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1.
Cell ; 186(23): 5114-5134.e27, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37875108

RESUMO

Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with mycobacterial disease from kindreds of different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete deficiency of this translation re-initiation factor impairs the translation of a subset of proteins, including the kinase JAK2 in all cell types tested, including T lymphocytes and phagocytes. JAK2 expression is sufficiently low to impair cellular responses to interleukin-23 (IL-23) and partially IL-12, but not other JAK2-dependent cytokines. Defective responses to IL-23 preferentially impair the production of IFN-γ by innate-like adaptive mucosal-associated invariant T cells (MAIT) and γδ T lymphocytes upon mycobacterial challenge. Surprisingly, the lack of MCTS1-dependent translation re-initiation and ribosome recycling seems to be otherwise physiologically redundant in these patients. These findings suggest that X-linked recessive human MCTS1 deficiency underlies isolated mycobacterial disease by impairing JAK2 translation in innate-like adaptive T lymphocytes, thereby impairing the IL-23-dependent induction of IFN-γ.


Assuntos
Interferon gama , Janus Quinase 2 , Infecções por Mycobacterium , Humanos , Masculino , Proteínas de Ciclo Celular/metabolismo , Interferon gama/imunologia , Interleucina-12 , Interleucina-23 , Janus Quinase 2/metabolismo , Mycobacterium/fisiologia , Infecções por Mycobacterium/imunologia , Infecções por Mycobacterium/metabolismo , Proteínas Oncogênicas/metabolismo
3.
Int Orthop ; 38(3): 495-501, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24252971

RESUMO

PURPOSE: The health related quality of life (HRQoL) outcomes of total hip arthroplasty (THA) present a pertinent and clinically important problem in modern orthopaedics. Our goal was to report and compare the health-related outcomes after THA in respect to type of fixation in patients with hip osteoarthritis (H-OA) one year after operation. METHODS: A total of 145 patients with H-OA who received THA were evaluated. Uncemented and cemented subjects were evaluated using generic measures, i.e. the EQ-5D questionnaire, and the disease-specific measures designed by the authors, i.e. the Total Hip Arthroplasty Questionnaire (THAQ). Obtained data was statistically processed at the level of pain, functionality and general health perception. Patient-reported outcomes were measured differences between pre-operative measures and those at one-year follow-up visit. RESULTS: Significant improvement in health outcomes was reached in both groups regardless of the type of fixation (p < 0.001). Uncemented fixation exhibited better results for EQ-5DINDEX, pain (p = 0.004) and self-care on EQ-5D (p = 0.043), as well as increased magnitude of change for functionality on THAQ (p = 0.002). However, additional analysis of the subset did not reveal a significant difference between cemented vs. uncemented groups with regard to function on THAQ, but the significant difference on self-care and pain dimensions of EQ-5D remained. CONCLUSIONS: Uncemented endoprosthesis generally achieved better short-term outcomes in some dimensions. However, painless mobility has been restored in most of the patients, regardless of the fixation type. Both methods reached good clinical outcomes in their respective domains; therefore, we would emphasise prevention of osteoarthritis and the quality of care as the more important predictors of good clinical outcomes.


Assuntos
Artroplastia de Quadril , Articulação do Quadril/fisiologia , Articulação do Quadril/cirurgia , Osteoartrite do Quadril/cirurgia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Artralgia/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Nível de Saúde , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
4.
Coll Antropol ; 32(2): 571-5, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18756912

RESUMO

The aim of this study was to assess the outcome of sanitary and epidemiologic measures undertaken in relation to alimentary infections in the military corps of the Croatian Defense Council (Hrvatsko vjece obrane) and civilian population in Mostar and Tomislavgrad regions during the 1992-1995 War in Bosnia and Herzegovina. A total of 25 (4.8%) of soldiers and 7 (7.1%) of non-military personnel were not being granted medical clearance to be employed in the food provision services. We recorded a total of 68 alimentary infections cases in military personnel (with an incidence of 536.2 per 100,000 persons), and 436 in civilian population (573.9 per 100,000 person), without significant difference between them (p=0.647). We did not record any alimentary infection outbreak in the military personnel, while two smaller epidemics of the abdominal typhus were recorded among civilian populations, but without lethal outcomes. The results of this study suggest that even the most basic adherence to the principle of standard sanitary and epidemiologic preventive measures may substantially reduce the probability of alimentary infections outbreaks, even in the highly disruptive, warfare environment.


Assuntos
Microbiologia de Alimentos , Abastecimento de Alimentos , Infecções/epidemiologia , Enteropatias/epidemiologia , Guerra , Adulto , Bósnia e Herzegóvina/epidemiologia , Humanos , Infecções/transmissão , Enteropatias/microbiologia , Masculino , Pessoa de Meia-Idade
5.
Mil Med ; 168(11): 951-6, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14680054

RESUMO

OBJECTIVE: The purpose of this study was to review the establishment and operation of the Croatian Medical Corps in Bosnia and Herzegovina in the 1992-1995 war. METHODS: We analyzed pertinent documents available to one of the authors (B.I.) who served on the Headquarter of the Corps, the study of the 17 published articles describing medical activities in various parts of Bosnia and Herzegovina during the war, as well as other relevant medical-military literature. RESULTS: The Corps functioned effectively and, in fact, served as a new health care system for the Croats in Bosnia and Herzegovina. It was initiated, planned, and operated voluntarily by members of the medical community, established before the defense forces, and later incorporated within them, but retaining its autonomy. CONCLUSIONS: The development of the Corps represents a unique phenomenon in the history of military medicine.


Assuntos
Medicina Militar/organização & administração , Militares , Guerra , Bósnia e Herzegóvina , Croácia , História do Século XX , Humanos
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