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1.
Am J Transplant ; 17(7): 1823-1832, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28497525

RESUMO

New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load <400 copies/mL, and CD4+ count ≥500 cells/µL, the 9-year cumulative incidence of ESRD was higher than that of their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive individuals with no comorbidities and well-controlled disease may be considered low-risk kidney donor candidates.


Assuntos
Rejeição de Enxerto/epidemiologia , Infecções por HIV/complicações , Falência Renal Crônica/epidemiologia , Transplante de Rim/efeitos adversos , Doadores Vivos , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Infecções por HIV/virologia , Soropositividade para HIV , HIV-1/fisiologia , Humanos , Incidência , Falência Renal Crônica/etiologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Nefrectomia , América do Norte/epidemiologia , Prognóstico , Fatores de Risco , Carga Viral
2.
Lancet ; 387(10028): 1619-28, 2016 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-26850983

RESUMO

BACKGROUND: Labour is induced in 20-30% of all pregnancies. In women with an unfavourable cervix, both oral misoprostol and Foley catheter are equally effective compared with dinoprostone in establishing vaginal birth, but each has a better safety profile. We did a trial to directly compare oral misoprostol with Foley catheter alone. METHODS: We did an open-label randomised non-inferiority trial in 29 hospitals in the Netherlands. Women with a term singleton pregnancy in cephalic presentation, an unfavourable cervix, intact membranes, and without a previous caesarean section who were scheduled for induction of labour were randomly allocated to cervical ripening with 50 µg oral misoprostol once every 4 h or to a 30 mL transcervical Foley catheter. The primary outcome was a composite of asphyxia (pH ≤7·05 or 5-min Apgar score <7) or post-partum haemorrhage (≥1000 mL). The non-inferiority margin was 5%. The trial is registered with the Netherlands Trial Register, NTR3466. FINDINGS: Between July, 2012, and October, 2013, we randomly assigned 932 women to oral misoprostol and 927 women to Foley catheter. The composite primary outcome occurred in 113 (12·2%) of 924 participants in the misoprostol group versus 106 (11·5%) of 921 in the Foley catheter group (adjusted relative risk 1·06, 90% CI 0·86-1·31). Caesarean section occurred in 155 (16·8%) women versus 185 (20·1%; relative risk 0·84, 95% CI 0·69-1·02, p=0·067). 27 adverse events were reported in the misoprostol group versus 25 in the Foley catheter group. None were directly related to the study procedure. INTERPRETATION: In women with an unfavourable cervix at term, induction of labour with oral misoprostol and Foley catheter has similar safety and effectiveness. FUNDING: FondsNutsOhra.


Assuntos
Cateterismo/métodos , Trabalho de Parto Induzido/métodos , Misoprostol/administração & dosagem , Ocitócicos/administração & dosagem , Administração Oral , Adulto , Índice de Apgar , Asfixia Neonatal/etiologia , Cateterismo/efeitos adversos , Maturidade Cervical/efeitos dos fármacos , Parto Obstétrico/métodos , Esquema de Medicação , Feminino , Humanos , Recém-Nascido , Trabalho de Parto Induzido/efeitos adversos , Misoprostol/efeitos adversos , Ocitócicos/efeitos adversos , Hemorragia Pós-Parto/etiologia , Gravidez , Nascimento a Termo , Cateterismo Urinário/instrumentação
3.
Lett Appl Microbiol ; 63(6): 412-418, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27577863

RESUMO

As the incidence of multidrug resistance (MDR) Salmonella enterica serotype Typhimurium is increasing, data regarding the antimicrobial interventions and pathogen internalization in marinated meat products are important. This study evaluated the antimicrobial intervention and internalization of Salm. Typhimurium in marinated beef sirloin steaks. Beef bottom sirloin flaps (IMPS #185A; USDA Select) inoculated (108  log10  CFU ml-1 ) with Salm. Typhimurium were sprayed (lactic acid (4%) and buffered vinegar (2%)) prior to vacuum-tumbled marination (0·35% sodium chloride and 0·45% sodium tripolyphosphate) for 30 min. Pathogen presence after antimicrobial spray, vacuum-tumbled marination, and translocation was determined by direct plating on Xylose Lysine Deoxycholate (XLD) agar with tryptic soy agar (TSA) overlay. The data imply varied internalization and antimicrobial susceptibility pattern of Salm. Typhimurium in marinated meat. Lactic acid (4%) spray (P < 0·0001) and buffered vinegar (2%; P < 0·0001) reduced surface populations of Salm. Typhimurium on inoculated beef sirloin flaps prior to vacuum marination. However, lactic acid treated sirloin flaps had greater reductions (~2 log10  CFU cm-2 ) than buffered vinegar when compared with control prior to vacuum marination. However, the translocation of Salm. Typhimurium following vacuum marination was not influenced (P < 0·333) by the application of a surface organic acid spray prior to marination. SIGNIFICANCE AND IMPACT OF THE STUDY: As detailed in the Federal Register FSIS final rule (9 CFR part 317), vacuum-marinated, vacuum-tumbled meat products are not designated as 'mechanically tenderized'. As such, the internalization and potential survival of Salmonella spp. in marinated beef products is a major concern. These results highlight the internalization of pathogens in vacuum-tumbled meat products and emphasize the importance of considering these products as nonintact. Similarly, these data confirm the efficacy and utility of interventions prior to vacuum-tumbled marination. Further research is needed to identify additional strategies to mitigate internalization and translocation of pathogens into vacuum-marinated meat products.


Assuntos
Antibacterianos/farmacologia , Manipulação de Alimentos/métodos , Produtos da Carne/microbiologia , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/isolamento & purificação , Animais , Bovinos , Contagem de Colônia Microbiana , Manipulação de Alimentos/instrumentação , Microbiologia de Alimentos , Salmonella typhimurium/genética
4.
Antimicrob Agents Chemother ; 59(11): 6824-33, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26282425

RESUMO

Limited access to HIV drug resistance testing in low- and middle-income countries impedes clinical decision-making at the individual patient level. An efficient protocol to address this issue must be established to minimize negative therapeutic outcomes for HIV-1-infected individuals in such settings. This is an observational study to ascertain the potential of newer genomic sequencing platforms, such as the Illumina MiSeq instrument, to provide accurate HIV drug resistance genotypes for hundreds of samples simultaneously. Plasma samples were collected from Canadian patients during routine drug resistance testing (n = 759) and from a Ugandan study cohort (n = 349). Amplicons spanning HIV reverse transcriptase codons 90 to 234 were sequenced with both MiSeq sequencing and conventional Sanger sequencing methods. Sequences were evaluated for nucleotide concordance between methods, using coverage and mixture parameters for quality control. Consensus sequences were also analyzed for disparities in the identification of drug resistance mutations. Sanger and MiSeq sequencing was successful for 881 samples (80%) and 892 samples (81%), respectively, with 832 samples having results from both methods. Most failures were for samples with viral loads of <3.0 log10 HIV RNA copies/ml. Overall, 99.3% nucleotide concordance between methods was observed. MiSeq sequencing achieved 97.4% sensitivity and 99.3% specificity in detecting resistance mutations identified by Sanger sequencing. Findings suggest that the Illumina MiSeq platform can yield high-quality data with a high-multiplex "wide" sequencing approach. This strategy can be used for multiple HIV subtypes, demonstrating the potential for widespread individual testing and annual population surveillance in resource-limited settings.


Assuntos
Farmacorresistência Viral/genética , Canadá , Técnicas de Genotipagem , Transcriptase Reversa do HIV/genética , HIV-1/efeitos dos fármacos , HIV-1/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Carga Viral
5.
Br J Dermatol ; 170(4): 832-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24641299

RESUMO

BACKGROUND: Pruritic papular eruption (PPE) of HIV is common in HIV-infected populations living in the tropics. Its aetiology has been attributed to insect bite reactions and it is reported to improve with antiretroviral therapy (ART). Its presence after at least 6 months of ART has been proposed as one of several markers of treatment failure. OBJECTIVES: To determine factors associated with PPE in HIV-infected persons receiving ART. METHODS: A case-control study nested within a 500-person cohort from a teaching hospital in Mbarara, Uganda. Forty-five cases and 90 controls were enrolled. Cases had received ART for ≥ 15 months and had an itchy papular rash for at least 1 month with microscopic correlation by skin biopsy. Each case was individually matched with two controls for age, sex and ART duration. RESULTS: Twenty-five of 45 cases (56%) had microscopic findings consistent with PPE. At skin examination and biopsy (study enrolment), a similar proportion of PPE cases and matched controls had plasma HIV RNA < 400 copies mL(-1) (96% vs. 85%, P = 0·31). The odds of having PPE increased fourfold with every log increase in viral load at ART initiation (P = 0·02) but not at study enrolment. CD4 counts at ART initiation and study enrolment, and CD4 gains and CD8(+) T-cell activation measured 6 and 12 months after ART commencement were not associated with PPE. Study participants who reported daily insect bites had greater odds of being cases [odds ratio (OR) 8·3, P < 0·001] or PPE cases (OR 8·6, P = 0·01). CONCLUSIONS: Pruritic papular eruption in HIV-infected persons receiving ART for ≥ 15 months was associated with greater HIV viraemia at ART commencement, independent of CD4 count. Skin biopsies are important to distinguish between PPE and other itchy papular eruptions.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Prurido/etiologia , Adulto , Mordeduras e Picadas/complicações , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Infecções por HIV/complicações , Humanos , Masculino , RNA Viral/metabolismo , Fatores de Risco , Fatores Socioeconômicos
6.
Acta Obstet Gynecol Scand ; 93(4): 374-81, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24392746

RESUMO

OBJECTIVE: To compare the costs of induction of labor and expectant management in women with preterm prelabor rupture of membranes (PPROM). DESIGN: Economic analysis based on a randomized clinical trial. SETTING: Obstetric departments of eight academic and 52 non-academic hospitals in the Netherlands. POPULATION: Women with PPROM near term who were not in labor 24 h after PPROM. METHODS: A cost-minimization analysis was done from a health care provider perspective, using a bottom-up approach to estimate resource utilization, valued with unit-costs reflecting actual costs. MAIN OUTCOME MEASURES: Primary health outcome was the incidence of neonatal sepsis. Direct medical costs were estimated from start of randomization to hospital discharge of mother and child. RESULTS: Induction of labor did not significantly reduce the probability of neonatal sepsis [2.6% vs. 4.1%, relative risk 0.64 (95% confidence interval 0.25-1.6)]. Mean costs per woman were €8094 for induction and €7340 for expectant management (difference €754; 95% confidence interval -335 to 1802). This difference predominantly originated in the postpartum period, where the mean costs were €5669 for induction vs. €4801 for expectant management. Delivery costs were higher in women allocated to induction than in women allocated to expectant management (€1777 vs. €1153 per woman). Antepartum costs in the expectant management group were higher because of longer antepartum maternal stays in hospital. CONCLUSIONS: In women with pregnancies complicated by PPROM near term, induction of labor does not reduce neonatal sepsis, whereas costs associated with this strategy are probably higher.


Assuntos
Ruptura Prematura de Membranas Fetais/economia , Ruptura Prematura de Membranas Fetais/terapia , Trabalho de Parto Induzido/economia , Conduta Expectante/economia , Adulto , Analgésicos/administração & dosagem , Analgésicos/economia , Controle de Custos , Redução de Custos , Análise Custo-Benefício , Cuidados Críticos/economia , Parto Obstétrico/economia , Feminino , Humanos , Incidência , Recém-Nascido , Terapia Intensiva Neonatal/economia , Trabalho de Parto Induzido/métodos , Tempo de Internação/economia , Monitorização Fisiológica/economia , Países Baixos/epidemiologia , Gravidez , Terceiro Trimestre da Gravidez , Sepse/epidemiologia
7.
Surg Innov ; 20(3): 292-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22918936

RESUMO

INTRODUCTION: In laparoscopy, suboptimal ergonomics frequently lead to morbidity for surgeons. Physical complaints are more commonly reported on the dominant upper extremity. This may be the consequence of challenging laparoscopic tasks being easier to perform with the dominant side. The authors hypothesized that specific training of the nondominant upper extremity may equip this side better and lead to a more equal distribution of physical load. MATERIALS AND METHODS: Participants (medical doctors) were randomized to a 3-week training schedule or no training. The training program consisted of training the nondominant upper extremity. Participants were not allowed to train on a laparoscopic box or virtual reality trainer during the study period. Baseline and outcome measurements after 3 weeks were examined with the use of EMG measurements during a validated task on a laparoscopic box trainer. Muscle strain of the trapezius and deltoid muscles and effective alternation of brachioradial and abductor pollicis brevis muscles were used as outcome variables. RESULTS: In all, 26 participants were included. EMG analysis revealed that participants in both intervention and control groups showed a decrease in muscle strain of trapezius and deltoid muscles. However, there were no significant differences between groups. Those in the intervention group showed significantly better alternation in the brachioradial muscle. CONCLUSION: Training the nondominant upper extremity leads to better alternated use of lower-arm muscles during a validated box trainer task. Repeating the task after 3 weeks led to less muscle tension in the trapezius and deltoid muscles.


Assuntos
Braço/fisiologia , Ergonomia/métodos , Laparoscopia/educação , Laparoscopia/métodos , Médicos , Entorses e Distensões/prevenção & controle , Adulto , Feminino , Escrita Manual , Humanos , Masculino , Pessoa de Meia-Idade , Destreza Motora , Análise e Desempenho de Tarefas
8.
Arch Soc Esp Oftalmol (Engl Ed) ; 98(5): 265-269, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37075840

RESUMO

OBJECTIVE: To apply artificial intelligence (AI) techniques, through deep learning algorithms, for the development and optimization of a system for predicting the age of a person based on a color retinography and to study a possible relationship between the evolution of retinopathy diabetes and premature ageing of the retina. METHODS: A convolutional network was trained to calculate the age of a person based on a retinography. Said training was carried out on a set of retinographies of patients with diabetes previously divided into three subsets (training, validation and test). The difference between the chronological age of the patient and the biological age of the retina was defined as the retinal age gap. RESULTS: A set of 98,400 images was used for the training phase, 1000 images for the validation phase and 13,544 for the test phase. The retinal gap of the patients without DR was 0.609 years and that of the patients with DR was 1905 years (p < 0.001), with the distribution by degree of DR being: mild DR: 1541 years, moderate DR: 3017 years, DR severe: 3117 years and proliferative DR: 8583 years. CONCLUSIONS: The retinal age gap shows a positive mean difference between diabetics with DR versus those without DR, and it increases progressively, according to the degree of DR. These results could indicate the existence of a relationship between the evolution of the disease and premature ageing of the retina.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico por imagem , Inteligência Artificial , Retina/diagnóstico por imagem , Algoritmos , Biomarcadores
9.
Genes Immun ; 13(3): 258-67, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22048453

RESUMO

Heme oxygenase-1 (HO-1) is an anti-inflammatory enzyme that maintains homeostasis during cellular stress. Given previous findings that shorter length variants of a HO-1 promoter region GT(n) microsatellite polymorphism are associated with increased HO-1 expression in cell lines, we hypothesized that shorter variants would also be associated with increased levels of HO-1 expression, less inflammation and lower levels of inflammation-associated viral replication in human immunodeficiency virus (HIV)-infected subjects. Healthy donors (n = 20) with shorter GT(n) repeats had higher HO-1 mRNA transcript in peripheral blood mononuclear cells stimulated with lipopolysaccharide (r = -0.38, P = 0.05). The presence of fewer GT(n) repeats in subjects with untreated HIV disease was associated with higher HO-1 mRNA levels in peripheral blood (r = -0.41, P = 0.02); similar observations were made in CD14(+) monocytes from antiretroviral-treated subjects (r = -0.36, P = 0.04). In African-Americans, but not Caucasians, greater GT(n) repeats were correlated with higher soluble CD14 levels during highly active antiretroviral therapy (r = 0.38, P = 0.007) as well as higher mean viral load off-therapy (r = 0.24, P = 0.04). These data demonstrate that the HO-1 GT(n) microsatellite polymorphism is associated with higher levels of HO-1 expression and that this pathway may have important effects on the association between inflammation and HIV replication.


Assuntos
Negro ou Afro-Americano/genética , Infecções por HIV/genética , Infecções por HIV/imunologia , HIV-1/imunologia , Heme Oxigenase-1/genética , Receptores de Lipopolissacarídeos/sangue , Repetições de Microssatélites , Adulto , Sequência de Bases , Feminino , Expressão Gênica , Infecções por HIV/etnologia , Infecções por HIV/virologia , Humanos , Imunofenotipagem , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Monócitos/imunologia , Monócitos/metabolismo , Polimorfismo Genético , Regiões Promotoras Genéticas , Carga Viral
10.
PLoS Med ; 9(4): e1001208, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22545024

RESUMO

BACKGROUND: At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term. METHODS AND FINDINGS: We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34(+0) and 37(+0) wk of gestation. Participants were randomly allocated in a 1:1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate. From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported. Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM. CONCLUSIONS: In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN29313500


Assuntos
Ruptura Prematura de Membranas Fetais , Doenças do Recém-Nascido/prevenção & controle , Trabalho de Parto Induzido , Trabalho de Parto , Monitorização Fisiológica/métodos , Complicações Infecciosas na Gravidez , Resultado da Gravidez , Adolescente , Adulto , Cesárea , Corioamnionite/prevenção & controle , Feminino , Feto , Idade Gestacional , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Países Baixos , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/prevenção & controle , Sepse , Adulto Jovem
11.
Minim Invasive Ther Allied Technol ; 21(4): 259-64, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21939399

RESUMO

INTRODUCTION: In laparoscopy, the surgeon's dominant arm will execute difficult tasks with less effort compared to the non-dominant arm. This leads to a relative overuse of muscles on this side. We hypothesized that training the non-dominant arm would improve laparoscopic skills. MATERIAL AND METHODS: At baseline, all participants performed three validated tasks on a virtual reality simulator. After randomization, subjects in the intervention group were assigned training tasks. All these tasks had to be performed with the non-dominant hand. Within a week after a three-week study period, participants performed the same three tasks as before. RESULTS: Twenty-six participants were included, 13 in each group. At baseline, there were no differences between groups on all tested parameters. Compliance to training tasks was good. At the end of three weeks, subjects in both groups showed similar improvement of skills on the non-dominant side. On the dominant side, however, subjects in the training group showed significant better improvement of skills on four out of eight parameters. CONCLUSION: Specific training of the non-dominant upper extremity appears to lead to improvement of skills on the dominant side, a phenomenon known in literature as intermanual transfer of skill learning. To improve laparoscopic skills, bimanual training is recommended.


Assuntos
Competência Clínica , Lateralidade Funcional/fisiologia , Laparoscopia Assistida com a Mão/métodos , Análise e Desempenho de Tarefas , Extremidade Superior , Simulação por Computador , Laparoscopia Assistida com a Mão/instrumentação , Humanos , Estatísticas não Paramétricas , Interface Usuário-Computador
12.
Gene Ther ; 18(7): 666-73, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21368900

RESUMO

Therapeutic RNA interference (RNAi) has emerged as a promising approach for the treatment of many incurable diseases, including cancer, infectious disease or neurodegenerative disorders. Demonstration of efficacy and safety in animal models is necessary before planning human application. Our group and others have previously shown the potential of this approach for the dominantly inherited neurological disease DYT1 dystonia by achieving potent short-hairpin RNA (shRNA)-mediated silencing of the disease protein, torsinA, in cultured cells. To establish the feasibility of this approach in vivo, we pursued viral delivery of shRNA in two different mouse models. Surprisingly, intrastriatal injections of adeno-associated virus serotype 2/1 (AAV2/1) vectors expressing different shRNAs, whether targeting torsinA expression or mismatched controls, resulted in significant toxicity with progressive weight loss, motor dysfunction and animal demise. Histological analysis showed shRNA-induced neurodegeneration. Toxicity was not observed in animals that received control AAV2/1 encoding no shRNA, and was independent of genotype, occurring in both DYT1 and wild-type animals. Interestingly, the different genetic background of both mouse models influenced toxicity, being earlier and more severe in 129/SvEv than in C57BL/6 mice. In conclusion, our studies demonstrate that expression of shRNA in the mammalian brain can lead to lethal toxicity. Furthermore, the genetic background of rodents modifies their sensitivity to this form of toxicity, a factor that should be taken into consideration in the design of preclinical therapeutic RNAi trials.


Assuntos
Corpo Estriado/metabolismo , Distonia/terapia , Terapia Genética/métodos , Chaperonas Moleculares/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/toxicidade , Animais , Dependovirus/genética , Distonia/genética , Distonia/mortalidade , Estudos de Viabilidade , Terapia Genética/efeitos adversos , Vetores Genéticos , Camundongos , Camundongos Transgênicos
13.
Adv Dent Res ; 23(1): 76-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21441485

RESUMO

Kaposi sarcoma-associated herpesvirus (KSHV) was discovered in 1994 and is now known to be a necessary but not sufficient causative agent of Kaposi sarcoma. While KSHV is likely also the causative agent of primary effusion lymphoma and multicentric Castleman's disease, its causal role has been refuted in the case of multiple myeloma, sarcoidosis, prostate cancer, and amyotrophic lateral sclerosis. The epidemiology of KSHV is both intriguing and challenging. Two epidemiologic findings are clear, but their explanation is unknown. The first is that KSHV is distributed disparately throughout the world, with the virus being common in the general population throughout Africa and the Middle East, but uncommon virtually everywhere else. The second is that even though the virus is uncommon in the general population in industrialized settings, it is disproportionately concentrated among homosexual men in these areas. KSHV has special importance to the dental profession because saliva is the body fluid that harbors it most commonly, although exactly in which ways saliva spreads the virus are not known.


Assuntos
Herpesvirus Humano 8/patogenicidade , Homossexualidade Masculina , Saliva/virologia , Sarcoma de Kaposi/virologia , África , Hiperplasia do Linfonodo Gigante/virologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Oriente Médio , Comportamento Sexual
14.
Trop Med Int Health ; 15(4): 442-53, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20149165

RESUMO

OBJECTIVES: In sub-Saharan Africa, many viral infections, including Epstein-Barr virus, cytomegalovirus, Kaposi's sarcoma-associated herpesvirus and hepatitis B are acquired in childhood. While saliva is an important transmission conduit for these viruses, little is known about how saliva is passed to African children. We endeavoured to identify the range and determinants of acts by which African children are exposed to saliva. METHODS: To identify the range of acts by which African children are exposed to saliva, we conducted focus groups, semi-structured interviews and participant observations in an urban and a rural community in South Africa. To measure the prevalence and determinants of the identified acts, we administered a questionnaire to a population-based sample of caregivers. RESULTS: We identified 12 caregiving practices that expose a child's oral-respiratory mucosa, cutaneous surfaces or anal-rectal mucosa to saliva. Several acts were heretofore not described in the contemporary literature (e.g., caregiver inserting finger lubricated with saliva into child's rectum to relieve constipation). Among 896 participants in the population-based survey, many of the acts were commonly practised by all respondent types (mothers, fathers, grandmothers and siblings). The most common were premastication of food, sharing sweets and premastication of medicinal plants that are spit onto a child's body. CONCLUSIONS: African children are exposed to saliva through a variety of acts, practised by a variety of caregivers, with no single predominant practice. This diversity poses challenges for epidemiologic work seeking to identify specific saliva-passing practices that transmit viruses. Most acts could be replaced by other actions and are theoretically preventable.


Assuntos
Cuidado da Criança/métodos , Transmissão Vertical de Doenças Infecciosas , Saliva/virologia , Viroses/transmissão , Atividades Cotidianas , Adolescente , Cuidadores , Criança , Pré-Escolar , Infecções por Citomegalovirus/transmissão , Infecções por Vírus Epstein-Barr/transmissão , Feminino , Grupos Focais , Hepatite B/transmissão , Infecções por Herpesviridae/transmissão , Humanos , Lactente , Masculino , População Rural , África do Sul , Inquéritos e Questionários , População Urbana
15.
BMC Pregnancy Childbirth ; 7: 11, 2007 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-17617892

RESUMO

BACKGROUND: Preterm prelabour rupture of the membranes (PPROM) is an important clinical problem and a dilemma for the gynaecologist. On the one hand, awaiting spontaneous labour increases the probability of infectious disease for both mother and child, whereas on the other hand induction of labour leads to preterm birth with an increase in neonatal morbidity (e.g., respiratory distress syndrome (RDS)) and a possible rise in the number of instrumental deliveries. METHODS/DESIGN: We aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management. Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34+0 weeks until 37+0 weeks will be included in a multicentre prospective randomised controlled trial. We will compare early delivery with expectant monitoring. The primary outcome of this study is neonatal sepsis. Secondary outcome measures are maternal morbidity (chorioamnionitis, puerperal sepsis) and neonatal disease, instrumental delivery rate, maternal quality of life, maternal preferences and costs. We anticipate that a reduction of neonatal infection from 7.5% to 2.5% after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity. Under these assumptions, we aim to randomly allocate 520 women to two groups of 260 women each. Analysis will be by intention to treat. Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management. Long term outcomes will be evaluated using modelling. DISCUSSION: This trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis. CONTROLLED CLINICAL TRIAL REGISTER: ISRCTN29313500.


Assuntos
Ruptura Prematura de Membranas Fetais/economia , Ruptura Prematura de Membranas Fetais/terapia , Trabalho de Parto Induzido/métodos , Resultado da Gravidez/economia , Nascimento a Termo , Análise Custo-Benefício , Feminino , Ruptura Prematura de Membranas Fetais/prevenção & controle , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Prematuro/economia , Doenças do Prematuro/prevenção & controle , Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos
16.
J Anim Sci ; 95(10): 4520-4525, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29108068

RESUMO

Liver abscesses are a major economic burden to beef producers. Although a few causative organisms have been cultured from purulent material, the full polymicrobial diversity of liver abscesses has not been reported. The objective of this study was to characterize purulent material collected from liver abscess in beef cattle produced in different production systems in 3 cattle producing states in the United States using 16S rRNA gene sequencing. Differences between purulent material microbial communities among geographic region of feeding and application of a common antimicrobial were also investigated. Cattle included in the study were fed in California (dairy type) and Colorado and Texas (both beef type). Liver abscesses from a cross section of feedlots, geographic areas, and tylosin phosphate-administered groups were collected at harvest; DNA from 34 liver abscess samples was extracted; and the V4 region of the 16S rRNA gene was amplified and sequenced. Sequences were classified into 5 phyla, 13 classes, and 17 orders in the domain Bacteria. The phyla identified included Bacteroidetes (35.2% of reads), Proteobacteria (28.6%), Fusobacteria (18.2%), Firmicutes (12.4%), and Actinobacteria (5.5%). Sequences matching the genera and , which have previously been identified as causative agents in liver abscesses, were both present in the abscess bacterial communities at a relative abundance of 15.1 and 3.2%, respectively, of the overall relative abundance. Furthermore, 3 of the most common phyla were Gram-negative bacteria. An analysis-of-similarities test was conducted on Euclidean distances to assess differences between cattle treated and not treated with tylosin as well as to assess differences between geographic regions. Geographical region and treatment with tylosin did affect the microbiome ( = 0.002 and = 0.026 respectively); however, a more robust sample scheme is needed to explore these differences. To our knowledge, this is the first publication describing the complex community of liver purulent material using next generation sequencing in cattle. These data provide a framework for research on a more targeted approach to liver abscess prevention and treatment.


Assuntos
Bactérias/classificação , Doenças dos Bovinos/prevenção & controle , Abscesso Hepático/veterinária , Microbiota , Animais , Antibacterianos/administração & dosagem , Bactérias/genética , Bactérias/isolamento & purificação , California , Bovinos , Doenças dos Bovinos/microbiologia , Colorado , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Abscesso Hepático/microbiologia , Abscesso Hepático/prevenção & controle , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/veterinária , Texas , Tilosina/administração & dosagem , Estados Unidos
17.
Transl Anim Sci ; 1(3): 320-332, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32704657

RESUMO

The National Beef Quality Audit (NBQA) is conducted every 5 yr and was most recently again conducted in 2016. Face-to-face interviews gauged progress in quality associated with live cattle production using procedures first utilized in NBQA 2011. The 2016 NBQA was the first in which interviews concerning fed steers and heifers were combined with an audit of market cow and bull beef. Face-to-face interviews were designed to illicit definitions for beef quality, estimate willingness to pay (WTP) for quality attributes, establish relative importance rankings for important quality factors, and assess images, strengths, weaknesses, potential threats, and shifting trends in the beef industry since the 2011 audit. Individuals making purchasing decisions in 5 market sectors of the steer/heifer and cow/bull beef supply chain were interviewed, including packers (n = 36), retailers (including large and small supermarket companies and warehouse food sales companies; n = 35), food service operators (including quick-serve, full-service, and institutional establishments; n = 29), further processors (n = 64), and peripherally-related government and trade organizations (GTO; n = 30). Face-to-face interviews were conducted between January and November of 2016 using a designed dynamic routing system. Definitions (as described by interviewees) for 7 pre-determined quality factors, including: (1) How and where the cattle were raised, (2) Lean, fat, and bone, (3) Weight and size, (4) Visual characteristics, (5) Food safety, (6) Eating satisfaction, and (7) Cattle genetics were recorded verbatim and categorized into similar responses for analysis. Compared to NBQA-2011, a higher percentage of companies were willing to pay premiums for guaranteed quality attributes, but overall were willing to pay lower average premiums than the companies interviewed in 2011. Food safety had the highest share of preference among all interviewees, generating a double-digit advantage over any other quality factor. The 2 beef industries have an overall positive image among interviewees, and despite lingering weaknesses, product quality continued to be at the forefront of the strengths category for both steer and heifer beef and market cow and bull beef.

18.
Transl Anim Sci ; 1(2): 229-238, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32704647

RESUMO

The National Beef Quality Audit-2016 (NBQA-2016) was conducted to assess current transportation, mobility, and quality characteristics of U.S. fed steers and heifers. Data were collected at 17 beef processing facilities between March and November 2016. About 8,000 live cattle were evaluated for transportation and mobility, and about 25,000 carcasses were evaluated on the slaughter floor. Cattle were in transit to the slaughter facility for a mean duration of 2.7 h from a mean distance of 218.5 km using trailers with dimensions ranging from 17.84 m2 to 59.09 m2. Area allotted per animal averaged 1.13 m2 and ranged from 0.85 m2 to 2.28 m2. A total of 96.8% of cattle received a mobility score of 1 (walks easily, no apparent lameness). Identification types (35.1% had multiple) were lot visual tags (61.5%), individual tags (55.0%), electronic tags (16.9%), metal-clip tags (9.2%), bar-coded tags (0.05%), wattles (0.01%), and other (2.6%). Cattle were black-hided (57.8%), Holstein (20.4%), red-hided (10.5%), yellow-hided (4.8%), gray-hided (2.9%), brown-hided (1.3%), and white-hided (1.1%). Unbranded hides were observed on 74.3% of cattle; 18.6% had brands located on the butt, 6.3% on the side, and 1.3% on the shoulder (values exceed 100% due to multiple brands). For hide-on carcasses, 37.7% displayed no mud or manure; specific locations for mud or manure were legs (40.8%), belly (33.0%), tail region (15.5%), side (6.8%), and top-line (3.9%). Cattle without horns represented 83.3% of the sample, and cattle that did have horns measured: < 2.54 cm (5.5%), 2.54 to 12.7 cm (8.3%), and > 12.7 cm (2.9%). Carcasses without bruises represented 61.1% of those sampled, whereas 28.2% had 1, 8.2% had 2, 2.1% had 3, and 0.3% had 4 bruises. Of those carcasses with a bruise, the bruise was located on the loin (29.7%), round (27.8%), chuck (16.4%), rib (14.4%), and brisket/plate/flank (11.6%). Frequencies of offal condemnations were livers (30.8%), lungs (18.2%), viscera (16.3%), hearts (11.1%), heads (2.7%), and tongues (2.0%). Compared to NBQA-2011, fewer cattle were identified for traceability, fewer were black-hided, a greater number were Holstein cattle, more with no brand and no horns, fewer without bruises, more liver, lung, and viscera condemnations, and fewer heads and tongues were condemned. The NBQA remains an influential survey for the U.S. beef industry to provide benchmarks and strategic plans for continued improvement of beef quality and consistency.

19.
Transl Anim Sci ; 1(4): 570-584, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32704679

RESUMO

The National Beef Quality Audit-2016 marks the fourth iteration in a series assessing the quality of live beef and dairy cows and bulls and their carcass counterparts. The objective was to determine the incidence of producer-related defects, and report cattle and carcass traits associated with producer management. Conducted from March through December of 2016, trailers (n = 154), live animals (n = 5,470), hide-on carcasses (n = 5,278), and hide-off hot carcasses (n = 5,510) were surveyed in 18 commercial packing facilities throughout the United States. Cattle were allowed 2.3 m2 of trailer space on average during transit indicating some haulers are adhering to industry handling guidelines for trailer space requirements. Of the mixed gender loads arriving at processing facilities, cows and bulls were not segregated on 64.4% of the trailers surveyed. When assessed for mobility, the greatest majority of cattle surveyed were sound. Since the inception of the quality audit series, beef cows have shown substantial improvements in muscle. Today over 90.0% of dairy cows are too light muscled. The mean body condition score for beef animals was 4.7 and for dairy cows and bulls was 2.6 and 3.3, respectively. Dairy cattle were lighter muscled, yet fatter than the dairy cattle surveyed in 2007. Of cattle surveyed, most did not have horns, nor any visible live animal defects. Unbranded hides were observed on 77.3% of cattle. Carcass bruising was seen on 64.1% of cow carcasses and 42.9% of bull carcasses. However, over half of all bruises were identified to only be minor in severity. Nearly all cattle (98.4%) were free of visible injection-site lesions. Current results suggest improvements have been made in cattle and meat quality in the cow and bull sector. Furthermore, the results provide guidance for continued educational and research efforts for improving market cow and bull beef quality.

20.
J Anim Sci ; 95(7): 3003-3011, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28727107

RESUMO

The instrument grading assessment portion of the National Beef Quality Audit (NBQA) - 2016 allows the unique opportunity to evaluate beef carcass traits over the course of a year. One week of instrument grading data was collected each month from 5 beef processing corporations encompassing 18 facilities from January 2016 through December 2016 ( = 4,544,635 carcasses). Mean USDA yield grade (YG) was 3.1 with 1.37 cm fat thickness (FT), 88.9 cm LM area, 393.6 kg HCW, and 2.1% KPH. Frequency distribution of USDA YG was 9.5% YG 1, 34.6% YG 2, 38.8% YG 3, 14.6% YG 4, and 2.5% YG 5. Increases in HCW and FT since the NBQA-2011 were major contributors to differences in mean YG and the (numerically) increased frequency of YG 3, 4, and 5 carcasses found in the current audit. Mean marbling score was Small, and the distribution of USDA quality grades was 4.2% Prime, 71.4% Choice, 21.7% Select, and 2.7% other. Frequency of carcasses grading Prime on Monday (6.43%) was numerically higher than the average frequency of carcasses grading Prime overall (4.2%). Monthly HCW means were 397.6 kg in January, 397.2 kg in February, 396.5 kg in March, 389.3 kg in April, 384.8 kg in May, 385.0 kg in June, 386.1 kg in July, 394.1 kg in August, 399.1 kg in September, 403.9 kg in October, 406.5 kg in November, and 401.9 kg in December. Monthly mean marbling scores were Small in January, Small in February, Small in March, Small in April, Small in May, Small in June, Small in July, Small in August, Small in September, Small in October, Small in November, and Small in December. Both mean HCW and mean marbling score declined in the months of May and June. The month with the greatest numerical frequency of dark cutters was October (0.74%). Comparison of overall data from in-plant carcass and instrument grading assessments revealed close alignment of information, especially for YG (3.1 for in-plant assessment versus 3.1 for instrument grading) and marbling (Small for in-plant assessment versus Small for instrument grading). These findings allow the beef industry access to the greatest volume of beef value-determining characteristics for the U.S. fed steer and heifer population than ever reported, resulting in potentially more precise targeting of future quality and consistency efforts.


Assuntos
Bovinos/fisiologia , Carne Vermelha/normas , Animais , Composição Corporal , Bovinos/crescimento & desenvolvimento , Feminino , Masculino , Inquéritos e Questionários , Estados Unidos
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