Helicobacter Genotyping and Detection in Peroperative Lavage Fluid in Patients with Perforated Peptic Ulcer

Introduction and Objectives Certain Helicobacter pylori genotypes are associated with peptic ulcer disease; however, little is known about associations between the H. pylori genotype and perforated peptic ulcer (PPU). The primary aim of this study was to evaluate which genotypes are present in patients with PPU and which genotype is dominant in this population. The secondary aim was to study the possibility of determining the H. pylori status in a way other than by biopsy. Materials and Methods Serum samples, gastric tissue biopsies, lavage fluid, and fluid from the nasogastric tube were collec

Cancer-related fatigue: clinical practice versus practice guidelines

Purpose This study investigated adherence to treatment guidelines on cancer-related anaemia and fatigue (CRA/CRF) and factors influencing the choice of intervention. Methods In this prospective, observational study, 136 cancer patients being treated with chemotherapy in a large community hospital completed a questionnaire at consecutive outpatient visits assessing fatigue (the Functional Assessment of Chronic Illness Therapy—Fatigue) and fatigue-related counselling and advice received. Data on administration of chemotherapy and use of epoetin or blood transfusions were abstracted from the medical records. Results Fifty-three percent of patients with severe anaemia (Hb<10 g/dl) and 6% of patients with less severe anaemia (Hb levels 10-12 g/dl) received treatment (epoetin and/or blood transfusions). Half of the patients with less severe anaemia reported clinically relevant levels of fatigue. More than 50% of all patients received fatigue-related counselling, primarily at the start of chemotherapy. Most counselling was directed at energy conservation. Fatigue was not associated significantly with the use of epoetin or blood transfusion. Patients receiving palliative treatment (17%), male patients (16%) and patients with a low Hb level (<6.2 g/dl, 38%) were treated significantly more often with epoetin. Conclusions In daily clinical practice, guidelines concerning the use of epoetin or blood transfusion in severe CRA are adhered to in about half of the cases. In patients with less severe anaemia, the level of fatigue did not play a significant role in the use of epoetin. According to current guidelines, counselling on CRF should be directed primarily at activity enhancement. However, only a minority of patients receive such counselling

A novel nucleo-cytoplasmic hybrid clone formed via androgenesis in polyploid gibel carp

<p>Abstract</p> <p>Background</p> <p>Unisexual vertebrates have been demonstrated to reproduce by gynogenesis, hybridogenesis, parthenogenesis, or kleptogenesis, however, it is uncertain how the reproduction mode contributes to the clonal diversity. Recently, polyploid gibel carp has been revealed to possess coexisting dual modes of unisexual gynogenesis and sexual reproduction and to have numerous various clones. Using sexual reproduction mating between clone D female and clone A male and subsequent 7 generation multiplying of unisexual gynogenesis, we have created a novel clone strain with more than several hundred millions of individuals. Here, we attempt to identify genetic background of the novel clone and to explore the significant implication for clonal diversity contribution.</p> <p>Methods</p> <p>Several nuclear genome markers and one cytoplasmic marker, the mitochondrial genome sequence, were used to identify the genetic organization of the randomly sampled individuals from different generations of the novel clone.</p> <p>Results</p> <p>Chromosome number, <it>Cot</it>-1 repetitive DNA banded karyotype, microsatellite patterns, AFLP profiles and transferrin alleles uniformly indicated that nuclear genome of the novel clone is identical to that of clone A, and significantly different from that of clone D. However, the cytoplasmic marker, its complete mtDNA genome sequence, is same to that of clone D, and different from that of clone A.</p> <p>Conclusions</p> <p>The present data indicate that the novel clone is a nucleo-cytoplasmic hybrid between the known clones A and D, because it originates from the offspring of gonochoristic sexual reproduction mating between clone D female and clone A male, and contains an entire nuclear genome from the paternal clone A and a mtDNA genome (cytoplasm) from the maternal clone D. It is suggested to arise via androgenesis by a mechanism of ploidy doubling of clone A sperm in clone D ooplasm through inhibiting the first mitotic division. Significantly, the selected nucleo-cytoplasmic hybrid female still maintains its gynogenetic ability. Based on the present and previous findings, we discuss the association of rapid genetic changes and high genetic diversity with various ploidy levels and multiple reproduction modes in several unisexual and sexual complexes of vertebrates and even other invertebrates.</p

Neuronal and astrocyte dysfunction diverges from embryonic fibroblasts in the Ndufs4 fky fky mouse

Mitochondrial dysfunction causes a range of early-onset neurological diseases and contributes to neurodegenerative conditions. The mechanisms of neurological damage however are poorly understood, as accessing relevant tissue from patients is difficult, and appropriate models are limited. Hence, we assessed mitochondrial function in neurologically relevant primary cell lines from a CI (complex I) deficient Ndufs4 KO (knockout) mouse (Ndufs4fky/fky) modelling aspects of the mitochondrial disease LS (Leigh syndrome), as well as MEFs (mouse embryonic fibroblasts). Although CI structure and function were compromised in all Ndufs4fky/fky cell types, the mitochondrial membrane potential was selectively impaired in the MEFs, correlating with decreased CI-dependent ATP synthesis. In addition, increased ROS (reactive oxygen species) generation and altered sensitivity to cell death were only observed in Ndufs4fky/fky primary MEFs. In contrast, Ndufs4fky/fky primary isocortical neurons and primary isocortical astrocytes displayed only impaired ATP generation without mitochondrial membrane potential changes. Therefore the neurological dysfunction in the Ndufs4fky/fky mouse may partly originate from a more severe ATP depletion in neurons and astrocytes, even at the expense of maintaining the mitochondrial membrane potential. This may provide protection from cell death, but would ultimately compromise cell functionality in neurons and astrocytes. Furthermore, RET (reverse electron transfer) from complex II to CI appears more prominent in neurons than MEFs or astrocytes, and is attenuated in Ndufs4fky/fky cells

The MUC1 mucin protects against Helicobacter pylori pathogenesis in mice by regulation of the NLRP3 inflammasome

OBJECTIVES: The mucin MUC1, best known for providing an epithelial barrier, is an important protective host factor in both humans and mice during Helicobacter pylori pathogenesis. This study aimed to identify the long-term consequences of MUC1 deficiency on H. pylori pathogenesis and the mechanism by which MUC1 protects against H. pylori gastritis. DESIGN: Wildtype and Muc1(-/-) mice were infected for up to 9 months, and the gastric pathology, immunological response and epigenetic changes assessed. The effects of MUC1 on the inflammasome, a potent inflammatory pathway, were examined in macrophages and H. pylori-infected mice deficient in both MUC1 and inflammasome components. RESULTS: Muc1(-/-) mice began to die 6 months after challenge, indicating Muc1 deficiency made H. pylori a lethal infection. Surprisingly, chimaeric mouse infections revealed MUC1 expression by haematopoietic-derived immune cells limits H. pylori-induced gastritis. Gastritis in infected Muc1(-/-) mice was associated with elevated interleukin (IL)-1β and epigenetic changes in their gastric mucosa similar to those in transgenic mice overexpressing gastric IL-1β, implicating MUC1 regulation of an inflammasome. In support of this, infected Muc1(-/-)Casp1(-/-) mice did not develop severe gastritis. Further, MUC1 regulated Nlrp3 expression via an nuclear factor (NF)-κB-dependent pathway and reduced NF-κB pathway activation via inhibition of IRAK4 phosphorylation. The importance of this regulation was proven using Muc1(-/-)Nlrp3(-/-) mice, which did not develop severe gastritis. CONCLUSIONS: MUC1 is an important, previously unidentified negative regulator of the NLRP3 inflammasome. H. pylori activation of the NLRP3 inflammasome is normally tightly regulated by MUC1, and loss of this critical regulation results in the development of severe pathology

Process contribution to the time-varying residual circulation in tidally dominated estuarine environments

In tide dominated environments residual circulation is the comparatively weak net flow in addition to the oscillatory tidal current. Understanding the 3D structure of this circulation is of importance for coastal management as it impacts the net (longer-term and event-scale) transport of suspended particles and the advection of tracer quantities. The Dee Estuary, northwest Britain, is used to understand which physical processes have an important contribution to the time-varying residual circulation. Model simulations are used to extract the time-varying contributions of tidal, riverine (baroclinicity and discharge), meteorological, external and wave processes, along with their interactions. Under hypertidal conditions strong semi-diurnal interaction within the residual makes it difficult to clearly see the affect of a process without filtering. An approach to separate the residual into the isolated process contribution and the contribution due to interaction is described. Applying this method to two hypertidal estuarine channels, one tide-dominant and one baroclinic-dominant, reveals that process interaction can be as important as the sub-tidal residual process contributions themselves. The time-variation of the residual circulation highlights the impact of different physical process components at the event-scale of tidal conditions (neap and spring cycles) and offshore storms (wind, wave and surge influence). This gives insight into short-term deviation from the typical estuarine residual. Both channels are found to react differently to the same local conditions, with different short-term change in process dominance during events of high and low energy