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1.
ACS Infect Dis ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34788533

RESUMO

Antimicrobial resistance-related infections of Gram-negative pathogens pose a huge threat to global public health. Lysins, peptidoglycan hydrolases from bacteriophages, are expected as an alternative weapon against drug-resistant bacteria. In the present study, we report a new lysin LysP53 from Acinetobacter baumannii phage 53. Bioinformatic analysis revealed that LysP53 contains a positively charged N-terminal region and a putative peptidase catalytic domain. In vitro biochemical experiments showed that LysP53 is active against multiple antibiotic-resistant Gram-negative bacteria, including A. baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, with a reduction of 5 logs in viable A. baumannii number after exposure to 100 µg/mL LysP53 for 1 h. Further studies showed that LysP53 contains a functional antimicrobial peptide, i.e., N-terminal 33 aa, with a comparable spectrum of activity to LysP53. In an A. baumannii-associated mouse model of burn infection, a single dose of 14 µg/mouse LysP53 (57.6 µM) showed higher decolonization efficacy than 4 µg/mouse minocycline- (874 µM; p < 0.05) and buffer-treated groups (p <0.001), leading to a bacterial reduction of 3 logs. Our findings collectively establish that LysP53 could be a promising candidate in the treatment of topical infections caused by multiple Gram-negative pathogens.

2.
Open Forum Infect Dis ; 8(6): ofab206, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34235228

RESUMO

Background: Chlamydia trachomatis (CT) is a major cause of infertility and adverse birth outcomes, but its epidemiology among childbearing-age women remains unclear in China. This study investigated the prevalence of CT and associated factors among Chinese women aged 16-44 years who were either (1) pregnant, (2) attending gynecology clinics, or (3) subfertile. Methods: We conducted a cross-sectional survey and recruited participants from obstetrics, gynecology, and infertility clinics in Guangdong between March and December 2019. We collected information on individuals' sociodemographic characteristics, previous medical conditions, and sexual behaviors. First-pass urine and cervical swabs were tested using nucleic acid amplification testing. We calculated the prevalence in each population and subgroup by age, education, and age at first sex. Multivariable binomial regression models were used to identify factors associated with CT. Results: We recruited 881 pregnant women, 595 gynecology clinic attendees, and 254 subfertile women. The prevalence of CT was 6.7% (95% CI, 5.2%-8.5%), 8.2% (95% CI, 6.2%-10.7%), and 5.9% (95% CI, 3.5%-9.3%) for the above 3 populations, respectively. The subgroup-specific prevalence was highest among those who first had sex before age 25 years and older pregnant women (>35 years). The proportion of asymptomatic CT was 84.8%, 40.0%, and 60.0% among pregnant women, gynecology clinic attendees, and subfertile women, respectively. Age at first sex (<25 years), multipara, and ever having more than 1 partner increased the risk of CT. Conclusions: Childbearing-age women in China have a high prevalence of CT. As most women with CT were asymptomatic, more optimal prevention strategies are urgently needed in China.

3.
Chem Res Toxicol ; 34(6): 1542-1555, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34081457

RESUMO

Perfluorotridecanoic acid (PFTrDA) is a long-chain (C13) perfluoroalkyl carboxylic acid. Here, we report the influence of PFTrDA exposure on the maturation of rat Leydig cells in late puberty in vivo. Male Sprague-Dawley rats were administered PFTrDA by gavage of 0, 1, 5, and 10 mg/kg/day from 35 days to 56 days postpartum. PFTrDA had no effect on body weight, testis weight, and epididymis weight. It significantly decreased the serum testosterone level after 5 and 10 mg/kg exposure, while it did not alter the serum estradiol level. The serum luteinizing hormone level was markedly reduced after 10 mg/kg PFTrDA exposure, while the follicle-stimulating hormone level was unchanged. Star, Cyp11a1, Cyp17a1, Hsd3b1, and Insl3 transcript levels in the testis were markedly lowered in the 1-5 mg/kg PFTrDA group and the Lhb transcript level in the pituitary in the 10 mg/kg group. CYP11A1 and HSD11B1-positive Leydig cell numbers were markedly reduced after 10 mg/kg PFTrDA exposure. Testicular triglyceride and free fatty acid (palmitic acid, oleic acid, and linoleic acid) levels were significantly reduced by PFTrDA, while Mgll (up-regulation) and Scarb1 and Elovl5 (down-regulation) expression were altered. AKT1 and AMPK phosphorylation was stimulated after 10 PFTrDA mg/kg exposure. In conclusion, PFTrDA delays the maturation of Leydig cells in late puberty mainly by altering the free fatty acid profile.


Assuntos
Ácidos Decanoicos/farmacologia , Fluorcarbonetos/farmacologia , Células Intersticiais do Testículo/efeitos dos fármacos , Lipídeos/análise , Hipófise/efeitos dos fármacos , Testículo/efeitos dos fármacos , Administração Oral , Animais , Ácidos Decanoicos/administração & dosagem , Relação Dose-Resposta a Droga , Fluorcarbonetos/administração & dosagem , Masculino , Hipófise/patologia , Ratos , Ratos Sprague-Dawley , Testículo/patologia
4.
J Vis Exp ; (169)2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33871452

RESUMO

Diagnosis of the ongoing SARS-CoV-2 pandemic is a priority for all countries across the globe. Currently, reverse transcription quantitative PCR (RT-qPCR) is the gold standard for SARS-CoV-2 diagnosis as no permanent solution is available. However effective this technique may be, research has emerged showing its limitations in detection and diagnosis especially when it comes to low abundant targets. In contrast, droplet digital PCR (ddPCR), a recent emerging technology with superior advantages over qPCR, has been shown to overcome the challenges of RT-qPCR in diagnosis of SARS-CoV-2 from low abundant target samples. Prospectively, in this article, the capabilities of RT-ddPCR are further expanded by showing steps on how to develop simplex, duplex, triplex probe mix, and quadruplex assays using a two-color detection system. Using primers and probes targeting specific sites of the SARS-CoV-2 genome (N, ORF1ab, RPP30, and RBD2), the development of these assays is shown to be possible. Additionally, step by step detailed protocols, notes, and suggestions on how to improve the assays workflow and analyze data are provided. Adapting this workflow in future works will ensure that the maximum number of targets can be sensitively detected in a small sample significantly improving on cost and sample throughput.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , SARS-CoV-2/isolamento & purificação , Primers do DNA , Humanos , Pandemias , RNA Viral/genética , Transcrição Reversa , Sensibilidade e Especificidade
5.
Environ Toxicol ; 36(6): 1206-1216, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33683001

RESUMO

Perfluorotridecanoic acid (PFTrDA) is a long-chain perfluoroalkyl substance, and its effect on the differentiation of fetal Leydig cells remains unclear. The objective of this study is to explore the effect of in utero PFTrDA exposure on the differentiation of fetal Leydig cells and investigate its underlying mechanisms. Pregnant Sprague-Dawley female rats were daily administered by gavage of PFTrDA at doses of 0, 1, 5, and 10 mg/kg from gestational day 14 to 21. PFTrDA had no effect on the body weight of dams, but significantly reduced the body weight and anogenital distance of male pups at birth at a dose of 10 mg/kg. PFTrDA significantly decreased serum testosterone levels as low as 1 mg/kg. PFTrDA did not affect fetal Leydig cell number, but promoted abnormal aggregation of fetal Leydig cells at doses of 5 and 10 mg/kg. PFTrDA down-regulated the expression of Insl3, Lhcgr, Scarb1, Star, Hsd3b1, Cyp17a1, Nr5a1, and Dhh as well as their proteins. PFTrDA lowered the levels of antioxidants (SOD1, CAT, and GPX1), induced autophagy as shown by increased levels of LC3II and beclin1, and reduced the phosphorylation of mTOR. In conclusion, PFTrDA inhibits the differentiation of fetal Leydig cells in male pups after in utero exposure mainly through increasing oxidative stress and inducing autophagy.


Assuntos
Testículo , Testosterona , Animais , Autofagia , Diferenciação Celular , Feminino , Células Intersticiais do Testículo/metabolismo , Masculino , Estresse Oxidativo , Gravidez , Ratos , Ratos Sprague-Dawley , Testículo/metabolismo , Testosterona/metabolismo
6.
Front Cell Infect Microbiol ; 11: 637313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33738267

RESUMO

The rapid spread and emergence of multidrug-resistant Acinetobacter baumannii and other pathogenic Gram-negative bacteria spurred scientists and clinicians to look for alternative therapeutic agents to conventional antibiotics. In the present study, an A. baumannii bacteriophage p54 was isolated and characterized. Morphological and genome analysis revealed that bacteriophage p54 belongs to Myoviridae family with a genome size of 165,813 bps. A novel endolysin, namely LysAB54, showing low similarity with other well-known related endolysins, was cloned, expressed, and characterized from the bacteriophage p54. LysAB54 showed significant bactericidal activity against multidrug-resistant A. baumannii and other Gram-negative bacteria, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, in the absence of outer membrane permeabilizers. Based on all those observations, LysAB54 could represent a potential agent for the treatment of multidrug-resistant Gram-negative superbugs.


Assuntos
Acinetobacter baumannii , Bacteriófagos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Endopeptidases , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa
7.
Toxicol Lett ; 342: 6-19, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33581290

RESUMO

2,2',4,4'-Tetrabromodiphenyl ether (BDE47), a flame retardant, is extensively distributed in the food chain. However, whether BDE47 affects Leydig cell development during prepuberty remains unclear. BDE47 was daily gavaged to 21-day-old Sprague-Dawley male rats with 0 (corn oil), 0.1, 0.2, and 0.4 mg/kg for 14 days. BDE47 did not affect the body weight or testis weight of rats. It significantly increased serum testosterone level at 0.4 mg/kg, but decreased luteinizing hormone (LH) level without affecting estradiol level. BDE47 induced Leydig cell hyperplasia (the number of CYP11A1-positive Leydig cells increased), and up-regulated the expression of Scarb1, Star, Hsd11b1, Pcna, and Ccnd1 in the testis. BDE47 significantly reduced p53 and p21 levels but increased CCND1 level. It also markedly increased the phosphorylation of AKT1, AKT2, ERK1/2, and CREB. BDE47 significantly up-regulated the expression of Scarb1, Star, and Hsd11b1 and stimulated androgen production by immature Leydig cells from rats under basal, LH, and 8Br-cAMP stimulated conditions at 100 nM in vitro. In conclusion, BDE47 increased Leydig cell number and up-regulated the expression of Scarb1 and Star, thereby leading to increased testosterone synthesis.


Assuntos
Éteres Difenil Halogenados/toxicidade , Células Intersticiais do Testículo/fisiologia , Maturidade Sexual/fisiologia , Células-Tronco/efeitos dos fármacos , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Animais , Células Cultivadas , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Relação Dose-Resposta a Droga , Hormônio Foliculoestimulante , Regulação da Expressão Gênica/efeitos dos fármacos , Éteres Difenil Halogenados/administração & dosagem , Éteres Difenil Halogenados/química , Hormônio Luteinizante , Masculino , Estrutura Molecular , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo
8.
Toxicol Appl Pharmacol ; 415: 115440, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33549592

RESUMO

Perfluoroundecanoic acid (PFUnA) is one of long-chain perfluoroalkyl carboxylic acids. However, the effect of PFUnA on pubertal development of Leydig cells remains unclear. The goal of this study was to investigate the effect of PFUnA on Leydig cell development in pubertal male rats. We orally dosed male Sprague-Dawley rats (age 35 days) with PFUnA at doses of 0, 1, 5, and 10 mg/kg/day from postnatal day (PND) 35 to PND 56. Serum testosterone and luteinizing hormone levels were remarkably reduced by PFUnA at ≥1 mg/kg while serum follicle-stimulating hormone levels were lowered at 5 and 10 mg/kg. PFUnA down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Hsd11b1, Insl3, Nr5a1, Fshr, Dhh, Sod1, and Sod2 and their proteins in the testis and the expression of Lhb and Fshb in the pituitary. PFUnA reduced Leydig cell number at 5 and 10 mg/kg. PFUnA induced oxidative stress and increased autophagy. These may result from the inhibition of phosphorylation of mTOR, AKT1, AKT2, and ERK1/2 in the testis. In conclusion, PFUnA exhibits inhibitory effects on pubertal Leydig cell development possibly via inducing oxidative stress and increasing autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Ácidos Graxos/toxicidade , Fluorcarbonetos/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fatores Etários , Animais , Proteínas Relacionadas à Autofagia/metabolismo , Hormônio Foliculoestimulante/sangue , Regulação Enzimológica da Expressão Gênica , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Hormônio Luteinizante/sangue , Masculino , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Ratos Sprague-Dawley , Desenvolvimento Sexual , Transdução de Sinais , Contagem de Espermatozoides , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testosterona/sangue
9.
Environ Res ; 195: 110834, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548292

RESUMO

OBJECTIVE: Ambient temperature extremes due to heat exposure was an established risk factor for preterm birth (<37 gestational weeks). However, there is insufficient epidemiological evidence on the effects of temperature variation(TV), although TV is also associated with heat exposure and can influence human health risk. This study aimed to investigate the relationship between inter- and intraday TV and preterm birth (PTB). METHOD: A total of 1,388,994 live singleton births were collected from January 2003 to December 2012, from the Shenzhen Birth registry system. Daily temperature range (DTR) was defined as the difference between the highest and lowest recorded daily temperature. Intraday TV was defined as the maximum daily diurnal temperature range in a given week (Max-DTR). Inter-day TV was defined as the maximum increase or decrease in daily mean temperature between days t and t-1in a given week; either an increase (Temp-inc) or a decrease (Temp-dec). We used Cox proportional hazards models to estimate TV-related PTB risks during the first trimester, the second trimester, and in late pregnancy. RESULTS: The maximum values for DTR, Temp-inc, and Temp-dec were 17 °C, 8 °C and 11 °C, respectively. The greatest TV-related PTB risk occurred in the second trimester, with 5.8% (95%CI: 3.3%, 8.3%), 23.7% (95%CI: 19.6%, 27.9%), and 4.4% (95%CI: 1.8%, 7.1%) differences per 1 °C increase in Max-DTR, Temp-inc, and Temp-dec, respectively. Greater TV was associated with elevated PTB risk during the warm season. The association between TV and PTB was modified by seasons, maternal education and chronic conditions. CONCLUSIONS: Sharp TV is a likely risk factor for PTB. Policy makers and clinicians should recognize the potential role of TV in the etiology of PTB so that interventions can be designed to protect pregnant women and their fetuses against extreme temperatures.


Assuntos
Nascimento Prematuro , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Segundo Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Fatores de Risco , Estações do Ano , Temperatura
10.
Int J Mol Sci ; 22(2)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477652

RESUMO

V2 proteins encoded by some whitefly-transmitted geminiviruses were reported to be functionally important proteins. However, the functions of the V2 protein of tobacco curly shoot virus (TbCSV), a monopartite begomovirus that causes leaf curl disease on tomato and tobacco in China, remains to be characterized. In our report, an Agrobacterium infiltration-mediated transient expression assay indicated that TbCSV V2 can suppress local and systemic RNA silencing and the deletion analyses demonstrated that the amino acid region 1-92 of V2, including the five predicted α-helices, are required for local RNA silencing suppression. Site-directed substitutions showed that the conserved basic and ring-structured amino acids in TbCSV V2 are critical for its suppressor activity. Potato virus X-mediated heteroexpression of TbCSV V2 in Nicotiana benthamiana induced hypersensitive response-like (HR-like) cell death and systemic necrosis in a manner independent of V2's suppressor activity. Furthermore, TbCSV infectious clone mutant with untranslated V2 protein (TbCSV∆V2) could not induce visual symptoms, and coinfection with betasatellite (TbCSB) could obviously elevate the viral accumulation and symptom development. Interestingly, symptom recovery occurred at 15 days postinoculation (dpi) and onward in TbCSV∆V2/TbCSB-inoculated plants. The presented work contributes to understanding the RNA silencing suppression activity of TbCSV V2 and extends our knowledge of the multifunctional role of begomovirus-encoded V2 proteins during viral infections.


Assuntos
Begomovirus/genética , Potexvirus/genética , Tabaco/virologia , Proteínas Virais/genética , Begomovirus/patogenicidade , China , Lycopersicon esculentum/crescimento & desenvolvimento , Lycopersicon esculentum/virologia , Doenças das Plantas/genética , Doenças das Plantas/virologia , Potexvirus/patogenicidade , Interferência de RNA , Tabaco/crescimento & desenvolvimento , Virulência/genética
11.
Toxicology ; 448: 152633, 2021 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-33220336

RESUMO

Perfluoroheptanoic acid (PFHpA) is a short-chain alternative to long-chain perfluoroalkyl substances, which have been reported to possess reproductive toxicity. However, it is unclear whether PFHpA affects Leydig cell development during puberty. The 35-day-old Sprague Dawley male rats were exposed to PFHpA by gavage with 0 (corn oil), 10, 50, and 100 mg/kg/day for 21 days. PFHpA did not affect the body weight of rats, but it reduced testis weight, relative testis weight, and epididymis weight at 100 mg/kg. It significantly increased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels at a dose of 100 mg/kg without affecting serum estradiol levels. PFHpA suppressed sperm production at a dose of 100 mg/kg. PFHpA induced Leydig cell hyperplasia (increased number of CYP11A1-positive Leydig cells) at a dose of 100 mg/kg, but down-regulated the expression of Cyp11a1, Hsd3b1, and Cyp17a1 in individual Leydig cell pe se and up-regulated the expression of Fshr in the Sertoli cell pe se. PFHpA did not affect the number of HSD11B1 (a biomarker for more mature Leydig cells) positive Leydig cells and SOX9 positive Sertoli cells. PFHpA increased BCL2, and the phosphorylation of AKT1, AKT2, ERK1/2, and JNK, but decreased BAX levels. However, it had no effect on SIRT1 and PGC-1α levels. In conclusion, PFHpA induces Leydig cell hyperplasia due to the increase in the secretion of luteinizing hormone through negative feedback after down-regulating the expression of steroidogenic enzymes and inhibiting testosterone production in individual Leydig cells. This proliferation may be mediated by increasing BCL2 and phosphorylation of AKT, ERK1/2, and JNK, and decreasing BAX level.


Assuntos
Fluorcarbonetos/toxicidade , Ácidos Heptanoicos/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/patologia , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Fatores Etários , Animais , Relação Dose-Resposta a Droga , Hiperplasia/induzido quimicamente , Hiperplasia/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Maturidade Sexual/fisiologia , Espermatogênese/fisiologia
12.
Expert Rev Mol Diagn ; 21(1): 119-129, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33380245

RESUMO

Introduction: With the ongoing SARS-CoV-2 pandemic, different articles have been published highlighting the superiority of droplet digital PCR (ddPCR) over the gold-standard reverse transcription PCR (RT-PCR) in SARS-CoV-2 detection. However, few studies have been reported on developing multiplex ddPCR assays for SARS-CoV-2 detection and their performance. This study shows steps on how to develop different ddPCR SAR-CoV-2 assays including higher order multiplex assays for SARS-CoV-2 detection and antiviral screening.Methods: Using multiple primer/probe sets, we developed, optimized, and analyzed the performance of simplex (1 target), duplex (2 targets), triplex probe mix (3 targets), and quadruplex (4 targets) SARS-CoV-2 ddPCR assays based on a two-color ddPCR detection system.Results: Results showed that the quadruplex assay had similar limits of detection and accuracy to the lower multiplex assays. Analyzing 94 clinical samples demonstrated that the ddPCR triplex probe mix assay had better sensitivity than the RT-qPCR assay. Additionally, the ddPCR multiplex assay showed that remdesivir could inhibit the growth of SARS-CoV-2 in vitro while another testing drug could not.Conclusion: Our research shows that developing multiplex ddPCR assays is possible by combing probe mix and amplitude-based multiplexing, which will help in developing multiplexed ddPCR assays for different SARS-CoV-2 applications.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , SARS-CoV-2/isolamento & purificação , Antivirais/farmacologia , Primers do DNA/genética , Reações Falso-Positivas , Humanos , Limite de Detecção , Pandemias , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Temperatura , Carga Viral/métodos
13.
Mol Genet Genomic Med ; 8(10): e1441, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32783365

RESUMO

BACKGROUND: CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) is a rare autosomal dominant hereditary disease characterized by multiple adnexal skin tumors including cylindromas, spiradenomas, and trichoepitheliomas. More than 100 germline mutations of the cylindromatosis (CYLD) gene have been reported in CCS and most of them are frameshift mutations or small alterations. METHODS: We identified a large, three-generation Chinese family with CCS, which consisted of 18 living family members, including six affected individuals. To explore the molecular biology of this family, we carried out targeted next-generation sequencing and Affymetrix CytoScan HD SNP array to analyze the mutation in the CYLD gene. RESULTS: A novel large deletion mutation, NC_000016.9:g.(50826498_50827517)_(50963389-50967346)del was found in the proband of this family. This deletion results in the loss of a nearly 140 kb fragment of the CYLD gene, spanning exons 17 ~ 20, which represent the coding regions of the ubiquitin-specific protease domain. Further quantitative polymerase chain reaction proved that all patients and two proband-related family members carried this large deletion. CONCLUSIONS: Our study expands the types of mutations in CCS and will undoubtedly provide valuable information for genetic counseling for families affected by the condition.


Assuntos
Enzima Desubiquitinante CYLD/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Cutâneas/genética , Adulto , Enzima Desubiquitinante CYLD/química , Feminino , Deleção de Genes , Heterozigoto , Humanos , Masculino , Síndromes Neoplásicas Hereditárias/patologia , Linhagem , Fenótipo , Domínios Proteicos , Neoplasias Cutâneas/patologia
14.
BMC Infect Dis ; 20(1): 455, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600260

RESUMO

BACKGROUND: Men who have sex with men (MSM) bear a high burden of syphilis infection. Expanding syphilis testing to improve timely diagnosis and treatment is critical to improve syphilis control. However, syphilis testing rates remain low among MSM, particularly in low- and middle-income countries. We describe the protocol for a randomised controlled trial (RCT) to assess whether provision of syphilis self-testing services can increase the uptake of syphilis testing among MSM in China. METHODS: Four hundred forty-four high-risk MSM will be recruited online and randomized in a 1:1:1 ratio to (1) standard syphilis self-testing arm; (2) a self-testing arm program enhanced with crowdsourcing and a lottery-based incentive, and (3) a standard of care (control). Self-testing services include a free syphilis self-test kit through the mail at monthly intervals. Participants in the lottery incentive arm will additionally receive health promotion materials generated from an open crowdsourcing contest and be given a lottery draw with a 10% chance to win 100 RMB (approximately 15 US Dollars) upon confirmed completion of syphilis testing. Syphilis self-test kits have step-by-step instructions and an instructional video. This is a non-blinded, open-label, parallel RCT. Participants in each arm will be followed-up at three and 6 months through WeChat (a social media app like Facebook messenger). Confirmation of syphilis self-test use will be determined by requiring participants to submit a photo of the used test kit to study staff via secure data messaging. Both self-testing and facility-based testing will be ascertained by sending a secure photographic image of the completed kit through an existing digital platform. The primary outcome is the proportion of participants who tested for syphilis in the past 3 months. DISCUSSION: Findings from this study will provide much needed insight on the impact of syphilis self-testing on promoting routine syphilis screening among MSM. The findings will also contribute to our understanding of the safety, effectiveness and acceptability of syphilis self-testing. These findings will have important implications for self-testing policy, both in China and internationally. TRIAL REGISTRATION: ChiCTR1900022409 (10 April, 2019).


Assuntos
Testes Diagnósticos de Rotina/métodos , Promoção da Saúde/métodos , Homossexualidade Masculina , Imunoensaio/métodos , Programas de Rastreamento/métodos , Minorias Sexuais e de Gênero , Sorodiagnóstico da Sífilis/métodos , Sífilis/diagnóstico , Treponema pallidum/imunologia , Sorodiagnóstico da AIDS/métodos , China , Crowdsourcing/métodos , Testes Diagnósticos de Rotina/efeitos adversos , Seguimentos , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/imunologia , HIV-2/imunologia , Humanos , Masculino , Programas de Rastreamento/efeitos adversos , Motivação , Mídias Sociais , Sífilis/microbiologia , Sorodiagnóstico da Sífilis/efeitos adversos
15.
Nucleic Acids Res ; 48(7): 3922-3934, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32055835

RESUMO

In Escherichia coli, the endoribonuclease E (RNase E) can recruit several other ribonucleases and regulatory proteins via its noncatalytic domain to form an RNA degradosome that controls cellular RNA turnover. Similar RNA degradation complexes have been found in other bacteria; however, their compositions are varied among different bacterial species. In cyanobacteria, only the exoribonuclease PNPase was shown to bind to the noncatalytic domain of RNase E. Here, we showed that Alr1240, a member of the RNB family of exoribonucleases, could be co-isolated with RNase E from the lysate of the cyanobacterium Anabaena PCC 7120. Enzymatic analysis revealed that Alr1240 is an exoribonuclease II (RNase II), as it only degrades non-structured single-stranded RNA substrates. In contrast to known RNase E-interacting ribonucleases, which bind to the noncatalytic domain of RNase E, the Anabaena RNase II was shown to associate with the catalytic domain of RNase E. Using a strain in which RNase E and RNase II were tagged in situ with GFP and BFP, respectively, we showed that RNase E and RNase II form a compact complex in vivo by a fluorescence resonance energy transfer (FRET) assay. RNase E activity on several synthetic substrates was boosted in the presence of RNase II, suggesting that the activity of RNase E could be regulated by RNase II-RNase E interaction. To our knowledge, Anabaena RNase II is an unusual ribonuclease that interacts with the catalytic domain of RNase E, and it may represent a new type of RNA degradosome and a novel mechanism for regulating the activity of the RNA degradosome. As Anabaena RNase E interacts with RNase II and PNPase via different regions, it is very likely that the three ribonucleases form a large complex and cooperatively regulate RNA metabolism in the cell.


Assuntos
Anabaena/enzimologia , Endorribonucleases/metabolismo , Exorribonucleases/metabolismo , Sítios de Ligação , Domínio Catalítico , Citoplasma/enzimologia , Endorribonucleases/química , Exorribonucleases/química
16.
JAMA Dermatol ; 156(2): 172-181, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31895418

RESUMO

Importance: Integrated information on the global prevalence and incidence of oral lichen planus (OLP) is lacking. Objective: To examine the global prevalence and incidence of OLP in a systematic review and meta-analysis. Data Sources: A systematic review of population-based studies and clinic-based studies reporting the prevalence and incidence of OLP was performed using 3 electronic medical databases (Cochrane Database of Systematic Reviews, Embase, and MEDLINE) from their inception to March 2019. The search terms included "(lichen planus or LP) and (prevalence or incidence or epidemiology)." No language restriction was applied. Study Selection: Observational descriptive studies investigating the prevalence and incidence of OLP were included. Data Extraction and Synthesis: Data were extracted by continent, sex, and other characteristics. The risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence. Main Outcomes and Measures: The primary outcome was the prevalence (with 95% CIs) of OLP among the overall population and among subgroups. Between-study heterogeneity was assessed using the I2 statistic. Results: Among 46 studies, the overall pooled estimated prevalence of OLP was 0.89% (95% CI, 0.38%-2.05%) among the general population (n = 462 993) and 0.98% (95% CI, 0.67%-1.43%) among clinical patients (n = 191 963). Among the 15 population-based studies, the prevalence of OLP was 0.57% (95% CI, 0.15%-2.18%) in Asia, 1.68% (95% CI, 1.09%-2.58%) in Europe, and 1.39% (95% CI, 0.58%-3.28%) in South America. Among the 31 clinic-based studies, the prevalence was 1.43% (95% CI, 1.12%-1.83%) in Africa, 0.87% (95% CI, 0.61%-1.25%) in Asia, 1.03% (95% CI, 0.51%-2.09%) in Europe, 0.11% (95% CI, 0.07%-0.16%) in North America, and 3.18% (95% CI, 0.97%-9.95%) in South America. The pooled prevalence of OLP by sex was 1.55% (95% CI, 0.83%-2.89%) for women and 1.11% (95% CI, 0.57%-2.14%) for men in the population-based studies and 1.69% (95% CI, 1.05%-2.70%) for women and 1.09% (95% CI, 0.67%-1.77%) for men in the clinic-based studies. In 5 clinic-based studies providing the age distribution of patients with OLP, the prevalence by age was 0.62% (95% CI, 0.33%-1.13%) among patients younger than 40 years and 1.90% (95% CI, 1.16%-3.10%) among patients 40 years and older. Conclusions and Relevance: This study identified the global prevalence and incidence of OLP in terms of its spatial, temporal, and population distribution. The overall estimated pooled prevalence of OLP was 0.89% among the general population and 0.98% among clinical patients. A higher prevalence of OLP was found in non-Asian countries, among women, and among people 40 years and older. The findings should be considered with caution because of the high heterogeneity of the included studies.


Assuntos
Saúde Global , Líquen Plano Bucal/epidemiologia , Fatores Etários , Humanos , Incidência , Líquen Plano Bucal/patologia , Prevalência , Fatores Sexuais
17.
J Cosmet Dermatol ; 19(1): 10-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654468

RESUMO

BACKGROUND: Photodynamic therapy (PDT) has emerged as the effective new method to treat acne vulgaris. However, no meta-analysis has been published on PDT for acne vulgaris currently. OBJECTIVE: The current meta-analysis and systematic review were carried out to assess the safety and effect of PDT on treating acne vulgaris. METHODS: The electronic databases, including EMBASE, Cochrane Library, and MEDLINE, were systemically retrieved to identify relevant articles for meta-analysis. The primary outcome included mean percentage reduction in the inflammatory lesion count (MPRILC), while the secondary outcome included the total effective response (TER). RESULTS: Altogether 13 randomized controlled trials (RCTs) involving 701 subjects had been enrolled into the current meta-analysis. PDT had certain effect on acne vulgaris in terms of the outcomes of MPRILC (MD: 15.97, 95% CI: 11.93 to 20.00, P < .00001) and TER (RR: 1.55, 95% CI: 1.38-1.74, P < .00001). Totally, 6 articles had been evaluated to have a low bias risk overall. Results of sensitivity and subgroup analyses were similar to meta-analysis results, reflecting the result reliability in this meta-analysis. CONCLUSIONS: PDT is beneficial for improving the clinical efficacy of inflammatory acne vulgaris, which can be widely used to treat inflammatory acne vulgaris in clinic.


Assuntos
Acne Vulgar/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Acne Vulgar/imunologia , Humanos , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Reprodutibilidade dos Testes , Resultado do Tratamento
18.
Clin Infect Dis ; 70(10): 2178-2186, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-31260513

RESUMO

BACKGROUND: Syphilis self-testing may help expand syphilis testing among men who have sex with men (MSM). China has rapidly scaled up human immunodeficiency virus (HIV) self-testing, creating an opportunity for integrated syphilis self-testing. However, there is a limited literature on implementing syphilis self-testing. METHODS: A cross-sectional online survey was conducted among Chinese MSM in 2018. Participants completed a survey instrument including sociodemographic characteristics, sexual behaviors, syphilis self-testing, and HIV self-testing history. Multivariable logistic regression was conducted to identify correlates of syphilis self-testing. We also recorded potential harms associated with syphilis self-testing. RESULTS: Six hundred ninety-nine MSM from 89 cities in 21 provinces in China completed the study. A total of 361/699 (51.7%) men tested for syphilis, of whom 174/699 (24.9%) men used syphilis self-testing. Among 174 who had self-tested, 90 (51.7%) reported that the self-test was their first syphilis test and 161 (92.5%) reported that they undertook syphilis self-testing together with HIV self-testing. After adjusting for covariates, syphilis self-testing was correlated with disclosure of sexual orientation to family or friends (adjusted odds ratio [aOR], 1.90; 95% confidence interval [CI], 1.32-2.73), reporting 2-5 male sexual partners (aOR, 1.81; 95% CI, 1.04-3.16), HIV self-testing (aOR, 39.90; 95% CI, 17.00-93.61), and never tested for syphilis in the hospital (aOR, 2.96; 95% CI, 1.86-4.72). Self-reported harms associated with syphilis self-testing were minimal. CONCLUSIONS: Scaling up syphilis self-testing could complement facility-based testing in China among MSM. Self-testing may increase first-time testing and has limited harms. Our findings suggest that syphilis self-testing could be integrated into HIV self-testing services.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Sífilis , China/epidemiologia , Cidades , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Comportamento Sexual , Inquéritos e Questionários , Sífilis/diagnóstico , Sífilis/epidemiologia
19.
Sci Total Environ ; 711: 135050, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31810701

RESUMO

Despite the fact that cold weather has been widely documented as a major factor that can elevate the mortality in a subtropical population due to a lack of adaptability, the disastrous impacts from a major cold event in East Asia caused by a super El Niño event in January 2016 have passed largely unreported. In order to minimize the catastrophic risk from such events given ongoing concerns about climate change, as also noted in the Sendai Framework for Disaster Risk Reduction 2015-2030 (SFDRR), it is important to evaluate the individual- and community-level shifts in mortality patterns during such cold waves, in order to develop health protocols for surveillance and disaster planning. This study evaluated the impacts of the 2016 cold wave on mortality patterns in Hong Kong because this city has been highlighted as a city with severe negative impacts from the disaster by social media. Based on a sensitivity analysis, we found significantly higher daily mortality for up to ten weeks during this cold wave compared to the same calendar days between 2007 and 2015. We also found that the short-term impact of the cold wave was prolonged and fatal, with the potential to increase the mortality across the city for up to five weeks compared to the pre-disaster period. An examination of the individual- and community-level shifts in mortality patterns reveals that the unmarried and economically inactive were most vulnerable during the 2016 cold wave, and respiratory diseases were the greatest medical problems, while age and gender effects as well as cardiovascular diseases did not enhance the fatal effect. The excessive mortality was citywide, and not limited to particular locations or specific characteristics of a community within the city. Based on the results, disaster education as well as social and health services should be provided to all local people for an extended period in order to minimize the fatal and prolonged effects of future cold waves.


Assuntos
Temperatura Baixa , El Niño Oscilação Sul , Cidades , Extremo Oriente , Hong Kong , Mortalidade
20.
Epidemiology ; 30 Suppl 1: S57-S66, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181007

RESUMO

BACKGROUND: This study aimed to assess if air pollutants and meteorological factors synergistically affect birth outcomes in Shenzhen, China. METHODS: A total of 1,206,158 singleton live births between 2005 and 2012 were identified from a birth registry database. Daily average measurements of particulate matter ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ambient air temperature (T), and dew point temperature (Td), a marker of humidity, were collected. Multivariable logistic regression models were used to evaluate associations between air pollution and small for gestational age (SGA), and full-term low birth weight (TLBW). We classified births into those conceived in the warm (May-October) and cold seasons (November-April) and then estimated interactions between air pollutants and meteorological factors. RESULTS: An interquartile range (IQR) increase in PM10 exposure during the first trimester (23.1 µg/m) and NO2 during both the first and second trimesters (15.1 and 13.4 µg/m) was associated with SGA and TLBW risk; odds ratios ranged from 1.01 (95% confidence interval [CI] = 1.00, 1.02) to 1.09 (1.07, 1.12). We observed interactive effects of both air temperature and humidity on PM10 and SGA for newborns conceived in the warm season. Each IQR increase in PM10 (11.1 µg/m) increased SGA risk by 90% (95% CI = 19%, 205%), 29% (23, 34%), 61% (10, 38%), and 26% (21, 32%) when T < 5th percentile, 5th < T < 95th percentile, Td < 5th percentile, and 5th < Td < 95th percentile, respectively. CONCLUSIONS: Our study found evidence of an interactive effect of air temperature and humidity on the relationship between PM10 exposure and SGA among newborns conceived in the warm season (May-October). Relatively low air temperature or humidity exacerbated the effects of PM10.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Peso ao Nascer , Tempo (Meteorologia) , Adulto , Peso ao Nascer/efeitos dos fármacos , China , Feminino , Idade Gestacional , Humanos , Umidade , Recém-Nascido , Masculino , Idade Materna , Dióxido de Nitrogênio/efeitos adversos , Material Particulado/efeitos adversos , Sistema de Registros , Dióxido de Enxofre/efeitos adversos , Temperatura
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