RESUMO
PURPOSE: The cognitive profiles of patients suffering from anorexia nervosa (AN) are currently explored as potential facilitating and/or maintenance factors. Specific data in restrictive AN (AN-R) remain contradictory. This study focused on women with AN-R to evaluate their cognitive functions to develop a more specific cognitive remediation program. METHODS: Female patients older than 15 years who were suffering from AN-R were recruited in a specialized unit for eating disorder management. Female healthy control (HC) participants were recruited who were matched with AN patients on age. All participants completed a cognitive evaluation (premorbid intelligence quotient (IQ), planning, information processing speed, cognitive flexibility) and a clinical evaluation (impulsivity, anxiety, depression). RESULTS: A total of 122 participants were included. Patients suffering from AN-R had significant impairment in information processing speed and planning. Patients exhibited significantly better cognitive flexibility than did the HC group when adjustments were made for other cognitive functions and impulsivity. Two distinct subgroups of patients were identified. The first subgroup had more marked cognitive impairment and fewer psychopathological symptoms than did the second subgroup of patients and the HC group. CONCLUSION: Our results highlight cognitive impairment in patients with AN who had normal premorbid IQ. Two distinct profiles emerge. In clinical practice, these results open up perspectives for the development of more specific cognitive remediation programs (one specific program for cold cognitions and another specific program targeting emotions and hot cognitions). These results warrant confirmation by larger studies with a more specific evaluation of the impact of emotional status. Trial registration NTC02381639, Date of registration. March 6, 2015.
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Anorexia Nervosa , Disfunção Cognitiva , Transtornos da Alimentação e da Ingestão de Alimentos , Anorexia Nervosa/complicações , Cognição , Disfunção Cognitiva/complicações , Emoções , Feminino , Humanos , Testes NeuropsicológicosRESUMO
This review on magnetic resonance elastography (MRE) of the breast provides an overview of available literature and describes current developments in the field of breast MRE, including new transducer technology for data acquisition and multi-frequency-derived power-law behaviour of tissue. Moreover, we discuss the future potential of breast MRE, which goes beyond its original application as an additional tool in differentiating benign from malignant breast lesions. These areas of ongoing and future research include MRE for pre-operative tumour delineation, staging, monitoring and predicting response to treatment, as well as prediction of the metastatic potential of primary tumours.
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Mama/diagnóstico por imagem , Técnicas de Imagem por Elasticidade , Imageamento por Ressonância Magnética , Módulo de Elasticidade , Humanos , PublicaçõesRESUMO
Pertussis morbidity is highest in infants too young to be fully protected by routine vaccination schedules. Alternate vaccine strategies are required to maximise protection in this age-group. To understand baseline pertussis epidemiology prior to the introduction of the maternal pertussis vaccination program in 2014, we conducted a retrospective case series analyses of 53 901 notifications and temporal trends from 1997 to 2014. Notifications were highest in infants younger than 4 months of age and highest annual notification rates in infants younger than 1 month of age (308/100 000 per year). Amongst Aboriginal and Torres Strait Islander infants aged younger than 1 month, this rate was 576/100 000 per year. Notification rates were 40% higher amongst women 15-44 years, 62·4/100 000 population compared with men (44·5/100 000) and 90% higher in Aboriginal and Torres Strait Islander women of the same age (38·2/100 000) compared with men (19·7/100 000). Six infant deaths were identified, all younger than 2 months of age. Monitoring epidemiology in at-risk groups - infants too young to be vaccinated, women of childbearing age and Aboriginal and Torres Strait Islander peoples - following implementation of the maternal pertussis vaccination program will be important to assess its impact and safety.
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Etnicidade/estatística & dados numéricos , Mães/estatística & dados numéricos , Coqueluche/epidemiologia , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Programas de Imunização , Lactente , Recém-Nascido , Masculino , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Vacina contra Coqueluche/uso terapêutico , Queensland/epidemiologia , Estudos Retrospectivos , População Branca/estatística & dados numéricos , Coqueluche/prevenção & controle , Adulto JovemRESUMO
A polymerase chain reaction-based method was used to screen sandflies for infection with Wolbachia (Rickettsiales: Rickettsiaceae), an intracellular bacterial endosymbiont found in many arthropods and filarial hosts. Positive results were obtained in five of 200 field-collected sandflies and were confirmed by sequencing. All sandflies were Lutzomyia longipalpis (Diptera: Psychodidae) captured in a region endemic for visceral leishmaniasis in Brazil. This is the first study to identify Wolbachia infection in this Lutzomyia species, which is the main vector of leishmaniasis in the study area. The low infection rate found in this study (2.5%), together with the lack of detection of Wolbachia in previous studies and the diversity found in the sequences analysed, suggests horizontal transmission to these sandflies.
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Insetos Vetores/microbiologia , Psychodidae/microbiologia , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Wolbachia/isolamento & purificação , Animais , Brasil , Controle de Doenças Transmissíveis/métodos , Feminino , Haplótipos , Leishmania infantum/fisiologia , Leishmaniose Visceral/transmissão , Masculino , Reação em Cadeia da Polimerase , Análise de Sequência de RNARESUMO
Non-alcoholic steatohepatitis (NASH) is characterized at histology by steatosis, hepatocyte ballooning and inflammatory infiltrates, with or without fibrosis. Although diamagnetic material in fibrosis and inflammation can be detected with quantitative susceptibility imaging, fatty acid composition changes in NASH relative to simple steatosis have also been reported. Therefore, our aim was to develop a single magnetic resonance (MR) acquisition and post-processing scheme for the diagnosis of steatohepatitis by the simultaneous quantification of hepatic fat content, fatty acid composition, T2 * transverse relaxation time and magnetic susceptibility in patients with non-alcoholic fatty liver disease. MR acquisition was performed at 3.0 T using a three-dimensional, multi-echo, spoiled gradient echo sequence. Phase images were unwrapped to compute the B0 field inhomogeneity (ΔB0 ) map. The ΔB0 -demodulated real part images were used for fat-water separation, T2 * and fatty acid composition quantification. The external and internal fields were separated with the projection onto dipole field method. Susceptibility maps were obtained after dipole inversion from the internal field map with single-orientation Bayesian regularization including spatial priors. Method validation was performed in 32 patients with biopsy-proven, non-alcoholic fatty liver disease from which 12 had simple steatosis and 20 NASH. Liver fat fraction and T2 * did not change significantly between patients with simple steatosis and NASH. In contrast, the saturated fatty acid fraction increased in patients with NASH relative to patients with simple steatosis (48 ± 2% versus 44 ± 4%; p < 0.05) and the magnetic susceptibility decreased (-0.30 ± 0.27 ppm versus 0.10 ± 0.14 ppm; p < 0.001). The area under the receiver operating characteristic curve for magnetic susceptibility as NASH marker was 0.91 (95% CI: 0.79-1.0). Simultaneous MR quantification of fat content, fatty acid composition, T2 * and magnetic susceptibility is feasible in the liver. Our preliminary results suggest that quantitative susceptibility imaging has a high diagnostic performance for the diagnosis of NASH.
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Adiposidade , Ácidos Graxos/metabolismo , Fígado/metabolismo , Imageamento por Ressonância Magnética/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de TempoRESUMO
Pertussis epidemics have displayed substantial spatial heterogeneity in countries with high socioeconomic conditions and high vaccine coverage. This study aims to investigate the relationship between pertussis risk and socio-environmental factors on the spatio-temporal variation underlying pertussis infection. We obtained daily case numbers of pertussis notifications from Queensland Health, Australia by postal area, for the period January 2006 to December 2012. A Bayesian spatio-temporal model was used to quantify the relationship between monthly pertussis incidence and socio-environmental factors. The socio-environmental factors included monthly mean minimum temperature (MIT), monthly mean vapour pressure (VAP), Queensland school calendar pattern (SCP), and socioeconomic index for area (SEIFA). An increase in pertussis incidence was observed from 2006 to 2010 and a slight decrease from 2011 to 2012. Spatial analyses showed pertussis incidence across Queensland postal area to be low and more spatially homogeneous during 2006-2008; incidence was higher and more spatially heterogeneous after 2009. The results also showed that the average decrease in monthly pertussis incidence was 3·1% [95% credible interval (CrI) 1·3-4·8] for each 1 °C increase in monthly MIT, while average increase in monthly pertussis incidences were 6·2% (95% CrI 0·4-12·4) and 2% (95% CrI 1-3) for SCP periods and for each 10-unit increase in SEIFA, respectively. This study demonstrated that pertussis transmission is significantly associated with MIT, SEIFA, and SCP. Mapping derived from this work highlights the potential for future investigation and areas for focusing future control strategies.
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Epidemias , Coqueluche/epidemiologia , Adolescente , Adulto , Idoso , Teorema de Bayes , Criança , Pré-Escolar , Transmissão de Doença Infecciosa , Meio Ambiente , Feminino , Humanos , Umidade , Incidência , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Queensland/epidemiologia , Fatores Socioeconômicos , Análise Espaço-Temporal , Temperatura , Topografia Médica , Coqueluche/transmissão , Adulto JovemRESUMO
PURPOSE: Over the last few years, disordered eating in athletes has received increasing attention. According to several studies, athletes could be more vulnerable to disordered eating and some characteristics specific to the athletic community could be in favour of an increased risk of poor body image and disturbed eating habits in athletes. However, the literature is sparse and some methodological issues in studies have been pointed out. In this context, we aimed at determining the prevalence of disordered eating in French high-level athletes using clinical interviews of three different clinicians and identifying what are the factors associated with disordered eating in athletes. METHODS: In France, all athletes registered on the French high-level list have to undergo a yearly evaluation. Data collected during the somatic assessment, the dietary consultation, and the psychological of the yearly evaluation were used. Multivariate analysis was performed for identification of factors associated with disordered eating. RESULTS: Out of the 340 athletes included, 32.9% have been detected with a disordered eating. They were difficult to detect by clinicians, as usual criteria did not seem to be reliable for athletes. Competing in sports emphasizing leanness or low body weight was associated with disordered eating; however, gender was not. CONCLUSION: These results highlight the need for the development of specific screening tools for high-level athletes. Furthermore, the identification of factors associated with disordered eating could improve early detection and prevention program effectiveness.
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Atletas/psicologia , Imagem Corporal/psicologia , Dopagem Esportivo/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Esportes/psicologia , Adolescente , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , França , Humanos , Masculino , Prevalência , Adulto JovemRESUMO
AIM: Pilocytic astrocytomas represent the most common paediatric tumours of the central nervous system. Dissemination through the ventricular system occurs rarely in patients with pilocytic astrocytomas; however, it is more common in infants with diencephalic tumours, and is associated with a poor outcome. Despite histological similarities with classic pilocytic astrocytomas, it is still unclear whether disseminated pilocytic astrocytomas may have specific molecular features. METHODS: Seventeen disseminated pilocytic astrocytomas were investigated using the molecular inversion probe array and screened for the presence of gene fusions (KIAA1549-BRAF) and mutations (BRAF, RAS and FGFR1). RESULTS: Along with evidence of a constitutive MAPK activation in all cases, the molecular inversion probe array, fluorescence in situ hybridization analysis and mutational study revealed KIAA1549-BRAF fusions in 66% and BRAF(V600E) mutations in 5% of cases. No KRAS, HRAS, NRAS or FGFR1 mutations were found. CONCLUSIONS: disseminated pilocytic astrocytomas showed genetic features similar to classic pilocytic astrocytoma, including a similar incidence of KIAA1549-BRAF fusions, BRAF mutations and a stable genetic profile. Given common activation of the MAPK pathway, the use of specific inhibitors can be hypothesized for the treatment of disseminated pilocytic astrocytomas, along with standard chemo- and/or radiotherapy.
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Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lactente , Masculino , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
Influenza and pertussis are the two most common vaccine-preventable infections notified in Australia. We assessed the role of polymerase chain reaction (PCR) diagnosis in influenza and pertussis cases notified to the Australian National Notifiable Diseases Surveillance System (NNDSS). There were a total of 2 10 786 notified influenza cases (2001-2013) and 2 55 866 notified pertussis cases (1991-2013). After 1 January 2007, the majority of influenza and pertussis notifications were PCR-based (80·5% and 59·6%, respectively). Before 31 December 2006, PCR-based notifications were limited (29·1% and 11·7%, respectively). By 2013, PCR-based notifications had largely replaced all other diagnostic methods, with the exception of serology-based notifications in pertussis cases in adults aged ⩾ 25 years.
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Influenza Humana/epidemiologia , Vigilância da População/métodos , Coqueluche/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Criança , Pré-Escolar , Notificação de Doenças , Humanos , Lactente , Recém-Nascido , Influenza Humana/virologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Coqueluche/microbiologia , Adulto JovemRESUMO
West Nile Virus is an arbovirus that has rapidly spread throughout the United States since the first case was described in Queens, New York in 1999. There has been increasing reports of both community-acquired and organ-derived infections in renal transplant recipients. In immunocompromised individuals, WNV infection is a life-threatening disease with significant neurological morbidity. We report the only pediatric case of community-acquired WNV disease in a renal transplant recipient to undergo detailed long-term neuropsychological assessment. Increased surveillance and prompt treatment of WNV meningoencephalitis is critical, and our report highlights the effectiveness of immunosuppression reduction without compromising allograft outcomes.
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Transplante de Rim , Meningoencefalite/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Febre do Nilo Ocidental/diagnóstico , Criança , Humanos , Hospedeiro Imunocomprometido , Masculino , Meningoencefalite/imunologia , Testes Neuropsicológicos , Complicações Pós-Operatórias/imunologia , Índice de Gravidade de Doença , Febre do Nilo Ocidental/imunologiaRESUMO
BACKGROUND: Patients with severe Anorexia Nervosa (AN) whose condition is life-threatening or who are not receiving adequate ambulatory care are hospitalized. However, 40 % of these patients leave the hospital prematurely, without reaching the target weight set in the treatment plan, and this can compromise outcome. This study set out to explore factors predictive of dropout from hospital treatment among patients with AN, in the hope of identifying relevant therapeutic targets. METHODS: From 2009 to 2011, 180 women hospitalized for AN (DSM-IV diagnosis) in 10 centres across France were divided into two groups: those under 18 years (when the decision to discharge belongs to the parents) and those aged 18 years and over (when the patient can legally decide to leave the hospital). Both groups underwent clinical assessment using the Morgan & Russell Global Outcome State questionnaire and the Eating Disorders Examination Questionnaire (EDE-Q) for assessment of eating disorder symptoms and outcome. Psychological aspects were assessed via the evaluation of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). Socio-demographic data were also collected. A number of factors identified in previous research as predictive of dropout from hospital treatment were tested using stepwise descending Cox regressions. RESULTS: We found that factors predictive of dropout varied according to age groups (being under 18 as opposed to 18 and over). For participants under 18, predictive factors were living in a single-parent family, severe intake restriction as measured on the "dietary restriction" subscale of the Morgan & Russell scale, and a low patient-reported score on the EDE-Q "restraint concerns" subscale. For those over 18, dropout was predicted from a low depression score on the HADS, low level of concern about weight on the EDE-Q subscale, and lower educational status. CONCLUSION: To prevent dropout from hospitalization for AN, the appropriate therapeutic measures vary according to whether patients are under or over 18 years of age. Besides the therapeutic adjustments required in view of the factors identified, the high dropout rate raises the issue of resorting more frequently to compulsory care measures among adults.
Assuntos
Anorexia Nervosa/terapia , Hospitalização , Pacientes Desistentes do Tratamento/psicologia , Adolescente , Adulto , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/psicologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Modelos de Riscos Proporcionais , Escalas de Graduação Psiquiátrica , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Intensified surveillance will be vital in the elimination phase to verify Ebola-free status and mitigate potential reemergence of the disease in West Africa. Zero-reporting from high-risk districts is a key strategy for surveillance. Our objective was to implement a pilot investigation to assess the feasibility of using short message service (SMS) texting for daily reporting of Ebola cases under investigation (CUI) in Guinea-Bissau in the context of an ongoing emergency-response training program known as Surveillance Training for Ebola Preparedness (STEP). STUDY DESIGN: Prospective cohort (pilot investigation) METHODS: The reporting period for the SMS pilot was January 24-March 24, 2015. STEP was conducted for two sequential groups during January 19-March 27, 2015 in Bissau, Guinea-Bissau. Training on SMS daily reporting occurred over one hour during the first week of didactic training of each group. Fourteen participants (nine from the first group and five from the second), including one surveillance officer from each of the 13 regions in Guinea-Bissau and one from the national laboratory, were selected as reporters, receiving a simple cell phone for sending SMS indicating the number of CUI for Ebola. The WHO suspect Ebola case definition was used initially and then modified on day 32 of the pilot. The text message was sent to the WiFi-connected smartphone at the Instituto Nacional Saúde Pública (INASA). The smartphone utilised an SMS-gateway application (Ushahidi SMSsync Android App) to upload the data to the Magpi cloud application. RESULTS: The average daily reporting from the first group was 7.7 of 9 (86%) and for the second group was 4.1 of 5 (82%). For the two groups combined, the reporting rate was 85%. Among the 14 reporters the median reporting rate was 85% (range 36%-100%). No cases meeting the definition for an Ebola CUI were reported during the 60 days. CONCLUSIONS: Real-time, SMS-based, daily zero-reporting can be implemented in a rapid, simple way in a low resource country. We believe that the high compliance rates were due to the simplicity and familiarity of SMS and heightened sensitivity that resulted from STEP to the importance of zero-reporting in the midst of an Ebola epidemic in neighbouring countries. This model could be useful for rapid scale-up and implementation of alert systems in other outbreaks and public health emergencies.
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Doença pelo Vírus Ebola/epidemiologia , Vigilância da População/métodos , Envio de Mensagens de Texto , Estudos de Viabilidade , Guiné-Bissau/epidemiologia , Humanos , Projetos Piloto , Estudos ProspectivosRESUMO
Seven commercial rotavirus antigen assays were compared with in-house PCR methods for detecting rotavirus in stool specimens. The assay sensitivities were 80% to 100%, while the specificities were 54.3% for one commercial immunochromatographic (ICT) method and 99.4% to 100% for other assays. Thus, except for one commercial ICT, all the assays were generally reliable for rotavirus detection.
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Cromatografia de Afinidade/métodos , Fezes/virologia , Reação em Cadeia da Polimerase/métodos , Infecções por Rotavirus/diagnóstico , Infecções por Rotavirus/virologia , Rotavirus/genética , Rotavirus/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in fair-skinned populations worldwide and its incidence is increasing. Despite previous observations of multiple genetic abnormalities in cSCC, the oncogenic process remains elusive. The purpose of this study was to elucidate key molecular events associated with progression from premalignant actinic keratoses (AKs) to invasive cSCC by transcriptome profiling. METHODS: We combined laser capture microdissection with the Affymetrix HGU133 Plus 2.0 microarrays to profile 30 cSCC and 10 AKs. RESULTS: We identified a core set of 196 genes that are differentially expressed between AK and cSCC, and are enriched for processes including epidermal differentiation, cell migration, cell-cycle regulation and metabolism. Gene set enrichment analysis highlighted a key role for the mitogen activated protein kinase (MAPK) pathway in cSCC compared with AK. Furthermore, the histological subtype of the tumour was shown to influence the expression profile. CONCLUSION: These data indicate that the MAPK pathway may be pivotal to the transition from AK to cSCC, thus representing a potential target for cSCC prevention. In addition, transcriptome differences identified between cSCC subtypes have important implications for future development of targeted therapies for this malignancy.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Ceratose Actínica/genética , Ceratose Actínica/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/irrigação sanguínea , Adesão Celular/genética , Ciclo Celular/genética , Diferenciação Celular/genética , Movimento Celular/genética , Proliferação de Células , Progressão da Doença , Epiderme/patologia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/genética , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Neoplasias Cutâneas/irrigação sanguínea , TranscriptomaRESUMO
Domestication might be a possible way to reduce the physiological response to long-term stressors and deleterious effects on immunity. The present study aimed to evaluate the chronic immune response induced by repeated emersions and the possible impact of domestication by comparing farmed Eurasian perch with short (F1) and long (F4) captive-life history. In the first experiment, fish were exposed to a single emersion and physiological stress response was measured in the short term to characterize fish sensitivity to the tested stressor. Serum cortisol and glucose elevated within 6h post-stress and splenosomatic index (SSI) decreased within 48h, indicating that the species was affected by emersion stressor. In the second experiment, F1 and F4 generations were submitted to repeated water emersions (3 times/week during 44days). On day 9, 18 and 44, samplings were performed 48h post-stressor to highlight any sustained disruption of immune system. Serum cortisol, glucose, SSI and lysozyme activity were evaluated and serum proteome was analyzed using 2D-DIGE. Any of the tested variables were affected by repeated emersions and proteomic analysis only revealed that alpha-2 macroglobulins (a2Ms) were up-regulated in the serum of stressed individuals. Domestication also resulted in the up-regulation of five a2M isoforms and down-regulation of complement C3 and Ig light chain proteins, independently of any stressor exposure. In conclusion, the results suggested that repeated emersions are not severe stressors for Eurasian perch, probably explaining why domestication had no influence on fish responses. Changes associated with domestication are highly complex and certainly need further investigations.
RESUMO
Posttransplant lymphoproliferative disorder (PTLD)-associated Epstein-Barr virus (EBV)+ B cell lymphomas are serious complications of solid organ and bone marrow transplantation. The EBV protein LMP2a, a B cell receptor (BCR) mimic, provides survival signals to virally infected cells through Syk tyrosine kinase. Therefore, we explored whether Syk inhibition is a viable therapeutic strategy for EBV-associated PTLD. We have shown that R406, the active metabolite of the Syk inhibitor fostamatinib, induces apoptosis and cell cycle arrest while decreasing downstream phosphatidylinositol-3'-kinase (PI3K)/Akt signaling in EBV+ B cell lymphoma PTLD lines in vitro. However, Syk inhibition did not inhibit or delay the in vivo growth of solid tumors established from EBV-infected B cell lines. Instead, we observed tumor growth in adjacent inguinal lymph nodes exclusively in fostamatinib-treated animals. In contrast, direct inhibition of PI3K/Akt significantly reduced tumor burden in a xenogeneic mouse model of PTLD without evidence of tumor growth in adjacent inguinal lymph nodes. Taken together, our data indicate that Syk activates PI3K/Akt signaling which is required for survival of EBV+ B cell lymphomas. PI3K/Akt signaling may be a promising therapeutic target for PTLD, and other EBV-associated malignancies.
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Infecções por Vírus Epstein-Barr/enzimologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Transtornos Linfoproliferativos/enzimologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Aminopiridinas , Animais , Apoptose , Linfócitos B/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Ativação Enzimática , Herpesvirus Humano 4 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Linfonodos/patologia , Linfoma de Células B/enzimologia , Linfoma de Células B/virologia , Transtornos Linfoproliferativos/virologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Morfolinas , Oxazinas/farmacologia , Complicações Pós-Operatórias , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Pirimidinas , Transdução de Sinais , Quinase Syk , Transplante HeterólogoRESUMO
The association of marfanoid habitus (MH) and intellectual disability (ID) has been reported in the literature, with overlapping presentations and genetic heterogeneity. A hundred patients (71 males and 29 females) with a MH and ID were recruited. Custom-designed 244K array-CGH (Agilent®; Agilent Technologies Inc., Santa Clara, CA) and MED12, ZDHHC9, UPF3B, FBN1, TGFBR1 and TGFBR2 sequencing analyses were performed. Eighty patients could be classified as isolated MH and ID: 12 chromosomal imbalances, 1 FBN1 mutation and 1 possibly pathogenic MED12 mutation were found (17%). Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%). These results suggest either that there are more loci with genes yet to be discovered or that MH can also be a relatively non-specific feature of patients with ID. The search for aortic complications is mandatory even if MH is associated with ID since FBN1 mutations or rearrangements were found in some patients. The excess of males is in favour of the involvement of other X-linked genes. Although it was impossible to make a diagnosis in 80% of patients, these results will improve genetic counselling in families.
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Testes Genéticos/métodos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Adolescente , Adulto , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Análise Citogenética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Análise de Sequência de DNA , Inativação do Cromossomo X , Adulto JovemRESUMO
INTRODUCTION: Aim of this study was to evaluate outcomes of operative as compared to conserveative treatment for two-part humerus fractures at the surgical neck. METHODS: Data from a prospective multi-centre cohort study on four treatment options (conservative treatment and three implants, i.e. LPHP, PHILOS and PHN) for proximal humerus fractures were evaluated in this post hoc analysis. All patients with two-part fractures of the surgical neck (AO types A2, n = 54 and A3, n = 110) were identified and included for the analysis. All operatively treated patients were gathered and compared to those receiving conservative treatment. Primary outcome parameters were pain, range of motion and absolute and relative Constant scores at 3, 6 and 12 months following injury and coronal plane alignment at 12 months. RESULTS: Operative (n = 133) and non-operative (n = 31) groups were comparable with regard to all parameters assessed including mean age (62.9 vs. 65.6, P = 0.479), gender (27 vs. 29 % male, P = 0.826) and fracture distribution (65 vs. 77 % A3 type, P = 0.207). 26 of the 31 conservatively treated and 103 of the 133 operatively treated patients (84 and 77 %, respectively) were available for final follow-up. There was a continuous improvement for all outcome parameters in both treatment groups (P < 0.001). Operative treatment resulted in a more effective reduction of pain at 3 months (51 vs. 76 % reporting pain at fracture site, P = 0.03) and a reduction of coronal plane malalignment. Both range of motion and Constant scores were, however, comparable in both groups at all follow-up visits. Relative and absolute Constant scores were generally excellent at final follow-up (74 vs. 74, P = 0.528 and 89 vs. 91, P = 0.494, respectively). CONCLUSIONS: Both non-operative treatment and operative treatment using modern implants (LPHP, PHILOS and PHN) can be considered safe and effective treatment options for two-part fractures of the proximal humerus. Operative treatment may result in better range of motion and reduced pain in the early postoperative course of treatment.
Assuntos
Fixação Intramedular de Fraturas , Imobilização , Fraturas do Ombro/terapia , Idoso , Terapia por Exercício , Feminino , Seguimentos , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Indicadores Básicos de Saúde , Humanos , Imobilização/métodos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Fraturas do Ombro/cirurgia , Lesões do Ombro , Articulação do Ombro/fisiologia , Articulação do Ombro/cirurgia , Resultado do TratamentoRESUMO
Q fever is a vaccine preventable disease; however, despite this, high notification numbers are still recorded annually in Australia. We investigated the seroprevalence of Coxiella burnetii, the Q fever agent, in a Queensland sample population. Notification data (N = 6425) from 1984-2008 were collated, identifying high risk areas of Q fever exposure. Of these 177 were recorded in children. Serum samples were collected from Queensland and screened using both an immunoflourescence assay at 1:10 dilution and a commercially available ELISA kit. Results were collated based on age, geographical location and sex. From 1988 Queensland samples screened, 103 were identified as Q fever IgG-positive, giving a seroprevalence of 5.2% (95% CI 4.3-6.2%). Seroprevalence in the rural/remote population was 5.3% (95% CI 4.6-6.6%), and the metropolitan Brisbane population, which is considered not at risk, was 5.0% (95% CI 3.7-6.7%). Sixty-three seropositive males and 40 females were identified, along with an increase in seropositivity with increasing age. The seropositivity of children was 1.3% (95% CI 0.7-2.3%) from 844 samples. We have shown that both metropolitan and paediatric populations which are considered low risk of Coxiella exposure have surprisingly high seropositivity. These emerging groups require further investigation and consideration for the introduction of preventive measures.
Assuntos
Anticorpos Antibacterianos/sangue , Coxiella burnetii/imunologia , Febre Q/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Queensland/epidemiologia , População Rural , Estudos Soroepidemiológicos , População Urbana , Adulto JovemRESUMO
The gonococcal porA pseudogene is a popular target for in-house Neisseria gonorrhoeae PCR methods. With this study we present two novel findings: the first case of an N. gonorrhoeae porA pseudogene PCR false-negative result caused by sequence variation, and in the same organism, the first description of a clinical N. gonorrhoeae strain harbouring an N. meningitidis porA sequence.