RESUMEN
BACKGROUND: Pediatric low-grade glioma incidence has been rising in the U.S., mirroring the rising rates of pediatric and maternal obesity. Recently, children of obese mothers were demonstrated to develop brain tumors at higher rates. Importantly, obesity in the U.S. is largely driven by diet, given the prevalence of high fat and high sugar (HFHS) food choices. Since high-fat diet exposure can increase embryonic neuroglial progenitor cell (NPC) proliferation, the potential cells of origin for low-grade glioma, we hypothesized that in utero exposure to an obesogenic diet would modify pediatric brain penetrance and latency by affecting the tumor cell of origin. METHODS: We employed several murine models of the Neurofibromatosis type 1 (NF1) pediatric brain tumor predisposition syndrome, in which optic pathway gliomas (Nf1-OPGs) arise from NPCs in the embryonic third ventricular zone (TVZ). We exposed dams and offspring to an obesogenic HFHS diet or control chow and analysed fetal neurodevelopment at E19.5 and tumor formation at 6w-3mo. RESULTS: Progeny from HFHS diet-exposed dams demonstrated increased TVZ NPC proliferation and glial differentiation. Dietary switch cohorts confirmed that these effects were dependent upon maternal diet, rather than maternal weight. Obesogenic diet (Ob) similarly accelerated glioma formation in a high-penetrance Nf1-OPG strain and increased glioma penetrance in two low-penetrance Nf1-OPG strains. In contrast, Ob exposure in the postnatal period alone did not recapitulate these effects. CONCLUSIONS: These findings establish maternal obesogenic diet as a risk factor for murine Nf1-OPG formation, acting in part through in utero effects on the tumor cell of origin.
RESUMEN
Influenza outbreaks are associated with significant morbidity. Our aim was to determine the factors associated with increased mortality in hospitalized patients admitted with diagnosis of influenza, at a tertiary care center in Pakistan. This study included all adult patients with an influenza infection, confirmed by realtime reverse-transcriptase polymerase-chain-reaction (RT-PCR) at Aga Khan University Hospital Pakistan. In our study, 112 patients with laboratory-confirmed influenza virus infection were admittedat our hospital from the 1st of January 2013 to the 31st of December 2018. Eighty-nine patients (79.46%) were managed in ward or special care units and 23 patients (20.5%) received treatment in intensive care unit (ICU). The overall mortality in our study was 15/112 (13.4%) with the mortality rate of ICU patients being 47.8% while the mortality rate of patients treated in special care units and wards was only 4.5%. The mean age of patients with influenza infection was 58.1 years (±16.6). Influenza virus type A was found in 87 patients (77.6%), while influenza type B was present in only 25 (22.4%) patients. Out of the 15 non-survivors, 14 had influenza A. Only 17 patients (15.2%) were found to have positive culture of respiratory specimen, out of which 3 were non-survivors and 14 were survivors. Our analysis identified septic shock (odds ratio 45.24; 95%, confidence interval 6.20-330; p<0.001), renal failure (odds ratio 10.88; 95%, confidence interval 1.61-73.52; p=0.01) and ICU stay (odds ratio 17.22; 95%, confidence interval 2.68-110.5; p=0.003) as independent risk factors associated with in-hospital mortality.