologia , Adulto , Idoso , Anisotropia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Estudos de Casos e Controles , Cognição/fisiologia , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Feminino , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/fisiopatologia , Oftalmopatia de Graves/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Tamanho do Órgão , Visão Ocular/fisiologiaRESUMO
S-Adenosyl-l-methionine-dependent methyltransferases (SAMMTases) modulate important cellular and metabolic activities in both prokaryotes and eukaryotes. Here, we functionally characterized an SAMMTase gene (MTase15) in the migratory brown planthopper (BPH), Nilaparvata lugens, which is the most notorious rice pest in Asia. The cDNA sequence of MTase15 is 2764 nt in length with an open reading frame of 1218 nt encoding 405 amino acid residues. Quantitative real-time PCR analysis showed that MTase15 was readily detected from egg to adult stages and extensively distributed in various body parts of adult females and males, with slightly high levels in ovary and testis, respectively. In addition, MTase15 was transcriptionally regulated by the insulin signalling pathway in BPH. RNA-interference-mediated knockdown of MTase15 (dsMtase15) resulted in deficiencies in vitellogenin synthesis and oogenesis, and female infertility. Males with Mtase15 knockdown retained the capability of producing sperms with normal viability, but less sperm was transferred to wild-type (wt) females during copulation, and eggs laid by these wt females arrested embryogenesis. These findings not only assign a functional role to MTase15, but also provide a link between the insulin signalling pathway and epigenetic regulation in BPH reproduction.
Assuntos
Regulação da Expressão Gênica , Hemípteros/fisiologia , Proteínas de Insetos/genética , Metiltransferases/genética , Animais , Feminino , Perfilação da Expressão Gênica , Hemípteros/genética , Hemípteros/crescimento & desenvolvimento , Proteínas de Insetos/metabolismo , Masculino , Metiltransferases/metabolismo , Ninfa/genética , Ninfa/metabolismo , Óvulo/metabolismo , Reprodução/genéticaRESUMO
Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12-1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29-3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07-1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06-1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01-19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41-24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.
Assuntos
Imunossupressores/uso terapêutico , Falência Renal Crônica/etiologia , Rim/patologia , Nefrite Lúpica/tratamento farmacológico , Adolescente , Adulto , Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/patologia , Nefrite Lúpica/complicações , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ácido Micofenólico/uso terapêutico , Pontuação de Propensão , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Taiwan , Resultado do Tratamento , Adulto JovemRESUMO
The Fracture Risk Assessment Tool (FRAX) has been used universally for the purpose of fracture risk assessment. However, the predictive capacity of FRAX for autoimmune diseases remains inconclusive. This study aimed to compare the applicability of FRAX for autoimmune disease patients. This retrospective study recruited rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS) patients with bone mineral density (BMD) tests. Patients with any osteoporotic fractures were identified. Taiwan-specific FRAX with and without BMD were then calculated. In total, 802 patients (451 RA, 233 SLE and 118 pSS) were enrolled in this study. The cumulative incidences of osteoporotic fractures in the RA, SLE and pSS patients were 43.0%, 29.2% and 33.1%, respectively. For those with a previous osteoporotic fracture, T-scores were classified as low bone mass. Overall, the patients' 10-year probability of major fracture risk by FRAX without BMD was 15.8%, which then increased to 20.3% after incorporation of BMD measurement. When analyzed by disease group, the fracture risk in RA patients was accurately predicted by FRAX. In contrast, current FRAX, either with or without BMD measurement, underestimated the fracture risk both in SLE and pSS patients, even after stratification by age and glucocorticoid treatment. For pSS patients with major osteoporotic fractures, FRAX risks imputed by RA were comparable to major osteoporotic fracture risks of RA patients. Current FRAX accurately predicted fracture probability in RA patients, but not in SLE and pSS patients. RA-imputed FRAX risk scores could be used as a temporary substitute for SLE and pSS patients.
Assuntos
Artrite Reumatoide/complicações , Indicadores Básicos de Saúde , Lúpus Eritematoso Sistêmico/complicações , Fraturas por Osteoporose/epidemiologia , Síndrome de Sjogren/complicações , Absorciometria de Fóton , Adulto , Idoso , Algoritmos , Densidade Óssea , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/etiologia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
We report a 49-year-old woman who presented with a hypertensive crisis and acute heart failure and reduced left ventricular systolic function. An abdominal ultrasonography revealed a huge lobulated heterogeneous mass at the lower pole of the right kidney and a mass over the left suprarenal area, which were further delineated by magnetic resonance imaging. The patient underwent laparoscopic right radical nephrectomy and left adrenalectomy. Histopathological analysis confirmed the diagnoses of clear cell renal cell carcinoma of the right kidney with metastasis to the lung; and atypical pheochromocytoma of the left adrenal gland. Target therapy was initiated, which resulted in stabilization of the patient's tumors and the recovery of her heart function. To avoid a delayed diagnosis and catastrophic outcome, clinicians should consider such rare causes of acute decompensated heart failure.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Carcinoma de Células Renais/diagnóstico , Insuficiência Cardíaca/etiologia , Hipertensão/etiologia , Neoplasias Renais/diagnóstico , Rim/diagnóstico por imagem , Feocromocitoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Adrenalectomia , Biópsia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Nefrectomia , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Resultado do TratamentoRESUMO
Accumulating studies have suggested that microRNA play a part in regulating multiple cellular processes, such as cell proliferation, apoptosis, the cell cycle, and embryo development. This study explored the effects of miR-101-2 on donor cell physiological status and the development of Holstein cow somatic cell nuclear transfer (SCNT) embryos in vitro. Holstein cow bovine fetal fibroblasts (BFF) overexpressing miR-101-2 were used as donor cells to perform SCNT; then, cleavage rate, blastocyst rate, inner cell mass-to-trophectoderm ratio, and the expression of some development- and apoptosis-related genes in different groups were analyzed. The miR-101-2 suppressed the expression of inhibitor of growth protein 3 (ING3) at mRNA and protein levels, expedited cell proliferation, and decreased apoptosis in BFF, suggesting that ING3, a target gene of miR-101-2, is a potential player in this process. Moreover, by utilizing donor cells overexpressing miR-101-2, the development of bovine SCNT embryos in vitro was significantly enhanced; the apoptotic rate in SCNT blastocysts was reduced, and the inner cell mass-to-trophectoderm ratio and SOX2, POU5F1, and BCL2L1 expression significantly increased, whereas BAX and ING3 expression decreased. Collectively, these findings suggest that miR-101-2 promotes BFF proliferation and vitality, reduces their apoptosis, and improves the early development of SCNT embryos.
Assuntos
Apoptose/genética , Bovinos/genética , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica/genética , MicroRNAs/metabolismo , Animais , Blastocisto/metabolismo , Bovinos/crescimento & desenvolvimento , Linhagem Celular , Proliferação de Células/genética , Feminino , Fibroblastos/metabolismo , MicroRNAs/genética , Técnicas de Transferência Nuclear/veterinária , RNA Mensageiro/metabolismoRESUMO
Intestinal microbes play an important role in human health. The development of various clinical diseases, such as obesity, diabetes and cardiovascular disease, is closely related to the imbalance of intestinal microflora. With the development of high-throughput sequencing technology, there has been a breakthrough in the understanding of intestinal microorganism. The interaction between intestinal epithelial cells and intestinal microbes has become one of the hotspots and difficulties of current research. Because of the constraints of ethical review and experimental cost, people are more interested in the development of interaction models between the intestinal microflora and the host cells. In this paper, interaction models between intestinal microflora and host cells, and its working principle and application prospect are reviewed, hoping to provide new techniques and new ideas for studying functions of intestinal microbes.
Assuntos
Diabetes Mellitus , Microbioma Gastrointestinal , Intestinos , Obesidade , Diabetes Mellitus/microbiologia , Células Epiteliais , Humanos , Intestinos/citologia , Intestinos/microbiologia , Obesidade/microbiologiaRESUMO
An (η5-cyclopentadienyl)cobalt(i) complex was covalently incorporated into an engineered variant of the transmembrane protein ferric hydroxamate uptake protein component: A, FhuA ΔCVFtev, using a thiol-ene reaction. A CD spectrum shows the structural integrity of the biohybrid catalyst. MALDI-TOF of the segment containing the anchoring site for the cobalt complex Cys545 confirmed successful conjugation. This biohybrid catalyst catalyzed the cyclotrimerization of phenylacetylene to give a mixture of regioisomeric 1,2,4- and 1,3,5-triphenylbenzene in aqueous medium.
Assuntos
Acetileno/análogos & derivados , Proteínas da Membrana Bacteriana Externa/química , Cobalto/química , Complexos de Coordenação/química , Proteínas de Escherichia coli/química , Escherichia coli/química , Acetileno/química , Acetileno/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Catálise , Ciclização , Dimerização , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Compostos Férricos/metabolismo , Ácidos Hidroxâmicos/metabolismo , Modelos Moleculares , Engenharia de ProteínasRESUMO
Although platinum-based chemotherapies have long been used as standard treatment in ovarian cancer, cisplatin resistance is a major problem that restricts its use. Herein, we investigate the biological function of SLC27A2 and its underlying mechanisms in regulating chemo-resistance in ovarian cancer. The findings show that SLC27A2 down-regulation in primary ovarian cancer tissues correlates with chemo-resistance and poor patient survival in our patient cohort. Significantly, we demonstrate that up-regulation of SLC27A2 by lentivirus-mediated p-SLC27A2 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo via apoptosis. Mechanistic investigation reveals that miR-411 is the most strikingly over-expressed gene in response to ectopic expression of SLC27A2, but under-expressed in recurrent ovarian cancer tissues. Lower miR-411 expression contributes to ovarian cancer chemo-resistance in vitro and in vivo. Furthermore, SLC27A2 directly binds specific sites in the miR-411 promoter region and promoter activity decreases after mutation of putative SLC27A2-binding sites. This indicates that SLC27A2 is required for the transcriptional induction of miR-411. The luciferase assays also confirm that miR-411 directly targets ABCG2 in ovarian cancer, and overall findings establish the SLC27A2-miR-411-ABCG2 pathway in the regulation of ovarian cancer chemo-resistance with potential therapeutic applications.
Assuntos
Antineoplásicos/farmacologia , Coenzima A Ligases/genética , Resistencia a Medicamentos Antineoplásicos , MicroRNAs/genética , Neoplasias Ovarianas/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Linhagem Celular Tumoral , Cisplatino , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia , Neoplasias Ovarianas/tratamento farmacológicoRESUMO
OBJECTIVES: We evaluated whether and how the effects of risk factors on periodontal disease (PD) were modified by measurement errors using community periodontal index (CPI) and loss attachment (LA) in the community-based survey. METHODS: A pilot validation study was performed to estimate the rates of false negative and false positive for both CPI and LA in 31 subjects from different regions using measurements from 12 well-trained dentists and a senior periodontist as a gold standard. Afterward, a Taiwanese nationwide survey was conducted by enrolling 3,860 participants to estimate the effect of each risk factor on PD calibrated with both sensitivity and specificity of two indices. RESULTS: The values obtained for the sensitivity to false-positive ratio for CPI ranged widely from 1.12 to 7.71, indicating regional variation in both errors. The calibrated adjusted odds ratio for smoking vs non-smoking was higher than the uncalibrated odds ratio for PD defined by CPI (2.75 (2.01, 3.77) vs 2.02 (1.63, 2.52)) and LA (3.85 (2.44, 6.13) vs 1.93 (1.47, 2.54)) scores. Similar underestimation was noted for other risk factors. CONCLUSION: The effects of risk factors on PD measured using CPI and LA in a large population-based survey were underestimated without correcting for measurement errors.
Assuntos
Doenças Periodontais/diagnóstico , Doenças Periodontais/epidemiologia , Índice Periodontal , Adolescente , Adulto , Calibragem , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Fatores de Risco , Sensibilidade e Especificidade , Fumar/epidemiologia , Taiwan/epidemiologia , Adulto JovemRESUMO
The T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is selectively expressed on terminally differentiated T helper 1 (Th1) cells and acts as a negative regulator that terminates Th1 responses. The dysregulation of TIM-3 expression on T cells is associated with several autoimmune phenotypes and with chronic viral infections; however, the mechanism of this regulation is unclear. In this study, we investigated the effect of DNA methylation on the expression of TIM-3. By analyzing the sequences of TIM-3 promoter regions in human and mouse, we identified a CpG island within the TIM-3 promoter and demonstrated that the promoter activity was controlled by DNA methylation. Furthermore, treatment with 5-aza-2'-deoxycytidine enhanced TIM-3 expression on mouse primary CD4(+) T cells under Th0-, Th1- or Th2-polarizing conditions. Finally, pyrosequencing analysis revealed that the methylation level of the TIM-3 promoter gradually decreased after each round of T-cell polarization, and this decrease was inversely correlated with TIM-3 expression. These data suggest that the DNA methylation of the TIM-3 promoter cooperates with lineage-specific transcription factors in the control of Th-cell development. In conclusion, DNA methylation-based regulation of TIM-3 may provide novel insights into understanding the dysregulation of TIM-3 expression under pathogenic conditions.
Assuntos
Metilação de DNA , Receptor Celular 2 do Vírus da Hepatite A/genética , Regiões Promotoras Genéticas , Linfócitos T Auxiliares-Indutores/metabolismo , Animais , Linhagem da Célula , Ilhas de CpG , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Células Jurkat , Camundongos , Linfócitos T Auxiliares-Indutores/citologia , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Asian women have a younger age at onset of breast cancer and a lower body mass index (BMI) than Western women. The link between obesity and risk of breast cancer in Asian women is still elusive. We aimed to investigate the effect of BMI on the risk of incident breast cancer in Taiwanese women. METHODS: A total of 1,393,985 women who had been cancer-free before recruitment and attended a nation-wide Taiwanese breast cancer-screening program between 1999 and 2009 were enrolled using a prospective cohort study. Obesity and other relevant variables (such as menopause status and other biochemical markers) were collected through in-person interviews, anthropometric measurements and blood samples at first screen. Incident breast cancers during follow-up were ascertained through the linkage of the cohort with the National Cancer Registry and the National Death Certification System. RESULTS: A total of 6969 and 7039 incident breast cancer cases were identified among women enrolled before and after menopause, respectively. Compared with a BMI range of 18.5-23.9 kg m(-)(2), the incremental level of BMI in the enrolled women before menopause revealed a lack of statistically significant association with the risk of incident breast cancer (adjusted hazard ratio=0.94, 0.98, 1.02, 1.01 and 0.82 for BMI <18.5, 24-26.9, 27-29.9, 30-34.9 and ⩾35, respectively), but the incremental level of BMI in the enrolled women after menopause led to a statistically significant incremental increase in the risk of breast cancer (adjusted hazard ratio=0.78, 1.19, 1.31, 1.53 and 1.65 for BMI <18.5, 24-26.9, 27-29.9, 30-34.9 and ⩾35, respectively) after adjusting for other explanatory risk factors. CONCLUSION: Obesity acts mainly as an influential promoter of the development of late-onset breast cancer after menopause in Taiwanese women.
Assuntos
Povo Asiático/estatística & dados numéricos , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Sobrepeso , Magreza , Adulto , Neoplasias da Mama/etiologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Vigilância da População , Estudos Prospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
OBJECTIVE: A four-fold increase of suicide mortality has been demonstrated in systemic lupus erythematosus (SLE) patients. Prior studies showed that the most common method of suicide attempts in SLE patients involves drug overdose. Therefore, we conducted a nationwide population-based case-control study to elucidate factors associated with drug overdose as suicide attempt in SLE patients. METHODS: This study was based on the National Health Insurance Research Database in Taiwan. We identified all SLE patients from January 1, 2000 to December 31, 2010. Patients who had suicidal drug overdose (SDO) were selected as cases while age- and gender-matched patients who did not have SDO were selected as controls. RESULTS: The incidence rate of SDO in SLE patients was 291 cases per 100,000 person-years, higher than that in the general population (160 cases per 100,000 person-years). In a multivariate logistic regression analysis, we observed that SDO was associated with psychiatric disorders such as depressive disorders (odds ratio: 8.36, 95% confidence interval (CI): 5.60-12.48) and insomnia (odds ratio: 2.71, 95% CI: 1.73-4.25), and lower monthly income (odds ratios: 2.74 to 3.50) in SLE patients. CONCLUSION: SDO is associated with psychiatric disorders such as depressive disorders and insomnia, and lower monthly income in SLE patients.
Assuntos
Overdose de Drogas/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/psicologia , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Overdose de Drogas/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pobreza/psicologia , Medição de Risco , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Taiwan/epidemiologiaRESUMO
The first large outbreak of hand, foot, and mouth disease (HFMD) with severe complications primarily caused by enterovirus 71 was reported in Taiwan in 1998. Surveillance of HFMD to evaluate the spread of HFMD with and without infection control policy is needed. We developed a new dynamic epidemic Susceptible-Infected-Recovered (SIR) model to fit the surveillance data on containing valuable information on the severity of HFMD in order to accurately estimate the basic reproductive number (R 0) of HFMD. After fitting the empirical data, in conjunction with other relevant parameters extracted from the literature, the estimated transmission coefficients were close to 5 × 10-7 (per day) and the proportion of severe HFMD cases ranged between 0 and 0·0036 (per day). Taking into account the distribution of all parameters considered in our dynamic epidemic model, the R 0 computed was 1·37 (95% confidence interval 0·24-5·84), suggesting a higher likelihood of the spread of HFMD if no infection control policy is provided. The isolation strategy against the spread of HFMD not only delayed the epidemic peak with the delayed time ranging from 4 weeks for only 20% isolation to 47 weeks for 100% isolation but also reduced total number of HFMD cases with the percentage of reduction ranging from 1·3% for only 20% isolation to 13·3% for 100% isolation. The proposed model can also be flexible for evaluating the effectiveness of two other possible policies for containing HFMD, quarantine and vaccination (if the vaccine can be developed).
Assuntos
Surtos de Doenças , Enterovirus Humano A/fisiologia , Doença de Mão, Pé e Boca/epidemiologia , Modelos Teóricos , Vigilância da População/métodos , Adolescente , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Doença de Mão, Pé e Boca/virologia , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Taiwan/epidemiologia , Adulto JovemRESUMO
Information is lacking on the integrated evaluation of mortality rates in healthcare-associated infections (HAIs). Our aim was to differentiate the risk factors responsible for the incidence from those for the case-fatality rates in association with HAIs. We therefore examined the time trends of both incidence and case-fatality rates over a 20-year period at a tertiary-care teaching medical centre in Taiwan and the mortality rate was expressed as the product of the incidence rate and the case-fatality rate. During the study period the overall mortality rate fell from 0·46 to 0·32 deaths/1000 patient-days and the incidence rate fell from 3·41 to 2·31/1000 patient-days, but the case-fatality rate increased marginally from 13·5% to 14·0%. The independent risk factors associated with incidence of HAIs were age, gender, infection site, admission type, and department of hospitalization. Significant prognostic factors for HAI case-fatality were age, infection site, intensive care, and clinical department. We conclude that the decreasing trend for the HAI mortality rate was accompanied by a significant decline in the incidence rate and this was offset by a slightly increasing trend in the case-fatality rate. This deconstruction approach could provide further insights into the underlying complex causes of mortality for HAIs.