Airway intervention in adult supraglottitis

Background The timing of aggressive airway intervention in adult epiglottitis is controversial. Aims To correlate Friedman’s staging of epiglottitis on admission with the airway interventions undertaken. Methods A retrospective study of 23 adult patients, mean age 51 years (range 29–81 years), who had been admitted with acute supraglottitis between March 1988 and December 2000 was undertaken. Results Three patients (13%) had airway interventions; two with tracheostomy and one with tracheal intubation. All were Friedman stage III and had rapid symptom progression during the 24 hours prior to admission. Three other stage III patients with symptom progression longer than 24 hours and all the remaining patients (stage II or less) were managed with observation and intravenous therapy. Conclusions Friedman originally advocated airway intervention in any patient stage II or worse, but this intubation threshold should probably be lowered to those patients with rapid-onset stage III (moderate respiratory distress, stridor, respiratory rate >30 per minute, pCO₂ >45mmHg) disease.     

The hematopoietic stem cells of alpha-thalassemic mice

The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy.     

Erythropoietin and IGF-1 signaling synchronize cell proliferation and maturation during erythropoiesis

Tight coordination of cell proliferation and differentiation is central to red blood cell formation. Erythropoietin controls the proliferation and survival of red blood cell precursors, while variations in GATA-1/FOG-1 complex composition and concentrations drive their maturation. However, clear evidence of cross-talk between molecular pathways is lacking. Here, we show that erythropoietin activates AKT, which phosphorylates GATA-1 at Ser310, thereby increasing GATA-1 affinity for FOG-1. In turn, FOG-1 displaces pRb/E2F-2 from GATA-1, ultimately releasing free, proproliferative E2F-2. Mice bearing a Gata-1^S310A mutation suffer from fatal anemia when a compensatory pathway for E2F-2 production involving insulin-like growth factor-1 (IGF-1) signaling is simultaneously abolished. In the context of the GATA-1^V205G mutation resulting in lethal anemia, we show that the Ser310 cannot be phosphorylated and that constitutive phosphorylation at this position restores partial erythroid differentiation. This study sheds light on the GATA-1 pathways that synchronize cell proliferation and differentiation for tissue homeostasis.     

Relationships of sleep duration with sociodemographic and health‐related factors,psychiatric disorders and sleep disturbances in a community sample of Korean adults

The aim of this study is to examine relationships of sleep duration with sociodemographic and health‐related factors, psychiatric disorders and sleep disturbances in a nationwide sample in Korea. A total of 6510 subjects aged 18–64 years participated in this study. Logistic regression was used to calculate the odd ratios and 95% confidence intervals of the covariates, psychiatric disorders and sleep disturbances across the following sleep duration categories: 5 h or less, 6, 7, 8 and 9 h or more per day. Low levels of education, unemployment and physical illness were associated with sleeping for 5 h or less and 9 h or more. Being older and widowed/divorced/separated, high levels of physical activity, pain/discomfort, obesity and high scores on the General Health Questionnaires were associated with sleeping for 5 h or less. Female, being younger and underweight were associated with sleeping for 9 h or more. Alcohol dependence, anxiety disorder and social phobia were associated significantly with sleeping for 5 h or less and 9 h or more. Other psychiatric disorders were more common in subjects who slept for 5 h or less (e.g. alcohol use disorder, mood disorder, major depressive disorder, dysthymic disorder, obsessive‐compulsive disorder and specific phobia) or 9 h or more (e.g. post‐traumatic stress disorder). In addition, subjects who slept for 5 h or less reported more sleep disturbances than did subjects who slept for 7 h. Short or long sleep is associated with psychiatric disorders and/or sleep disturbance, therefore attention to the mental health of short or long sleepers is needed.     

Sleep duration and sleep disturbances partly explain the association between depressive symptoms and cardiovascular mortality: the Whitehall II cohort study

Depressive symptoms are associated with an increased risk of death, but most of this association remains unexplained. Our aim was to explore the contribution of sleep duration and disturbances to the association between depressive symptoms, all‐cause and cardiovascular disease mortality. A total of 5813 (4220 men and 1593 women) aged 50–74 years at baseline, participants of the British Whitehall II prospective cohort study, were included. Depressive symptoms, sleep duration and disturbances were assessed in 2003–04. Mortality was ascertained through linkage to the national mortality register until August 2012, with a mean follow‐up of 8.8 years. Depressive symptoms were associated with an increased risk of mortality from all causes [hazard ratio (HR) = 1.51; 95% confidence interval (CI): 1.16–1.97)] and cardiovascular diseases (HR = 1.63; 95% CI: 1.01–2.64) after adjustment for sociodemographic characteristics. Further adjustment for sleep duration and disturbances reduced the association between depressive symptoms and cardiovascular mortality by 21% (HR = 1.53; 95% CI: 0.91–2.57). Sleep seems to have a role, as a mediator or confounder, in explaining the association between depressive symptoms and cardiovascular mortality. These findings need replication in larger studies with longer follow‐up.