Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis

To understand the developmental trajectories in early lymphocyte differentiation, we identified differentially expressed surface markers on lineage-negative lymphoid progenitors (LPs). Single-cell polymerase chain reaction experiments allowed us to link surface marker expression to that of lineage-associated transcription factors (TFs) and identify GFRA2 and BST1 as markers of early B cells. Functional analyses in vitro and in vivo as well as single-cell gene expression analyses supported that surface expression of these proteins defined distinct subpopulations that include cells from both the classical common LPs (CLPs) and Fraction A compartments. The formation of the GFRA2-expressing stages of development depended on the TF EBF1, critical both for the activation of stage-specific target genes and modulation of the epigenetic landscape. Our data show that consecutive expression of Ly6D, GFRA2, and BST1 defines a developmental trajectory linking the CLP to the CD19(+) progenitor compartment.Peer reviewe

Shiftwork Problems

U radu se raspravlja o negativnim utjecajima smjenskog rada koji su klasifi cirani u četiri kategorije učinaka: na biološke funkcije, radnu efi kasnost, društvene / obiteljske aspekte života te na zdravlje. Dan je sustavni pregled dosadašnjih istraživanja zdravstvenih problema smjenskih radnika u čijoj je osnovi narušavanje cirkadijurnih ritmova organizma koju nameće smjenski / noćni rad. Zdravstveni problemi koji se dovode u vezu sa smjenskim radom su ovi: problemi sa spavanjem, gastrointestinalne i kardiovaskularne bolesti, karcinom, problemi s reproduktivnim funkcijama žena te lošije psihičko zdravlje. U radu se također raspravlja o toleranciji smjenskog rada. Pri tome je kao teoretski okvir povezanosti smjenskog rada i negativnih zdravstvenih posljedica rabljen procesni model koji su postavili Smith i suradnici 1999. Poseban naglasak stavljen je na individualne i organizacijske faktore o kojima ovisi mogućnost prilagodbe na smjenski rad te tolerancija takvog rada. Značajni prediktori tolerancije smjenskog rada su: dob, spol, jutarnjost-večernjost, rigidnost-fl eksibilnost u navikama spavanja, obiteljska situacija, higijena spavanja te zdrava prehrana. S obzirom na rezultate istraživanja koji upućuju na povezanost nekih karakteristika organizacije smjenskog rada s tolerancijom prema smjenskom radu, kao što su: broj radnih smjena i trajanje smjene, broj sukcesivnih noćnih smjena, regularnost smjena, brzina i smjer rotacije smjena, preporučene su intervencijske strategije u organizaciji smjenskog rada.This paper discusses the negative effects of shiftwork which are classified into four categories: biological functions, efficiency, social / family domains and health. It presents systematic review of previous studies which indicated at health problems in shiftworkers which can, at least in part, be attributed to disturbation of circadian rhythms imposed by shift / night work. Health probles which are connected with shiftork are: sleeping problems, gastrointestinal and cardiovascular diseases, carcinoma, problems with reproductive health in women and lower levels of psychological health. The paper also discusses about shiftwork tolerance. The process model of shiftwork and health, made by Smith and his coworkers in 1999, is used as theoretical framework. An accent is put on individual and organisational factors which are important for shiftwork adaptation and tolerance. Significant predictors of shiftwork tolerance are: age, gender, morningness–eveningness, rigidity-flexibility of sleeping habits, family situation, sleep hygiene and food intake. Regarding studies which indicated important aspects of shiftwork organization, such as: number of working shifts and working hours, regularity of shifts, pace and direction of shifts’ rotation, recommendations for shiftwork management are giv

Prognosis following upper gastrointestinal bleeding: Record linkage study

Upper gastrointestinal (GI) bleeding is one of the most common, high risk emergency disorders in the western world. Almost nothing has been reported on longer term prognosis following upper GI bleeding. The aim of this study was to establish mortality up to three years following hospital admission with upper GI bleeding and its relationship with aetiology, co-morbidities and socio-demographic factors.Systematic record linkage of hospital inpatient and mortality data for 14 212 people in Wales, UK, hospitalised with upper GI bleeding between 1999 and 2004 with three year follow-up to 2007. The main outcome measures were mortality rates, standardised mortality ratios (SMRs) and relative survival.Mortality at three years was 36.7% overall, based on 5215 fatalities. It was highest for upper GI malignancy (95% died within three years) and varices (52%). Compared with the general population, mortality was increased 27-fold during the first month after admission. It fell to 4.3 by month four, but remained significantly elevated during every month throughout the three years following admission. The most important independent prognostic predictors of mortality at three years were older age (mortality increased 53 fold for people aged 85 years and over compared with those under 40 years); oesophageal and gastric/duodenal malignancy (48 and 32 respectively) and gastric varices aetiologies (2.8) when compared with other bleeds; non-upper GI malignancy, liver disease and renal failure co-morbidities (15, 7.9 and 3.9); social deprivation (29% increase for quintile V vs I); incident bleeds as an inpatient (31% vs admitted with bleeding) and male patients (25% vs female).Our study shows a high late as well as early mortality for upper GI bleeding, with very poor longer term prognosis following bleeding due to malignancies and varices. Aetiologies with the worst prognosis were often associated with high levels of social deprivation