RESUMO
Gulf War Illness (GWI) collectively describes the multitude of central and peripheral disturbances affecting soldiers who served in the 1990-1991 Gulf War. While the mechanisms responsible for GWI remain elusive, the prophylactic use of the reversible acetylcholinesterase inhibitor, pyridostigmine bromide (PB), and war-related stress have been identified as chief factors in GWI pathology. Post-deployment stress is a common challenge faced by veterans, and aberrant cholinergic and/or immune responses to these psychological stressors may play an important role in GWI pathology, especially the cognitive impairments experienced by many GWI patients. Therefore, the current study investigated if an immobilization stress challenge would produce abnormal responses in PB-treated rats three months later. Results indicate that hippocampal cholinergic responses to an immobilization stress challenge are impaired three months after PB administration. We also assessed if an immune or stress challenge reveals deficits in PB-treated animals during hippocampal-dependent learning and memory tasks at this delayed timepoint. Novel object recognition (NOR) testing paired with either acute saline or lipopolysaccharide (LPS, 30 µg/kg, i.p.), as well as Morris water maze (MWM) testing was conducted approximately three months after PB administration and/or repeated restraint stress. Rats with a history of PB treatment exhibited 24-hour hippocampal-dependent memory deficits when challenged with LPS, but not saline, in the NOR task. Similarly, in the same cohort, PB-treated rats showed 24-hour memory deficits in the MWM task. Ultimately, these studies highlight the long-term effects of PB treatment on hippocampal function and provide insight into the progressive cognitive deficits observed in veterans with GWI.
Assuntos
Disfunção Cognitiva , Síndrome do Golfo Pérsico , Ratos , Animais , Guerra do Golfo , Lipopolissacarídeos , Acetilcolinesterase , Inibidores da Colinesterase/farmacologia , Brometo de Piridostigmina/farmacologia , Transtornos da Memória , Modelos Animais de DoençasRESUMO
There is conflicting evidence whether single-suture craniosynostosis (SSC), is linked to adversities of cognitive development. To assess the evidence for a link between SSC and cognition, a systematic literature search was conducted and eligible studies assessed for inclusion by two independent readers. Forty-eight studies met inclusion criteria. Small to medium but persistent effects on both general and some specific cognitive functions across age bands were found in higher quality studies for SSC overall. There was limited evidence for effects related to surgical correction. Methodologies varied substantially and there was a lack of longitudinal studies using broad assessment batteries.
Assuntos
Craniossinostoses , Humanos , Craniossinostoses/complicações , Craniossinostoses/cirurgia , Craniossinostoses/psicologia , Cognição , Estudos Longitudinais , SuturasRESUMO
BACKGROUND: Tuberculosis (TB) is the leading opportunistic infection in children with human immunodeficiency virus (HIV), but is uncommon in low prevalence regions. We aim to describe the changing epidemiology and clinical presentation of TB-HIV co-infection in a cohort of HIV-infected children in Spain.METHODS: Children diagnosed with TB between 1995 and 2016 in the paediatric HIV cohort were identified. The incidence and clinical presentation were compared in three periods: 1995-1999 (P1, before initiation of combined antiretroviral therapy, cART), 2000-2009 (P2, increase in immigration), and 2010-2016 (P3, decrease in immigration).RESULTS: We included 29 TB cases among 1183 children aged <18 years (2.4%, 243/100 000 person-years). The proportion was stable in P1 and P2 (1.3%), but decreased in P3 (0.8%). The median age at TB diagnosis was 6.4 years (IQR 4-10.6); most children in P3 were aged >10 years (20% vs. 23.1% vs. 83.3%, P = 0.01). TB was diagnosed at HIV presentation in 11/29 children (37.9%). Foreign-born children accounted for respectively 0%, 8% and 67% of the total number of children in each period (P ≤ 0.0001). One third had extrapulmonary TB; four children died (13.8%).CONCLUSION: In our cohort, the incidence of TB-HIV co-infection decreased with decline in immigration. In regions with adequate cART coverage and low TB transmission, paediatric TB-HIV coinfection is uncommon, but associated with significant morbidity. Strategies for TB surveillance, diagnosis and treatment in this vulnerable population should be reinforced.
Assuntos
Coinfecção , Infecções por HIV , Tuberculose , Adolescente , Criança , Estudos de Coortes , Coinfecção/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Estudos Retrospectivos , Espanha/epidemiologia , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologiaRESUMO
INTRODUCTION: Zika virus (ZIKV) infection has caused the most challenging worldwide infectious epidemic outbreak in recent months. ZIKV causes microcephaly and other congenital malformations. There is a need to perform updated systematic reviews on ZIKV infection periodically because this epidemic is bringing up new evidence with extraordinary speed. Areas covered: Evidence related to ZIKV infection in the gestational, perinatal, and early infant periods covering epidemiology, virology, pathogenesis, risk factors, time of infection during pregnancy, newborn symptoms, treatment, and vaccines. To this end, a search was performed using terms ['Zika'] AND ['Perinatal Infection'] OR ['Congenital Infection'] in the PubMed® international electronic database. Out of a total of 1,538 articles published until 30 November 2017, we finally assessed 106 articles articles that were relevant to the research areas included in this study. Expert commentary: ZIKV is a new teratogenic/neurotropic virus affecting fetuses. Many challenges are still far from being solved regarding the epidemiology, case definition, clinical and laboratory diagnosis, and preventive measures. An approach using 'omics' and new biomarkers for diagnosis, and a ZIKV-vaccine for treatment, might finally give us the tools to solve these challenges.
Assuntos
Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Infecção por Zika virus/complicações , Animais , Surtos de Doenças , Feminino , Humanos , Recém-Nascido , Microcefalia/prevenção & controle , Microcefalia/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Fatores de Risco , Vacinas Virais/administração & dosagem , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controleRESUMO
Candida yeasts are ubiquitous commensals, which can cause opportunistic infection in any location of the body. The source of infection may be both endogenous and exogenous. Invasive candidiasis encompasses different entities ranging from invasive candidiasis to disseminated multiorgan infection. Invasive candidiasis is the third leading cause of nosocomial bloodstream infection and the fourth of all nosocomial infections. It is also the most common invasive fungal infection in non-neutropenic critically ill patients, with a remarkable increase in the last 20 years owing to the increased survival of these patients and to more complex diagnostic, therapeutic and surgical procedures. Its incidence in infants, according to recent reviews, stands at 38.8 cases/100,000 children younger than 1 year. Candida albicans remains the most frequent isolate in invasive infections, although infections caused by other species have risen in the last years, such as C. kruzsei, C. glabrata and C. parapsilosis; the latter causing invasive candidiasis mainly associated with central venous catheter management, especially in neonatal units. The overall mortality of invasive candidiasis is high, with 30-day mortality reaching 20-44% in some series involving paediatric patients. This report provides an update on incidence, epidemiology, clinical presentation, diagnosis, treatment and outcome of invasive infection by Candida spp. in the paediatric patient.
Assuntos
Candidíase Invasiva/diagnóstico , Candidíase Invasiva/terapia , Candidíase Invasiva/complicações , Candidíase Invasiva/epidemiologia , Humanos , Lactente , Recém-NascidoRESUMO
The present investigation was designed to determine whether the inhibition of gap junction-mediated intercellular communication (GJIC) induced by TPA (12-O-tetradecanoylphorbol-13-acetate) in rat liver epithelial (WB-F344) cells in vitro is mediated through free radical production. As assessed by fluorescence redistribution after photobleaching (FRAP) analysis, GJIC was significantly inhibited in cells treated for 1 hr with either 10 ng/ml TPA or 500 microM hydrogen peroxide (H2O2). Addition of 1000 U/ml catalase or 25 microM N',N'-diphenyl-p-phenylenediamine (DPPD) to TPA-treated cells did not alleviate the TPA-induced inhibition of GJIC. However, the concurrent addition of 1000 U/ml catalase to the culture medium prevented the H2O2 inhibition of GJIC. 2'-7'-dichlorofluorescein-mediated fluorescence, a measure of free radical production utilizing the Meridian ACAS 470 interactive laser cytometer, was not significantly increased in WB-F344 cells treated with 10 and 100 ng/ml TPA when compared to control cells. However, polymorphonuclear leukocytes (PMNs) treated for 10 min with 100 ng/ml TPA showed a substantial oxidative burst, as did WB-F344 cells treated for 1 hr with 500 microM H2O2. The concurrent addition of 1000 U/ml catalase to the culture medium attenuated H2O2-mediated free radical production in both PMNs and WB-F344 cells. Data from this study do not support a role for free radicals in the TPA-induced inhibition of GJIC in WB-F344 cells.