Design and methods of the REMOVAL-HD study: a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients.

BACKGROUND: Removal of uraemic toxins is inadequate using current dialysis strategies. A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. The REMOVAL-HD study (a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients) will address safety, efficacy and the impact on patient-centred outcomes with the use of a mid cut-off (MCO) dialyser in a chronic haemodialysis (HD) population. METHODS: REMOVAL-HD is an open label, prospective, non-randomised, single-arm, multi-centre device study in 85 chronic HD participants. All visits will be conducted during regular HD sessions and participants will undergo a 1 month wash-in period using a standardised high flux dialyser, 6 months of intervention with a MCO dialyser and 1 month of wash-out using a high flux dialyser. The primary endpoint is change in pre-dialysis concentrations of serum albumin, with secondary endpoints including the efficacy of clearance of free light chains and ß-2 microglobulin, and patient-centred outcomes including quality of life, symptom burden, functional status, nutritional status, hospitalisation and death. DISCUSSION: MCO dialysers are a novel form of HD membrane. The REMOVAL-HD study is a pivotal study designed to monitor the immediate and medium-term effects following exposure to this dialyser. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482 . Date of registration - 21/06/2016.

Assessing changes in the UK pet cat and dog populations: numbers and household ownership.

The main aim of this study was to replicate methodology used to estimate the size of the UK pet cat and dog populations in 2006 and the proportion of households owning cats/dogs in 2007, to produce updated data to compare trends in ownership and population sizes. A cross-sectional study design was used to collect telephone interview data from 3155 households in the UK. 2011 UK human census data were used to predict the size of the cat and dog populations owned by households in the UK in 2011. Of the households, 23 per cent (714/3155) owned one or more cats and 30 per cent (940/3155) owned one or more dogs. There was some overlap in pet ownership with 7 per cent (210/3155) of households owning both one or more cats and one or more dogs. There was a small but significant decrease in the proportion of households that owned one or more cats in 2011 compared with 2007, with no change in the proportion owning dogs. However, overall, the total number of cats and dogs that were estimated to be owned by UK households did not change significantly between 2006 and 2011. The estimated size (and 95% CIs) of the pet cat and dog populations in the UK in 2011 was 10,114,764 cats (9,138,603-11,090,924) and 11,599,824 dogs (10,708,070-12,491,578).

Atlantic bluefin tuna Thunnus thynnus feeding ecology in the northern Gulf of Mexico: a preliminary description of diet from the western Atlantic spawning grounds.

A combination of stomach contents, nitrogen stable-isotope and tissue C:N values are presented to demonstrate feeding activity of Atlantic bluefin tuna Thunnus thynnus on the Gulf of Mexico (GOMEX) spawning grounds. Diets include teleosts, cephalopods, crustaceans and a pelagic tunicate (Pyrosoma atlanticum). Results reveal the need to classify the GOMEX as a T. thynnus feeding ground.

Poor owner knowledge of feline reproduction contributes to the high proportion of accidental litters born to UK pet cats.

'Accidental' litters contribute to population growth and the number of unwanted animals entering animal welfare organisations. Assessing the problem's extent and determining risk factors enables identification of education targets. Data were obtained from 715 cat-owning households in a cross-sectional telephone survey. Demographic and lifestyle factors were assessed for their association with accidental litters and with owner knowledge of cat reproduction. A total of 128 litters were reported from 552 female cats, and the proportion of accidental litters reported by owners was 80 per cent. Multivariable analysis identified that respondents were more likely to report an accidental litter of kittens if they believed a female cat should have a litter prior to being neutered, if they had more than one cat and if they rented rather than owned their home. Misconceptions relating to cat reproduction were common. The opinion that the youngest age a cat could get pregnant was five months of age (or older) was held by 83.5 per cent of cat-owning respondents, with over a quarter (26.4 per cent; 174/659) believing a queen is unable to conceive until at least a year of age. Almost half the respondents (49.0 per cent; 334/682) believed a female cat should have a litter before being neutered or were not sure; 38.8 per cent (264/681) thought that un-neutered, related cats would not mate or were not sure. This study suggests that improving cat-owner knowledge of the reproductive capacity of cats is likely to have a significant impact on the numbers of accidental litters born.

Number and ownership profiles of cats and dogs in the UK.

A random sample of 2980 households in the UK in 2007 showed that 26 per cent and 31 per cent of households owned cats and dogs, respectively. Households with gardens were more likely to own cats and dogs than households without gardens. Households in which someone was qualified to degree level were more likely to own cats and less likely to own dogs than other households. Cats were more likely to be owned by semi-urban/rural households and by female respondents. Dog ownership significantly decreased the likelihood of cat ownership, and respondents aged 65 years or more were less likely to report that their household owned a cat than younger respondents. Households with one or more dogs and children aged 11 to 15 years were more likely to own a cat than other households. The likelihood of dog ownership increased as household size increased. Dogs were more likely to be owned by rural households, and less likely to be owned by households with cats or children aged 10 years or younger. Female respondents and those aged less than 55 years were more likely to report dog ownership than other respondents. The estimated size (and 95 per cent confidence intervals) of the owned cat and dog populations in the UK in 2006 was 10,332,955 (9,395,642 to 11,270,269) cats and 10,522,186 (9,623,618 to 11,420,755) dogs.

[Rational antibacterial therapy of acute surgical diseases of abdominal organs].

Comparative analysis of medical documents, concerning 1055 patients, aged 18-92 yrs old, operated for an acute surgical diseases of abdominal organs in 2007-2009 yrs, was performed. Preoperative antibioticotherapy was performed in all the patients, in 877 of them ceftazidim (ceftadim) was administered as the main antibacterial preparation and in 178--other antibacterial preparations. Application of ceftadim, as a basic preparation in antibioticotherapy, had permitted to lower the purulent-septic complications rate by 61% and to reduce the stationary treatment duration of the patients.

Survey of the characteristics of cats owned by households in the UK and factors affecting their neutered status.

Data were collected on 1260 cats owned by a random sample of UK households in 2007, by means of telephone questionnaires, which were completed by 33 per cent of the households contacted. Cats were owned by 26 per cent of these households, 42 per cent of which owned more than one cat. The owners of 622 female cats reported a total of 110 unplanned litters of kittens. Excluding cats with an unknown neutered status 92 per cent of the cats aged six months or more were neutered, but only 66 per cent of the cats aged six to 12 months were neutered. Multivariable logistic regression, based on data collected for one randomly selected cat aged four months or more in each cat-owning household, was used to identify factors affecting the cats' neutered status. Analysis of 48 sexually entire cats and 501 neutered cats showed that cats aged 10 months or more, with indoor access, that had been vaccinated within the last year or were currently registered with a veterinary practice, were more likely to be neutered than cats aged less than 10 months, without indoor access, that had been vaccinated more than one year ago or were not registered with a veterinary practice.

Fish oil for kidney transplant recipients.

BACKGROUND: Calcineurin inhibitors used in kidney transplantation for immunosuppression have adverse effects that may contribute to nephrotoxicity and increased cardiovascular risk profile. Fish oils are rich in very long chain omega-3 fatty acids, which may reduce nephrotoxicity by improving endothelial function and reduce rejection rates through their immuno-modulatory effects. They may also modify the cardiovascular risk profile. Hence, fish oils may potentially prolong graft survival and reduce cardiovascular mortality. OBJECTIVES: To assess the benefits and harms of fish oil supplementation on kidney transplant recipients on a calcineurin inhibitor-based immunosuppressive regimen. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library, issue 2 2005), MEDLINE (1966-April 2005) and EMBASE (1980-April 2005). SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs of fish oils in kidney transplant recipients on a calcineurin inhibitor-based immunosuppressive regimen. RCTs of fish oil versus statins were included. DATA COLLECTION AND ANALYSIS: Data was extracted and the quality of studies assessed by two authors, with differences resolved by discussion with a third independent author. Dichotomous outcomes were reported as relative risk (RR) and continuous outcome measures were reported as the mean difference (MD) with 95% confidence intervals using the random effects model. Heterogeneity was assessed using a Chi(2) test on n-1 degrees of freedom and the I(2) statistic. Data not suitable for pooling were tabulated and described. MAIN RESULTS: Sixteen studies (733 patients) were suitable for analysis. Fish oil did not significantly affect patient or graft survival, acute rejection rates, calcineurin inhibitor toxicity or renal function, when compared to placebo. Fish oil treatment was associated with a lower diastolic blood pressure (MD 4.5 mmHg; P = 0.004) compared to placebo. Patients receiving fish oil for more than six months had a modest increase in HDL (MD 0.12 mmol/L; P = 0.01) compared to placebo. Fish oil effects on lipids were not significantly different from low-dose statins. There was insufficient data to analyse cardiovascular outcomes. Fishy aftertaste and gastrointestinal upset were common but did not result in significant patient drop-out. AUTHORS' CONCLUSIONS: There is insufficient evidence from currently available RCTs to recommend fish oil therapy to improve renal function, rejection rates, patient survival or graft survival. The improvements in HDL cholesterol and diastolic blood pressure were too modest to recommend routine use. To determine a benefit in clinical outcomes, future RCTs will need to be adequately powered with these outcomes in mind.

Supernumerary pregnancy, collective harm, and two forms of the nonidentity problem.

An interesting question, in both the moral and the legal context, is whether babies born of an infertility treatment-induced supernumerary pregnancy (or ITISP) are properly considered to have been harmed. One might wonder how such a question could even arise in the face of data that clearly demonstrate that ITISP leaves an unduly large number of babies blind, deaf, and palsied, and facing lifelong disabilities. In fact, however, a number of arguments, based on the problem of collective form and two forms of the so-called "nonidentity problem," challenge the claim of harm in the ITISP context. The purpose of the present paper is to establish, as against these arguments, that harm has been imposed on the ITISP-damaged offspring.

Single and serial measurements of cardiac troponin I in asymptomatic patients on chronic hemodialysis.

AIMS: Coronary artery disease is the major cause of death in patients with end-stage renal failure on dialysis. This study aimed to assess the predictive value of a single cardiac troponin I (cTnI), and also the kinetics of serial values. METHODS: Since cTnI is a potential biomarker of cardiac outcome, the present study examined single cTnI measurements (n = 88 patients) and its predictive value for future cardiac events, and a kinetic substudy of serial weekly cTnI measured for 8 weeks (n = 57) in a group of patients on hemodialysis. RESULTS: Single cTnI measurements: 9 patients (10.2%) had a detectable cTnI at baseline and 79 patients (89.8%) had a negative baseline cTnI. There were no significant differences in age, sex, history of ischemic heart disease, diabetes, smoking or dyslipidemia between patients with detectable and negative cTnI. At the end of 9 months, the rate of combined primary endpoints, which included myocardial infarction, cardiac death and cardiac revascularization, was significantly higher in the patients with a detectable baseline cTnI (55.6%), compared to patients with a negative cTnI (6.3%) (p = 0.0007). Serial weekly cTnI measurements: significant fluctuations in cTnI were noted over time; 27% of patients with an undetectable cTnI measured at baseline had subsequent detectable levels in the serial follow-up. CONCLUSION: A single detectable cTnI in asymptomatic patients on hemodialysis defines patients at high risk of future cardiac events. However, the incidence of detectable cTnI levels is markedly increased when serial weekly measurements are performed. The clinical significance of detectable serial measurements of cTnI is the focus of ongoing studies.

Treatment for lupus nephritis.

BACKGROUND: Lupus nephritis is the renal manifestation of systemic lupus erythematosus (SLE) - a disease mainly affecting young women with substantial morbidity and mortality. It is classified by the World Health Organization (WHO) criteria I - VI based on histology. WHO Class IV is a diffuse proliferative glomerulonephritis which has the worst prognosis without treatment, with a reported 17% five year survival in the era 1953-1969. This survival was 82% in the early 1990's and continues to improve. An important factor behind this has been the use of cytotoxics such as cyclophosphamide in addition to steroids. OBJECTIVES: To assess the benefits and harms of different treatments in biopsy-proven proliferative lupus nephritis (LN). SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register (January 2003), the Cochrane Central Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 1, 2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing treatments for PLN in both adult and paediatric patients with Class III, IV, Vc, Vd lupus nephritis were included. All treatments were considered. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity. MAIN RESULTS: Of 920 articles identified, 25 were RCTs suitable for inclusion, which enrolled 915 patients. The majority compared cyclophosphamide or azathioprine plus steroids versus steroids alone. Cyclophosphamide plus steroids reduced the risk of doubling of serum creatinine (RR 0.59, 95% CI 0.40 to 0.88) compared to steroids alone but had no impact on mortality (RR 0.98, 95% CI 0.53 to 1.82). The risk of ovarian failure was significantly increased (RR 2.18, 95% CI 1.10 to 4.34). Azathioprine plus steroids reduced the risk of all cause mortality compared to steroids alone (RR 0.60, 95% CI 0.36 to 0.99), but did not alter renal outcomes. Neither therapy was associated with increased risk of major infection. No benefit was found with addition of plasma exchange to cyclophosphamide or azathioprine plus steroids for mortality ( RR 0.71, 95% CI 0.50 to 1.02), doubling of serum creatinine (RR 0.17, 95% CI 0.02 to 1.26) or end-stage renal failure (RR 1.24, 95% CI 0.60 to 2.57). There was also no increased risk of major infection (RR 0.69, 95% CI 0.35 to 1.37). REVIEWER'S CONCLUSIONS: Until future RCTs of newer agents are completed, the current use of cyclophosphamide combined with steroids remains the best option to preserve renal function in proliferative LN. The smallest effective dose and shortest duration of treatment should be used to minimise gonadal toxicity, without compromising efficacy.

Molecular and mesoscale structures in hydrophobically driven aqueous solutions.

Since Kauzmann's seminal 1959 paper, the hydrophobic interaction has dominated thinking on the forces that control protein folding and stability. Despite its wide importance in chemistry and biology, our understanding of this interaction at the molecular level remains poor, with little experimental evidence to support the idea of water ordering close to a non-polar group that is at the centre of the standard model for the source of the entropic driving force. Developments over recent years in neutron techniques now enable us to see directly how a non-polar group actually affects the molecular structure of the water in its immediate neighbourhood. On the basis of such work on aqueous solutions of small alcohols, the generally accepted standard model is found to be wanting, and alternative sources of the entropic driving force are suggested. Moreover, the fact that we can now follow changes in hydrogen bonding as the alcohol concentration is varied gives us the possibility of explaining the concentration dependence of the enthalpy of mixing. Complementary studies of solute association on the mesoscopic scale show a rich concentration and temperature behaviour, which reflects a complex balance of polar and non-polar interactions. Unravelling the detailed nature of this balance in simple aqueous amphiphiles may lead to a better understanding of the forces that control biomolecular structural stability and interactions.

Molecular analysis of the Drosophila miniature-dusky ( m-dy) gene complex: m-dy mRNAs encode transmembrane proteins with similarity to C. elegans cuticulin.

Mutations in the Drosophila miniature-dusky ( m-dy) gene complex were first reported by Morgan and Bridges about 90 years ago. m-dy mutants have abnormally small wings, a phenotype attributed to a cell-autonomous reduction in the size of the epidermal cells comprising the differentiated wing. Using a molecular genetic approach, we have characterized the m-dy chromosomal interval and identified a pair of adjacent transcription units corresponding to m and dy. A dy mutant known as dy (And) has a single base substitution within the protein-coding region that is predicted to result in an amber stop codon and premature translational termination. We show that dy mRNA is expressed at two discrete periods during the life cycle--one during embryonic development and early larval instars, the second during adult development, coincident with wing differentiation. In agreement with the phenotypic similarity of m and dy mutants, sequence comparisons reveal a similarity between the predicted MINIATURE and DUSKY proteins, and indicate that the m and dy genes are members of a larger Drosophila gene family. Both m and dy, as well as other members of this superfamily, are predicted to encode transmembrane proteins with similarity to C. elegans cuticle proteins known as cuticulins. We postulate that m, dy and other members of this protein superfamily function as structural components of the Drosophila cuticulin layer. Such a role for m and dy products in wing differentiation is sufficient to explain the morphological phenotypes associated with m-dy mutants.

Protein energy supplements in unwell elderly patients--a randomized controlled trial.

BACKGROUND: To determine whether oral protein energy supplements, prescribed during hospitalization to elderly medical admissions, affect nutritional status and if baseline nutritional state influences this status. We also considered the effects on mortality, length of hospital stay, functional recovery, and institutionalization. METHODS: A prospective randomized controlled trial with no placebo. Consenting patients were stratified in 3 nutritional categories, and patients from each stratum were randomized into treatment or control. Observers were blinded to randomization. The participants were emergency admissions from home to a Medicine for the Elderly Unit in a Scottish hospital. The inclusion criteria were as follows: no known malignancy, the ability to swallow, and nonobesity (BMI < 75th percentile). The intervention was a prescription of 120 mL sip feed, 3 times daily (540 kcal, 22.5 g protein per day) throughout hospitalization, using the medicine prescription chart. The trial was powered to detect change in mean percentage weight. The following outcomes were also considered: anthropometry; mortality, length of hospital stay, functional recovery, and rates of institutionalization. RESULTS: Included in the trial were 381 patients. Nutritional supplementation was associated with significantly better energy intake (p = .001) and weight gain (p = .003) pooled across all nutritional categories. In the most poorly nourished patients, the intervention was associated with reduced mortality (5/34 versus 14/40, p < .05) and more patients improved functionally (17/25 versus 11/28, p < .04). Overall mortality results were 21/186 versus 33/195, odds ratio (OR) 0.62, 95% confidence interval (CI) 0.35, 1.13. CONCLUSIONS: Prescribing sip feed supplements in the medicine prescription chart during hospital stay reduces weight loss. Our data also support other evidence for a reduction in mortality noted in elderly patients on nutritional supplementation. There were suggestions of other clinical benefits.

Genomics: food and nutrition.

Nutrition is traditionally a multidisciplinary field applying principles of molecular biochemistry and statistical epidemiology to integrative metabolism and population health. Genomics, with its global perspective, is now reinventing the future of human metabolic health. Creative experimental designs are addressing metabolic questions in nutrition ranging from energy regulation to aging, and from mechanisms of absorption to the interspecies molecular crosstalk of bacteria and human cells within the intestine.

Genetic analysis of functional domains within the Drosophila LARK RNA-binding protein.

LARK is an essential Drosophila RNA-binding protein of the RNA recognition motif (RRM) class that functions during embryonic development and for the circadian regulation of adult eclosion. LARK protein contains three consensus RNA-binding domains: two RRM domains and a retroviral-type zinc finger (RTZF). To show that these three structural domains are required for function, we performed a site-directed mutagenesis of the protein. The analysis of various mutations, in vivo, indicates that the RRM domains and the RTZF are required for wild-type LARK functions. RRM1 and RRM2 are essential for viability, although interestingly either domain can suffice for this function. Remarkably, mutation of either RRM2 or the RTZF results in the same spectrum of phenotypes: mutants exhibit reduced viability, abnormal wing and mechanosensory bristle morphology, female sterility, and flightlessness. The severity of these phenotypes is similar in single mutants and double RRM2; RTZF mutants, indicating a lack of additivity for the mutations and suggesting that RRM2 and the RTZF act together, in vivo, to determine LARK function. Finally, we show that mutations in RRM1, RRM2, or the RTZF do not affect the circadian regulation of eclosion, and we discuss possible interpretations of these results. This genetic analysis demonstrates that each of the LARK structural domains functions in vivo and indicates a pleiotropic requirement for both the LARK RRM2 and RTZF domains.

Separation of iota-, kappa and lambda-carrageenans by capillary electrophoresis.

The present study reports a novel method for the separation of the high-molecular-weight anionic polysaccharides, iota, kappa, and lambda carrageenans, in capillary electrophoresis (CE). Carrageenan samples are first derivatised with 9-aminopyrene-1,4,6-trisulfonic acid (APTS), separated in an ammonium acetate background electrolyte (BGE) and detected with laser-induced fluorescence (LIF). The effects of changes of instrumental parameters (temperature, injection mode, field strength) and the composition of the BGE (concentration and pH) are reported, and are explained in terms of the physical chemistry of the BGE and the biopolymers. Optimal separation conditions for kappa, iota, and lambda carrageenans, including an APTS internal standard, were found in a polyvinyl alcohol coated capillary with an ammonium acetate BGE of low concentration (25 mM) and moderate pH (8.0). This BGE gave the best reproducibility in tests on iota/kappa mixtures, with relative standard deviations (RSDs) in migration times and normalised peak areas (relative to the APTS internal standard) of less than 0.1% and 1%, respectively. Using this BGE at 50 degrees C and a voltage of 30 kV, all three carrageenan subtypes were separated in a run time of 3 min.