Umbilical hernia rupture with evisceration of omentum from massive ascites: a case report

<p>Abstract</p> <p>Introduction</p> <p>The incidence of hernias is increased in patients with alcoholic liver disease with ascites. To the best of our knowledge, this is the first report of an acute rise in intra-abdominal pressure from straining for stool as the cause of a ruptured umbilical hernia.</p> <p>Case presentation</p> <p>An 81-year-old Caucasian man with a history of alcoholic liver disease presented to our emergency department with an erythematous umbilical hernia and clear, yellow discharge from the umbilicus. On straining for stool, after initial clinical assessment, our patient noted a gush of fluid and evisceration of omentum from the umbilical hernia. An urgent laparotomy was performed with excision of the umbilicus and devitalized omentum.</p> <p>Conclusion</p> <p>We report the case of a patient with a history of alcoholic liver disease with ascites. Ascites causes a chronic increase in intra-abdominal pressure. A sudden increase in intra-abdominal pressure, such as coughing, vomiting, gastroscopy or, as in this case, straining for stool can cause rupture of an umbilical hernia. The presence of discoloration, ulceration or a rapid increase in size of the umbilical hernia signals impending rupture and should prompt the physician to reduce the intra-abdominal pressure.</p

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-α and dexamethasone

<p>Abstract</p> <p>Background</p> <p>CD38 is expressed in human airway smooth muscle (HASM) cells, regulates intracellular calcium, and its expression is augmented by tumor necrosis factor alpha (TNF-α). CD38 has a role in airway hyperresponsiveness, a hallmark of asthma, since deficient mice develop attenuated airway hyperresponsiveness compared to wild-type mice following intranasal challenges with cytokines such as IL-13 and TNF-α. Regulation of CD38 expression in HASM cells involves the transcription factor NF-κB, and glucocorticoids inhibit this expression through NF-κB-dependent and -independent mechanisms. In this study, we determined whether the transcriptional regulation of CD38 expression in HASM cells involves response elements within the promoter region of this gene.</p> <p>Methods</p> <p>We cloned a putative 3 kb promoter fragment of the human <it>cd38 </it>gene into pGL3 basic vector in front of a luciferase reporter gene. Sequence analysis of the putative <it>cd38 </it>promoter region revealed one NF-κB and several AP-1 and glucocorticoid response element (GRE) motifs. HASM cells were transfected with the 3 kb promoter, a 1.8 kb truncated promoter that lacks the NF-κB and some of the AP-1 sites, or the promoter with mutations of the NF-κB and/or AP-1 sites. Using the electrophoretic mobility shift assays, we determined the binding of nuclear proteins to oligonucleotides encoding the putative <it>cd38 </it>NF-κB, AP-1, and GRE sites, and the specificity of this binding was confirmed by gel supershift analysis with appropriate antibodies.</p> <p>Results</p> <p>TNF-α induced a two-fold activation of the 3 kb promoter following its transfection into HASM cells. In cells transfected with the 1.8 kb promoter or promoter constructs lacking NF-κB and/or AP-1 sites or in the presence of dexamethasone, there was no induction in the presence of TNF-α. The binding of nuclear proteins to oligonucleotides encoding the putative <it>cd38 </it>NF-κB site and some of the six AP-1 sites was increased by TNF-α, and to some of the putative <it>cd38 </it>GREs by dexamethasone.</p> <p>Conclusion</p> <p>The EMSA results and the cd38 promoter-reporter assays confirm the functional role of NF-κB, AP-1 and GREs in the cd38 promoter in the transcriptional regulation of CD38.</p

Strongyloides stercoralis age-1: A Potential Regulator of Infective Larval Development in a Parasitic Nematode

Infective third-stage larvae (L3i) of the human parasite Strongyloides stercoralis share many morphological, developmental, and behavioral attributes with Caenorhabditis elegans dauer larvae. The ‘dauer hypothesis’ predicts that the same molecular genetic mechanisms control both dauer larval development in C. elegans and L3i morphogenesis in S. stercoralis. In C. elegans, the phosphatidylinositol-3 (PI3) kinase catalytic subunit AGE-1 functions in the insulin/IGF-1 signaling (IIS) pathway to regulate formation of dauer larvae. Here we identify and characterize Ss-age-1, the S. stercoralis homolog of the gene encoding C. elegans AGE-1. Our analysis of the Ss-age-1 genomic region revealed three exons encoding a predicted protein of 1,209 amino acids, which clustered with C. elegans AGE-1 in phylogenetic analysis. We examined temporal patterns of expression in the S. stercoralis life cycle by reverse transcription quantitative PCR and observed low levels of Ss-age-1 transcripts in all stages. To compare anatomical patterns of expression between the two species, we used Ss-age-1 or Ce-age-1 promoter::enhanced green fluorescent protein reporter constructs expressed in transgenic animals for each species. We observed conservation of expression in amphidial neurons, which play a critical role in developmental regulation of both dauer larvae and L3i. Application of the PI3 kinase inhibitor LY294002 suppressed L3i in vitro activation in a dose-dependent fashion, with 100 µM resulting in a 90% decrease (odds ratio: 0.10, 95% confidence interval: 0.08–0.13) in the odds of resumption of feeding for treated L3i in comparison to the control. Together, these data support the hypothesis that Ss-age-1 regulates the development of S. stercoralis L3i via an IIS pathway in a manner similar to that observed in C. elegans dauer larvae. Understanding the mechanisms by which infective larvae are formed and activated may lead to novel control measures and treatments for strongyloidiasis and other soil-transmitted helminthiases

The Acute Satellite Cell Response and Skeletal Muscle Hypertrophy following Resistance Training

The extent of skeletal muscle hypertrophy in response to resistance training is highly variable in humans. The main objective of this study was to explain the nature of this variability. More specifically, we focused on the myogenic stem cell population, the satellite cell (SC) as a potential mediator of hypertrophy. Twenty-three males (aged 18–35 yrs) participated in 16 wk of progressive, whole body resistance training, resulting in changes of 7.9±1.6% (range of −1.9–24.7%) and 21.0±4.0% (range of −7.0 to 51.7%) in quadriceps volume and myofibre cross-sectional area (CSA), respectively. The SC response to a single bout of resistance exercise (80% 1RM), analyzed via immunofluorescent staining resulted in an expansion of type II fibre associated SC 72 h following exercise (pre: 11.3±0.9; 72 h: 14.8±1.4 SC/type II fibre; p<0.05). Training resulted in an expansion of the SC pool associated with type I (pre: 10.7±1.1; post: 12.1±1.2 SC/type I fibre; p<0.05) and type II fibres (pre: 11.3±0.9; post: 13.0±1.2 SC/type II fibre; p<0.05). Analysis of individual SC responses revealed a correlation between the relative change in type I associated SC 24 to 72 hours following an acute bout of resistance exercise and the percentage increase in quadriceps lean tissue mass assessed by MRI (r2 = 0.566, p = 0.012) and the relative change in type II associated SC following 16 weeks of resistance training and the percentage increase in quadriceps lean tissue mass assessed by MRI (r2 = 0.493, p = 0.027). Our results suggest that the SC response to resistance exercise is related to the extent of muscular hypertrophy induced by training

A missense variant in CST3 exerts a recessive effect on susceptibility to age-related macular degeneration resembling its association with Alzheimer’s disease

Age-related macular degeneration (AMD) and Alzheimer’s disease (AD) are degenerative, multifactorial diseases involving age-related accumulation of extracellular deposits linked to dysregulation of protein homeostasis. Here, we strengthen the evidence that an nsSNP (p.Ala25Thr) in the cysteine proteinase inhibitor cystatin C gene CST3, previously confirmed by meta-analysis to be associated with AD, is associated with exudative AMD. To our knowledge, this is the first report highlighting a genetic variant that increases the risk of developing both AD and AMD. Furthermore, we demonstrate that the risk associated with the mutant allele follows a recessive model for both diseases. We perform an AMD-CST3 case–control study genotyping 350 exudative AMD Caucasian individuals. Bringing together our data with the previously reported AMD-CST3 association study, the evidence of a recessive effect on AMD risk is strengthened (OR = 1.89, P = 0.005). This effect closely resembles the AD-CST3 recessive effect (OR = 1.73, P = 0.005) previously established by meta-analysis. This resemblance is substantiated by the high correlation between CST3 genotype and effect size across the two diseases (R2 = 0.978). A recessive effect is in line with the known function of cystatin C, a potent enzyme inhibitor. Its potency means that, in heterozygous individuals, a single functional allele is sufficient to maintain its inhibitory function; only homozygous individuals will lack this form of proteolytic regulation. Our findings support the hypothesis that recessively acting variants account for some of the missing heritability of multifactorial diseases. Replacement therapy represents a translational opportunity for individuals homozygous for the mutant allele

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Novel germline variants identified in the inner mitochondrial membrane transporter TIMM44 and their role in predisposition to oncocytic thyroid carcinomas

Familial Non-Medullary Thyroid Carcinoma (fNMTC) represents 3–7% of all thyroid tumours and is associated with some of the highest familial risks among all cancers, with an inheritance pattern compatible with an autosomal dominant model with reduced penetrance. We previously mapped a predisposing locus, TCO (Thyroid tumour with Cell Oxyphilia) on chromosome 19p13.2, for a particular form of thyroid tumour characterised by cells with an abnormal proliferation of mitochondria (oxyphilic or oncocytic cells). In the present work, we report the systematic screening of 14 candidate genes mapping to the region of linkage in affected TCO members, that led us to identify two novel variants respectively in exon 9 and exon 13 of TIMM44, a mitochondrial inner membrane translocase for the import in the mitochondria of nuclear-encoded proteins. These variants were co-segregating with the TCO phenotype, were not present in a large group of controls and were predicted to negatively affect the protein (exon 9 change) or the transcript (exon 13 change). Functional analysis was performed in vitro for both changes and although no dramatic loss of function effects were identified for the mutant alleles, subtler effects might still be present that could alter Timm44 function and thus promote oncocytic tumour development. Thus we suggest that TIMM44 should be considered for further studies in independent samples of affected individuals with TCO