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1.
BMC Musculoskelet Disord ; 23(1): 559, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35681162

RESUMO

BACKGROUND: We have developed a model of stratified exercise therapy that distinguishes three knee osteoarthritis (OA) subgroups ('high muscle strength subgroup', 'low muscle strength subgroup', 'obesity subgroup'), which are provided subgroup-specific exercise therapy (supplemented by a dietary intervention for the 'obesity subgroup'). In a large clinical trial, this intervention was found to be no more effective than usual exercise therapy. The present qualitative study aimed to explore experiences from users of this intervention, in order to identify possible improvements. METHODS: Qualitative research design embedded within a cluster randomized controlled trial in a primary care setting. A random sample from the experimental arm (i.e., 15 patients, 11 physiotherapists and 5 dieticians) was interviewed on their experiences with receiving or applying the intervention. Qualitative data from these semi-structured interviews were thematically analysed. RESULTS: We identified four themes: one theme regarding the positive experiences with the intervention and three themes regarding perceived barriers. Although users from all 3 perspectives (patients, physiotherapists and dieticians) generally perceived the intervention as having added value, we also identified several barriers, especially for the 'obesity subgroup'. In this 'obesity subgroup', physiotherapists perceived obesity as difficult to address, dieticians reported that more consultations are needed to reach sustainable weight loss and both physiotherapists and dieticians reported a lack of interprofessional collaboration. In the 'high muscle strength subgroup', the low number of supervised sessions was perceived as a barrier by some patients and physiotherapists, but as a facilitator by others. A final theme addressed barriers to knee OA treatment in general, with lack of motivation as the most prominent of these. CONCLUSION: Our qualitative study revealed a number of barriers to effective application of the stratified exercise therapy, especially for the 'obesity subgroup'. Based on these barriers, the intervention and its implementation could possibly be improved. Moreover, these barriers are likely to account at least partly for the lack of superiority over usual exercise therapy. TRIAL REGISTRATION: The Netherlands National Trial Register (NTR): NL7463 (date of registration: 8 January 2019).


Assuntos
Osteoartrite do Joelho , Fisioterapeutas , Terapia por Exercício , Humanos , Obesidade/terapia , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/terapia , Pesquisa Qualitativa
2.
Rev Med Liege ; 76(3): 145-151, 2021 Mar.
Artigo em Francês | MEDLINE | ID: mdl-33682381

RESUMO

Tracheomalacia (TM) is characterized by tracheal collapse due to an intrinsic anomaly resulting in a lack of rigidity of the cartilaginous rings and/or the posterior membrane during expiration, coughing or crying. It may also be secondary to external compression or acquired during endobronchial diseases. TM is commonly associated with other syndromes or airway abnormalities. Tracheomalacia can be localized or diffused and if the main bronchi are involved, the term of tracheobronchomalacia (TBM) is used. The most common symptoms include expiratory stridor, barking cough and recurrent respiratory tract infections. If tracheal weakness is severe, Acute Life Threating Events (ALTE) or Brief Resolved Unexplained Event (BRUE) can occur. While mild forms usually do not require any treatment, severe TBM may require medical and/or surgical management. Amongst several possible treatments, including tracheostomy, noninvasive ventilation and airway stenting, the pexy surgical approach (posterior, anterior tracheopexy or aortopexy) is currently the favoured option.


La trachéomalacie (TM) est caractérisée par un collapsus trachéal plus ou moins important durant l'expiration, lors des efforts de toux ou des pleurs. Elle peut être due à une anomalie intrinsèque, par manque de rigidité des anneaux cartilagineux et/ou de la membrane postérieure. Elle peut aussi avoir une origine extrinsèque, soit secondaire à une compression externe, soit acquise dans le cadre de pathologies endo-bronchiques. Elle peut enfin être associée à certains syndromes ou malformations des voies respiratoires. La TM peut être localisée ou généralisée, et si les bronches principales sont atteintes, on parlera de trachéobronchomalacie (TBM). Les symptômes les plus courants sont : un stridor expiratoire, une toux aboyante, et des infections respiratoires récurrentes. Dans les cas les plus sévères, des événements menaçant la vie de l'enfant (Acute Life-Threatening Event «ALTE¼ ou Brief Resolved Unexplained Event «BRUE¼) peuvent survenir. Alors que les formes légères ne requièrent généralement pas de traitement, la TBM sévère peut nécessiter une prise en charge médicale et/ou chirurgicale. Parmi les divers choix thérapeutiques, incluant notamment la trachéostomie, la ventilation non invasive et les stents trachéaux, l'approche chirurgicale par pexie (aortopexie, trachéopexie postérieure ou antérieure) est actuellement l'option favorite.


Assuntos
Traqueobroncomalácia , Traqueomalácia , Brônquios , Criança , Tosse , Humanos , Traqueia , Traqueobroncomalácia/diagnóstico , Traqueobroncomalácia/terapia , Traqueomalácia/diagnóstico , Traqueomalácia/terapia
3.
J Cancer Educ ; 31(1): 187-90, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26561426

RESUMO

Cervical cancer risk is increased among women living with HIV (WLH). Human papillomavirus (HPV) vaccination has been shown to be safe and immunogenic among WLH. We examined HPV vaccine awareness and HPV knowledge among WLH. This cross-sectional study collected data from 145 WLH between March 2011 and April 2012. An interviewer-administered survey assessed HPV vaccine awareness and knowledge. Stata/IC 13 was used to perform chi-square tests and multivariate logistic regression analyses. Our sample was 90 % non-Hispanic black and 64 % earned <$10,000/year. Few (38 %) had heard of the HPV vaccine. Half (50 %) knew that HPV caused cervical cancer. HPV vaccine awareness was ten times higher among WLH who knew HPV caused cervical cancer (OR = 10.17; 95 % CI 3.82-27.06). HPV vaccine awareness is low among WLH. Cancer prevention efforts aimed at raising awareness about the HPV vaccine and increasing knowledge about HPV are necessary first steps in reducing cervical cancer disparities among WLH.


Assuntos
Infecções por HIV/complicações , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Estudos Transversais , Feminino , Seguimentos , HIV/patogenicidade , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/psicologia , Infecções por Papillomavirus/virologia , Prognóstico , Neoplasias do Colo do Útero/psicologia , Neoplasias do Colo do Útero/virologia
4.
Mol Psychiatry ; 19(6): 724-32, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23999524

RESUMO

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.


Assuntos
Anorexia Nervosa/genética , Epóxido Hidrolases/genética , Variação Genética , Adulto , Anorexia Nervosa/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Colesterol/metabolismo , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Psicometria , População Branca/genética , Adulto Jovem
5.
Anim Genet ; 46(2): 122-32, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25643727

RESUMO

Mycobacterium avium subspecies paratuberculosis (MAP) is a pathogenic bacterium responsible for the lethal Johne's disease in cattle. So far, several genome-wide association studies (GWAS) have been carried out to identify chromosomal regions highly associated with Johne's disease. The aim of this study was to investigate the genetic variability within a pool of seven genes (LAMB1, DLD, WNT2, PRDM1, SOCS5, PTGER4 and IL10) indicated by former GWAS/RNA-Seq studies as putatively associated with MAP infections and to achieve a confirmation study of association with paratuberculosis susceptibility in a population of 324 German Holstein cattle (162 cases MAP positive and 162 controls MAP negative) using ELISA and fecal cultural tests. SNP validation and genotyping information are provided, quick methods for allelic discrimination were set up and transcription factor binding analyses were performed. The rs43390642:G>TSNP in the WNT2 promoter region is associated with paratuberculosis susceptibility (P = 0.013), suggesting a protective role of the T allele (P = 0.043; odds ratio 0.50 [0.25-0.97]). The linkage disequilibrium with the DLD rs134692583:A>T might suggest a combined mechanism of action of these neighboring genes in resistance to MAP infection, which is also supported by a significant effect shown by the haplotype DLD(T) /WNT2(T) (P = 0.047). In silico analysis predicted rs43390642:G>T and rs134692583:A>T as essential parts of binding sites for the transcription factors GR, C/EBPß and GATA-1, hence suggesting a potential influence on WNT2 and DLD gene expression. This study confirmed the region on BTA 4 (UMD 3.1: 50639460-51397892) as involved in tolerance/resistance to Johne's disease. In addition, this study clarifies the involvement of the investigated genes in MAP infection and contributes to the understanding of genetic variability involved in Johne's disease susceptibility.


Assuntos
Formação de Anticorpos , Doenças dos Bovinos/genética , Bovinos/genética , Paratuberculose/genética , Animais , Sítios de Ligação/genética , Bovinos/microbiologia , Doenças dos Bovinos/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Mycobacterium avium subsp. paratuberculosis , Paratuberculose/imunologia , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/metabolismo
6.
Anim Genet ; 45(1): 114-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24320212

RESUMO

The aim of the study was the analysis of the nucleotide-binding oligomerization domain containing 2 (NOD2, formerly CARD15) as a candidate gene for Mycobacterium avium ssp. paratuberculosis infection in cattle. Eleven SNPs in the NOD2 gene were identified, and finally, four SNPs were included in a case-control study using 324 German Holstein cows tested for paratuberculosis using fecal culture and ELISA. The SNP (GenBank) AY518738S04:g.521G>A in exon 4 showed a significant association between the fecal culture status of the animals and NOD2 allele variants. The other three SNPs showed no associations in German Holstein cows.


Assuntos
Doenças dos Bovinos/genética , Bovinos/genética , Proteína Adaptadora de Sinalização NOD2/genética , Paratuberculose/genética , Polimorfismo de Nucleotídeo Único , Animais , Estudos de Casos e Controles , Doenças dos Bovinos/microbiologia , Feminino , Frequência do Gene , Haplótipos , Desequilíbrio de Ligação , Dados de Sequência Molecular , Mycobacterium avium subsp. paratuberculosis
7.
Front Public Health ; 12: 1321173, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500722

RESUMO

Background: The COVID-19 pandemic has convoluted hesitancy toward vaccines, including the seasonal influenza (flu) vaccine. Because of COVID-19, the flu season has become more complicated; therefore, it is important to understand all the factors influencing the uptake of these vaccines to inform intervention targets. This article assesses factors related to the uptake of influenza and COVID-19 vaccines among adults in Tennessee. Methods: A cross-sectional, secondary data analysis of 1,400 adults was conducted in Tennessee. The adult sample came from two data sources: Data source 1 completed a baseline survey from January to March 2022, and data source 2 was completed from May to August 2022. Data on vaccine attitudes, facilitators and barriers, and communication needs were collected via random digit dial by Scientific Telephone Samples (STS). Two multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to predict sociodemographic and overall vaccine-related factors associated with receipt or non-receipt (referent) of COVID-19 and influenza vaccines. Results: Approximately 78% of the adult sample had received the COVID-19 vaccination. A significant positive association for COVID-19 vaccine uptake was seen among those who were older (aged 50-65) (aOR = 1.9; 95% CI: 1.2-3.2), Black (aOR = 2.0; 95% CI:1.3-2.8), and had a college education and higher (aOR = 2.3; 95% CI: 1.5-3.6). However, there was a significant negative association for persons reporting they were extremely religious (aOR = 0.5; 95% CI:0.3-0.9). Over 56% of the adult sample had received the influenza vaccination this season. Those who had a higher annual household income ($80,000+) (aOR = 1.9; 95% CI: 1.3-2.6) and had health insurance (aOR = 2.6; 95% CI: 1.4-4.8) had a significant positive association with influenza vaccine receipt. However, those who were employed part-time or were unemployed had a significant negative association for influenza vaccine receipt (aOR = 0.7; 95% CI: 0.5-0.9). Both COVID-19 and influenza vaccine receipt had strongly significant positive trends with increasing belief in effectiveness and trust (p < 0.0001) and strongly significant negative trends with higher levels of overall vaccine hesitancy (p < 0.0001). Conclusion: Strategies to increase COVID-19 and influenza vaccination should be age-specific, focus on increasing geographical and financial access, and offer tailored messages to address concerns about these vaccines.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Adulto , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Vacinas contra COVID-19 , Estações do Ano , Tennessee/epidemiologia , Estudos Transversais , Pandemias , Cobertura Vacinal , COVID-19/epidemiologia , COVID-19/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Vacinação
8.
Environ Microbiol ; 15(11): 3077-86, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23682956

RESUMO

Biological oxidation of methane to methanol by aerobic bacteria is catalysed by two different enzymes, the cytoplasmic or soluble methane monooxygenase (sMMO) and the membrane-bound or particulate methane monooxygenase (pMMO). Expression of MMOs is controlled by a 'copper-switch', i.e. sMMO is only expressed at very low copper : biomass ratios, while pMMO expression increases as this ratio increases. Methanotrophs synthesize a chalkophore, methanobactin, for the binding and import of copper. Previous work suggested that methanobactin was formed from a polypeptide precursor. Here we report that deletion of the gene suspected to encode for this precursor, mbnA, in Methylosinus trichosporium OB3b, abolishes methanobactin production. Further, gene expression assays indicate that methanobactin, together with another polypeptide of previously unknown function, MmoD, play key roles in regulating expression of MMOs. Based on these data, we propose a general model explaining how expression of the MMO operons is regulated by copper, methanobactin and MmoD. The basis of the 'copper-switch' is MmoD, and methanobactin amplifies the magnitude of the switch. Bioinformatic analysis of bacterial genomes indicates that the production of methanobactin-like compounds is not confined to methanotrophs, suggesting that its use as a metal-binding agent and/or role in gene regulation may be widespread in nature.


Assuntos
Cobre/metabolismo , Imidazóis/metabolismo , Methylosinus trichosporium/genética , Oligopeptídeos/metabolismo , Oxigenases/genética , Oxigenases/metabolismo , Transporte Biológico , Deleção de Genes , Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Metano/metabolismo , Metanol/metabolismo , Methylosinus trichosporium/metabolismo , Oligopeptídeos/biossíntese , Óperon , Oxirredução , Oxigenases/biossíntese
9.
Appl Environ Microbiol ; 79(19): 5918-26, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23872554

RESUMO

Many methanotrophs have been shown to synthesize methanobactin, a novel biogenic copper-chelating agent or chalkophore. Methanobactin binds copper via two heterocyclic rings with associated enethiol groups. The structure of methanobactin suggests that it can bind other metals, including mercury. Here we report that methanobactin from Methylosinus trichosporium OB3b does indeed bind mercury when added as HgCl2 and, in doing so, reduced toxicity associated with Hg(II) for both Alphaproteobacteria methanotrophs, including M. trichosporium OB3b, M. trichosporium OB3b ΔmbnA (a mutant defective in methanobactin production), and Methylocystis sp. strain SB2, and a Gammaproteobacteria methanotroph, Methylomicrobium album BG8. Mercury binding by methanobactin was evident in both the presence and absence of copper, despite the fact that methanobactin had a much higher affinity for copper due to the rapid and irreversible binding of mercury by methanobactin. The formation of a gray precipitate suggested that Hg(II), after being bound by methanobactin, was reduced to Hg(0) but was not volatilized. Rather, mercury remained associated with methanobactin and was also found associated with methanotrophic biomass. It thus appears that although the mercury-methanobactin complex was cell associated, mercury was not removed from methanobactin. The amount of biomass-associated mercury in the presence of methanobactin from M. trichosporium OB3b was greatest for M. trichosporium wild-type strain OB3b and the ΔmbnA mutant and least for M. album BG8, suggesting that methanotrophs may have selective methanobactin uptake systems that may be based on TonB-dependent transporters but that such uptake systems exhibit a degree of infidelity.


Assuntos
Imidazóis/metabolismo , Cloreto de Mercúrio/metabolismo , Cloreto de Mercúrio/toxicidade , Methylosinus trichosporium/efeitos dos fármacos , Methylosinus trichosporium/metabolismo , Oligopeptídeos/metabolismo , Alphaproteobacteria/efeitos dos fármacos , Inativação Metabólica , Methylococcaceae/efeitos dos fármacos , Methylocystaceae/efeitos dos fármacos , Oxirredução
10.
Vaccine ; 41(25): 3772-3781, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37198022

RESUMO

BACKGROUND: In the United States (US), half of new human papillomavirus (HPV) infections occur among young people aged 15-24 years. Despite the effectiveness of HPV vaccination in protecting against HPV-associated cancers, its coverage among adolescents remains suboptimal. This study examined the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage in five US states with disproportionately low adolescent coverage rates compared to the national average. METHODS: Responses to an online Qualtrics survey from 926 parents of children aged 9-17 years in Arkansas, Mississippi, Missouri, Tennessee, and Southern Illinois in July 2021 were analyzed using multivariate logistic regression to estimate the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage. RESULTS: Of the parents, 78 % were female, 76 % were non-Hispanic White, 61.9 % lived in rural areas, 22 % were classified as HPV vaccine hesitant, and 42 % had vaccinated their oldest child between the ages of 9-17 years against HPV. Children of vaccine hesitant parents were less likely to have received any doses of the HPV vaccine than children of non-vaccine hesitant parents (AOR: 0.17, 95 % CI:0.11-0.27). Male children were less likely to have initiated the HPV vaccine series than female children (AOR: 0.70, 95 % CI:0.50-0.97). Older children (13-17 vs 9-12 years), receiving the meningococcal conjugate or most recent seasonal influenza vaccine were all associated with higher likelihoods of receiving any doses of the HPV vaccine (AOR: 6.01, 95 % CI:3.98-9.08; AOR: 2.24, 95 % CI:1.27-3.95; AOR: 2.41, 95 % CI:1.73-3.36, respectively). CONCLUSIONS: Adolescent HPV vaccination coverage remains low in our targeted states. Children's age, sex, and parental vaccine hesitancy were significantly associated with likelihood of HPV vaccination. These findings offer the opportunity for targeted interventions among parents in regions with low vaccine uptake and underscore the importance of developing and implementing strategies to address parental HPV vaccination hesitancy to improve uptake in the US.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Criança , Estados Unidos , Humanos , Masculino , Feminino , Hesitação Vacinal , Cobertura Vacinal , Infecções por Papillomavirus/prevenção & controle , Vacinação , Pais , Arkansas , Conhecimentos, Atitudes e Prática em Saúde
11.
J Dairy Sci ; 95(5): 2734-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22541503

RESUMO

The objective of this study was to estimate genetic manifestation of Mycobacterium avium ssp. paratuberculosis (MAP) infection in German Holstein cows. Incorporated into this study were 11,285 German Holstein herd book cows classified as MAP-positive and MAP-negative animals using fecal culture results and originating from 15 farms in Thuringia, Germany involved in a paratuberculosis voluntary control program from 2008 to 2009. The frequency of MAP-positive animals per farm ranged from 2.7 to 67.6%. The fixed effects of farm and lactation number had a highly significant effect on MAP status. An increase in the frequency of positive animals from the first to the third lactation could be observed. Threshold animal and sire models with sire relationship were used as statistical models to estimate genetic parameters. Heritability estimates of fecal culture varied from 0.157 to 0.228. To analyze the effect of prevalence on genetic parameter estimates, the total data set was divided into 2 subsets of data into farms with prevalence rates below 10% and those above 10%. The data set with prevalence above 10% show higher heritability estimates in both models compared with the data set with prevalence below 10%. For all data sets, the sire model shows higher heritabilities than the equivalent animal model. This study demonstrates that genetic variation exists in dairy cattle for paratuberculosis infection susceptibility and furthermore, leads to the conclusion that MAP detection by fecal culture shows a higher genetic background than ELISA test results. In conclusion, fecal culture seems to be a better trait to control the disease, as well as an appropriate feature for further genomic analyses to detect MAP-associated chromosome regions.


Assuntos
Doenças dos Bovinos/genética , Mycobacterium avium subsp. paratuberculosis , Paratuberculose/genética , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/microbiologia , Fezes/microbiologia , Feminino , Predisposição Genética para Doença/genética , Alemanha/epidemiologia , Masculino , Paratuberculose/epidemiologia , Prevalência
12.
J Anim Breed Genet ; 127(5): 411-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20831566

RESUMO

Husbandry of beef cattle requires animals that do not behave aggressively or timidly. The enzyme monoamine oxidase A and the coding gene (MAOA) play an important role in the complex regulation of behaviour. The complete coding region and a part of the non-coding sequence of the bovine MAOA gene have been analysed in 20 German Angus and 20 German Simmental bulls and cows with the aim of detecting genetic variability. These two cattle breeds are known to differ regarding their behaviour during handling. Five single nucleotide polymorphisms (SNPs) were identified, three of which were found in the coding region of the gene (exons III and XV). One of the SNPs located in exon XV (NC_007331.3:g.80340C>T) was found to be a non-synonymous mutation. The minor allele frequency of this resulting amino acid substitution was significantly different between 543 German Angus and 417 German Simmental calves (0.39 and 0.49, respectively). The potential functional impact of this polymorphism has been tested by in silico analysis, as well as by association analysis using behaviour scores of the genotyped calves for three behaviour tests that assessed the animals' temperament during tethering, weighing or social separation. In silico analysis did not deliver consistent results arguing for or against a functional impact of the studied amino acid substitution on the function of the biological protein. No significant association was found between this MAOA polymorphism and the behaviour-related scores analysed in the study.


Assuntos
Bovinos/genética , Monoaminoxidase/genética , Polimorfismo de Nucleotídeo Único , Criação de Animais Domésticos , Animais , Comportamento Animal , Bovinos/fisiologia , Feminino , Frequência do Gene , Masculino , Fenótipo , Análise de Sequência de DNA
13.
Eat Weight Disord ; 15(3): e186-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21150253

RESUMO

We assessed the relation between season of birth and eating disorder symptoms and personality characteristics in a sample of 880 women with eating disorders and 580 controls from two Price Foundation Studies. Eating disorder symptoms were assessed using the Structured Interview of Anorexic and Bulimic Disorders and the Structured Clinical Interview for DSM-IV. Personality traits were assessed using the Temperament and Character Inventory and the Frost Multidimensional Perfectionism Scale. Date of birth was obtained from a sociodemographic questionnaire. No significant differences were observed 1) in season of birth across eating disorder subtypes and controls; nor 2) for any clinical or personality variables and season of birth. We found no evidence of season of birth variation in eating disorders symptoms or personality traits. Contributing to previous conflicting findings, the present results do not support a season of birth hypothesis for eating disorders.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Personalidade , Adolescente , Adulto , Fatores Etários , Idoso , Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Parto , Estações do Ano , Inquéritos e Questionários , Adulto Jovem
14.
Sci Adv ; 6(5): eaay4458, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32064351

RESUMO

In cancer, the programmed death-1 (PD-1) pathway suppresses T cell stimulation and mediates immune escape. Upon stimulation, PD-1 becomes phosphorylated at its immune receptor tyrosine-based inhibitory motif (ITIM) and immune receptor tyrosine-based switch motif (ITSM), which then bind the Src homology 2 (SH2) domains of SH2-containing phosphatase 2 (SHP2), initiating T cell inactivation. The SHP2-PD-1 complex structure and the exact functions of the two SH2 domains and phosphorylated motifs remain unknown. Here, we explain the structural basis and provide functional evidence for the mechanism of PD-1-mediated SHP2 activation. We demonstrate that full activation is obtained only upon phosphorylation of both ITIM and ITSM: ITSM binds C-SH2 with strong affinity, recruiting SHP2 to PD-1, while ITIM binds N-SH2, displacing it from the catalytic pocket and activating SHP2. This binding event requires the formation of a new inter-domain interface, offering opportunities for the development of novel immunotherapeutic approaches.


Assuntos
Complexos Multiproteicos , Receptor de Morte Celular Programada 1 , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Linhagem Celular , Ativação Enzimática , Humanos , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Receptor de Morte Celular Programada 1/química , Receptor de Morte Celular Programada 1/metabolismo , Domínios Proteicos , Proteína Tirosina Fosfatase não Receptora Tipo 11/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo
15.
J Med Genet ; 45(5): 298-302, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18234730

RESUMO

BACKGROUND: Germ-line mutations in CYLD are found in patients with familial skin appendage tumours. The protein product functions as a deubiquitinase enzyme, which negatively regulates NF-kappaB and c-Jun N-terminal kinase signalling. Brooke-Spiegler syndrome (BSS) is characterised by cylindromas, trichoepitheliomas and spiradenomas, whereas in familial cylindromatosis (FC) patients present with cylindromas and in multiple familial trichoepitheliomas (MFT) with trichoepitheliomas as the only skin tumour type. Although described as distinct entities, recent studies suggest that they are within the spectrum of a single entity. OBJECTIVE: To investigate the mutation spectrum of CYLD and possible genotype-phenotype correlations. METHODS: 25 families including 13 BSS, 3 FC, and 9 MFT families were examined and evaluated for mutations in the CYLD gene. RESULTS: In total, 18 mutations in CYLD, including 6 novel mutations, were identified in 25 probands (72%). The mutation frequencies among distinct phenotypes were 85% for BSS, 100% for FC, and 44% for MFT. The majority of the mutations were insertions, deletions or nonsense mutations leading to formation of truncated proteins. All mutations were located between exons 9 to 20, encoding the NEMO binding site and the catalytic domain. Genotype-phenotype analysis failed to reveal a correlation between the types of mutations and their location within the gene and the patients' phenotypes and disease severity. CONCLUSIONS: This study provides further evidence on the role of CYLD in the pathogenesis of skin appendage tumours characterised by cylindromas, trichoepitheliomas and/or spiradenomas, but the molecular mechanisms of CYLD in skin tumorigenesis and the reasons for phenotypic variability remain to be explored.


Assuntos
Carcinoma de Apêndice Cutâneo/genética , Mutação , Neoplasias Cutâneas/genética , Proteínas Supressoras de Tumor/genética , Carcinoma de Apêndice Cutâneo/metabolismo , Enzima Desubiquitinante CYLD , Éxons , Família , Genótipo , Humanos , Modelos Genéticos , Fenótipo , Neoplasias Cutâneas/metabolismo , Síndrome
16.
Clin Exp Dermatol ; 34(8): 890-1, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19094128

RESUMO

We report a 52-year-old woman with micronychia of the index fingers. Radiographic examination revealed a Y-shaped bifurcation of the distal phalanx of both index fingers. She was diagnosed with congenital onychodysplasia of the index fingers (COIF) or Iso-Kikuchi syndrome. COIF is a rare condition characterized by a variety of nail dysplasia of the index fingers. Five criteria characterize COIF: congenital occurrence, unilateral or bilateral index finger involvement, variability in nail appearance, hereditary involvement and frequently associated bone abnormalities. Micronychia, polyonychia, anonychia, hemionychrogryphosis and malalignment are the observed index finger defects. Most cases have been described in Japan, and to our knowledge, this is the first case of COIF reported in South America.


Assuntos
Dedos/anormalidades , Unhas Malformadas/congênito , Feminino , Dedos/diagnóstico por imagem , Humanos , Japão , Pessoa de Meia-Idade , Unhas Malformadas/diagnóstico por imagem , Radiografia
17.
Animal ; 13(10): 2146-2155, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30854999

RESUMO

Black and White dual-purpose cattle (DSN) are kept in diverse production systems, but the same set of genetic parameters is used for official national genetic evaluations, neglecting the herd or production system characteristics. The aim of the present study was to infer genetic (co)variance components within and across defined herd descriptor groups or clusters, considering only herds keeping the local and endangered DSN breed. The study considered 3659 DSN and 2324 Holstein Friesian (HF) cows from parities one to three. The 46 herds always kept DSN cows, but in most cases, herds were 'mixed' herds (Mixed), including both genetic lines HF and DSN. In order to study environmental sensitivity, we had a focus on the naturally occurring negative energy balance in the early lactation period. In consequence, traits were records from the 1st official test-day after calving for milk yield (Milk-kg), somatic cell score (SCS) and fat-to-protein ratio (FPR). Genetic parameters were estimated in bivariate runs (separate runs for the three genetic lines Mixed, HF and DSN), defining the same trait from different herd groups or clusters as different traits. Additive-genetic variances and heritabilities were larger in herd groups that indicated superior herd management, implying that cow records from these herds allow a better genetic differentiation. Superior herd management included larger herds, low calving age, high herd production levels and low intra-herd somatic cell count. Herd descriptor group differences in additive-genetic variances for Milk-kg were stronger in HF than in DSN, indicating environmental sensitivity for DSN. Similar variance components and heritabilities across groups, clusters and genetic lines were found for data stratification according to geographical descriptors altitude and latitude. Considering 72 bivariate herd group runs, 29 genetic correlations were very close to 1 (mostly for Milk-kg). Somatic cell score was the trait showing the smallest genetic correlations, especially in the DSN analyses, and when stratifying herds according to genetic line compositions (rg=0.11), or according to the percentage of natural service sires (rg=0.08). For estimations based on the results of a cluster analysis considering several herd descriptors simultaneously, indications for genotype × environment interactions could be found for SCS, but genetic correlations were larger than 0.80 for Milk-kg and FPR. In conclusion, we suggest multiple-trait animal model applications in genetic evaluations, in order to select the best sires for specific herd environments or herd clusters.


Assuntos
Bovinos/genética , Interação Gene-Ambiente , Leite/metabolismo , Animais , Contagem de Células/veterinária , Análise por Conglomerados , Feminino , Genótipo , Lactação , Masculino , Fenótipo
18.
Vet Parasitol ; 155(1-2): 74-9, 2008 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-18502584

RESUMO

Groups of White Leghorn and New Hampshire male and female chicks were reared under helminth-free conditions and divided into two groups at an age of 8 weeks. One group was artificially infected with 100 embryonated Heterakis gallinarum eggs, while the other group was kept as uninfected control. After 8 weeks all animals were harvested and worm burden was established. Maximum of 60 worms per bird randomly selected were measured for length. Body weights were recorded at 8 and 16 weeks of age. Total worm burden was significantly (P<0.0001) higher in infected males than in infected females. Furthermore, White Leghorns showed a significantly (P=0.011) higher number of worms when compared with New Hampshire animals. Average worm lengths were not significantly different between the breeds (P=0.155) and sexes (P=0.062). Correlations between worm burden and worm length was 0.08 (P=0.140). The daily weight gains between 8 and 16 weeks of age of the infected animals were significantly (P=0.038) lower when compared with the control group. There was no significant correlation between daily weight gain and worm burden. The estimated heritabilities for logarithm (ln) worm burden were 0.41 (S.E.+/-0.086) in White Leghorn and 0.31 (S.E.+/-0.126) in New Hampshire, respectively. Based on the estimated heritabilities it is possible to select for H. gallinarum resistance in both genetically distinct chicken breeds. This approach may be of importance for chickens kept in floor husbandry systems.


Assuntos
Galinhas/genética , Infecções por Nematoides/veterinária , Doenças das Aves Domésticas/genética , Animais , Galinhas/parasitologia , Feminino , Predisposição Genética para Doença , Masculino , Infecções por Nematoides/genética , Doenças das Aves Domésticas/parasitologia
19.
Anim Reprod Sci ; 103(1-2): 69-77, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17204379

RESUMO

Due to the genetic determination of susceptibility to scrapie and other forms of transmissible spongiform encephalopathy (TSE) in sheep breeding to the less susceptible prion protein (PrP) genotype ARR/ARR was advanced within EU. In 4961 ewes of nine German sheep breeds (Coburg Fox sheep, Gray Horned Heath sheep, Merinoland sheep, Rhoen sheep, German Blackheaded Mutton sheep, Shropshire, Suffolk, Texel and White East Friesian Milk sheep) representing local and cosmopolitan breeds the reproductive traits number of lambs born, dead (including abortion at the end of pregnancy, stillbirth and death during the first 56 days post natum), weaned and rearing rate at each lambing were recorded and in 1641 of these ewes the PrP genotype was determined. A linear model was used to evaluate associations between PrP genotype and reproduction traits including the effects of PrP genotype (four classes: ewes with two, one and no copy of the ARR allele and with unknown PrP genotype), breed, interaction of PrP genotype and breed, number of lambing, lambing season and stock. Significant associations were only observed between the PrP genotype and the number of dead lambs at each lambing in Shropshire and Merinoland sheep and the rearing rate at each lambing in Shropshire. These significant associations were mainly caused by differences between animals with unknown PrP genotype and animals of the other PrP classes. In conclusion, breeding for TSE resistant sheep will not lead to a reduction in economically important reproduction traits.


Assuntos
Príons/genética , Reprodução/fisiologia , Scrapie/genética , Ovinos/fisiologia , Alelos , Animais , Feminino , Predisposição Genética para Doença , Alemanha , Análise dos Mínimos Quadrados , Polimorfismo Genético , Reprodução/genética , Scrapie/prevenção & controle , Ovinos/genética
20.
J Dairy Sci ; 91(8): 3237-44, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18650301

RESUMO

The objective of this study was to estimate heritability of antibody response to Mycobacterium avium ssp. paratuberculosis (MAP) in 4,524 German Holstein cows by applying linear and threshold models. Data were collected within a paratuberculosis voluntary control program in Thuringia, Germany, in 2005. The MAP-positive prevalence of the 12 farms in the data set varied between 5 and 36.9%. A nearly linear increase in prevalence was observed from 2- to 3-yr-old cows, whereas prevalence declined in cows older than 5 yr. This could be explained by greater culling rates associated with increasing age. Classification as MAP positive, questionable, and negative was available for all cows, and the optical density values of the Svanovir ELISA test existed for 2,084 of the animals originating from 6 farms. The heritability estimates of linear and threshold animal and sire models were compared. For the available data sets with an average of 8 progeny per sire, animal models were more robust and yielded more reliable results than did sire models. Heritability estimates from sire models led to overestimation of genetic variances because of a low number of progeny per sire and average relationship within sire progeny of greater than one-fourth, as expected between half-sibs. For all animal models, a heritability of about 0.1 was estimated for antibody response to MAP. Furthermore, it can be concluded that for the estimation of breeding values for antibody response to MAP optical density values of the ELISA test as a normally distributed trait (log-transformed) should be used rather than MAP status (positive or negative) as a binary trait because of the greater heritability and more robust parameter estimates when sire or animal models are used.


Assuntos
Anticorpos Antibacterianos/genética , Anticorpos Antibacterianos/imunologia , Doenças dos Bovinos/genética , Doenças dos Bovinos/imunologia , Paratuberculose/genética , Paratuberculose/imunologia , Animais , Cruzamento , Bovinos , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/epidemiologia , Feminino , Alemanha/epidemiologia , Hereditariedade/genética , Masculino , Mycobacterium avium subsp. paratuberculosis/imunologia , Paratuberculose/diagnóstico , Paratuberculose/epidemiologia
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