Is MED13L-related intellectual disability a recognizable syndrome?

Introduction

MED13L-related intellectual disability is characterized by moderate intellectual disability (ID), speech impairment, and dysmorphic facial features. We present 8 patients with MED13L-related intellectual disability and review the literature for phenotypical and genetic aspects of previously described patients.

The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10

Sepsis caused by gram-positive bacteria lacking lipopolysaccharide (LPS) has become a major and increasing cause of mortality in intensive-care units. We have recently demonstrated that the gram-positive-specific bacterial cell wall component lipoteichoic acid (LTA) stimulates the release of the proinflammatory cytokines in Kupffer cells in culture. In the present study, we have started to assess the signal transduction events by which LTA induces the production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and the anti-inflammatory cytokine IL-10 in rat Kupffer cells. LTA was found to trigger phosphorylation of mitogen-activated protein kinases (MAPK) (p38 MAPK and ERK 1/2) and protein kinase B (PKB). Compared to LPS, LTA was more potent in inducing PKB phosphorylation after 40 min, although we found that the cytokine responses were similar. For both bacterial molecules, blocking phosphatidylinositol 3-kinase (PI3-K; Ly294002) or Janus kinase 2 (JAK-2; AG490) particularly affected the induction of IL-6 and IL-10 release, whereas TNF-alpha levels were strongly reduced by inhibition of Src family tyrosine kinases (PP2). All three cytokines were reduced by inhibition of p38 MAPK (SB202190) or the broad-range tyrosine kinase inhibitor genistein, whereas IL-6 release was particularly blocked by inhibition of ERK 1/2 (PD98059). Divergences in the regulatory pathways controlling TNF-alpha, IL-10, and IL-6 production in Kupffer cells following LPS or LTA stimulation may create a basis for understanding how the balance between pro- and anti-inflammatory cytokines is regulated in the liver following infections by gram-positive or gram-negative bacteria.     

Kidney function during 12 months of strict metabolic control in insulin-dependent diabetic patients with incipient nephropathy

Thirty-six patients with insulin-dependent diabetes mellitus who had Albustix-negative urine but elevated urinary albumin excretion (30 to 300 mg per 24 hours) were matched in pairs according to their urinary albumin level, blood glycosylated hemoglobin level, and sex and assigned randomly to either unchanged conventional treatment or continuous insulin infusion. During the next 12 months a significant improvement in glycemic control was observed in the insulin-infusion group, with a reduction in the mean glycosylated hemoglobin level from 9.5 to 7.3 percent. There was no change in the control group (9.3 to 9.2 percent). No significant change in albumin excretion was observed in either group. The mean blood pressure increased slightly in both groups (from 98 to 101 mm Hg in the insulin-infusion group and from 98 to 103 mm Hg in the control group). Kidney size was significantly reduced in all patients during insulin infusion, but no consistent change was observed in the control group. No significant change was observed in the glomerular filtration rate. Our data suggest that the pathologic processes causing microalbuminuria in early renal disease are not reversed during 12 months of strict metabolic control.     

Peptide-Based OspC Enzyme-Linked Immunosorbent Assay for Serodiagnosis of Lyme Borreliosis

Sera from 210 patients with Lyme borreliosis (LB) were studied by an enzyme-linked immunosorbent assay (ELISA) based on a synthetic peptide (pepC10) comprising the C-terminal 10-amino-acid residues of OspC of Borrelia burgdorferi. We found that 36.3 and 45.0% of the serum samples from patients with erythema migrans (EM) and neuroborreliosis (NB), respectively, displayed immunoglobulin M (IgM) anti-pepC10 reactivities, while these samples rarely (≤8%) displayed IgG antibody reactivities. Sera from patients with acrodermatitis chronica atrophicans did not contain anti-pepC10 antibodies. The diagnostic performance of this newly developed peptide ELISA was compared with those of an ELISA based on the full-length recombinant OspC protein (rOspC) and a commercially available ELISA based on the B. burgdorferi flagellum (Fla). The sensitivity of the IgM pepC10 ELISA was slightly lower (P < 0.04) than that of the rOspC ELISA for EM patients (36.3 versus 43.8%), while there was no difference for NB patients (45.0 versus 48.0%). However, the optical density values obtained by the pepC10 ELISA were generally higher than those obtained by the rOspC ELISA, leading to a significantly better quantitative discrimination between seropositive patients with NB and controls (P < 0.008). The specificity of the pepC10 ELISA was similar to those of the rOspC ELISA and the Fla ELISA for relevant controls including patients with syphilis and mononucleosis. Although the overall diagnostic sensitivity of the Fla ELISA was superior, 8.8 and 12.0% of the EM and NB patients, respectively, were antibody positive only by the pepC10 ELISA. Thus, use of a diagnostic test for LB based on the detection of IgM antibodies to pepC10 and Fla has increased sensitivity for the diagnosis of early LB.     

Surgeons’ experience of venous risk with CPA surgery

Neurosurgical Review - The study aims to systematize neurosurgeons’ practical knowledge of venous sacrifice as applied to the posterior fossa region and to analyze the collected data to...     

Cardiovascular events in patients undergoing hip fracture surgery treated with remote ischaemic preconditioning: 1-year follow-up of a randomised clinical trial

Remote ischaemic preconditioning reduces the risk of myocardial injury within 4 days of hip fracture surgery. We aimed to investigate the effect of remote ischaemic preconditioning on the incidence of major adverse cardiovascular events 1 year after hip fracture surgery. We performed a phase-2, multicentre, randomised, observer-blinded, clinical trial between February 2015 and September 2017. We studied patients aged ≥ 45 years with a hip fracture and a minimum of one cardiovascular risk factor. Patients were allocated randomly to remote ischaemic preconditioning applied just before surgery or no treatment (control group). Remote ischaemic preconditioning was performed on the upper arm with a tourniquet in four cycles of 5 min ischaemia and 5 min reperfusion. Primary outcome was the occurrence of major adverse cardiovascular events within 1 year of surgery. A total of 316 patients were allocated randomly to the remote ischaemic preconditioning group and 309 patients to the control group. Major adverse cardiovascular events occurred in 43 patients (13.6%) in the remote ischaemic preconditioning group compared with 51 patients (16.5%) in the control group (adjusted hazard ratio (95%CI) 0.83 (0.55–1.25); p = 0.37). Fewer patients in the remote ischaemic preconditioning group had a myocardial infarction (11 (3.5%) vs. 22 (7.1%); hazard ratio (95%CI) 0.48 (CI 0.23–1.00); p = 0.04). Remote ischaemic preconditioning did not reduce the occurrence of major adverse cardiovascular events within 1 year of hip fracture surgery. The effect of remote ischaemic preconditioning on clinical cardiovascular outcomes in non-cardiac surgery needs confirmation in appropriately powered randomised clinical trials.     

The influence of social class, strain and social support on symptoms of anxiety and depression in mothers of toddlers

Background: The aim of the study was to identify risk and protective factors for anxiety and depression among mothers of toddlers. Methods: A population-based sample of 921 Norwegian mothers with 18-month-old children completed a questionnaire designed to examine the impact of socioeconomic and demographic factors, somatic health problems, negative life events, chronic strain and social support on symptoms of anxiety and depression (HSCL-25). Results: There was a moderate aversive effect of negative life events and chronic strain and a moderate protective effect of social support on the symptom level, but no interaction effects were found between the risk and protective factors. Behaviour problems among the children clearly seemed to affect the mothers' symptom level. The symptom level varied with background factors like the mothers' education, employment status and age even after controlling for the effect of strain and social support. The largest effect of the background factors seemed to be indirect, however, mediated through their effect on the risk and protective factors. Conclusions: Although problems with the children's behaviour and child care arrangements were observed to have a strong impact on the mothers' symptom level, the frequencies of such problems appeared to be less dependent on socioeconomic conditions than did other types of strain. Accepted: 21 July 1998