Effect of Laparoscopic-assisted Gastropexy on Gastrointestinal Transit Time in Dogs.

BackgroundProphylactic gastropexy has been promoted as a means of preventing gastric volvulus during gastric dilatation and volvulus (GDV) syndrome. Little is known about the impact of gastropexy on gastrointestinal transit time.HypothesisLaparoscopic-assisted gastropexy (LAG) will not alter gastrointestinal transit times when comparing gastric (GET), small and large bowel (SLBTT), and whole gut transit times (TTT) before and after surgery.Animals10 healthy client-owned large-breed dogs.MethodsProspective clinical trial. Before surgery, all dogs underwent physical examination and diagnostic evaluation to ensure normal health status. Dogs were fed a prescription diet for 6 weeks before determination of gastrointestinal transit with a wireless motility capsule. LAG was then performed, and dogs were fed the diet for 6 additional weeks. Measurement of transit times was repeated 6 weeks after surgery.ResultsTen dogs of various breeds at-risk for GDV were enrolled. No complications were encountered associated with surgery or capsule administration. There were no significant differences in GET 429 [306-1,370] versus 541 [326-1,298] (P = 0.80), SLBTT 1,243 [841-3,070] versus 1,540 [756-2,623] (P = 0.72), or TTT 1,971 [1,205-3,469] versus 1,792 [1,234-3,343] minutes (median, range) (P = 0.65) before and after LAG.Conclusions and clinical importanceAn effect of LAG on gastrointestinal transit time was not identified, and wireless motility capsule can be safely administered in dogs after LAG

Closely Related Tree Species Differentially Influence the Transfer of Carbon and Nitrogen from Leaf Litter Up the Aquatic Food Web

Decomposing leaf litter in streams provides habitat and nutrition for aquatic insects. Despite large differences in the nutritional qualities of litter among different plant species, their effects on aquatic insects are often difficult to detect. We evaluated how leaf litter of two dominant riparian species (Populus fremontii and P. angustifolia) influenced carbon and nitrogen assimilation by aquatic insect communities, quantifying assimilation rates using stable isotope tracers (13C, 15N). We tested the hypothesis that element fluxes from litter of different plant species better define aquatic insect community structure than insect relative abundances, which often fail. We found that (1) functional communities (defined by fluxes of carbon and nitrogen from leaf litter to insects) were different between leaf litter species, whereas more traditional insect communities (defined by relativized taxa abundances) were not different between leaf litter species, (2) insects assimilated N, but not C, at a higher rate from P. angustifolia litter compared to P. fremontii, even though P. angustifolia decomposes more slowly, and (3) the C:N ratio of material assimilated by aquatic insects was lower for P. angustifolia compared to P. fremontii, indicating higher nutritional quality, despite similar initial litter C:N ratios. These findings provide new evidence for the effects of terrestrial plant species on aquatic ecosystems via their direct influence on the transfer of elements up the food web. We demonstrate how isotopically labeled leaf litter can be used to assess the functioning of insect communities, uncovering patterns undetected by traditional approaches and improving our understanding of the association between food web structure and element cycling

Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange–treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody–targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody–mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample siz

Distributed brain co-processor for tracking spikes, seizures and behaviour during electrical brain stimulation

Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a handheld device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from nine humans and eight canines with epilepsy, and then implemented prospectively in out-of-sample testing in two pet canines and four humans with drug-resistant epilepsy living in their natural environments. Accurate seizure diaries are needed as the primary clinical outcome measure of epilepsy therapy and to guide brain-stimulation optimization. The brain co-processor system described here enables tracking interictal epileptiform spikes, seizures and correlation with patient behavioural reports. In the future, correlation of spikes and seizures with behaviour will allow more detailed investigation of the clinical impact of spikes and seizures on patients

Ileosigmoid fistula and delayed ileal obstruction secondary to blunt abdominal trauma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Abdominal trauma is a source of significant mortality and morbidity. Bowel injury as a result of blunt abdominal trauma is usually evident within hours or days of the accident.</p> <p>Case presentation</p> <p>A 38-year-old Caucasian Greek man presented with a subtle and delayed small bowel obstruction caused by a post-traumatic ileosigmoid fistula and ileal stricture four months after a road traffic accident.</p> <p>Conclusion</p> <p>Delayed occurrence of post-traumatic small bowel stricture and ileosigmoid fistula is an uncommon surgical emergency. General surgeons as well as emergency physicians should bear this manifestation in mind should a patient return to the hospital several weeks or even years after blunt abdominal trauma with symptoms or signs of bowel obstruction.</p

Long-term outcomes and response to treatment in diacylglycerol kinase epsilon nephropathy

Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.009/million/year and so-called DGKE MPGN as 0.006/million/year, giving a combined incidence of 0.015/million/year. Here, we describe a cohort of sixteen individuals with DGKE nephropathy. One presented with isolated nephrotic syndrome. Analysis of pathological features reveals that DGKE mutations give an MPGN-like appearance to different extents, with but more often without changes in arterioles or arteries. In 15 patients presenting with aHUS, ten had concurrent substantial proteinuria. Identified triggering events were rare but coexistent developmental disorders were seen in six. Nine with aHUS experienced at least one relapse, although in only one did a relapse of aHUS occur after age five years. Persistent proteinuria was seen in the majority of cases. Only two individuals have reached end stage renal disease, 20 years after the initial presentation, and in one, renal transplantation was successfully undertaken without relapse. Six individuals received eculizumab. Relapses on treatment occurred in one individual. In four individuals eculizumab was withdrawn, with one spontaneously resolving aHUS relapse occurring. Thus we suggest that DGKE-mediated aHUS is eculizumab non-responsive and that in individuals who currently receive eculizumab therapy it can be safely withdrawn. This has important patient safety and economic implications

Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy

BACKGROUND: Primary membranoproliferative GN, including complement 3 (C3) glomerulopathy, is a rare, untreatable kidney disease characterized by glomerular complement deposition. Complement gene mutations can cause familial C3 glomerulopathy, and studies have reported rare variants in complement genes in nonfamilial primary membranoproliferative GN. METHODS: We analyzed whole-genome sequence data from 165 primary membranoproliferative GN cases and 10,250 individuals without the condition (controls) as part of the National Institutes of Health Research BioResource–Rare Diseases Study. We examined copy number, rare, and common variants. RESULTS: Our analysis included 146 primary membranoproliferative GN cases and 6442 controls who were unrelated and of European ancestry. We observed no significant enrichment of rare variants in candidate genes (genes encoding components of the complement alternative pathway and other genes associated with the related disease atypical hemolytic uremic syndrome; 6.8% in cases versus 5.9% in controls) or exome-wide. However, a significant common variant locus was identified at 6p21.32 (rs35406322) (P=3.29×10−8; odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.53 to 2.44), overlapping the HLA locus. Imputation of HLA types mapped this signal to a haplotype incorporating DQA1*05:01, DQB1*02:01, and DRB1*03:01 (P=1.21×10−8; OR, 2.19; 95% CI, 1.66 to 2.89). This finding was replicated by analysis of HLA serotypes in 338 individuals with membranoproliferative GN and 15,614 individuals with nonimmune renal failure. CONCLUSIONS: We found that HLA type, but not rare complement gene variation, is associated with primary membranoproliferative GN. These findings challenge the paradigm of complement gene mutations typically causing primary membranoproliferative GN and implicate an underlying autoimmune mechanism in most cases

Zinc-Chelation Contributes to the Anti-Angiogenic Effect of Ellagic Acid on Inhibiting MMP-2 Activity, Cell Migration and Tube Formation

Ellagic acid (EA), a dietary polyphenolic compound, has been demonstrated to exert anti-angiogenic effect but the detailed mechanism is not yet fully understood. The aim of this study was to investigate whether the zinc chelating activity of EA contributed to its anti-angiogenic effect.The matrix metalloproteinases-2 (MMP-2) activity, a zinc-required reaction, was directly inhibited by EA as examined by gelatin zymography, which was reversed dose-dependently by adding zinc chloride. In addition, EA was demonstrated to inhibit the secretion of MMP-2 from human umbilical vein endothelial cells (HUVECs) as analyzed by Western blot method, which was also reversed by the addition of zinc chloride. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), known to down-regulate the MMP-2 activity, was induced by EA at both the mRNA and protein levels which was correlated well with the inhibition of MMP-2 activity. Interestingly, zinc chloride could also abolish the increase of EA-induced RECK expression. The anti-angiogenic effect of EA was further confirmed to inhibit matrix-induced tube formation of endothelial cells. The migration of endothelial cells as analyzed by transwell filter assay was suppressed markedly by EA dose-dependently as well. Zinc chloride could reverse these two effects of EA also in a dose-dependent manner. Since magnesium chloride or calcium chloride could not reverse the inhibitory effect of EA, zinc was found to be involved in tube formation and migration of vascular endothelial cells.Together these results demonstrated that the zinc chelation of EA is involved in its anti-angiogenic effects by inhibiting MMP-2 activity, tube formation and cell migration of vascular endothelial cells. The role of zinc was confirmed to be important in the process of angiogenesis