Comprehensive approach to high-resolution KIR typing

Multiple studies suggest that prospective KIR typing may be beneficial for the outcome of bone marrow transplants, but to date no practical high-resolution KIR typing system has been developed. Here we propose a comprehensive high-resolution typing approach that provides allele level KIR typing. Based on the low-resolution typing obtained by SSO, the 14 KIR loci are divided in groups according to the level of polymorphism in exons coding for extracellular Ig-like domains and cytoplasmic tail. The first group is typed by sequence-specific oligonucleotide only; the second is typed by sequence-based typing (SBT) based on the amplification of a fragment coding the Ig-like domains; and the third is typed by SBT based on amplification of a fragment coding the cytoplasmic tail. SBT for the fourth group includes both the Ig-like and cytoplasmic domains. Because of a considerable number of polymorphisms scattered throughout all nine KIR exons, SBT results may still produce a number of ambiguities, which can be resolved by sequence-specific primers. This combined high-resolution approach was applied to the complete KIR typing of 205 Caucasian hematopoietic stem cell donors in support of the National Marrow Donor Program High-resolution KIR Typing Pilot Project. High-resolution typing of several KIR loci produced numerous novel alleles, whereas some loci demonstrated very limited polymorphism. Several of the novel alleles appeared in more than four donors, suggesting that these alleles are not rare. Our results showed that the comprehensive KIR typing approach presented here provides the balance of high-resolution typing and cost effectiveness.     

T cell independent mechanism for copolymer-1-induced neuroprotection

Despite active investigation of copolymer-1 (Cop-1) for nearly 40 years the mechanisms underlying its neuroprotective properties remain contentious. Nonetheless, current dogma for Cop-1 neuroprotective activities in autoimmune and neurodegenerative diseases include bystander suppression of autoimmune T cells and attenuation of microglial responses. In this report, we demonstrate that Cop-1 interacts directly with primary human neurons and decreases neuronal cell death induced by staurosporine or oxidative stress. This neuroprotection is mediated through protein kinase Calpha and brain-derived neurotrophic factor. Dendritic cells (DC) uptake Cop-1, deliver it to the injury site, and release it in an active form. Interactions between Cop-1 and DC enhance DC blood brain barrier migration. In a rat model with optic nerve crush injury, Cop-1-primed DC induce T cell independent neuroprotection. These findings may facilitate the development of neuroprotective approaches using DC-mediated Cop-1 delivery to diseased nervous tissue.     

Programs for Preventing Depression in Adolescence: Who Benefits and Who Does Not? An Introduction to the Supplemental Issue

We introduce this supplemental issue of Prevention Science, which brings together a set of papers from leading investigators who have conducted trials testing whether intervention programs prevent adolescent depression. Using data from these trials, these papers explore a series of factors that might account for variation in intervention benefit, employing several novel methods for assessing effect heterogeneity. These studies follow two general paradigms: three papers report findings from single randomized preventive intervention trials, while the remaining papers develop and apply new methods for combining data from multiple studies to evaluate effect heterogeneity more broadly. Colleagues from NIMH and SAMHSA also provide commentaries on these studies. They conclude that synthesis of findings from multiple trials holds great promise for advancing the field, and progress will be accelerated if collaborative data sharing becomes the norm rather than the exception.     

Bonded versus banded first molar attachments: a randomized controlled clinical trial

OBJECTIVE: To compare the clinical failure rates of bonded first molar tubes with those of cemented bands during fixed appliance therapy. DESIGN: Prospective randomized controlled clinical trial. SETTING: Two UK hospital orthodontic clinics, February 2001-December 2004. PARTICIPANTS: Hospital waiting list patients needing fixed appliances (n = 110). METHOD: Patients were randomly allocated to two groups. Experimental group patients (n = 55) received single first molar tubes (n = 181) bonded with a no-mix chemically cured composite (Rely-A-Bond) after a 30-second etch. Control group patients (n = 55) were treated with bands (n = 186) cemented with Intact glass ionomer cement (GIC). First-time failures were recorded together with the time of failure. All patients were followed to the end or discontinuation of treatment. RESULTS: First-time failures: bands = 18.8%; bonds = 33.7 %. Bonded tubes were more likely to fail [RR 2.4; 95% CI (1.4, 4.1)] compared with bands. Experimental group patients also had more bracket failures (P = 0.009), when analysed at patient level. CONCLUSION: First molar tubes bonded with Rely-A-Bond composite showed a significantly higher first-time failure rate than bands cemented with Intact GIC.     

In vitro Candida colonization on acrylic resins and denture liners: influence of surface free energy, roughness, saliva, and adhering bacteria

This study aimed to determine the influence of surface roughness (Ra), surface free energy (SFE), saliva, and bacteria on Candida adhesion to denture materials. The Ra and SFE of 2 acrylic resin specimens and 2 denture liner specimens were measured and assayed in a flow chamber for bacteria culture perfusion plus Candida albicans or C glabrata cultures. Adhesion was determined by counting under light microscopy. Candida adhesion showed significant differences depending on the factors involved. The overall colonization was significantly decreased by saliva and influenced by bacteria. Candida adhesion was strongly affected by Ra, saliva, and bacteria, but not by SFE.     

Antioxidant treatment prevented late memory impairment in an animal model of sepsis

OBJECTIVE: Assess the effect of antioxidant treatment on late memory impairment and early hippocampus oxidative stress after cecal ligation and perforation. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats underwent sham operation or cecal ligation and perforation. Animals that underwent cecal ligation and perforation were divided into groups: 1) treated with basic support (50 mL/kg saline, 30 mg/kg ceftriaxone, and 25 mg/kg clindamycin every 6 hrs), 2) treated with basic support plus N-acetylcysteine (20 mg/kg N-acetylcysteine at 3, 6, 12, 18, and 24 hrs after cecal ligation and perforation), 3) treated with basic support plus deferoxamine (20 mg/kg deferoxamine at 3 and 24 hrs after cecal ligation and perforation), 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. MEASUREMENTS AND MAIN RESULTS: On days 10 and 30 after surgery, the animals underwent behavioral tasks: inhibitory avoidance task, habituation to an open field, and continuous multiple-trials step-down inhibitory avoidance task. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the sepsis group presented memory impairment after sepsis. In the continuous multiple-trials step-down inhibitory avoidance task, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine treatment, but not its isolate use. In addition, the combined use of antioxidants attenuated oxidative damage in hippocampus 6 hrs after sepsis induction. CONCLUSIONS: Antioxidant treatment prevented the development of late cognitive deficits in an animal model of sepsis.     

Microsurgical clipping vs Woven EndoBridge (WEB) device for the management of unruptured wide-neck bifurcation aneurysms

Neurosurgical Review - The Woven EndoBridge device (WEB) was introduced in 2010 to treat wide-neck bifurcation aneurysms (WNBAs). Three landmark studies have been conducted to assess its safety and...     

Photobiomodulation via a cluster device associated with a physical exercise program in the level of pain and muscle strength in middle-aged and older women with knee osteoarthritis: a randomized placebo-controlled trial

Osteoarthritis (OA) is a chronic joint disease that leads to pain and functional incapacity. The aim of the study is to investigate the effects of the incorporation of photobiomodulation (PBM) (via cluster) into a physical exercise program on the level of pain, lower limb muscle strength, and physical capacity, in patients with knee OA. Sixty-two female volunteers with a diagnosis of knee OA were distributed in 4 groups: exercise associated with placebo PBM group, exercise associated with active PBM group, active PBM group, and placebo PBM group. Sixteen sessions of lower limb strength exercises and PBM via cluster (808 nm, 100 mW, 7 points each side, 56 J total) were performed. The level of pain, physical capacity, and lower limb muscle strength were evaluated with the use of the numeric pain rating scale (NPRS), 6-min walking test (6-MWT) and timed up and go (TUG), and maximal voluntary isometric torque (MVIT) before and after the interventions. Both groups presented a significant decrease in the level of pain when compared with the placebo-treated women. Furthermore, the 6-MWT showed that the trained groups (with or without PBM) demonstrated higher values in the distance walked comparing pre and post-treatment values. The same behavior was found for the MVIT load before and after intervention. TUG was higher for all the treated with exercise groups comparing the pre and post-treatment values. Physical exercise and PBM showed analgesic effects. However, PBM did not have any extra effect along with the effects of exercise in improving the distance walked, the TUG, and the muscle strength.

Trial registration: RBR-7t6nzr