Safe Brain Tumor Resection Does not Depend on Surgery Alone - Role of Hemodynamics

Aim of this study was to determine if perioperative hemodynamics have an impact on perioperative infarct volume and patients' prognosis. 201 cases with surgery for a newly diagnosed or recurrent glioblastoma were retrospectively analyzed. Clinical data and perioperative hemodynamic parameters, blood tests and time of surgery were recorded. Postoperative infarct volume was quantitatively assessed by semiautomatic segmentation. Mean diastolic blood pressure (dBP) during surgery (rho -0.239, 95% CI -0.11 - -0.367, p = 0.017), liquid balance (rho 0.236, 95% CI 0.1-0.373, p = 0.017) and mean arterial pressure (MAP) during surgery (rho -0.206, 95% CI -0.07 - -0.34, p = 0.041) showed significant correlation to infarct volume. A rank regression model including also age and recurrent surgery as possible confounders revealed mean intraoperative dBP, liquid balance and length of surgery as independent factors for infarct volume. Univariate survival analysis showed mean intraoperative dBP and MAP as significant prognostic factors, length of surgery also remained as significant prognostic factor in a multivariate model. Perioperative close anesthesiologic monitoring of blood pressure and liquid balance is of high significance during brain tumor surgery and should be performed to prevent or minimize perioperative infarctions and to prolong survival

Smooth muscle hyperplasia due to loss of smooth muscle α-actin is driven by activation of focal adhesion kinase, altered p53 localization and increased levels of platelet-derived growth factor receptor-β

Mutations in ACTA2, encoding the smooth muscle cell (SMC)-specific isoform of α-actin (α-SMA), cause thoracic aortic aneurysms and dissections and occlusive vascular diseases, including early onset coronary artery disease and stroke. We have shown that occlusive arterial lesions in patients with heterozygous ACTA2 missense mutations show increased numbers of medial or neointimal SMCs. The contribution of SMC hyperplasia to these vascular diseases and the pathways responsible for linking disruption of α-SMA filaments to hyperplasia are unknown. Here, we show that the loss of Acta2 in mice recapitulates the SMC hyperplasia observed in ACTA2 mutant SMCs and determine the cellular pathways responsible for SMC hyperplasia. Acta2−/− mice showed increased neointimal formation following vascular injury in vivo, and SMCs explanted from these mice demonstrated increased proliferation and migration. Loss of α-SMA induced hyperplasia through focal adhesion (FA) rearrangement, FA kinase activation, re-localization of p53 from the nucleus to the cytoplasm and increased expression and ligand-independent activation of platelet-derived growth factor receptor beta (Pdgfr-β). Disruption of α-SMA in wild-type SMCs also induced similar cellular changes. Imatinib mesylate inhibited Pdgfr-β activation and Acta2−/− SMC proliferation in vitro and neointimal formation with vascular injury in vivo. Loss of α-SMA leads to SMC hyperplasia in vivo and in vitro through a mechanism involving FAK, p53 and Pdgfr-β, supporting the hypothesis that SMC hyperplasia contributes to occlusive lesions in patients with ACTA2 missense mutation

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

The Age-Specific Cumulative Incidence of Infection with Pandemic Influenza H1N1 2009 Was Similar in Various Countries Prior to Vaccination

Background: During the influenza pandemic of 2009 estimates of symptomatic and asymptomatic infection were needed to guide vaccination policies and inform other control measures. Serological studies are the most reliable way to measure influenza infection independent of symptoms. We reviewed all published serological studies that estimated the cumulative incidence of infection with pandemic influenza H1N1 2009 prior to the initiation of population-based vaccination against the pandemic strain. Methodology and Principal Findings: We searched for studies that estimated the cumulative incidence of pandemic influenza infection in the wider community. We excluded studies that did not include both pre- and post-pandemic serological sampling and studies that included response to vaccination. We identified 47 potentially eligible studies and included 12 of them in the review. Where there had been a significant first wave, the cumulative incidence of pandemic influenza infection was reported in the range 16%-28% in pre-school aged children, 34%-43% in school aged children and 12%-15% in young adults. Only 2%-3% of older adults were infected. The proportion of the entire population infected ranged from 11%-18%. We re-estimated the cumulative incidence to account for the small proportion of infections that may not have been detected by serology, and performed direct age-standardisation to the study population. For those countries where it could be calculated, this suggested a population cumulative incidence in the range 11%-21%. Conclusions and Significance: Around the world, the cumulative incidence of infection (which is higher than the cumulative incidence of clinical disease) was below that anticipated prior to the pandemic. Serological studies need to be routine in order to be sufficiently timely to provide support for decisions about vaccination. © 2011 Kelly et al.published_or_final_versio

Individual Preferences and Social Interactions Determine the Aggregation of Woodlice

n°e17389.info:eu-repo/semantics/publishe

Pincher-generated Nogo-A endosomes mediate growth cone collapse and retrograde signaling

RhoA is activated from internalized Nogo-A to promote growth cone collapse and inhibit neurite outgrowth

Risk Factors and Immunity in a Nationally Representative Population following the 2009 Influenza A(H1N1) Pandemic

Understanding immunity, incidence and risk factors of the 2009 influenza A(H1N1) pandemic (2009 H1N1) through a national seroprevalence study is necessary for informing public health interventions and disease modelling.We collected 1687 serum samples and individual risk factor data between November-2009 to March-2010, three months after the end of the 2009 H1N1 wave in New Zealand. Participants were randomly sampled from selected general practices countrywide and hospitals in the Auckland region. Baseline immunity was measured from 521 sera collected during 2004 to April-2009. Haemagglutination inhibition (HI) antibody titres of ≥1∶40 against 2009 H1N1 were considered seroprotective as well as seropositive. The overall community seroprevalence was 26.7% (CI:22.6–29.4). The seroprevalence varied across age and ethnicity. Children aged 5–19 years had the highest seroprevalence (46.7%;CI:38.3–55.0), a significant increase from the baseline (14%;CI:7.2–20.8). Older adults aged ≥60 had no significant difference in seroprevalence between the serosurvey (24.8%;CI:18.7–30.9) and baseline (22.6%;CI:15.3–30.0). Pacific peoples had the highest seroprevalence (49.5%;CI:35.1–64.0). There was no significant difference in seroprevalence between both primary (29.6%;CI:22.6–36.5) and secondary healthcare workers (25.3%;CI:20.8–29.8) and community participants. No significant regional variation was observed. Multivariate analysis indicated age as the most important risk factor followed by ethnicity. Previous seasonal influenza vaccination was associated with higher HI titres. Approximately 45.2% of seropositive individuals reported no symptoms.Based on age and ethnicity standardisation to the New Zealand Population, about 29.5% of New Zealanders had antibody titers at a level consistent with immunity to 2009 H1N1. Around 18.3% of New Zealanders were infected with the virus during the first wave including about one child in every three. Older people were protected due to pre-existing immunity. Age was the most important factor associated with infection followed by ethnicity. Healthcare workers did not appear to have an increased risk of infection compared with the general population

Contribution of limbic norepinephrine to cannabinoid-induced aversion

RATIONALE: The cannabinoid system has risen to the forefront in the development of novel treatments for a number of pathophysiological processes. However, significant side effects have been observed in clinical trials raising concerns regarding the potential clinical utility of cannabinoid-based agents. Understanding the neural circuits and neurochemical substrates impacted by cannabinoids will provide a better means of gaging their actions within the central nervous system that may contribute to the expression of unwanted side effects. OBJECTIVES: In the present study, we investigated whether norepinephrine (NE) in the limbic forebrain is a critical determinant of cannabinoid receptor agonist-induced aversion and anxiety in rats. METHODS: An immunotoxin lesion approach was combined with behavioral analysis using a place conditioning paradigm and the elevated zero maze. RESULTS: Our results show that the non-selective CB1/CB2 receptor agonist, WIN 55,212-2, produced a significant place aversion in rats. Further, NE in the nucleus accumbens was critical for WIN 55,212-2-induced aversion but did not affect anxiety-like behaviors. Depletion of NE from the bed nucleus of the stria terminalis was ineffective in altering WIN 55,212-2-induced aversion and anxiety. CONCLUSIONS: These results indicate that limbic, specifically accumbal, NE is required for cannabinoid-induced aversion but is not essential to cannabinoid-induced anxiety.This works was supported by PHS grant DA 020129. Ana Franky Carvalho was supported by the Portuguese Foundation for Science and Technology (SFRH/BD/33236/2007)

Seroprevalence and Severity of 2009 Pandemic Influenza A H1N1 in Taiwan

BACKGROUND: This study is to determine the seroprevalence of the pandemic influenza A H1N1 virus (pH1N1) in Taiwan before and after the 2009 pandemic, and to estimate the relative severity of pH1N1 infections among different age groups. METHODOLOGY/PRINCIPAL FINDINGS: A total of 1544 and 1558 random serum samples were collected from the general population in Taiwan in 2007 and 2010, respectively. Seropositivity was defined by a hemagglutination inhibition titer to pH1N1 (A/Taiwan/126/09) ≥1:40. The seropositivity rate of pH1N1 among the unvaccinated subjects and national surveillance data were used to compare the proportion of infections that led to severe diseases and fatalities among different age groups. The overall seroprevalence of pH1N1 was 0.91% (95% confidence interval [CI] 0.43-1.38) in 2007 and significantly increased to 29.9% (95% CI 27.6-32.2) in 2010 (p<0.0001), with the peak attack rate (55.4%) in 10-17 year-old adolescents, the lowest in elderly ≥65 years (14.1%). The overall attack rates were 20.6% (188/912) in unvaccinated subjects. Among the unvaccinated but infected populations, the estimated attack rates of severe cases per 100,000 infections were significantly higher in children aged 0-5 years (54.9 cases, odds ratio [OR] 4.23, 95% CI 3.04-5.90) and elderly ≥ 65 years (22.4 cases, OR 2.76, 95% CI 1.99-3.83) compared to adolescents aged 10-17 years (13.0 cases). The overall case-fatality rate was 0.98 per 100,000 infections without a significant difference in different age groups. CONCLUSIONS/SIGNIFICANCE: Pre-existing immunity against pH1N1 was rarely identified in Taiwanese at any age in 2007. Young children and elderly--the two most lower seroprotection groups showed the greatest vulnerability to clinical severity after the pH1N1 infections. These results imply that both age groups should have higher priority for immunization in the coming flu season

Prevalence of 2009 Pandemic Influenza A (H1N1) Virus Antibodies, Tampa Bay Florida — November–December, 2009

BACKGROUND: In 2009, a novel influenza virus (2009 pandemic influenza A (H1N1) virus (pH1N1)) caused significant disease in the United States. Most states, including Florida, experienced a large fall wave of disease from September through November, after which disease activity decreased substantially. We determined the prevalence of antibodies due to the pH1N1 virus in Florida after influenza activity had peaked and estimated the proportion of the population infected with pH1N1 virus during the pandemic. METHODS: During November-December 2009, we collected leftover serum from a blood bank, a pediatric children's hospital and a pediatric outpatient clinic in Tampa Bay Florida. Serum was tested for pH1N1 virus antibodies using the hemagglutination-inhibition (HI) assay. HI titers ≥40 were considered seropositive. We adjusted seroprevalence results to account for previously established HI assay specificity and sensitivity and employed a simple statistical model to estimate the proportion of seropositivity due to pH1N1 virus infection and vaccination. RESULTS: During the study time period, the overall seroprevalence in Tampa Bay, Florida was 25%, increasing to 30% after adjusting for HI assay sensitivity and specificity. We estimated that 5.9% of the population had vaccine-induced seropositivity while 25% had seropositivity secondary to pH1N1 virus infection. The highest cumulative incidence of pH1N1 virus infection was among children aged 5-17 years (53%) and young adults aged 18-24 years (47%), while adults aged ≥50 years had the lowest cumulative incidence (11-13%) of pH1N1 virus infection. CONCLUSIONS: After the peak of the fall wave of the pandemic, an estimated one quarter of the Tampa Bay population had been infected with the pH1N1 virus. Consistent with epidemiologic trends observed during the pandemic, the highest burdens of disease were among school-aged children and young adults