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1.
Orphanet J Rare Dis ; 19(1): 89, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409029

RESUMO

BACKGROUND: Rett syndrome (RTT) and tuberous sclerosis complex (TSC) are two rare disorders presenting with a range of different epileptic seizures. Seizure management requires careful therapy selection, thereby necessitating development of high-quality treatment guidelines. This targeted literature review (TLR) aimed to characterise country-specific and international treatment guidelines available for pharmacological management of seizures in RTT and TSC. METHODS: A TLR was performed between 25-Jan and 11-Mar 2021. Manual searches of online rare disease and guideline databases, and websites of national heath technology assessment bodies were conducted for the following countries: Australia, Canada, France, Germany, Israel, Italy, Japan, Spain, Switzerland, UK, and US as defined by pre-specified eligibility criteria. Search terms were developed for each condition and translated into local languages where appropriate. Eligible publications were defined as guidelines/guidance reporting pharmacological management of seizures in patients with RTT and TSC. Guideline development methodology, geographical focus, author information and treatment recommendations were extracted from guidelines. An author map was generated using R version 3.5.1 to visualise extent of collaboration between authors. RESULTS: 24 total guidelines were included, of which three and six contained only recommendations for RTT and TSC, respectively (some provided recommendations for ≥ 1 condition). Guideline development processes were poorly described (50% [12 guidelines] had unclear/absent literature review methodologies); reported methodologies were variable, including systematic literature reviews (SLRs)/TLRs and varying levels of expert consultation. Most (83% [20/24]) were country-specific, with guideline authors predominantly publishing in contained national groups; four guidelines were classified as 'International,' linking author groups in the US, UK, Italy and France. High levels of heterogeneity were observed in the availability of treatment recommendations across indications, with 13 and 67 recommendations found for RTT and TSC, respectively. For RTT, all treatment recommendations were positive and sodium valproate had the highest number of positive recommendations (Khwaja, Sahin (2011) Curr Opin Pediatr 23(6):633-9). All TSC treatments (21 medications) received either exclusively negative (National Organization for Rare Disorders (2019)) or positive (Chu-Shore et al. (2010) Epilepsia 51(7):1236-41) recommendations; vigabatrin received the highest number of positive recommendations (Kaur, Christodoulou (2019)). CONCLUSIONS: This review highlights the need for the development of international high-quality and comprehensive consensus-based guidance for the management of seizures with pharmacological therapy in RTT and TSC. TRIAL REGISTRATION: Not applicable.


Assuntos
Epilepsia , Síndrome de Rett , Esclerose Tuberosa , Humanos , Síndrome de Rett/tratamento farmacológico , Esclerose Tuberosa/complicações , Esclerose Tuberosa/tratamento farmacológico , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Ácido Valproico/uso terapêutico
2.
Seizure ; 108: 49-52, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37080124

RESUMO

PURPOSE: People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort. METHODS: We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations. RESULTS: There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability. CONCLUSIONS: COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.


Assuntos
COVID-19 , Epilepsia , Deficiência Intelectual , Adulto , Humanos , Feminino , Idoso , Estudos de Coortes , Vacinas contra COVID-19 , Estudos Retrospectivos , País de Gales/epidemiologia , COVID-19/prevenção & controle , Epilepsia/epidemiologia , Vacinação
3.
IDCases ; 27: e01459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242563

RESUMO

Rothia aeria is a gram-positive, pleomorphic bacteria forming part of human oral microflora usually only causing periodontal and dental infections. We describe the case of a 68-year-old immunocompetent male with lumbar vertebral discitis/osteomyelitis caused by R. aeria. A review of the literature demonstrated seventeen cases of non-dental R. aeria infection of which only six were in immunocompetent individuals. This is the first reported case of R. aeria vertebral discitis/osteomyelitis.

4.
Trials ; 22(1): 542, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404454

RESUMO

BACKGROUND: The Sustainable Development Goals (SDGs) highlight the importance of investments in early childhood care and education (ECCE) and youth development. Given Pakistan's large young population, and gender and urban-rural inequalities in access to education, training, and employment, such investments offer opportunities. LEAPS is a youth-led ECCE program that trains female youth, 18-24 years, as Community Youth Leaders (CYLs) to deliver high-quality ECCE for children, 3.5-5.5 years, in rural Sindh, Pakistan. METHODS: We use a stepped wedge cluster-randomized trial to evaluate implementation of LEAPS. Ninety-nine clusters will be randomized to receive the intervention in one of three 7-month steps (33 clusters/step). The primary outcome is children's school readiness (indexed by the total score on the International Development and Early Learning Assessment (IDELA)). Secondary child outcomes are children's IDELA domain scores and executive functions. Data are collected in cross-sectional surveys of 1089 children (11 children/cluster from 99 clusters) aged 4.5-5.5 years at four timepoints (baseline and at the end of each step). Additionally, we will enroll three non-randomized youth participant open cohorts, one per step (33 CYLs: 66 comparison youth per cohort; 99:198 in total). Youth cohorts will be assessed at enrollment and every 7 months thereafter to measure secondary outcomes of youth personal and professional development, depressive symptoms, and executive functions. A non-randomized school cohort of 330 LEAPS students (10 students/cluster from 33 clusters) will also be enrolled and assessed during Step 1 after intervention rollout and at endline. The quality of the learning environment will be assessed in each LEAPS ECCE center and in a comparison center at two timepoints midway following rollout and at endline. A concurrent mixed-methods implementation evaluation will assess program fidelity and quality, and the extent to which a technical support strategy is successful in strengthening systems for program expansion. A cost evaluation will assess cost per beneficiary. Data collection for implementation and cost evaluations will occur in Step 3. DISCUSSION: Youth-led models for ECCE offer a promising approach to support young children and youth. This study will contribute to the evidence as a means to promote sustainable human development across multiple SDG targets. TRIAL REGISTRATION: ClinicalTrials.gov NCT03764436 . Registered on December 5, 2018.


Assuntos
População Rural , Instituições Acadêmicas , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Aprendizagem , Paquistão , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Dev Psychopathol ; 33(2): 634-646, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33762032

RESUMO

Early childhood mental health consultation (ECMHC) has been promoted by the federal government as a promising model for reducing early childhood expulsions and suspensions and is now implemented by numerous states. Despite growing ECMHC proliferation, this study is only the second randomized controlled trial of ECMHC, extending the methodologies of the first to include assessment of effects on random peers. Classrooms were assigned randomly to treatment or waitlist-control condition (n = 51 classrooms, 57 preschool teachers, and 190 preschoolers). Evaluation measures were collected at both pretreatment and posttreatment, following approximately six consultation visits. Classroom and teacher outcomes were evaluated with ordinary least squares regressions, while hierarchical linear modeling was used to evaluate child-level outcomes, accounting for the nested study design. Treatment children (both the target children who prompted the referral for ECMHC and random peers) evidenced significant improvements in social and emotional skills. Promising trend findings were noted for child behavior problem reduction and teacher pedagogical approach and locus of control. No significant effects were found on likelihood of expulsion and classroom mental health climate. This is the first ECMHC to demonstrate effects on nontarget peers in a rigorous randomized controlled trial. Programmatic and methodologic limitations and implications are discussed.


Assuntos
Saúde Mental , Professores Escolares , Criança , Comportamento Infantil , Pré-Escolar , Humanos , Ohio , Encaminhamento e Consulta
6.
Sci Rep ; 9(1): 17057, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745223

RESUMO

Transcranial magnetic stimulation combined with electroencephalography is a powerful tool to probe human cortical excitability. The EEG response to TMS stimulation is altered by drugs active in the brain, with characteristic "fingerprints" obtained for drugs of known mechanisms of action. However, the extraction of specific features related to drug effects is not always straightforward as the complex TMS-EEG induced response profile is multi-dimensional. Analytical approaches can rely on a-priori assumptions within each dimension or on the implementation of cluster-based permutations which do not require preselection of specific limits but may be problematic when several experimental conditions are tested. We here propose an alternative data-driven approach based on PARAFAC tensor decomposition, which provides a parsimonious description of the main profiles underlying the multidimensional data. We validated reliability of PARAFAC on TMS-induced oscillations before extracting the features of two common anti-epileptic drugs (levetiracetam and lamotrigine) in an integrated manner. PARAFAC revealed an effect of both drugs, significantly suppressing oscillations in the alpha range in the occipital region. Further, this effect was stronger under the intake of levetiracetam. This study demonstrates, for the first time, that PARAFAC can easily disentangle the effects of subject, drug condition, frequency, time and space in TMS-induced oscillations.


Assuntos
Anticonvulsivantes/normas , Eletroencefalografia/métodos , Lamotrigina/farmacologia , Levetiracetam/farmacologia , Lobo Occipital/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Algoritmos , Anticonvulsivantes/farmacologia , Ondas Encefálicas/fisiologia , Estudos Cross-Over , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Adulto Jovem
7.
PLoS One ; 13(12): e0208335, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30566498

RESUMO

BACKGROUND: The United Nation's Sustainable Development Goals encompass lifelong learning from birth to youth to adulthood (Goal 4) and economic opportunities for young people (Goal 8). The targets include improving access to quality early childhood care and education (ECCE) as well as learning and training opportunities for adolescents and youth. Cross-generational models for young children and youth may offer opportunities to address the interconnections between goals and targets for the next generation. We investigated whether an ECCE programme for young children (3.5-6.5 years) delivered by female youth (18-24 years) in rural Pakistan would be effective on children's school readiness. METHODS: In partnership with the National Commission for Human Development in Pakistan, we implemented the 'Youth Leaders for Early Childhood Assuring Children are Prepared for School' (LEAPS) programme to train female youth to deliver ECCE. The effectiveness of the LEAPS programme on children's school readiness was evaluated in a cluster-randomised controlled trial. We randomly allocated five clusters (villages) to receive the intervention (n = 170 children) and five clusters to control (n = 170 children). Children's school readiness was assessed after nine months of intervention exposure using the International Development and Early Learning Assessment tool. Analyses was by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT02645162. FINDINGS: At endline, the intervention group had significantly higher school readiness scores (n = 166, mean percentage score 59.4, 95% CI 52.7 to 66.2) compared with the control group (n = 168, mean percentage score 45.5, 95% CI 38.8 to 52.3). The effect size (Cohen's d) was 0.3. CONCLUSION: Trained female youth delivered an ECCE programme that was effective in benefitting young children's school readiness. The cross-generational model is a promising approach to support early child development; however, further evaluation of the model is needed to assess the specific benefits to youth including their skills and economic development.


Assuntos
Desenvolvimento Infantil , Adolescente , Adulto , Criança , Pré-Escolar , Intervenção Educacional Precoce , Feminino , Humanos , Masculino , Paquistão , População Rural/estatística & dados numéricos , Instituições Acadêmicas/estatística & dados numéricos , Adulto Jovem
8.
J Neural Eng ; 15(4): 046024, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29781808

RESUMO

OBJECTIVE: Constant changes in developing children's brains can pose a challenge in EEG dependant technologies. Advancing signal processing methods to identify developmental differences in paediatric populations could help improve function and usability of such technologies. Taking advantage of the multi-dimensional structure of EEG data through tensor analysis may offer a framework for extracting relevant developmental features of paediatric datasets. A proof of concept is demonstrated through identifying latent developmental features in resting-state EEG. APPROACH: Three paediatric datasets ([Formula: see text]) were analyzed using a two-step constrained parallel factor (PARAFAC) tensor decomposition. Subject age was used as a proxy measure of development. Classification used support vector machines (SVM) to test if PARAFAC identified features could predict subject age. The results were cross-validated within each dataset. Classification analysis was complemented by visualization of the high-dimensional feature structures using t-distributed stochastic neighbour embedding (t-SNE) maps. MAIN RESULTS: Development-related features were successfully identified for the developmental conditions of each dataset. SVM classification showed the identified features could accurately predict subject at a significant level above chance for both healthy and impaired populations. t-SNE maps revealed suitable tensor factorization was key in extracting the developmental features. SIGNIFICANCE: The described methods are a promising tool for identifying latent developmental features occurring throughout childhood EEG.


Assuntos
Bases de Dados Factuais , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Aprendizado de Máquina , Processamento de Sinais Assistido por Computador , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia/diagnóstico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
9.
Avian Dis ; 62(1): 94-100, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29620457

RESUMO

The flagellate parasite Histomonas meleagridis causes a severe disease in turkeys. Since nitarsone, the last antiflagellate feed additive, was withdrawn from the market, H. meleagridis has gained increasing clinical and economic importance, and frequently entire turkey flocks are lost to the disease. Even before the antiflagellate market withdrawal, H. meleagridis has been recognized as a noteworthy disease in commercial turkeys. The aim of this study was to compile and analyze data on histomoniasis outbreaks diagnosed by the California Animal Health and Food Safety System in the years 2000 through 2014 while nitarsone was still available. Sixty-two cases were included in the study. In all cases, the parasite was detected by histopathology. Five cases were from breeder flocks, 44 from commercial meat turkey flocks, and 13 from other flocks such as backyard flocks or pet turkeys. There were between one and eight cases each year with no clear trend over time. Most cases occurred in the warmer months between April and October with a clear peak in August. Turkeys in the flocks with the disease were aged between 2 wk and 15 mo, with a median age of 9 wk. In cases for which mortality was reported, daily mortality ranged between 0.04% and 2% with an average of 0.34% and a median of 0.15%. Five-week mortality in infected houses on three infected ranches was between 1.3% and 68%. In 12 cases, the parasite was observed in organs other than ceca and liver. These included spleen, kidney, bursa of Fabricius, proventriculus, lung, pancreas, and crop. In 58 cases, histomoniasis was considered the most significant and primary diagnosis; in four cases histomoniasis was regarded as an incidental finding. In 14 other outbreaks, detailed information was available. In 11 cases, more than one house on the ranch was affected; in five cases the disease spread to all houses. Total mortality in turkeys from affected flocks ranged between 12% and 65%. In eight flocks, the birds were marketed with a weight that was considered too light. In conclusion, the present study shows that even with nitarsone available as antiflagellate feed, additive histomoniasis was a serious disease of turkeys in the United States with an epidemiology similar to that observed in Europe.


Assuntos
Doenças das Aves Domésticas/epidemiologia , Infecções Protozoárias em Animais/epidemiologia , Trichomonadida/isolamento & purificação , Perus , Animais , California/epidemiologia , Feminino , Incidência , Masculino , Doenças das Aves Domésticas/parasitologia , Infecções Protozoárias em Animais/parasitologia , Estudos Retrospectivos
10.
Anaesth Intensive Care ; 46(1): 97-101, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29361262

RESUMO

We describe the successful use of cannula cricothyroidotomy and the Rapid-O2™ oxygen insufflation device (Meditech Systems Ltd, Dorset, UK) for rescue of a can't intubate/can't oxygenate (CICO) scenario in a patient with severe airway haemorrhage post-debridement of laryngeal amyloidosis. This case highlights the practical utility of a cannula technique for CICO rescue when appropriate equipment is used and when institutional measures are taken to prepare for this rare anaesthetic crisis.


Assuntos
Manuseio das Vias Aéreas/métodos , Cânula , Cartilagem Cricoide/cirurgia , Oxigênio/administração & dosagem , Hemorragia Pós-Operatória/complicações , Tireoidectomia/métodos , Manuseio das Vias Aéreas/instrumentação , Humanos , Insuflação/instrumentação , Insuflação/métodos , Masculino , Pessoa de Meia-Idade
11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2017: 3797-3800, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29060725

RESUMO

Brain-computer interfaces (BCI) have the potential to provide non-muscular rehabilitation options for children. However, progressive changes in electrophysiology throughout development may pose a potential barrier in the translation of BCI rehabilitation schemes to children. Tensors and multiway analysis could provide tools which help characterize subtle developmental changes in electroencephalogram (EEG) profiles of children, thus supporting translation of BCI paradigms. Spatial, spectral and subject information of age-matched pediatric subjects in two EEG datasets were used to form 3-dimensional tensors for use in parallel factor analysis (PARAFAC) and direct projection comparison. Within dataset cross-validation results indicate PARAFAC can extract age-sensitive factors which accurately predict subject age in 90% of cases. Cross-dataset validation revealed extracted age-dependent factors correctly identified age in 3 of 4 test subjects. These findings demonstrate that tensor analysis can be applied to characterize the age-specific subtleties in EEG, which provide a means for tracking developmental changes in pediatric rehabilitation BCIs.


Assuntos
Eletroencefalografia , Interfaces Cérebro-Computador , Criança , Análise Fatorial , Humanos
12.
Opt Express ; 25(15): 17695-17700, 2017 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-28789261

RESUMO

We present a fiber-coupled pump-module emitting more than 1kW of mode-stripped power at 976nm from a detachable 225µm, 0.22NA fiber. The electrical-to-optical efficiency at 1kW is ~50%. Six of these pump modules attached to a (6 + 1):1 multimode combiner enable a 5-6kW, single-mode, Yb-doped fiber amplifier.

13.
Sci Rep ; 6: 35854, 2016 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-27775025

RESUMO

Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Idoso , Animais , Biomarcadores Tumorais/genética , Diferenciação Celular/genética , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos SCID , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/cirurgia , Fosfatases cdc25/genética
14.
J Am Acad Child Adolesc Psychiatry ; 55(9): 754-61, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27566116

RESUMO

OBJECTIVE: Despite recent federal recommendations calling for increased funding for early childhood mental health consultation (ECMHC) as a means to decrease preschool expulsions, no randomized-controlled evaluations of this form of intervention have been reported in the scientific literature. This study is the first attempt to isolate the effects of ECMHC for enhancing classroom quality, decreasing teacher-rated behavior problems, and decreasing the likelihood of expulsion in targeted children in early childhood classrooms. METHOD: The sample consisted of 176 target children (3-4 years old) and 88 preschool classrooms and teachers randomly assigned to receive ECMHC through Connecticut's statewide Early Childhood Consultation Partnership (ECCP) or waitlist control treatment. Before randomization, teachers selected 2 target children in each classroom whose behaviors most prompted the request for ECCP. Evaluation measurements were collected before and after treatment, and child behavior and social skills and overall quality of the childcare environment were assessed. Hierarchical linear modeling was used to evaluate the effectiveness of ECCP and to account for the nested structure of the study design. RESULTS: Children who received ECCP had significantly lower ratings of hyperactivity, restlessness, externalizing behaviors, problem behaviors, and total problems compared with children in the control group even after controlling for gender and pretest scores. No effects were found on likelihood of expulsion and quality of childcare environment. CONCLUSION: ECCP resulted in significant decreases across several domains of teacher-rated externalizing and problem behaviors and is a viable and potentially cost-effective means for infusing mental health services into early childhood settings. Clinical and policy implications for ECMHC are discussed.


Assuntos
Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/prevenção & controle , Serviços de Saúde da Criança , Serviços de Saúde Mental , Encaminhamento e Consulta , Pré-Escolar , Feminino , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Professores Escolares , Instituições Acadêmicas
15.
Avian Dis ; 60(2): 437-43, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27309284

RESUMO

In April 2014, poor fertility in a major commercial goose breeder operation in California triggered the submission of six live affected Toulouse ganders ( Anser anser ) to the California Animal Health and Food Safety Laboratory, Turlock branch (University of California-Davis). Toulouse were principally affected among all breeds, and their egg fertility dropped from 65.7% to less than 33.9% in the first 40 days of the 2014 breeding season. The flock consisted of 410 adult birds, 90 males and 320 females, between 2 and 5 yr of age. Inspection of the flock revealed that 44.4% of the Toulouse ganders had severe phallic deformities that prevented them from mating. At postmortem examination, severe yellowish fibrocaseous exudate disrupted the architecture of the phallus and occasionally produced fistulating tracts through the wall of the organ. Microscopically, multifocal lymphoid nodules were noted in the mucosa and submucosa of the phallus and were associated with extensive granulomatous reaction, intralesional bacteria, and spermatozoa. Mycoplasma spp. were isolated from the phallus of affected and nonaffected birds, and PCR protocols targeting the 16S-23S ribosomal RNA intergenic spacer regions and the RNA polymerase beta subunit gene were performed to identify the isolates. Three distinct species were identified on sequencing and analysis using the National Center for Biotechnology Information basic local alignment search tool: Mycoplasma cloacale , Mycoplasma anseris , and an unknown novel Mycoplasma sp. Additionally, Pasteurella multocida , in combination with other bacteria, was also isolated from the phallic lesions and identified as serotype 3 with a DNA profile of 1511 (National Veterinary Service Laboratory). This is the first report of these Mycoplasma spp. and other bacteria associated with reproductive disease in ganders in the United States.


Assuntos
Gansos , Infecções por Mycoplasma/veterinária , Mycoplasma/classificação , Mycoplasma/fisiologia , Doenças das Aves Domésticas/patologia , Animais , Proteínas de Bactérias/genética , California/epidemiologia , RNA Polimerases Dirigidas por DNA/genética , Feminino , Masculino , Mycoplasma/genética , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/patologia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/microbiologia , Prevalência , RNA Bacteriano/genética
16.
J Gen Virol ; 97(8): 1865-1876, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27147296

RESUMO

An effective immune response against hepatitis C virus (HCV) requires the early development of multi-specific class 1 CD8+ and class II CD4+ T-cells together with broad neutralizing antibody responses. We have produced mammalian-cell-derived HCV virus-like particles (VLPs) incorporating core, E1 and E2 of HCV genotype 1a to produce such immune responses. Here we describe the biochemical and morphological characterization of the HCV VLPs and study HCV core-specific T-cell responses to the particles. The E1 and E2 glycoproteins in HCV VLPs formed non-covalent heterodimers and together with core protein assembled into VLPs with a buoyant density of 1.22 to 1.28 g cm-3. The HCV VLPs could be immunoprecipited with anti-ApoE and anti-ApoC. On electron microscopy, the VLPs had a heterogeneous morphology and ranged in size from 40 to 80 nm. The HCV VLPs demonstrated dose-dependent binding to murine-derived dendritic cells and the entry of HCV VLPs into Huh7 cells was blocked by anti-CD81 antibody. Vaccination of BALB/c mice with HCV VLPs purified from iodixanol gradients resulted in the production of neutralizing antibody responses while vaccination of humanized MHC class I transgenic mice resulted in the prodution of HCV core-specific CD8+ T-cell responses. Furthermore, IgG purified from the sera of patients chronically infected with HCV genotypes 1a and 3a blocked the binding and entry of the HCV VLPs into Huh7 cells. These results show that our mammalian-cell-derived HCV VLPs induce humoral and HCV-specific CD8+ T-cell responses and will have important implications for the development of a preventative vaccine for HCV.


Assuntos
Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Linfócitos T/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Animais , Anticorpos Neutralizantes/sangue , Linhagem Celular , Células Cultivadas , Hepacivirus/genética , Hepatócitos/virologia , Humanos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Microscopia Eletrônica , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/isolamento & purificação , Proteínas do Core Viral/genética , Proteínas do Core Viral/imunologia , Proteínas do Core Viral/metabolismo , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/metabolismo , Virossomos/genética , Virossomos/imunologia , Virossomos/metabolismo , Virossomos/ultraestrutura
17.
J Viral Hepat ; 23(9): 730-43, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27167351

RESUMO

In recurrent hepatitis C (HCV) post-liver transplantation (OLT), the combination of immunosuppressants and HCV is postulated to increase hepatocyte apoptosis and liver fibrosis. We evaluated hepatocyte apoptosis within the liver tissue of patients with postOLT HCV recurrence compared to HCV-negative individuals and correlated these findings with the effects of immunosuppressants on HCV-induced cell death and its inhibition in primary mouse hepatocytes (PMoH). Liver biopsies from patients with and without HCV were evaluated by immunohistochemistry for markers of apoptosis M30 CytoDEATH (M30) and cleaved PARP (clPARP). PMoH from C57BL/6 mice were infected with recombinant adenoviruses (rAdHCV) that expressed HCV proteins in hepatocytes. Infected cells were treated with cyclosporine, tacrolimus, sirolimus and/or MMF with or without pan-caspase inhibitor Q-VD-Oph. Cell viability and apoptosis were evaluated using crystal violet assays and Western immunoblots probed for cleaved caspase-3 (clCas3) and clPARP. Both M30 and clPARP were increased in the liver biopsies of patients with postOLT HCV recurrence compared to HCV-negative individuals. Treatment of rAdHCV-infected PMoH with cyclosporine, tacrolimus or sirolimus reduced cell viability and increased clCas3 and clPARP compared to rAdHCV infection alone. Addition of MMF to cyclosporine, tacrolimus or sirolimus further reduced cell viability and increased clCas3 and clPARP. Q-VD-Oph improved cell viability in HCV-infected PMoH treated with immunosuppressants alone and in combination and reduced clCas3 and clPARP by approximately 90%. Immunosuppressive agents, especially in combination, enhanced apoptosis in HCV-infected hepatocytes. The finding that Q-VD-Oph reversed hepatocyte death suggests that treatments utilizing apoptosis inhibition might reduce liver injury in postOLT HCV recurrence.


Assuntos
Apoptose , Hepatite C/patologia , Hepatócitos/fisiologia , Hepatócitos/virologia , Imunossupressores/uso terapêutico , Transplante de Fígado , Animais , Biópsia , Sobrevivência Celular , Células Cultivadas , Humanos , Imuno-Histoquímica , Fígado/patologia , Camundongos Endogâmicos C57BL
18.
J Nutr Health Aging ; 20(4): 391-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26999238

RESUMO

OBJECTIVES: There is a growing demand to reduce ethnic health disparities. The Healthy Habits Program (HHP) was implemented to provide a community-based physical activity and education intervention for Chinese older adults living in Boston, Massachusetts. This study evaluated the HHP by assessing outcomes that are critical for maintaining independence of older persons. DESIGN, SETTING AND PARTICIPANTS: Quantitative evaluation was performed on 50 Chinese older adults enrolled in the HHP. The community members were trained in data collection and management. MEASUREMENTS: Cognition (Mini Mental State Examination (MMSE), Trail Making Test and Complex Walking Task), mobility (Short Physical Performance Battery (SPPB) and maximal gait speed), depressive symptoms (Patient Health Questionnaire-9), perceived disability (World Health Organization Disability Assessment 2.0), nutritional status (Mini Nutrition Assessment®), and strength (grip and leg strength) were assessed at baseline and at 6 months. All tests were translated into Chinese. RESULTS: Of the 50 participants (mean age 68.4 years; 68% female), 78% achieved the goal of performing exercise ≥3 times/week. After 6 months, clinically meaningful improvements were observed in mobility (mean SPPB score changed from 10.3 to 11.1 points; p=0.01) and cognition (mean MMSE score changed from 26.0 to 27.8 points; p=0.001). There were also statistically significant improvements in executive function, depressive symptoms and perceived disability (p<0.05). CONCLUSION: Culturally sensitive community interventions, such as the HHP, are effective for improving mobility and cognition of Chinese older adults. This reveals the potential of promoting successful aging in minority populations through community settings, and should be advocated to reduce ethnic health disparities in the U.S.


Assuntos
Cognição , Exercício Físico/fisiologia , Hábitos , Comportamentos Relacionados com a Saúde , Educação em Saúde , Avaliação de Programas e Projetos de Saúde , Caminhada , Idoso , Envelhecimento , Boston , China/etnologia , Estudos de Coortes , Avaliação da Deficiência , Função Executiva , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Estado Nutricional , Inquéritos e Questionários , Teste de Sequência Alfanumérica , Velocidade de Caminhada
19.
Avian Dis ; 59(3): 447-51, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26478166

RESUMO

Three outbreaks of necrotic enteritis-like disease associated with Clostridium sordelii were diagnosed in commercial broiler chicken flocks with 18,000 to 31,000 birds between 18 and 26 days old. Clinical signs in the affected flocks included high mortality up to 2% a day, depression, and diarrhea. The main gross changes included segmental dilation of the small intestine with watery contents, gas, mucoid exudate, and roughened and uneven mucosa, occasionally covered with a pseudomembrane. Microscopic lesions in the small intestine were characterized by extensive areas of coagulative necrosis of the villi, fibrinous exudate in the lumen, and high numbers of large, Gram-positive rods, occasionally containing subterminal spores, seen in the necrotic tissue and lumen. These rods were identified as C. sordellii by immunohistochemistry. Clostridium sordellii was isolated in an almost pure culture from the intestine of affected birds. A retrospective study of commercial broiler chicken and turkey submissions to the California Animal Health and Food Safety Laboratory System revealed that C. sordellii had been isolated from intestinal lesions in outbreaks of necrotic enteritis-like disease in 8 of 39 cases, 5 times together with Clostridium perfringens and 3 times alone. The latter three cases are reported here.


Assuntos
Galinhas , Infecções por Clostridium/veterinária , Clostridium sordellii/isolamento & purificação , Enterite/veterinária , Doenças das Aves Domésticas/microbiologia , Animais , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Surtos de Doenças/veterinária , Enterite/microbiologia , Enterite/patologia , Doenças das Aves Domésticas/patologia
20.
Avian Dis ; 59(1): 130-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26292546

RESUMO

Ornithobacterium rhinotracheale is a rod-shaped, gram-negative, and mostly oxidase-positive bacterium that causes respiratory infections in chickens and turkeys worldwide and can also spread to nonrespiratory organs. The present report analyzes 294 cases in which O. rhinotracheale was isolated from turkeys or chickens in central California in the years 2000 through 2012. Two hundred sixteen cases were from turkey flocks and 78 from chicken flocks. The median age of turkey flocks was 8.7 wk; the median age of chicken flocks was 6.4 wk. From turkeys, O. rhinotracheale was more often isolated from August to January than during the rest of the year. Chickens cases were more evenly distributed throughout the year. The organs with the highest isolation rate were the infraorbital sinus and trachea, followed by lungs and air sacs. Isolation from other organs was rare. Pure cultures were obtained from relatively more turkey organs than chicken organs. The organ from which there was the highest chance to obtain a pure culture was the air sac. In 108 turkey flocks (50.0%) and 64 chicken flocks (82.1%) at least one other respiratory pathogen was detected. The most common gross lesions were increased mucus in trachea, caseous or fibrinous exudate in the air sacs, consolidated lungs indicating pneumonia, congested and edematous lungs, and a flattened trachea. For most types of lesions, the percentage of affected turkeys was higher than the percentage of affected chickens. The percentage of birds with lesions was higher if other respiratory pathogens were present. Overall, the host species (turkey or chicken) was a more important factor for the prevalence of most lesions than the detection of other respiratory pathogens. The most common histopathologic lesions in the sinus and trachea were heterophilic or mononuclear inflammatory cell infiltration. In the lungs and air sacs, the inflammation was characterized by heterophilic infiltration and/or fibrin accumulation. These results are helpful in selecting the most appropriate samples for isolation of O. rhinotracheale. In addition, they show the incidence of the bacterium in turkeys and chickens and which lesions can be expected after infection with O. rhinotracheale, and they indicate that in some cases O. rhinotracheale can be the primary, or at least the major, pathogen.


Assuntos
Galinhas/microbiologia , Infecções por Flavobacteriaceae/veterinária , Ornithobacterium/isolamento & purificação , Doenças das Aves Domésticas/microbiologia , Perus/microbiologia , Animais , California , Infecções por Flavobacteriaceae/epidemiologia , Infecções por Flavobacteriaceae/microbiologia , Ornithobacterium/classificação , Doenças das Aves Domésticas/epidemiologia , Estudos Retrospectivos
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