Commitments to help by children: Effects on subsequent prosocial self-attributions

Children of both sexes and at several ages were or were not induced to make a commitment to help hospitalized children by sorting papers

Effect of intraoperative fluid optimisation on renal function in patients undergoing emergency abdominal surgery; a randomised controlled pilot study (ISRCTN 11799696) Fluid optimisation for emergency surgery

<b>Background:</b> Emergency abdominal surgery carries a high risk of postoperative morbidity and mortality. Goal directed therapy has been advocated to improve outcome in high-risk surgery. The aim of the present pilot study was to examine the effect of goal directed therapy using fluid alone on postoperative renal function and organ failure score in patients undergoing emergency abdominal surgery. <b>Methods:</b> This prospective randomised pilot study included patients over the age of 50 undergoing emergency abdominal surgery. In the intervention group pulse pressure variation measurements were used to guide fluid boluses of 6% Hydroxyethylstarch 130/0.4. The control group received standard care. Serum urea, creatinine and cystatin C levels were measured prior to and at the end of surgery and postoperatively on day 1, day 3 and day 5. <b>Results:</b> Thirty patients were recruited. One patient died prior to surgery and was excluded from the analysis. The intervention group received a median of 750ml of hydroxyethylstarch. The peak values of postoperative urea were 6.9 (2.7–31.8) vs. 6.4 (3.5–11.5)mmol/l (p=0.425), creatinine 100 (60–300) vs. 85 (65–150) μmol/l (p=0.085) and cystatin C 1.09 (0.66–4.94) vs. 1.01 (0.33–2.29)mg/dl (p=0.352) in the control and intervention group, respectively. <b>Conclusions:</b> In the present pilot study replacing the identified fluid deficit was not associated with a change in renal function. These results do not preclude that goal directed therapy using fluid alone may have an effect on renal function but they would suggest that the effect size of fluid optimisation alone on renal function is small

Cardiac Allograft Vasculopathy in Redo-transplants: Is it More or Less the Same the Second Time Around?

Purpose: Cardiac allograft vasculopathy (CAV) continues to hinder the long-term success of heart transplant recipients.  Redo-transplantation is currently the only definitive treatment for advanced CAV. We examined whether these patients are at similar CAV-risk with the second transplantMethods: Heart recipients from 1985 to 2011 at the UTAH program were included in the study and those with CAV as an indication for redo-transplantation were identified. CAV diagnosis was made by coronary angiography and based on the 2010 ISHLT standardized nomenclature for CAV. Patient demographics, rejection history, and CAV incidence were analyzed. Results: Of the 1,169 eligible patients, 135 (11.5%) developed CAV post their first transplant; 78 cases within 10 years and 54 beyond 10 years. The mean time to CAV was 6.58 years. Of the 135 patients who developed CAV, only 21 (15.5%) ended up requiring a redo-transplant. Of the 21 retransplanted patients, 4 (19.0%) developed CAV again; 2 patients within 10 years and 2 patients beyond 10 years indicating a similar risk for CAV occurrence for first and redo-transplant. Conclusions: Our results indicate that CAV is as likely to develop in redo-transplants despite recent advances in immunosuppression and the standardized use of lipid-lowering agents. Although outcomes in redo-transplantation for the indication of CAV are favorable, efforts to better understand and minimize CAV are needed, especially in the face of scarce donor organs

Gene targeting in adult rhesus macaque fibroblasts

<p>Abstract</p> <p>Background</p> <p>Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT) has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in primary culture of adult rhesus macaque fibroblasts as a first step in creating nonhuman primate models of genetic disease using nuclear transfer technology.</p> <p>Results</p> <p>A primary culture of adult male fibroblasts was transfected with hTERT to overcome senescence and allow long term <it>in vitro </it>manipulations. Successful gene targeting of the HPRT locus in rhesus macaques was achieved by electroporating S-phase synchronized cells with a construct containing a SV40 enhancer.</p> <p>Conclusion</p> <p>The cell lines reported here could be used for the production of null mutant rhesus macaque models of human genetic disease using SCNT technology. In addition, given the close evolutionary relationship and biological similarity between rhesus macaques and humans, the protocols described here may prove useful in the genetic engineering of human somatic cells.</p

Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota

Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease