The use of etoricoxib to treat an idiopathic stabbing headache: a case report

According to the International Headache Society, idiopathic stabbing headache (ISH), an indomethacin-responsive headache syndrome, is a paroxysmal disorder of short duration manifested as head pain occurring as a single stab or a series of stabs involving the area supplied in the distribution of the first division of the trigeminal nerve. Stabs last for approximately a few seconds, occurring and recurring from once to multiple times per day in an irregular frequency, with no underlying attributable disorder

Clinical relevance of heparin-PF4 complex antibody in DVT after total joint replacement

<p>Abstract</p> <p>Background</p> <p>Antibodies to the heparin-platelet factor-4 (HPF-4) complex (HIT antibodies) have been observed in patients with heparin-induced thrombocytopenia (HIT). These antibodies are thought to be involved in thrombosis through activation of platelet/endothelial cells. This prospective study was conducted to determine the incidence of post-operative HIT antibodies to assess the associated risk of deep vein thrombosis (DVT) in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).</p> <p>Methods</p> <p>We studied 104 patients who underwent unilateral primary TKA (n = 44) and primary THA (n = 60) with short-duration prophylaxis (1–2 days of a fixed dose of unfractionated heparin). HIT antibodies were assayed using a sandwich-type ELISA before the operation and after heparin treatment (post-operative day 7).</p> <p>Results</p> <p>In the clinical outcome, the incidence of symptomatic DVT was 15.4% (16/104, TKA; 10, THA 6) and pulmonary embolism (PE) was not observed. The total seroconversion rate of HIT antibodies at post-operative day 7 was 34.6% (36/104). Among 36 seroconverted patients, 11 (30.6%) developed symptomatic DVT and 5 out of 68 of the non-seroconverted patients (7.4%) developed symptomatic DVT. The incidence for DVT was significantly higher in the seroconverted patients compared with that of the non-seroconverted patients (odds ratio 5.5, 95%CI: 1.7–17.6 <it>p </it>= 0.0028). Furthermore, in the patients with symptomatic DVT, the titer of HIT antibodies at post-operative day 7 was significantly higher compared with those without symptomatic DVT.</p> <p>Conclusion</p> <p>Our data therefore suggest that seroconversion for HIT antibodies generated by heparin is associated with a risk of DVT in patients undergoing total joint replacement.</p

Disparities in appendicitis rupture rate among mentally ill patients

<p>Abstract</p> <p>Background</p> <p>Many studies have been carried out that focus on mental patients' access to care for their mental illness, but very few pay attention on these same patients' access to care for their physical diseases. Acute appendicitis is a common surgical emergency. Our population-based study was to test for any possible association between mental illness and perforated appendicitis. We hypothesized that there are significant disparities in access to timely surgical care between appendicitis patients with and without mental illness, and more specifically, between patients with schizophrenia and those with another major mental illness.</p> <p>Methods</p> <p>Using the National Health Insurance (NHI) hospital-discharge data, we compared the likelihood of perforated appendix among 97,589 adults aged 15 and over who were hospitalized for acute appendicitis in Taiwan between the years 1997 to 2001. Among all the patients admitted for appendicitis, the outcome measure was the odds of appendiceal rupture vs. appendicitis that did not result in a ruptured appendix.</p> <p>Results</p> <p>After adjusting for age, gender, ethnicity, socioeconomic status (SES) and hospital characteristics, the presence of schizophrenia was associated with a 2.83 times higher risk of having a ruptured appendix (odds ratio [OR], 2.83; 95% confidence interval [CI], 2.20–3.64). However, the presence of affective psychoses (OR, 1.15; 95% CI: 0.77–1.73) or other mental disorders (OR, 1.58; 95% CI: 0.89–2.81) was not a significant predictor for a ruptured appendix.</p> <p>Conclusion</p> <p>These findings suggest that given the fact that the NHI program reduces financial barriers to care for mentally ill patients, they are still at a disadvantage for obtaining timely treatment for their physical diseases. Of patients with a major mental illness, schizophrenic patients may be the most vulnerable ones for obtaining timely surgical care.</p

IL-2 Mediates CD4+ T Cell Help in the Breakdown of Memory-Like CD8+ T Cell Tolerance under Lymphopenic Conditions

Background: Lymphopenia results in the proliferation and differentiation of naïve T cells into memory-like cells in the apparent absence of antigenic stimulation. This response, at least in part due to a greater availability of cytokines, is thought to promote anti-self responses. Although potentially autoreactive memory-like CD8 + T cells generated in a lymphopenic environment are subject to the mechanisms of peripheral tolerance, they can induce autoimmunity in the presence of antigen-specific memory-like CD4 + T helper cells. Methodology/Principal Findings: Here, we studied the mechanisms underlying CD4 help under lymphopenic conditions in transgenic mice expressing a model antigen in the beta cells of the pancreas. Surprisingly, we found that the self-reactivity mediated by the cooperation of memory-like CD8 + and CD4 + T cells was not abrogated by CD40L blockade. In contrast, treatment with anti-IL-2 antibodies inhibited the onset of autoimmunity. IL-2 neutralization prevented the CD4-mediated differentiation of memory-like CD8 + T cells into pathogenic effectors in response to self-antigen cross-presentation. Furthermore, in the absence of helper cells, induction of IL-2 signaling by an IL-2 immune complex was sufficient to promote memory-like CD8 + T cell self-reactivity. Conclusions/Significance: IL-2 mediates the cooperation of memory-like CD4 + and CD8 + T cells in the breakdown of crosstolerance, resulting in effector cytotoxic T lymphocyte differentiation and the induction of autoimmune disease

Volume and outcomes relationship in laparoscopic diaphragmatic hernia repair

BackgroundThere is no published data regarding the relationship between hospital volume and outcomes in patients undergoing laparoscopic diaphragmatic hernia repair. We hypothesize that hospitals performing high case volume have improved outcomes compared to low-volume hospitals.Materials and methodsWe reviewed the National Inpatient Sample (NIS) database between 2008 and 2012 for adults with the diagnosis of diaphragmatic hernia who underwent elective laparoscopic repair of diaphragmatic Hernia and/or Nissen fundoplication. Pediatric, emergent, and open cases were excluded. Main outcome measures included logistic regression analysis of factors predictive of in-hospital mortality and outcomes according to annual hospital case volume.ResultsA total of 31,228 laparoscopic diaphragmatic hernia operations were analyzed. The overall in-hospital mortality was 0.14%. Risk factors for higher in-hospital mortality included renal failure (AOR: 6.26; 95% CI: 2.48-15.78; p &lt; 0.001), age&gt;60 years (AOR: 5.06; 95% CI: 2.38-10.76; p &lt; 0.001), and CHF (AOR: 3.80; 95% CI: 1.39-10.38; p = 0.009) while an incremental increase in volume of 10 cases/year (AOR: 0.89; 95% CI: 0.81-0.98; p = 0.019) and diabetes (AOR: 0.34; 95% CI: 0.12-0.93; p = 0.036) decreases mortality. There was a small but significant inverse relationship between hospital case volume and mortality with a 10% reduction in adjusted odds of in-hospital mortality for every increase in 10 cases per year. Using 10 cases per year as the volume threshold, low-volume hospitals (≤10 cases/year) had almost a twofold higher mortality compared to high-volume hospitals (0.23 vs. 0.12%, respectively, p = 0.02).ConclusionsThere was a small but significant inverse relationship between the hospitals' case volume and mortality in laparoscopic diaphragmatic hernia repair

A transcriptome-wide association study among 97,898 women to identify candidate susceptibility genes for epithelial ovarian cancer risk

Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in non-coding regions, and causal genes underlying these associations remain largely unknown. Here we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian-tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P<2.2×10-6, we identified 35 genes including FZD4 at 11q14.2 (Z=5.08, P=3.83×10-7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly-associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and 3 genes remained (P<1.47 x 10-3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis

Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression:Identification of a modifier of breast cancer risk at locus 11q22.3

Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways.Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of similar to 320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2.We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 x 10(-6)). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance.We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.</p

In vitro nuclear interactome of the HIV-1 Tat protein

<p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

Healthism and the experiences of social, healthcare and self-stigma of women with higher weight

This study analyses how the discourse of healthism contributes to the social construction of weight stigma in women with higher-weight. In-depth semi-structured interviews were conducted with nine women who had undergone bariatric surgery and had lived with higher-weight during many years. A thematic analysis from a latent and constructionist perspective showed how the discourse of healthism was behind the experiences of stigma lived by the participants in the social and healthcare field. Even instances of self-stigma were found in our data. This study also illustrates how people influenced by healthism assumed individualism and the importance of body shape, core values of neoliberal consumer societies. In this way, people tended to blame women with higher-weight for their weight and to discriminate against for being far from the socially established ideal body. The findings can be useful to prevent weight stigmatization and to promote more appropriate and respectful strategies for obesity prevention and treatment