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BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).
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Hansenostáticos , Hanseníase , Mycobacterium leprae , Rifampina , Humanos , Incidência , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Hanseníase/transmissão , Rifampina/administração & dosagem , Rifampina/análogos & derivados , Hansenostáticos/administração & dosagem , Hansenostáticos/uso terapêutico , Características da FamíliaRESUMO
Functional metamaterials can be constructed by assembling nanoparticles (NPs) into well-ordered structures, which show fascinating properties at different length scales. Using polymer-grafted NPs (PGNPs) as a building block, flexible composite metamaterials can be obtained, of which the structure is significantly affected by the property of polymer ligands. Here, it is demonstrated that the crystallization of polymer ligands determines the assembly behavior of NPs and reveal a pathway-dependent self-assembly of PGNPs into different metastructures in solution. By changing the crystallization degree of polymer ligands, the arrangement structure of NPs can be tailored. When the polymer ligands highly crystallize, the PGNPs assemble into diamond-shaped platelets, in which the NPs arrange disorderedly. When the polymer ligands lowly crystallize, the PGNPs assemble into highly ordered 3D superlattices, in which the NPs pack into a body-centered-cubic structure. The structure transformation of PGNP assemblies can be achieved by thermal annealing to regulate the crystallization of polymer ligands. Interestingly, the diamond-shaped platelets remain "living" for seeded epitaxial growth of newly added crystalline species. This work demonstrates the effects of ligand crystallization on the crystallization of NP, providing new insights into the structure regulation of metamaterials.
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BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.
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Fatores de Crescimento de Fibroblastos , Humanos , Masculino , Feminino , Fatores de Crescimento de Fibroblastos/genética , Pessoa de Meia-Idade , Adulto , Imageamento por Ressonância Magnética , Sistema Nervoso Simpático/fisiopatologia , Sistema Nervoso Simpático/patologia , Idoso , Linhagem , Expansão das Repetições de Trinucleotídeos/genética , Sequências de Repetição em Tandem/genética , Degenerações EspinocerebelaresRESUMO
Shape transformation of polymer particles is generally a nonequilibrium dynamics process. Controlling the shape transformation of polymers is increasingly attractive and challenging for scientists due to their extensive use in drug delivery and cancer therapy. Herein, we investigated the UV-triggered shape transformation pathway of polymeric vesicles assembled from Polystyrene-block-poly(4-vinylpyridine) and 4-hydroxyazobenzene (PS-b-P4VP(Azo-OH)) and the direct assembly pathway of UV-irradiated PS-b-P4VP(Azo-OH) homogeneous solution. In the shape transformation process, well-assembled vesicles can be transformed into toroid, cylindrical, rod-like, and spherical micelles. In the direct assembly pathway, rod-like and spherical micelles can be obtained. Interestingly, the toroid micelles can be obtained only from the UV-triggered shape transformation pathway. Contrasting the two pathways reveals the pathway dependence of PS-b-P4VP(Azo-OH) assembly, suggesting that the final assembly morphology is determined by the initial state and dynamic process. The speed of UV-triggered shape transformation and the final morphology of assemblies can be tuned easily by adjusting the UV illuminance, time, and content of Azo-OH addition. Moreover, the light-responsive polymeric vesicles can be used as drug carriers and have the potential to release drugs precisely.
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Cholesterol is regarded as a signaling molecule in regulating the metabolism and function of fat cells, in which 7-Dehydrocholesterol reductase (DHCR7) is a key enzyme that catalyzes the conversion of 7-dehydrocholesterol to cholesterol, however, the exact function of DHCR7 in goat adipocytes remains unknown. Here, the effect of DHCR7 on the formation of subcutaneous and intramuscular fat in goats was investigated in vitro, and the result indicated that the mRNA level of DHCR7 showed a gradual downward trend in subcutaneous adipogenesis, but an opposite trend in intramuscular adipogenesis. In the process of subcutaneous preadipocytes differentiation, overexpression of DHCR7 inhibited the expression of adipocytes differentiation marker genes (CEBP/α, CEBP/ß, SREBP1 and AP2), lipid metabolism-related genes (AGPAT6, FASN, SCD1 and LPL), and the lipid accumulation. However, in intramuscular preadipocyte differentiation, DHCR7 overexpression showed a promoting effect on adipocyte differentiation marker genes (CEBP/α, CEBP/ß, PPARγ and SREBP1) and lipid metabolism-related genes (GPAM, AGPAT6, DGAT1 and SCD1) expression, and on lipid accumulation. In summary, our work demonstrated that DHCR7 played an important role in regulating adipogenic differentiation and lipid metabolism in preadipocytes in goats, which is of great significance for uncovering the underlying molecular mechanism of adipocyte differentiation and improving goat meat quality.
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Cabras , Oxirredutases , Animais , Cabras/genética , Diferenciação Celular/genética , Adipogenia/genética , Adipócitos/metabolismo , Antígenos de Diferenciação/metabolismo , Antígenos de Diferenciação/farmacologia , Colesterol/metabolismo , Lipídeos , PPAR gama/metabolismoRESUMO
PURPOSE: This study aimed to investigate the vitamin D deficiency of patients with BPPV recurrence and to evaluate the differences of 25-hydroxy vitamin D (25(OH)D) and serum calcium levels among gender and age categories. METHODS: This cross-sectional study enrolled patients with BPPV. The diagnosis of BPPV was based on positional nystagmus and vertigo induced by certain head positions (The Dix-Hallpike maneuver and head roll tests). All patients' age, serum 25(OH)D, calcium measurements and recurrence data were collected and analyzed. RESULTS: The median of 25(OH)D was 15.32 (IQR 10.61, 20.90) ng/ml. The recurrent group showed lower 25(OH)D levels than that of non-recurrent group [13.28 (IQR 9.47, 17.57) ng/ml vs 16.21 (IQR 11.49, 21.13) ng/ml]. There were significant differences of 25(OH)D levels among age categories. The proportion of vitamin D deficiency in patients ≥60 years old was lower than that in the other two groups. CONCLUSION: Our study suggested that BPPV patients had a decreased 25(OH)D level and a high incidence of vitamin D deficiency. The 25(OH)D level of recurrent BPPV patients was lower than that in non-recurrent ones. Among them, the elderly group (≥60 years) took the preponderance, which had the lowest incidence of vitamin D deficiency and the highest incidence of vitamin D sufficiency.
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Vertigem Posicional Paroxística Benigna , Cálcio , Recidiva , Deficiência de Vitamina D , Vitamina D , Vitamina D/análogos & derivados , Humanos , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Vitamina D/sangue , Vertigem Posicional Paroxística Benigna/etiologia , Vertigem Posicional Paroxística Benigna/epidemiologia , Vertigem Posicional Paroxística Benigna/sangue , Vertigem Posicional Paroxística Benigna/diagnóstico , Idoso , Adulto , Cálcio/sangue , Fatores Etários , Fatores Sexuais , IncidênciaRESUMO
The spontaneous organization of two types of nanoparticles (NPs) with different shapes or properties into binary nanoparticle superlattices (BNSLs) with different configurations has recently attracted significant attention due to the coupling or synergistic effect of the two types of NPs, providing an efficient and general route for designing new functional materials and devices. Here, this work reports the co-assembly of polystyrene (PS) tethered anisotropic gold nanocubes (AuNCs@PS) and isotropic gold NPs (AuNPs@PS) via an emulsion-interface self-assembly strategy. The distributions and arrangements of the AuNCs and spherical AuNPs in the BNSLs can be precisely controlled by adjusting the effective size ratio (λeff ) of the effective diameter (deff ) of the embedded spherical AuNPs to the polymer gap size (L) between the neighboring AuNCs. λeff determines not only the change of the conformational entropy of the grafted polymer chains (∆Scon ) but also the mixing entropy (∆Smix ) of the two types of NPs. During the co-assembly process, ∆Smix tends to be as high as possible, and the -∆Scon tends to be as low as possible, leading to free energy minimization. As a result, well-defined BNSLs with controllable distributions of spherical and cubic NPs can be obtained by tuning λeff . This strategy can also be applied for other NPs with different shapes and atomic properties, thus largely enriching the BNSL library and enabling the fabrication of multifunctional BNSLs, which have potential applications in photothermal therapy, surface-enhanced Raman scattering, and catalysis.
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BACKGROUND: Mycobacterium leprae (ML) is the pathogen that causes leprosy, which has a long history and still exists today. ML is an intracellular mycobacterium that dominantly induces leprosy by causing permanent damage to the skin, nerves, limbs and eyes as well as deformities and disabilities. Moreover, ML grows slowly and is nonculturable in vitro. Given the prevalence of leprosy, a highly sensitive and rapid method for the early diagnosis of leprosy is urgently needed. RESULTS: In this study, we devised a novel tool for the diagnosis of leprosy by combining restriction endonuclease, real-time fluorescence analysis and multiple cross displacement amplification (E-RT-MCDA). To establish the system, primers for the target gene RLEP were designed, and the optimal conditions for E-RT-MCDA at 67 °C for 36 min were determined. Genomic DNA from ML, various pathogens and clinical samples was used to evaluate and optimize the E-RT-MCDA assay. The limit of detection (LoD) was 48.6 fg per vessel for pure ML genomic DNA, and the specificity of detection was as high as 100%. In addition, the detection process could be completed in 36 min by using a real-time monitor. CONCLUSION: The E-RT-MCDA method devised in the current study is a reliable, sensitive and rapid technique for leprosy diagnosis and could be used as a potential tool in clinical settings.
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Hanseníase , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Sensibilidade e Especificidade , Hanseníase/diagnóstico , Hanseníase/microbiologia , Pele/microbiologia , DNA , DNA Bacteriano/genética , Técnicas de Amplificação de Ácido Nucleico/métodosRESUMO
BACKGROUND: Type 1 diabetes is one of the chronic autoimmune diseases. Its features include the immune-triggered pancreatic beta-cells destruction. Ubiquitin ligases RNF20 and RNF40 have been discovered to participate into beta cells gene expression, insulin secretion, and expression of vitamin D receptors (VDRs). However, no reports about the role of RNF20/RNF40 in type 1 diabetes are known till now. The aim of this study was to clarify the role of RNF20/RNF40 in type 1 diabetes and explore the mechanism. METHODS: In this study, streptozotocin (STZ)-induced mice type 1 diabetes model was used. The protein expressions of genes were examined through Western blot analysis. Fasting blood glucose was detected through glucose meter. The plasma insulin was tested through the commercial kit. Hematoxylin and eosin staining was utilized to observe pathological changes of pancreatic tissues. Immunofluorescence assay was performed to evaluate the level of insulin. The levels of pro-inflammatory cytokines in serum were assessed by enzyme-linked-immunosorbent serologic assay. The cell apoptosis was measured through terminal deoxynucleotidyl transferase dUTP nick end labelling assay. RESULTS: STZ was used to stimulate mice model for type 1 diabetes. At first, both RNF20 and RNF40 expressions were down-regulated in STZ-mediated type 1 diabetes. Additionally, RNF20/RNF40 improved hyperglycemia in STZ-stimulated mice. Moreover, RNF20/RNF40 relieved pancreatic tissue injury in STZ-induced mice. Further experiments found that RNF20/RNF40 rescued the strengthened inflammation mediated by STZ treatment. The cell apoptosis was enhanced in the pancreatic tissues of STZ-triggered mice, but this effect was weakened by overexpression of RNF20/RNF40. Besides, the VDR expression was positively regulated by RNF20/RNF40. Finally, VDR knockdown reversed improved hyperglycemia, inflammation, and cell apoptosis stimulated by overexpression of RNF20/RNF40. CONCLUSION: Our findings proved that RNF20/RNF40 activated VDR to relieve type 1 diabetes. This work might highlight the functioning of RNF20/RNF40 in the treatment of type 1 diabetes.
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Diabetes Mellitus Tipo 1 , Hiperglicemia , Animais , Camundongos , Estreptozocina , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Receptores de Calcitriol/genética , Insulina/metabolismo , Modelos Animais de Doenças , InflamaçãoRESUMO
The spontaneous self-assembly of metal nanocrystals into two-dimensional (2D) monolayer superlattices with highly ordered symmetry and configuration paves the way towards the fabrication of functional materials. However, there remains great challenge for anisotropic nanocrystals to self-assembly into high quality superlattice because of the orientation and configuration consistency. Here, a facile yet universal solvent annealing driven 2D interfacial assembly of synthetic dried metal nanocrystals is firstly developed to realize the construction of the non-close-packing 2D monolayer gold nanocube (AuNC) superlattice with tunable interparticle distance and internal configurations (i.e. face-to-face and hexagonally-packed arrangement), which is achieved by precisely controlling molecular weight of polymer ligands tethered on AuNCs and the van der Waals forces between the adjacent AuNCs. In addition, the scale of the generated 2D monolayer AuNC superlattice with highly ordered internal arrangement and orientation can reach up to hundreds of micrometers, thus acquiring significant surface-enhanced Raman scattering performance of the large scale superlattice due to the strong plasma coupling effect. This strategy not only provides a robust route to fabricate nanocrystal superlattice structures but also offers a promising platform for preparing diverse functional materials with potential applications in electronics, photonics, detections, and others.
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BACKGROUND: A paucity of studies focused on the genetic association that tuberculosis (TB) patients with non-communicable diseases (NCDs) are more likely to be infected with Mycobacterium tuberculosis (MTB) with more potent virulence on anti-TB drug resistance than those without NCDs. The study aimed to document the predominant genotype, determine the association between MTB genotypes and NCD status and drug resistance. METHODS: We conducted a molecular study in 105 TB patients based on a cross-sectional study focused on the comorbid relationship between chronic conditions and TB among 1773 subjects from September 1, 2019 to August 30, 2020 in Guizhou, China. The participants were investigated through face-to-face interviews, followed by NCDs screening. The DNA of MTB isolates was extracted prior to genotyping using 24 loci MIRU-VNTR. The subsequent evaluations were performed by phylogenetic trees, combined with tests of statistical power, Chi-square or Fisher and multivariate logistic regression analysis. RESULTS: The Beijing family of Lineage 2 (East Asia) was the predominant genotype accounting for 43.8% (46/105), followed by Lineage 4 (Euro-America) strains, including Uganda I (34.3%, 36/105), and the NEW-1 (9.5%, 10/105). The proportion of Beijing strain in patients with and without NCDS was 28.6% (8/28) and 49.4% (38/77), respectively, with a statistical power test value of 24.3%. No significant association was detected between MTB genotype and NCD status. A low clustering rate (2.9%) was identified, consisting of two clusters. The rates of global, mono-, poly- and multi-drug resistance were 16.2% (17/105), 14.3% (15/105), 1.0% (1/105) and 4.8% (5/105), respectively. The drug-resistant rates of rifampicin, isoniazid, and streptomycin, were 6.7% (7/105), 11.4% (12/105) and 5.7% (6/105), respectively. Isoniazid resistance was significantly associated with the Beijing genotype of Lineage 2 (19.6% versus 5.1%). CONCLUSIONS: The Lineage 2 East Asia/Beijing genotype is the dominant genotype of the local MTB with endogenous infection preponderating. Not enough evidence is detected to support the association between the MTB genotype and diabetes/hypertension. Isoniazid resistance is associated with the Lineage 2 East Asia/Beijing strain.
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Diabetes Mellitus , Hipertensão , Mycobacterium tuberculosis , Doenças não Transmissíveis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Estudos Transversais , Diabetes Mellitus/epidemiologia , Genótipo , Humanos , Isoniazida , Filogenia , Tuberculose/epidemiologia , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
OBJECTIVE: To establish and validate a predictive formula for calculating the possibility of developing delayed neurological sequelae (DNS) after acute carbon monoxide (CO) poisoning to facilitate better decision-making about treatment strategies. METHODS: This study retrospectively enrolled 605 consecutive patients who had been newly diagnosed with CO poisoning from the Central Hospital of Enshi Prefecture between January 1, 2015 and December 31, 2020. The cohort was randomly divided into two subgroups: the development cohort (n = 104) and validation cohort (n = 44). Univariate analysis and backward elimination of multivariate logistic regression were used to identify predictive factors, and a predictive formula was established. The performance was assessed using the area under the curve (AUC), the mean AUC of five-fold cross-validation, and calibration plots. RESULTS: The formula included four commonly available predictors: initial GCS score, duration of exposure, CK, and abnormal findings on MRI. We next created a formula to calculate the risk score for developing DNS: Risk score = -4.54 + 3.35 * (Abnormal findings on MRI = yes) - 0.51 * (Initial GCS score) + 0.65 * (Duration of exposure) + 0.01 * (CK). Then, the probability of developing DNS could be calculated: Probability of DNS = 1/(1 + e Risk score). The model revealed good discrimination with AUC, and mean AUC of fivefold cross-validation in two cohort, and the calibration plots showed good calibration. CONCLUSIONS: This study established a prediction predictive formula for predicting developing of DNS, which could facilitate better decision-making about treatment strategies.
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Intoxicação por Monóxido de Carbono/complicações , Transtornos Mentais/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Idoso , Intoxicação por Monóxido de Carbono/diagnóstico por imagem , China , Progressão da Doença , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de RiscoRESUMO
In our study, we retrospectively enrolled 606 women with newly diagnosed polycystic ovary syndrome. Participants were divided into two cohorts: development cohort (n = 424) and validation cohort (n = 182). Multivariate logistic regression analyses were used to identify predictive indicators, and nomograms were developed and validated. We found that waist hip rate (WHR), testosterone levels, and fasting blood glucose (FBG) levels (WTF) could predict the small for gestational age; BMI, WHR and modified Ferriman-Gallwey Score (BWM) correlated with low Apgar scores; and BMI, WHR, modified Ferriman-Gallwey Score, testosterone levels, and FBG levels (BWMTF) correlated with adverse neonatal outcomes. The BWMTF nomogram was established, revealing perfect discrimination with the area under the receiver operating characteristic curve (AUC) and stratified five-fold cross-validation in development cohort (AUC = 0.75, Mean AUC = 0.75) and validation cohort (AUC = 0.68, Mean AUC = 0.75). Calibration plots showed good calibration. We established and validated three models for predicting adverse perinatal effects to guide preventive treatment protocols. Impact statementWhat is already known on this subject? Many studies have identified a large number of predictors, but also lack a comprehensively quantified tool to predict adverse neonatal outcomes in women with PCOS to guide the development of clinical treatment programs.What do the results of this study add? This article screened the high risks factors of adverse neonatal outcomes in women with PCOS, and three nomograms were established and validated. Also, the area under the receiver operating characteristic curve (AUC) and stratified five-fold cross-validation in development cohort and validation cohort showed good discrimination; Calibration plots showed good calibration.What are the implications of these findings for clinical practice and/or further research? Our scoring system could help clinicians evaluate these risks and conduct proper screening, prevention, and management to ameliorate the risk of neonatal disease in these patients.
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Síndrome do Ovário Policístico , Glicemia , Feminino , Humanos , Recém-Nascido , Nomogramas , Síndrome do Ovário Policístico/complicações , Gravidez , Estudos Retrospectivos , TestosteronaRESUMO
About 25% of patients with newly diagnosed acute myeloid leukaemia (AML) have normal cytogenetics and no nucleophosmin 1 (NPM1) mutation or Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). The prognosis and best therapy for these patients is controversial. We evaluated 158 newly diagnosed adults with this genotype who achieved histological complete remission within two cycles of induction therapy and were assigned to two post-remission strategies with and without an allotransplant. Targeted regional sequencing at diagnosis was performed and data were used to estimate their prognosis, including relapse and survival. In multivariable analyses, having wild-type or mono-allelic mutated CCAAT/enhancer-binding protein alpha (CEBPA) [hazard ratio (HR) 2·39, 95% confidence interval (CI) 1·08-5·30; P = 0·032), mutated NRAS (HR 2·67, 95% CI 1·36-5·25; P = 0·004), mutated colony-stimulating factor 3 receptor (CSF3R) (HR 2·85, 95% CI 1·12-7·27; P = 0·028) and a positive measurable residual disease (MRD)-test after the second consolidation cycle (HR 2·88, 95% CI 1·32-6·30; P = 0·008) were independently correlated with higher cumulative incidence of relapse (CIR). These variables were also significantly associated with worse survival (HR 3·02, 95% CI 1·17-7·78, P = 0·022; HR 3·62, 95% CI 1·51-8·68, P = 0·004; HR 3·14, 95% CI 1·06-9·31, P = 0·039; HR 4·03, 95% CI 1·64-9·89, P = 0·002; respectively). Patients with ≥1 of these adverse-risk variables benefitted from a transplant, whereas the others did not. In conclusion, we identified variables associated with CIR and survival in patients with AML and normal cytogenetics without a NPM1 mutation or FLT3-ITD.
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Análise Citogenética/métodos , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Sequências de Repetição em Tandem , Adulto JovemRESUMO
Electrical noise significantly limits the detectivity of infrared photodiode detectors. In this paper, we investigated the dark current and noise spectra for long-wave-infrared InAs/GaSb type-II superlattice (T2SL) detectors to study the origin of noise under various work conditions. The temperature-dependent I-V characteristics reveal a turning point near 90 K, below which the dominant dark current mechanism changes from Shockley-Hall-Read generation current and diffusion current to shunt current and trap-assisted tunneling (TAT) current. The contribution of shunt and tunneling process to the total 1/f noise are analyzed by fitting the noise power spectral density at 77 K for detectors. It is found that the TAT current dominates the 1/f noise at the reverse bias stronger than -0.1 V, while shunt current exhibits a larger contribution at the reverse bias less than -0.1 V with the shunt noise coefficient αshunt of 5×10-8. Furthermore, the leakage routes related to the shunt process and their temperature dependence are illustrated by two-dimensional photocurrent mapping.
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BACKGROUND: Currently, the prognostic stratification and therapeutic evaluation systems for multiple myeloma (MM) lack specific molecular indicators. OC-STAMP is a new gene and is also highly expressed in MM. METHODS: A total of 160 MM patients have been investigated with both quantitative reverse transcription PCR (RT-qPCR), flow cytometry (FCM) and cytogenetic FISH on the same mononuclear cells isolated from bone marrow specimens. RESULTS: We found that OC-STAMP mRNA levels were significantly higher in newly diagnosed cases of MM than in healthy donors (median, 0.52% vs. 0.02%, P < .001). Moreover, the changes in the OC-STAMP mRNA levels paralleled the disease stages and minimal residual disease, as detected by FCM. Furthermore, we found that patients with high OC-STAMP mRNA levels were more likely to develop ≥3 bone lesions, be diagnosed with Durie-Salmon stages III, and have the P53 (17p13) deletion. In addition, advanced stage patients with high OC-STAMP mRNA levels had a lower 4-year progression-free survival (5.6% vs. 22.9%, P = .0055) and a worse 4-year overall survival (25.8% vs. 48.8%, P = .0137) compared to patients with low mRNA levels of this indicator. CONCLUSIONS: OC-STAMP may be a promising molecular indicator to monitor treatment effects and participate in the prognostic stratification of MM.
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Biomarcadores Tumorais , Proteínas de Membrana/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Medula Óssea/patologia , Linhagem Celular Tumoral , Aberrações Cromossômicas , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Humanos , Imunofenotipagem , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Análise de Sobrevida , Translocação Genética , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) brings major challenges to the health care workers (HCWs). This study is to determine the risk factors for MDR-TB, latent tuberculosis infection (LTBI), and tuberculosis (TB) disease among HCWs in China. METHODS: A meta-analysis was conducted to evaluate the risk factors for MDR-TB, LTBI, and TB disease among HCWs using a random-effects model, and the pooled odds ratios (ORs) with 95% confidence interval (CI) were used as effect indicators. RESULTS: We identified 46 eligible studies and found eight factors were associated with MDR. The ORs with 95% CI are migrant population 1.96 (95% CI, 1.50-2.57), low family income 2.23 (95% CI, 1.74-2.85), retreatment 7.22 (95% CI, 5.63-9.26), anti-TB treatment history 5.65 (95% CI, 4.80-6.65), multiple episodes of treatment 3.28 (95% CI, 2.60-4.13), adverse reactions 3.48 (95% CI, 2.54-4.76), interrupted treatment 3.18 (95% CI, 2.60-3.89), and lung cavities 1.42 (95% CI, 1.14-1.77). Work duration as a HCW for 5 years and above increased the risk of LTBI and TB. HCWs aged 30 years and above were more susceptible to TB (OR = 1.70, 95% CI: 1.37-2.09). CONCLUSION: The risk factors for MDR-TB in China are possibly migrant population, low family income, retreatment, anti-TB treatment history, adverse reactions, interrupted treatment, and lung cavities. Longer work duration and greater age are risk factors for LTBI and TB among HCWs.
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Pessoal de Saúde/estatística & dados numéricos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , China/epidemiologia , Humanos , Tuberculose Latente/epidemiologia , Fatores de Risco , Tuberculose/epidemiologiaRESUMO
In this paper, deep level transient spectroscopy (DLTS) characterization was performed on Beryllium compensation doping of InGaAs/GaAsSb type-II superlattice photodiode. Three electron traps with the energy levels located at Ec-0.11 eV (E1), Ec-0.28 eV (E2), Ec-0.17 eV (E3), and a hole trap situated at Ev + 0.25 eV (H1) were revealed. The position distribution and depth concentration of these traps in SL absorption region was also explored. Furthermore, the bandlike states (E2) and localized states (E1 and H1) of extended defects were confirmed by DLTS measurements as a function of the filling-pulse time, these traps as generation-recombination centers are responsible for dominant dark current.
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V-set and transmembrane domain-containing 1 (VSTM1), which is downregulated in bone marrow cells from leukemia patients, may provide a diagnostic and treatment target. Here, a triple-regulated oncolytic adenovirus was constructed to carry a VSTM1 gene expression cassette, SG611-VSTM1, and contained the E1a gene with a 24-nucleotide deletion within the CR2 region under control of the human telomerase reverse transcriptase promoter, E1b gene directed by the hypoxia response element, and VSTM1 gene controlled by the cytomegalovirus promoter. Real-time quantitative PCR and Western blot analyses showed that SG611-VSTM1 expressed VSTM1 highly efficiently in the human leukemic cell line K562 compared with SG611. In Cell Counting Kit-8 and flow cytometric assays, SG611-VSTM1 exhibited more potent anti-proliferative and pro-apoptotic effects in leukemic cells compared with SG611 and exerted synergistic cytotoxicity with low-dose daunorubicin (DNR) in vitro. In xenograft models, SG611-VSTM1 intratumorally injected at a dose of 1 × 10(9) plaque forming units combined with intraperitoneally injected low-dose DNR displayed significantly stronger antitumor effects than either treatment alone. Histopathologic examination revealed that SG611-VSTM1 induced apoptosis of leukemic cells. These results implicate an important role for VSTM1 in the pathogenesis of leukemia, and SG611-VSTM1 may be a promising agent for enhancing chemosensitivity in leukemia therapy.
Assuntos
Adenoviridae/genética , Antineoplásicos/administração & dosagem , Daunorrubicina/administração & dosagem , Leucemia/terapia , Vírus Oncolíticos/genética , Receptores Imunológicos/genética , Adenoviridae/fisiologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Terapia Genética , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Humanos , Leucemia/tratamento farmacológico , Leucemia/fisiopatologia , Leucemia/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia Viral Oncolítica , Vírus Oncolíticos/fisiologia , Receptores Imunológicos/metabolismoRESUMO
Although leprosy in China is controlled at a low endemic level, the number of new cases in Guizhou province has shown no significant decrease over the past 20 years. Guizhou remains the province with the second highest prevalence in China. The authors conducted a study in which the characteristics of newly detected leprosy cases, found between 2008 and 2012 in Guizhou, were analysed. These cases represented people from pocket areas of leprosy in a generally low endemic environment. The purpose of the study was to understand characters of newly detected cases, strong points and weakness of routine detection approaches for improving the effectiveness of early case detection in the future. The analysis considered data that was collected from a 'Leprosy Management Information' report system and also from annual statistical reports of leprosy that reflect the situation throughout the province. 1274 new patients were detected in Guizhou from 2008 to 2012. That number included 58 (4.6%) children (0-14 years old). The average age of patients at diagnosis was 42.6 ± 16.5 years. The proportion of people with WHO Grade 2 disability (WHO DG2) among new patients was 35.7% and the proportion of people with Grade 1 disability (DG1) constituted 10.1%. The average delay before diagnosis after the onset of symptoms of leprosy was 41.7 ± 49.8 months. Suspect survey was a major method by which most cases were detected. Trough this method 790 (62.0%) new patients were detected. It was also in this group that the highest proportion of people with WHO DG2 359 of 790 (45.4%) was reported. Self- reporting, diagnosis at a general skin clinic, household contact examination, and spot surveys accounted for 13.0%, 11.8%, 11.5% and 1.7% of other cases detected respectively. It was generally found that cases detected through household contact examinations were earlier cases (delay to diagnosis < 24 months = 70.7%). It was also recorded that fewer of these had WHO DG2 (12.9%). The proportion of men with WHO DG2 was higher than that of females (38.2% compared with 28.8%). The proportion of Han Chinese new cases with WHO DG2 was significantly higher than that of the main minority group (41.5% compared with 29.2%). The proportion of new cases among the main minority group who self-reported (50%) was significantly higher than those detected through other detection approaches. Detecting leprosy early in low endemic situations where pockets persist was difficult to achieve. The authors suggest that if more early patients are to be detected earlier, the quality of suspect surveys and household contact examination should be improved. Professional training and supervision might affect that result. Greater emphasis should be given to the role of general skin clinics as surveillance sites and advocacy for new health policy that will enhance the detection leprosy should be sustained.