Effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal disease in people 60 years or older

Background  

The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended in elderly and high-risk adults. However, its efficacy in preventing pneumococcal infections remains controversial. This study assessed the clinical effectiveness of vaccination against invasive pneumococcal disease (IPD) among people over 60 years.     

The experiences of pregnancy in women with SSA/Ro52 autoantibodies

Objective: Congenital heart block may develop in the foetus during pregnancy in SSA/Ro52 autoantibody‐positive women. The aim of this study was to investigate how women with SSA/Ro52 autoantibodies experience their pregnancy in terms of the risk of developing foetal heart block, and in undergoing serial ultrasound Doppler echocardiography to detect early signs of congenital heart block. Methods: Data were collected through individual semi‐structured interviews with SSA/Ro52‐positive women post‐pregnancy (n = 14). The interviews were audio‐taped, transcribed verbatim and analysed according to qualitative content analysis. Results: Three categories emerged from the responses: information, emotional response and support. The information received prior to and during early pregnancy was focused on the need for attending a specialized antenatal clinic, and information on the risk for congenital heart block was scarce or missing. During gestational weeks 18–24, when the ultrasound/Doppler examinations were performed, all women described increased stress. However, the interaction with the caregivers made the women feel more safe and secure. Several women also said that they did not emotionally acknowledge the pregnancy until after gestational week 24. None had been offered psychological support. Conclusion: There is a need for structured information and organized programmes for the surveillance of women who are SSA/Ro52 positive during their pregnancy. Further, offering psychological support to the women and their families to manage the stress and to facilitate the early attachment to the child should be considered. Copyright © 2010 John Wiley & Sons, Ltd.     

Influence of a nucleotide oligomerization domain 1 （NOD1） polymorphism and NOD2 mutant alleles on Crohn＇s disease phenotype

AIM： To examine genetic variation of nucleotide oligomerization domain 1 （NOD/） and NOD2, their respective influences on Crohn＇s disease phenotype and gene-gene interactions.
METHODS： （ND1＋32656＊1） NOD1 polymorphism and SNPS, SNP12 and SNP13 of NOD2 were analyzed in 97 patients and 50 controls. NOD2 variants were determined by reaction restriction fragment length polymorphism analysis. NOD1 genotyping and NOD2 variant confirmation were performed by specific amplification and sequencing.
RESULTS： The distribution of NOD1 polymorphism in patients was different from controls （P = 0.045） and not altered by existence of NOD2 mutations. In this cohort, 30.92% patients and 6% controls carried at least one NOD2 variant （P 〈 0.001） with R702W being the most frequent variant. Presence of at least one NOD2 mutation was inversely associated with colon involvement （9.09% with colon vs 36.4% with ileal or ileocolonic involvement, P = 0.04） and indicative of risk of penetrating disease （52.63% with penetrating vs 25.64% with non-penetrating or stricturing behavior, P = 0.02）. L1007finsC and double NOD2 mutation conferred the highest risk for severity of disease （26.3% with penetrating disease vs 3.8% with non-penetrating or stricturing behavior presented L1007finsC, P = 0.01 and 21.0% with penetrating disease vs 2.5% with non-penentrating or stricturing behavior carried double NOD2 mutation, P = 0.007）. Exclusion of patients with NOD2 mutations from phenotype/NODl-genotype analysis revealed higher prevalence of ＊1＊1 genotype in groups of younger age at onset and colonic location.
CONCLUSION： This study suggests population differences in the inheritance of risk NOD1 polymorphism and NOD2 mutations. Although no interaction between NOD1-NOD2 was noticed, a relationship between disease location and Nod-like receptor molecules was established.     

A reassessment of the neuropathology of frontotemporal dementia linked to chromosome 3

ABSTRACT: A large Danish family has previously been reported in which autosomal dominant frontotemporal dementia (FTD) is genetically linked to chromosome 3 (FTD-3). A mutation was recently identified in the CHMP2B gene that is probably responsible for causing disease in this family. Because of its neuropathologic findings, FTD-3 was originally categorized as a subtype of frontotemporal lobar degeneration, termed "dementia lacking distinctive histopathology." We now report a reevaluation of the neuropathologic changes in this family. Postmortem material from 4 affected family members was available for examination. Gross examination revealed generalized cortical atrophy that was most severe in frontal and temporal cortices. Microscopy showed loss of cortical neurons, microvacuolation of layer II, mild gliosis, and demyelination of the deep white matter. Results of immunohistochemical staining for alpha-synuclein, prion protein, neurofilament, and tau protein were unremarkable. Variable numbers of small, round, ubiquitin-positive cytoplasmic inclusions were present in the dentate granule layer of the hippocampus in all 4 cases. Rare ubiquitin-positive inclusions were also found in frontal and temporal cortical neurons. These inclusions were also positive for p62 but not for TDP-43. The finding of ubiquitin- and p62-positive, TDP-43-negative cytoplasmic inclusions in the hippocampus and neocortex suggests reclassification of the neuropathology of FTD-3 as a unique subtype of frontotemporal lobar degeneration with ubiquitin-positive inclusions that are TDP-43-negative.     

Localization of syntactic and semantic brain responses using magnetoencephalography

Electrophysiological methods have been used to study the temporal sequence of syntactic and semantic processing during sentence comprehension. Two responses associated with syntactic violations are the left anterior negativity (LAN) and the P600. A response to semantic violation is the N400. Although the sources of the N400 response have been identified in the left (and right) temporal lobe, the neural signatures of the LAN and P600 have not been revealed. The present study used magnetoencephalography to localize sources of syntactic and semantic activation in Finnish sentence reading. Participants were presented with sentences that ended in normally inf lected nouns, nouns in an unacceptable case, verbs instead of nouns, or nouns that were correctly inflected but made no sense in the context. Around 400 msec, semantically anomalous last words evoked strong activation in the left superior temporal lobe with significant activation also for word class errors (N400). Weaker activation was seen for the semantic errors in the right hemisphere. Later, 600-800 msec after word onset, the strongest activation was seen to word class and morphosyntactic errors (P600). Activation was significantly weaker to semantically anomalous and correct words. The P600 syntactic activation was localized to bilateral sources in the temporal lobe, posterior to the N400 sources. The results suggest that the same general region of the superior temporal cortex gives rise to both LAN and N400 with bilateral reactivity to semantic manipulation and a left hemisphere effect to syntactic manipulation. The bilateral P600 response was sensitive to syntactic but not semantic factors.     

Effects of subunit selective nACh receptors on operant ethanol self-administration and relapse-like ethanol-drinking behavior

Rationale and objectives  The sensitivity to ethanol central effects is partially determined by the subunit composition of brain nicotinic acetylcholine receptors (nAChRs). Thus, the effects of intraventral tegmental area (VTA) administration of the nicotinic subunit-specific antagonist, α-conotoxin MII (αCtxMII, α₃β₂*, β₃*, α₆*), were compared to those of systemic mecamylamine (MEC, an allosteric negative modulator of the nAChR), dihydro-β-erythroidine (DHβE, α₄β₂*), and methyllycaconitine (MLA, α₇*) to elucidate involvement of different subunits of nAChRs in operant ethanol self-administration and relapse-like activation of ethanol consumption after ethanol deprivation in rats. Methods  The effects of drugs were studied in rats trained for operant oral self-administration of ethanol (FR = 1). For ethanol deprivation, trained animals were subjected to a period of alcohol deprivation for 10 days. αCtxMII was given directly into the VTA through implanted permanent intracranial cannulae, whereas MEC, DHβE, and MLA were administered systemically. Results  αCtxMII reduced operant ethanol self-administration and blocked the deprivation-induced relapse-like ethanol consumption. MEC reduced operant ethanol self-administration and inhibited the deprivation-induced increase in alcohol consumption. DHβE did not alter ethanol self-administration in the lower-dose range but inhibited ethanol intake at a higher dose (4 mg/kg), although this effect might have been nonspecific. MLA failed to block self-administration of ethanol and relapse-like drinking after deprivation. Conclusions  Our results indicate that nAChRs are involved in the modulation of operant alcohol self-administration and relapse-like alcohol drinking behavior in rats. Our observations support the working hypothesis that systemically active selective ligands for nAChR α₃β₂*, β₃, and/or α₆* receptor subunits might be of therapeutic value for the treatment of alcoholism.     

Work disability in rheumatoid arthritis--development over 15 years and evaluation of predictive factors over time

OBJECTIVE: To investigate work disability rates over 15 years in an early rheumatoid arthritis (RA) cohort and to evaluate predictive factors during the course of the study. METHODS: All patients with early RA of working age (n = 148) were followed and treated at a team care unit. Mean disease duration at inclusion was 1 year. Work characteristics and disease-related variables were recorded annually. Logistic regression analyses were performed to identify predictors for work disability after 5, 10, and 15 years. RESULTS: Work disability rates were 28%, 35%, 39%, and 44% at study start and after 5, 10, and 15 years, respectively. Forty-seven patients reduced working hours and 34 changed work tasks during the study time. Older age, less education, heavy manual work, and much activity limitation assessed by Health Assessment Questionnaire (HAQ) were predictors of work disability. Demographics and work factors had best predictive value in the early phase, while HAQ was a strong predictor at all points in time. Odds ratios for baseline HAQ, 5 year HAQ, and 10 year HAQ were 6.3, 9.6, and 4.1 for work disability after 5, 10, and 15 years, respectively. CONCLUSION: The prevalence of work disability was 28% at inclusion. After 15 years' followup the prevalence was 44%, which is lower than previously reported. HAQ was the single prognostic factor with strong predictive value throughout the study.