Human Keratinocytes Adopt Neuronal Fates After In Utero Transplantation in the Developing Rat Brain.

Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this article we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injection. For this purpose, keratinocytes were transduced with lentivirus that contained the coding sequence of green fluorescent protein. Cell sorting was employed to select cells with high fluorescence. Unexpectedly, 4 days after grafting these cells in the ventricles, both control and neural-induced cells expressed green fluorescent protein together with the neuronal proteins ßIII-Tubulin and Microtubule-Associated Protein 2. These results support the notion that in vivo environment provides appropriate signals to evaluate the neuronal differentiation potential of keratinocytes or other non-neural cell populations.

Incidence and outcome of in-hospital cardiac arrest in Italy: a multicentre observational study in the Piedmont Region.

AIMS: to report the incidence, characteristics, and outcome of in-hospital cardiac arrest (IHCA) in a large Italian region. SETTING: all hospitals participating in the IHCA Registry Initiative of Piedmont. METHODS: observational cohort study in adult (>18year old) inpatients resuscitated from IHCA during three consecutive years (2012-2014). The main outcome measures were IHCA incidence and survival to hospital discharge. RESULTS: A total of1539 arrests in adult inpatients were recorded in the study period, yielding an overall incidence of 1.51 arrests/1000 admissions. The incidence was highest at day 1 after hospital admission and in the morning hours, with a peak at 9.00 a.m. Median age was 77 (interquartile range 68-83) years. The presenting rhythm was ventricular fibrillation/pulseless ventricular tachycardia in 291/1539 (18.9%) cases. A total of 549/1539 (35.7%) patients achieved recovery of spontaneous circulation (ROSC) and 228/1539(14.8%) survived hospital discharge, with 207 (90.8%) of the latter having good neurological outcome (Cerebral Performance Categories [CPC] 1 or 2).After adjustment for major confounders, a pre-arrest CPC=1, a cardiac cause of arrest, a shockable presenting rhythm, and a shorter duration of resuscitation were independently associated with a higher likelihood of survival to discharge. CONCLUSIONS: in this Italian registry the incidence of IHCA and its circadian distribution were comparable to those in the NCAA registry in the UK. Patients were older and had a lower ROSC rate than these observed in other large IHCA registries, but post-ROSC survival rate and factors affecting survival to discharge were similar.

Factors affecting attitudes and barriers to a medical emergency team among nurses and medical doctors: a multi-centre survey.

AIM: To identify factors underlying attitudes towards the medical emergency team (MET) and barriers to its utilisation among ward nurses and physicians. METHODS: Multicentre survey using an anonymous questionnaire in hospitals with a fully operational MET system in the Piedmont Region, Italy. Response to questions was scored on a 5-point Likert-type agreement scale. Dichotomised results were included in a logistic regression model. RESULTS: Among 2279 staff members who were contacted, 1812 (79.6%) completed the survey. The vast majority of respondents valued the MET. Working in a surgical vs. medical ward and having participated in either the MET educational programme (METal course) or MET interventions were associated with better acceptance of the MET system. Reluctance by nurses to call the covering doctor first instead of the MET for deteriorating patients (62%) was significantly less likely in those working in surgical vs. medical wards or having a higher seniority or a METal certification (OR 0.51 [0.4-0.65], 0.69 [0.47-0.99], and 0.6 [0.46-0.79], respectively). Reluctance to call the MET in a patient fulfilling calling criteria (21%), was less likely to occur in medical doctors vs. nurses and in surgical vs. medical ward staff, and it was unaffected by the METal certification. CONCLUSIONS: The MET was well accepted in participating hospitals. Nurse referral to the covering physician was the major barrier to MET activation. Medical status, working in surgical vs. medical wards, seniority and participation in the METal educational programme were associated with lower likelihood of showing barriers to MET activation.

Liquidity, Technological Opportunities, and the Stage Distribution of Venture Capital Investments.

This paper explores the determinants of the stage distribution of European venture capital investments from 1990 to 2011. Consistent with liquidity risk theory, we find that the likelihood of investing in earlier stages increases relative to all private equity investments during liquidity crisis years. While liquidity is the main driver of acquisition investments and, to some extent, of expansion financings, technological opportunities are overall the main driver of early and late stage venture capital investments. In contrast to the dotcom crash, the recent financial crisis negatively affected the relative likelihood of expansion investments, but not of early and late stage investments.