Drivers of ecological assembly in the hindgut of Atlantic Cod fed a macroalgal supplemented diet.

It is difficult to disentangle the many variables (e.g. internal or external cues and random events) that shape the microbiota in the gastrointestinal tract of any living species. Ecological assembly processes applied to microbial communities can elucidate these drivers. In our study, farmed Atlantic cod (Gadus morhua) were fed a diet of 10% macroalgae supplement (Ulva rigida [ULVA] or Ascophyllum nodosum [ASCO] or a non-supplemented control diet [CTRL]) over 12 weeks. We determined the influence of ecological assembly processes using a suite of null-modelling tools. We observed dissimilarity in the abundance of common OTUs over time, which was driven by deterministic assembly. The CTRL samples showed selection as a critical assembly process. While dispersal limitation was a driver of the gut microbiome for fish fed the macroalgae supplemented diet at Week 12 (i.e., ASCO and ULVA). Fish from the ASCO grouping diverged into ASCO_N (normal) and ASCO_LG (lower growth), where ASCO_LG individuals found the diet unpalatable. The recruitment of new taxa overtime was altered in the ASCO_LG fish, with the gut microbiome showing phylogenetic underdispersion (nepotistic species recruitment). Finally, the gut microbiome (CTRL and ULVA) showed increasing robustness to taxonomic disturbance over time and lower functional redundancy. This study advances our understanding of the ecological assembly and succession in the hindgut of juvenile Atlantic cod across dietary treatments. Understanding the processes driving ecological assembly in the gut microbiome, in fish research specifically, could allow us to manipulate the microbiome for improved health or resilience to disease for improved aquaculture welfare and production.

Sweat Testing in Ireland

Introduction Quick, painless, cheap and reliable, the sweat test remains the gold standard diagnostic test for cystic fibrosis. We aimed to describe the pattern of testing in Ireland over a calendar year. Methods Information on sweat test practices was requested from each centre between 1st January 2011 and 31st December 2011, and the number of positive, negative, equivocal, and insufficient samples was recorded. Results In 2011 there were 2555 sweat tests performed in 15 centres, ranging from 35 to over 450 tests per centre. 35 (1.4%) were in the diagnostic range. The overall quantity not sufficient (QNS) rate was 10.3% (range 0-28.3%). Testing was performed across a wide age range (2.5 weeks to 75 years). The mean sweat chloride value was 16.5 mmol/L (SD 16.1 mmol/L). Discussion Our study demonstrates a high number of sweat tests performed in Ireland with significant variation in sweat testing practices across 15 different sites.

A decision impact, decision conflict and economic assessment of routine Oncotype DX testing of 146 women with node-negative or pNImi, ER-positive breast cancer in the U.K.

BACKGROUND: Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in early breast cancer patients. This study aims to examine the implications of routine Oncotype DX testing in the U.K. METHODS: Women with oestrogen receptor positive (ER+), pNO or pN1mi breast cancer were assessed for adjuvant chemotherapy and subsequently offered Oncotype DX testing, with changes in chemotherapy decisions recorded. A subset of patients completed questionnaires about their uncertainties regarding chemotherapy decisions pre- and post-testing. All patients were asked to complete a diary of medical interactions over the next 6 months, from which economic data were extracted to model the cost-effectiveness of testing. RESULTS: Oncotype DX testing resulted in changes in chemotherapy decisions in 38 of 142 (26.8%) women, with 26 of 57 (45.6%) spared chemotherapy and 12 of 85 (14.1%) requiring chemotherapy when not initially recommended (9.9% reduction overall). Decision conflict analysis showed that Oncotype DX testing increased patients' confidence in treatment decision making. Economic analysis showed that routine Oncotype DX testing costs £6232 per quality-adjusted life year gained. CONCLUSION: Oncotype DX decreased chemotherapy use and increased confidence in treatment decision making in patients with ER+ early-stage breast cancer. Based on these findings, Oncotype DX is cost-effective in the UK setting.

A mouse model of autosomal recessive polycystic kidney disease with biliary duct and proximal tubule dilatation.

Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the polycystic kidney and hepatic disease (PKHD1) gene encoding the protein fibrocystin/polyductin. The aim of our study was to produce a mouse model of ARPKD in which there was no functional fibrocystin/polyductin to study the pathophysiology of cystic and fibrocystic disease in renal and non-renal tissues. Exon 2 of the gene was deleted and replaced with a neomycin resistance cassette flanked by loxP sites, which could be subsequently removed by Cre-lox recombinase. Homozygous Pkhd1(del2/del2) mice were viable, fertile and exhibited hepatic, pancreatic, and renal abnormalities. The biliary phenotype displayed progressive bile duct dilatation, resulting in grossly cystic and fibrotic livers in all animals. The primary cilia in the bile ducts of these mutant mice had structural abnormalities and were significantly shorter than those of wild-type (WT) animals. The Pkhd1(del2/del2) mice often developed pancreatic cysts and some exhibited gross pancreatic enlargement. In the kidneys of affected female mice, there was tubular dilatation of the S3 segment of the proximal tubule (PT) starting at about 9 months of age, whereas male mice had normal kidneys up to 18 months of age. Inbreeding the mutation onto BALBc/J or C57BL/6J background mice resulted in females developing PT dilatation by 3 months of age. These inbred mice will be useful resources for studying the mechanisms underlying the pathogenesis of ARPKD.

Statistics on cancer in China: cancer registration in 2002.

The objective of this study was to determine how many population-based cancer registries exist in China, what methods are being used, and the statistical data that are available from them, and to identify future needs with respect to technical support. A two-stage survey was conducted in 2002 at provincial and cancer registry level. Based on the questionnaire used in these two stages, the basic distribution and descriptive information on population-based cancer registry practices in China are addressed. There are 48 cancer registries in China, covering 73 million people (5.7% of the total population of China in 2000). The oldest three registries are LinZhou, ShangHai and QiDong. There are marked variations in practice between registries, with respect to data collection, data management and coding. Differences are also found in administrative aspects and sources of financial support. In conclusion, this first national survey of Chinese cancer registry practice provides a benchmark against which development and standardization can be evaluated in the future. The survey suggests that lack of qualified personnel, insufficient funding support and lack of stability of the population are major problems in carrying out registration work in China. It also indicates several ways in which registry practice, and hence availability and quality of incidence and survival data can be improved.

Human glioma PKC-iota and PKC-betaII phosphorylate cyclin-dependent kinase activating kinase during the cell cycle.

Cell cycle phase transition is regulated in part by the trimeric enzyme, cyclin-dependent kinase activating kinase (CAK) which phosphorylates and activates cyclin-dependent kinases (cdks). Protein kinase C (PKC) inhibitors prevent cell cycle phase transition, suggesting a fundamental role for PKCs in cell cycle regulation. We report that in glioma cells, CAK (cdk7) is constitutively associated with PKC-iota. In vitro phosphorylation, co-immunoprecipitation, and analysis of phosphorylated proteins by autoradiography indicate that CAK (cdk7) is a substrate for PKC-iota and PKC-betaII hyperphosphorylation. These results establish a role for PKC-iota and PKC-betaII in the activation of CAK during the glioma cell cycle.

Intercessory prayer and cardiovascular disease progression in a coronary care unit population: a randomized controlled trial.

OBJECTIVE: To determine the effect of intercessory prayer, a widely practiced complementary therapy, on cardiovascular disease progression after hospital discharge. PATIENTS AND METHODS: In this randomized controlled trial conducted between 1997 and 1999, a total of 799 coronary care unit patients were randomized at hospital discharge to the intercessory prayer group or to the control group. Intercessory prayer, ie, prayer by 1 or more persons on behalf of another, was administered at least once a week for 26 weeks by 5 intercessors per patient. The primary end point after 26 weeks was any of the following: death, cardiac arrest, rehospitalization for cardiovascular disease, coronary revascularization, or an emergency department visit for cardiovascular disease. Patients were divided into a high-risk group based on the presence of any of 5 risk factors (age = or >70 years, diabetes mellitus, prior myocardial infarction, cerebrovascular disease, or peripheral vascular disease) or a low-risk group (absence of risk factors) for subsequent primary events. RESULTS: At 26 weeks, a primary end point had occurred in 25.6% of the intercessory prayer group and 29.3% of the control group (odds ratio [OR], 0.83 [95% confidence interval (CI), 0.60-1.14]; P=.25). Among high-risk patients, 31.0% in the prayer group vs 33.3% in the control group (OR, 0.90 [95% CI, 0.60-1.34]; P=.60) experienced a primary end point. Among low-risk patients, a primary end point occurred in 17.0% in the prayer group vs 24.1% in the control group (OR, 0.65 [95% CI, 0.20-1.36]; P=.12). CONCLUSIONS: As delivered in this study, intercessory prayer had no significant effect on medical outcomes after hospitalization in a coronary care unit.

Head and neck cancer: a global perspective on epidemiology and prognosis.

Head and neck cancers (ICD-9 categories 140-149 and 161) are common in several regions of the world where tobacco use and alcohol consumption is high. The age standardized incidence rate of head and neck cancer (around 1990) in males exceeds 30/100, 000 in regions of France, Hong Kong, the Indian sub-continent, Central and Eastern Europe, Spain, Italy, Brazil, and among US blacks. High rates (> 10/100,000) in females are found in the Indian sub-continent, Hong Kong and Philippines. The highest incidence rate reported in males is 63.58 (France, Bas-Rhin) and in females 15.97 (India, Madras). The variation in incidence of cancers by subsite of head and neck is mostly related to the relative distribution of major risk factors such as tobacco or betel quid chewing, cigarette or bidi smoking, and alcohol consumption. Some degree of misclassification by subsites is a clear possibility in view of the close proximity of the anatomical subsites. While mouth and tongue cancers are more common in the Indian sub-continent, nasopharyngeal cancer is more common in Hong Kong; pharyngeal and/or laryngeal cancers are more common in other populations. While the overall incidence rates show a declining trend in both sexes in India, Hong Kong, Brazil and US whites, an increasing trend is observed in most other populations, particularly in Central and Eastern Europe, Scandinavia, Canada, Japan and Australia. The overall trends are a reflection of underlying trends in cancers of major subsites which seem to be related to the changing prevalence of risk factors. The five year relative survival varies from 20-90% depending upon the subsite of origin and the clinical extent of disease. While primary prevention is the potential strategy for long term disease control, early detection and treatment may have limited potential to improve mortality in the short term.

Cancer in Gabon, 1984-1993: a pathology registry based relative frequency study.

A pathology based cancer registry was established in 1977 in the pathology department of the faculty of health sciences of the University of Omar Bongo in Librevile, Gabon, which is the only pathology service catering to the needs of the population of approximately 1 million of Gabon. Analysis of the histologically diagnosed cancers during 1984 through 1993 revealed 1,367 male and 1,235 female cases. The leading sites in males were: skin (11.0%), liver (8.9%), non-Hodgkin's lymphoma (8.7%), prostate (7.8%), lung (6.9%), mouth (4.9%) and tongue (4.7%). The predominant sites in females were: uterine cervix (26.3%), breast (13.9%), non-Hodgkin's lymphoma (7.1%), skin (5.1%), liver (3.9%) and ovary (3.3%). Considering the little information available on cancer patterns in Africa, even relative frequency data for different periods from different sources are of considerable interest. We propose to establish population based cancer registration in Libreville (pop 400,000) where 40% of the national population lives, in the near future, which should provide reliable information on the cancer burden and patterns in Gabon.

Induction of stress proteins in chicken embryo cells by low-level zinc contamination in amino acid-free media.

It has been reported that chicken embryo cells deprived of exogenous amino acids for 4 hours synthesize stress (heat-shock) proteins. Herein, we show that amino acid deprivation is not sufficient to cause induction of stress proteins. Zinc contaminating a component of commercial cell culture medium used to prepare amino acid-free medium was an inducer in our cultures. In the absence of exogenous amino acids, the concentration of zinc ions needed for half-maximal induction of stress proteins was an order of magnitude lower than the dose required for cells in complete medium. Histidine and cystine, which have high affinities for zinc ions, were the amino acids most effective in blocking the induction of stress proteins by zinc. Problems posed by heavy metal ions in culture media and biologic fluids for searches for in vivo inducers of the cellular stress (heat shock) response are discussed.

Kinetics of gentamicin after intravenous, intramuscular, and intratracheal administration in sheep.

Kinetics of gentamicin (2.2 mg/kg of body weight) were investigated in 7 sheep after IV bolus administration. The mean serum concentration profile could be described by a 2-compartment open model with a distribution rate constant (alpha) of 3.112 +/- 1.681 hour-1 [half-life, t1/2(alpha) = 17.22 +/- 8.63 minutes] and an overall elimination rate constant (beta) of 0.485 +/- 0.028 hour-1 [t1/2(beta) - 85.87 +/- 5.03 minutes]. The apparent volume of distribution was somewhat restricted [Vd(area) = 0.194 +/- 0.059 L/Kg], and the total body clearance was 1.559 +/- 0.400 ml/kg/min. Equal dosages of gentamicin (2.2 mg/kg) were also given IM and intratracheally (IT). after IM injection, gentamicin reached peak serum concentration at postinjection minutes (PIM) 45, surpassing concentrations after the IV injection for the remainder of the experiment. The IT injection produced detectable serum concentrations at PIM 5, with a peak concentration at PIM 60. The serum drug concentrations after IT injections remained well below concentrations after IV and IM injections. Radiographic analysis of an IT injection of a gentamicin-tantalum suspension revealed good distribution throughout the trachea and proximal bronchi, with physical clearance of the tantalum occurring after greater than or equal to 10 minutes. Aspiration biopsy of the tracheal wash 6 hours after IT gentamicin injection revealed no cytologic response to gentamicin in 6 of 7 sheep, with the single response that of a purulent exudate.