Analytical quality control in neonatal screening

This critical review questions the present understanding in monitoring of analytical quality control in neonatal screening. Current status and historical background of the analytical quality control, particularly of the tests intended for the screening of congenital hypothyroidism and some inborn errors of metabolism, is reviewed. The reasons why attempts to standardize immunoassays through the preparation of a so-called “gold standard” (e.g. for thyrotropin) will not resolve noncomparability of results are discussed. The review presents arguments for the necessity of elaboration of international guidelines for methods assessment and comparison with an emphasis on their clinical relevance.     

The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a significant gastrointestinal disorder with unknown etiology. The symptoms can greatly weaken patients' quality of life and account for notable economical costs for society. Contribution of the gastrointestinal microbiota in IBS has been suggested. Our objective was to characterize putative differences in gastrointestinal microbiota between patients with IBS and control subjects. These differences could potentially have a causal relationship with the syndrome. METHODS: Microbial genomes from fecal samples of 24 patients with IBS and 23 controls were collected, pooled in a groupwise manner, and fractionated according to their guanine cytosine content. Selected fractions were analyzed by extensive high-throughput 16S ribosomal RNA gene cloning and sequencing of 3753 clones. Some of the revealed phylogenetic differences were further confirmed by quantitative polymerase chain reaction assays on individual samples. RESULTS: The coverage of the clone libraries of IBS subtypes and control subjects differed significantly (P < .0253). The samples were also distinguishable by the Bayesian analysis of bacterial population structure. Moreover, significant (P < .05) differences between the clone libraries were found in several bacterial genera, which could be verified by quantitative polymerase chain reaction assays of phylotypes belonging to the genera Coprococcus, Collinsella, and Coprobacillus. CONCLUSIONS: The study showed that fecal microbiota is significantly altered in IBS. Further studies on molecular mechanisms underlying these alterations are needed to elucidate the exact role of intestinal bacteria in IBS.     

Do alcohol restrictions reduce suicide mortality?

AIM: Blood alcohol concentration (BAC) at the time of suicide was examined in relation to the marked falls in suicide rates and per capita alcohol consumption in Estonia during the major Soviet anti-alcohol campaign from 1 June 1985. DESIGN AND PARTICIPANTS: In all, 5054 suicide cases (76% males, 24% females) were examined with respect to the official autopsy reports of the Estonian Bureau of Forensic Medicine (autopsy rates: 95% of males, 88% of females) before (1981-84), during (1986-88) and after (1989-92) the campaign. Cases were divided by gender and BAC level (0.5-1.49, 1.5-2.49 and > 2.5 per thousand). FINDINGS: During the campaign, annual per capita alcohol consumption in Estonia fell from 10.9 to 6.6 l. Alcohol in blood was found in 47.9% before, 35.1% during and 40.9% after the campaign. During the intervention, BAC-positive, i.e. alcohol-positive, suicides decreased by 39.2% for males and 41.4% for females, with the largest fall occurring at the BAC 2.5 per thousand + level for both sexes. Changes in BAC-negative suicides were modest. When the campaign ended suicide rates started to rise. CONCLUSIONS: Investigation on an individual level showed that alcohol consumption was a common precursor to suicide and that rigorous alcohol restrictions were accompanied particularly by a decrease in BAC-positive suicide mortality among both sexes. However, the 'natural experiment' does not, in terms of study design, demonstrate convincingly that the fall in the suicide rate was due specifically to the decrease in alcohol use as such.     

Adenoviral-encoded antigens are presented efficiently by a subset of dendritic cells expressing high levels of alpha(v)beta3 integrins

Dendritic cells (DC) play a central role in antigen presentation and are often targeted by adenoviral (Ad)-based gene therapy. However, DC lack the coxsackie-Ad receptor, and little is known about the process by which they acquire and present Ad-encoded antigens. We examined the expression of alpha(v)beta3 integrins (CD51/CD61) on mouse bone marrow-derived DC (BM-DC) and their susceptibility to transduction by Ad vectors. Less than 10% of BM-DC precursors expressed CD51, but expression increased over time in culture with granulocyte macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. After 7 days, 28 +/- 1.7% of CD11c+ DC expressed high levels of CD51 (CD51(hi)), and the remaining DC expressed low levels of CD51 (CD51(lo)). CD51(hi) CD express higher major histocompatibility complex type 1 (MHC I); however, both of the DC subsets expressed similar levels of MHC II and costimulatory molecules. When exposed to a first-generation Ad vector, transgene expression was restricted to the CD51(hi) DC subset and blocked by soluble peptides expressing an arginine, glycine, aspartic acid (RGD) sequence, confirming the role of integrins in viral entry. Consistent with this, a modified Ad expressing an RGD-binding sequence in its fiber knob (Ad-RGD) transduced the CD51(hi) DC subset with significantly higher efficiency. When BM-DC were transduced with an Ad-expressing ovalbumin (Ad-OVA), the CD51(hi) subset proved superior in activating OT-I (T cell receptor-OVA) T cells. Similar to in vitro effects, systemic administration of GM-CSF/IL-4 increased the expression of CD51 on splenic DC and rendered these cells susceptible to Ad transduction. These results suggest that a limited subset of DC expressing high levels of alpha(v)beta3 integrins is preferentially transduced by Ad vectors and activates CD8+ T cell responses against Ad-encoded antigens.     

Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers

Background  

A growing amount of scientific evidence suggests that microbes are involved in the aetiology of irritable bowel syndrome (IBS), and the gastrointestinal (GI) microbiota of individuals suffering from diarrhoea-predominant IBS (IBS-D) is distinguishable from other IBS-subtypes. In our study, the GI microbiota of IBS-D patients was evaluated and compared with healthy controls (HC) by using a high-resolution sequencing method. The method allowed microbial community analysis on all levels of microbial genomic guanine plus cytosine (G+C) content, including high G+C bacteria.     

Is Religiosity a Protective Factor Against Attempted Suicide: A Cross-Cultural Case-Control Study

This cross-cultural study investigates whether religiosity assessed in three dimensions has a protective effect against attempted suicide. Community controls (n = 5484) were more likely than suicide attempters (n = 2819) to report religious denomination in Estonia (OR = 0.5) and subjective religiosity in four countries: Brazil (OR = 0.2), Estonia (OR = 0.5), Islamic Republic of Iran (OR = 0.6), and Sri Lanka (OR = 0.4). In South Africa, the effect was exceptional both for religious denomination (OR = 5.9) and subjective religiosity (OR = 2.7). No effects were found in India and Vietnam. Organizational religiosity gave controversial results. In particular, subjective religiosity (considering him/herself as religious person) may serve as a protective factor against non-fatal suicidal behavior in some cultures.     

The Complex Impact of Risk and Protective Factors on Suicide Mortality: A Study of the Ukrainian General Population

This study assesses the complex impact of risk and protective factors on suicide mortality in the Ukrainian general population. Data on suicide rates and socioeconomic and medical factors were obtained from the Ukrainian State Statistical Office, WHO, and the European Social Survey. Structural equation modeling was used for data analysis. Religion and education were negatively associated with suicide. The relationship between drug addiction/alcoholism and suicide was positive. The association between urbanization and suicide mortality was negative. The relationship between gross regional product (GRP) and female suicide was slightly negative. Religiosity was the protective factor most strongly linked with suicide mortality followed by urbanization. The harmful role of drug addiction and alcoholism was confirmed. The role of education and GRP is controversial. No striking gender differences were found.     

An observer-blind,randomized, multi-center trial assessing long-term safety and immunogenicity of AS03-adjuvanted or unadjuvanted H1N1/2009 influenza vaccines in children 10–17 years of age

Background

Vaccination is an effective strategy to prevent influenza. This observer-blind, randomized study in children 10–17 years of age assessed whether the hemagglutination inhibition (HI) antibody responses elicited by H1N1/2009 vaccines adjuvanted with AS03 (an adjuvant system containing α-tocopherol and squalene in an oil-in-water emulsion) or without adjuvant, met the European regulatory immunogenicity criteria at Days 21 and 182.

Methods

Three hundred and ten healthy children were randomized (3:3:3:5) to receive one dose of 3.75 μg hemagglutinin (HA) AS03_A-adjuvanted vaccine, one or two doses of 1.9 μg HA AS03_B-adjuvanted vaccine, or one dose of 15 μg HA pandemic vaccine. All children received a booster dose of the allocated vaccine at Day 182. Serum samples were tested for HI antibody response at Days 21, 42, 182 and 189.

Results

All vaccination regimens elicited HI antibody responses that met the European regulatory criteria at Days 21 and 42. HI antibody responses fulfilling European regulatory criteria were still observed six months after the first vaccine dose in all study vaccines groups. Two doses of 1.9 μg HA AS03_B-adjuvanted vaccine elicited the strongest HI antibody response throughout the study. The non-adjuvanted 15 μg HA vaccine elicited a lower HI antibody response than the AS03-adjuvanted vaccines. At Day 189, the European regulatory criteria were met for all vaccines with baseline HI antibody titers as reference. An anamnestic response for all vaccines was suggested at Day 189, based on the rapid increase in HI antibody geometric mean titers (1.5–2.5-fold increase). Injection site reactogenicity was higher following the AS03-adjuvanted vaccines compared with the non-adjuvanted vaccine. No safety concerns were identified for any study vaccine.

Conclusion

All study vaccines elicited HI antibody responses that persisted at purported protective levels through six months after vaccination and fulfilled the European regulatory criteria.