bluuebunny/crossref_metadata_2025 huggingface dataset:
Coverage of alcohol consumption by national surveys in South Africa
Authors: Probst Charlotte , Shuper Paul A. , Rehm Jürgen
Published: November 2016

Background and aims

Evidence suggests that adult per‐capita alcohol consumption, as estimated from self‐reports of nationally representative surveys, underestimates ‘true’ consumption, as measured as the sum of recorded and unrecorded consumption. The proportion of total adult alcohol per capita reported in representative surveys is usually labelled ‘coverage’. The aim of the present paper was to estimate coverage for South Africa under different scenarios of alcohol use assessment and ‘true’ consumption.

Design

Five nationally representative surveys from South Africa were used to estimate the prevalence of drinking and the grams per day among current drinkers. All surveys used a complex multi‐stage sampling frame that was accounted for by using survey weights. The total (recorded and unrecorded), the recorded and the adjusted total adult per‐capita alcohol consumption in South Africa served as different estimates of the ‘true’ consumption.

Setting

South Africa.

Participants

Alcohol use information was assessed on a total of 8115, 16 398 and 13 181 adults (15 years or older) in surveys from the years 2003, 2005 and 2008, respectively. Two surveys in 2012 included 27 070 and 18 688 adults.

Measurements

Coverage of the alcohol use reported in the surveys was calculated, compared with the ‘true’ adult per‐capita alcohol.

Findings

The survey data covered between 11.8% [2005; 95% uncertainty interval (UI) = 9.3–16.2%)] and 19.4% (2003; 95% UI = 14.9–24.2%) of the total alcohol used per capita. The highest coverage of 27.9% (95% UI = 22.4–36.8%) was observed when looking only at recorded alcohol in 2003.

Conclusions

Evidence from five nationally representative surveys assessing alcohol use suggests that less than 20% of the total adult per‐capita alcohol consumption in South Africa is reported in surveys.
New neovascular age‐related macular degeneration is associated with systemic leucocyte activity
Authors: Subhi Yousif , Lykke Sørensen Torben
Published: November 2016

Purpose

To investigate systemic leucocyte activity in subtypes of age‐related macular degeneration (AMD) and onset of neovascular AMD.

Methods

Patients with early and late AMD and age‐matched control individuals were recruited consecutively, and venous blood was sampled for differential leucocyte counts. Patients with neovascular AMD were grouped based on time of blood sampling in relation to diagnosis of neovascular AMD: diagnosis of new neovascular AMD more than 30 days before blood sampling, within 30 days of blood sampling and more than 30 days after blood sampling.

Results

Of 347 recruited participants, 330 fulfilled the eligibility criteria (77 age‐matched controls, 33 with early AMD, 56 with geographic atrophy and 164 with neovascular AMD). We did not find any differences in the differential counts between patients at different stages of AMD and age‐matched control individuals. However, lymphocyte and monocytes–basophils–eosinophils mixed (MXD) counts were both significantly increased in patients with new neovascular AMD. Among these patients; higher MXD correlated with lower BCVA, larger central foveal thickness and larger total lesion size; higher lymphocytes correlated with smaller total lesion size; higher neutrophils correlated with CNV lesion size; and higher neutrophil‐to‐lymphocyte ratio correlated with larger lesion size.

Conclusions

Systemic leucocyte activity is associated with onset of CNV in patients with AMD and correlate with lesion size and BCVA, which suggest that acute systemic immune activity may play a role in neovascular flaring of AMD.
Prevalence and distribution of Chlamydia trachomatis genovars in Indian infertile patients: a pilot study
Authors: Rawre Jyoti , Dhawan Benu , Malhotra Neena , Sreenivas Vishnubhatla , Broor Shobha , Chaudhry Rama
Published: November 2016

To determine the prevalence and distribution of Chlamydia trachomatis genovars in patients with infertility by PCR‐RFLP and ompA gene sequencing. Prevalence of other etiological agents (viz., Ureaplasma spp. and Mycoplasma hominis) were also assessed. Endocervical swabs were collected from 477 women and urine was collected from 151 men attending the Infertility Clinic. The samples were screened for C. trachomatis by cryptic plasmid, ompA gene and nested ompA gene PCR. Genotyping was performed by PCR‐RFLP and sequencing. Samples were screened for Ureaplasma spp. and M. hominis. The prevalence of C. trachomatis in infertile women and their male partners were 15.7% (75 of 477) and 10.0% (15 of 151) respectively. Secondary infertility was significantly associated with chlamydial infection. Genovar E was the most prevalent followed by genovar D and F. Twenty‐four C. trachomatis strains were selected for ompA gene sequencing. No mixed infection was picked. Variability in ompA sequences was seen in 50.0%. Both PCR‐RFLP and ompA gene sequencing showed concordant results. High prevalence of C. trachomatis in infertile couples warrants routine screening for C. trachomatis infection in all infertile couples. Genotyping of the ompA gene of C. trachomatis may be a valuable tool in understanding the natural history of C. trachomatis infection.
SOX12: a novel potential target for acute myeloid leukaemia
Authors: Wan Haixia , Cai Jiayi , Chen Fangyuan , Zhu Jianyi , Zhong Jihua , Zhong Hua
Published: November 2016

The role of SRY‐related high‐mobility‐group box (SOX) 12 in leukaemia progression and haematopoiesis remains elusive. This study aimed to examine the expression and function of SOX12 in acute myeloid leukaemia (AML) using human myeloid leukaemia samples and the acute myeloid cell line THP1. Mononuclear cells were isolated from the bone marrow of AML patients and healthy donors. SOX12 expression in haematopoietic cells was evaluated by reverse transcription polymerase chain reaction (RT‐PCR). SOX12 short hairpin RNAs (shRNAs) were transduced into THP1 cells, and gene knockdown was confirmed by quantitative RT‐PCR and Western blot analysis. SOX12 was preferentially expressed in CD34+ cells in AML patients. The THP1 cells transduced with SOX12 shRNAs exhibited significantly reduced SOX12 expression and cell proliferation. SOX12 knockdown had no effect on apoptosis, but it induced cell cycle arrest at G1 phase and reduced the number of colonies. The transduced THP1 and primary AML cells were reconstituted in non‐obese diabetic‐severe combined immunodeficient (NOD/SCID) mice, and their numbers were significantly reduced 6–12 weeks after transplantation. The mRNA and protein levels of β‐catenin were significantly diminished following SOX12 knockdown, accompanied by a decrease in TCF/Wnt activity. SOX12 may be involved in leukaemia progression by regulating the expression of β‐catenin and then interfering with TCF/Wnt pathway, which may be a target for AML.
A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide‐containing regimens
Authors: Sanchez Larysa , Vesole David H. , Richter Joshua R. , Biran Noa , Bilotti Elizabeth , McBride Laura , Anand Palka , Ivanovski Kristin , Siegel David S.
Published: November 2016

Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open‐label, single‐institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide‐refractory patients. Patients were considered lenalidomide‐refractory if they had no clinical response (<minimal response) on a previous lenalidomide‐containing regimen (lenalidomide non‐responsive) or if they had progressive disease on or within 60 days of discontinuing a previous lenalidomide‐containing regimen (lenalidomide relapsed/refractory). Patients received oral vorinostat 400 mg days 1–7 and 15–21, lenalidomide 25 mg days 1–21, and dexamethasone 40 mg days 1, 8, 15 and 22 in 28‐day cycles. Twenty‐five patients were enrolled, median age was 65 years and patients had received a median of 5 prior regimens. The overall response rate was 24% (6 partial responses) and clinical benefit rate (≥stable disease) was 80%. Median time to a partial response was 1·9 months and median duration of response was 3·3 months. Median progression‐free survival was 5·3 months. Most common grade 3/4 adverse events were neutropenia (48%), thrombocytopenia (32%), anaemia (20%) and gastrointestinal toxicities (16%). In this heavily pre‐treated population, vorinostat in combination with lenalidomide and dexamethasone was active in lenalidomide‐refractory patients.
Visualization of Biomolecular Structures: State of the Art Revisited
Authors: Kozlíková B. , Krone M. , Falk M. , Lindow N. , Baaden M. , Baum D. , Viola I. , Parulek J. , Hege H.‐C.
Published: November 2016

Structural properties of molecules are of primary concern in many fields. This report provides a comprehensive overview on techniques that have been developed in the fields of molecular graphics and visualization with a focus on applications in structural biology. The field heavily relies on computerized geometric and visual representations of three‐dimensional, complex, large and time‐varying molecular structures. The report presents a taxonomy that demonstrates which areas of molecular visualization have already been extensively investigated and where the field is currently heading. It discusses visualizations for molecular structures, strategies for efficient display regarding image quality and frame rate, covers different aspects of level of detail and reviews visualizations illustrating the dynamic aspects of molecular simulation data. The survey concludes with an outlook on promising and important research topics to foster further success in the development of tools that help to reveal molecular secrets.
LIFE INSURANCE HOLDINGS AND WELL‐BEING OF SURVIVING SPOUSES
Authors: Harris Timothy F. , Yelowitz Aaron
Published: November 2016

Premature death of a breadwinner can have devastating financial consequences on surviving dependents. This study investigates the role of life insurance in mitigating the long‐run financial consequences of spousal mortality. Using the Health and Retirement Study, we examine individuals whose spouses died during or soon after his or her peak earnings years. After controlling for socioeconomic status, we find that sizable lump‐sum life insurance payouts do not significantly influence spousal well‐being. (JEL D31, G22, I31, J32, J33, J38)
Compliance with a COPD bundle of care in an Australian emergency department: A cohort study
Authors: Gerber Alexis , Moynihan Catriona , Klim Sharon , Ritchie Peter , Kelly Anne‐Maree
Published: November 2016

Introduction

Bundles of care are gaining popularity for treating acute severe illness.

Objective

To describe compliance with bundle of care elements (individually and as a “bundle”) for patients treated for chronic obstructive pulmonary disease (COPD) exacerbations in the emergency department (ED).

Methods

Retrospective observational study of patients presenting in the 2014 calendar year with an ED diagnosis of COPD. The primary outcomes of interest were compliance with key bundle of care elements (individually and as a “bundle”). Analysis is descriptive.

Results

381 patients were studied. Median age was 71 (IQR 64‐80), 60% were male and 77% arrived by ambulance. Median duration of symptoms was 3 days (IQR 2‐6 days). Compliance with the bundle elements was 90% for administration of controlled oxygen therapy (if oxygen given), 87% for administration of inhaled bronchodilators, 79% for administration of systemic corticosteroids, 75% of administration of antibiotics if evidence of infection, 77% for taking of a blood gas in non‐mild disease, 98% for taking of a chest X‐ray, and 74% for administration of NIV if pH <7.3. Compliance with all appropriate elements of the defined bundle of care was 49%. There was no difference in mean length of stay for admitted patients (P = .44), in‐hospital mortality (P = 1.00) or re‐admission within 30 days (P = .72) by bundle compliance.

Conclusion

Compliance with individual assessment and treatment recommendations was generally high; however, compliance with the overall recommended bundle was only 49%. This indicates that there is an opportunity to improve care in these patients.
Can Service Climate Detract from Employee Performance? The Role of Experience in Optimizing Satisfaction and Performance Outcomes
Authors: Gabler Colin B. , Rapp Adam , Richey Robert Glenn , Adams Frank G.
Published: November 2016

In this research, we test the curvilinear relationships between service climate perceptions and two employee performance outcomes. Specifically, we propose that while service climate can be beneficial, high levels can actually be detrimental to customer satisfaction and sales performance. Additionally, we propose that a global assessment of employee experience that captures knowledge, skills, and abilities, or KSAs, moderates these curvilinear relationships by providing a means to balance outcome goals. We test our theory using data obtained from 312 employees in a service setting, which we pair with their managers’ assessments of their sales performance as well as satisfaction ratings from their customers. Our results reveal two things: (1) an inverted U‐shaped relationship between service climate and sales performance and (2) the level of experience moderates the relationship. These findings suggest that more experienced employees are better able to adjust behaviors to achieve high levels of performance than less experienced employees. Based on these results, we offer theoretical implications and applications for managerial practice.
Socio‐economic factors influencing the development of end‐stage renal disease in people with Type 1 diabetes – a longitudinal population study
Authors: Toppe C. , Möllsten A. , Schön S. , Dahlquist G.
Published: November 2016

Aims

The development of end‐stage renal disease (ESRD) in Type 1 diabetes is multifactorial. Familial socio‐economic factors may influence adherence to and understanding of diabetes treatment, and also general health behaviour. We investigate how parental and personal education level and exposure to low economic status, indicated by the need for income support, influence the development of ERSD caused by Type 1 diabetes.

Methods

Participants were retrieved from the nationwide Swedish Childhood Diabetes Registry, which was linked to the Swedish Renal Registry, to find people with ESRD caused by Type 1 diabetes, and to Statistic Sweden to retrieve longitudinal socio‐economic data on participants and their parents. Data were analysed using Cox regression modelling.

Results

Of 9287 people with diabetes of duration longer than 14 years, 154 had developed ESRD due to diabetes. Median diabetes duration (range) for all participants was 24.2 years (14.0–36.7 years). Low maternal education (≤ 12 years) more than doubled the risk of developing ESRD, hazard ration (HR) = 2.9 [95% confidence interval (95% CI): 1.7‐4.8]. For people with a low personal level of education HR was 5.7 (3.4–9.5). In an adjusted model, the person's own education level had the highest impact on the risk of ESRD. If at least one of the parents had ever received income support the HR was 2.6 (1.9–3.6).

Conclusions

Socio‐economic factors, both for the parents and the person with diabetes, have a strong influence on the development of ESRD in Type 1 diabetes. It is important for caregivers to give enough support to more vulnerable people and their families.
Epidemiology of post‐treatment disease
Authors: Hülsmann Michael
Published: November 2016

Endodontic treatment aims to eliminate or prevent diseases of the pulp and the apical periodontium. Although several strategies have been developed to combat pulpal and periapical inflammation and infection, success rates in endodontics still seem to range considerably below 100%. A critical review of epidemiological studies demonstrates that post‐treatment endodontic disease needs to be acknowledged as a common outcome of endodontic treatment. The following review presents the data of available epidemiological studies from different continents and countries. The overall prevalence of post‐endodontic apical lesions ranges clearly higher than the failure rates obtained from well‐designed clinical studies demonstrating severe deficits in endodontic treatment in daily general dental practice.
Statistical and other methodological issues in the production of reliable experimental endodontic research and why they matter
Authors: Brunette Donald M.
Published: November 2016

It has long been assumed that science is self‐correcting and that lack of reproducibility or even fraud will be uncovered in subsequent attempts to replicate observations or experiments. Recent studies have cast doubt on that assumption, which is a central tenet of scientific method, even for research that is published in high‐impact journals and uses state‐of‐the‐art methodology. Ironically, endodontic research, like most biomedical research, is moving toward highly sophisticated procedures such as gene arrays and proteomics, which are often plagued by false positives and false negatives. This “reproducibility crisis” is thought to arise from many sources including poorly described methodology, inappropriate statistical analysis, the positive bias for article acceptance by journals, the lack of incentives to repeat experiments, and the hypercompetitive research environment that pressures investigators to publish quickly in impact journals. This article outlines the scope of the reproducibility crisis and some of the steps that may be used to ameliorate it. Attention is focused on common statistical errors and pitfalls, the use of confidence intervals in place of the standard Null Hypothesis Statistical Testing (NHST), and the promise of Bayesian statistics in endodontic research.
A comparative study of approaches to forecast the correct trading actions
Authors: Baía Luís , Torgo Luís
Published: November 2016

This paper addresses the problem of decision making in the context of financial markets, more specifically, the problem of forecasting the correct trading action for a certain future horizon. We study and compare two alternative ways of addressing these forecasting tasks: (a) using standard numeric prediction models to forecast the variation on the prices of the target asset and, on a second stage, transform these numeric predictions into a decision according to some predefined decision rules; and (b) use models that directly forecast the right decision thus ignoring the intermediate numeric forecasting task. The objective of our study is to determine if both strategies provide identical results or if there is any particular advantage worth being considered that may distinguish each alternative in the context of financial markets.
Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes
Authors: Annis Ryan P. , Swahari Vijay , Nakamura Ayumi , Xie Alison X. , Hammond Scott M. , Deshmukh Mohanish
Published: November 2016

Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR‐29 family of microRNAs (miRNAs) are induced with neuronal maturation and that overexpression of miR‐29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR‐29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR‐29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR‐29‐deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR‐24 as another miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR‐29 by targeting a similar repertoire of prodeath BH3‐only genes. Overall, our results reveal that mature neurons engage multiple redundant brakes to restrict the apoptotic pathway and ensure their long‐term survival.
Activation and clustering of a Plasmodium falciparum var gene are affected by subtelomeric sequences
Authors: Duffy Michael F. , Tang Jingyi , Sumardy Fransisca , Nguyen Hanh H. T. , Selvarajah Shamista A. , Josling Gabrielle A. , Day Karen P. , Petter Michaela , Brown Graham V.
Published: November 2016

The Plasmodium falciparum var multigene family encodes the cytoadhesive, variant antigen PfEMP1. P. falciparum antigenic variation and cytoadhesion specificity are controlled by epigenetic switching between the single, or few, simultaneously expressed var genes. Most var genes are maintained in perinuclear clusters of heterochromatic telomeres. The active var gene(s) occupy a single, perinuclear var expression site. It is unresolved whether the var expression site forms in situ at a telomeric cluster or whether it is an extant compartment to which single chromosomes travel, thus controlling var switching. Here we show that transcription of a var gene did not require decreased colocalisation with clusters of telomeres, supporting var expression site formation in situ. However following recombination within adjacent subtelomeric sequences, the same var gene was persistently activated and did colocalise less with telomeric clusters. Thus, participation in stable, heterochromatic, telomere clusters and var switching are independent but are both affected by subtelomeric sequences. The var expression site colocalised with the euchromatic mark H3K27ac to a greater extent than it did with heterochromatic H3K9me3. H3K27ac was enriched within the active var gene promoter even when the var gene was transiently repressed in mature parasites and thus H3K27ac may contribute to var gene epigenetic memory.
Shifts in Intergenerational Mobility of Indian Immigrant Entrepreneurs
Authors: Chavan Meena , Taksa Lucy
Published: November 2016

The objective of this article is to examine the shift in the intergenerational mobility of Indian immigrant entrepreneurs in Australia. Based on a qualitative methodology, this article reports on the differences in the entrepreneurial attitudes of push and pull and the aptitudes of social and human capital between pre 2000 and post 2000 immigrant entrepreneurs. The findings suggest that the post 2000 Indian migrant entrepreneurs in Australia are mostly pull motivated, have higher qualifications than the pre 2000 arrivals, speak better English, have professional educational qualifications relevant to their business, and operate predominantly in the service sector. They take fewer years to get into business and are less dependent on immigrant social capital resources than pre 2000 arrivals. The study proposes that, compared with social capital resources, human capital resource have a greater impact on entrepreneurial propensity in the case of second generation Indian migrant entrepreneurs in Australia.

Policy Implications

This research has implication for Australian immigration policy, labour laws and settlement services of migrants. It recommends successful implementation of policies and durable solutions for Indian immigrants in the labour market in Australia.

The Australian Government will be assisted in examining and identifying future options for the intake of temporary and permanent migrants that improve the income, wealth and living standards of Australian citizens, improve the budgets and balance sheets of Australian governments, minimize administration and compliance costs associated with immigration, and provide pathways both for Australian citizens to be altruistic towards foreigners, and for Australia's international responsibilities and obligations to foreign residents to be met. Improvements in the labour laws would promote the effective integration of Indian immigrants into society.

Further, Indians in the USA have contributed immensely to the entrepreneurial spirit due to the government support for migrant SMEs and the small business venture funds. The Australian government can replicate this policy, reduce restriction on employment opportunities and enhance entrepreneurship for all migrants.
A Comparison of Women and Men Undergoing Catheter Ablation for Sustained Monomorphic Ventricular Tachycardia
Authors: BALDINGER SAMUEL H. , KUMAR SAURABH , ROMERO JORGE , FUJII AKIRA , EPSTEIN LAURENCE M. , MICHAUD GREGORY F. , JOHN ROY , TEDROW USHA B. , STEVENSON WILLIAM G.
Published: November 2016

Ventricular Tachycardia Ablation in Women Compared to Men

Introduction

Women are underrepresented in clinical studies on catheter ablation (CA) for ventricular tachycardia (VT). The role of gender as a predictor for VT recurrence after CA is unclear and complication rates have not been compared in a large cohort.

Methods and Results

We analyzed data of consecutive patients undergoing CA for sustained monomorphic VT at our center between 2005 and 2015.

A total of 948 patients underwent 1314 ablation procedures: 114 patients without structural heart disease (SHD) (48% female), 486 with coronary artery disease (CAD) (9% female), 301 with nonischemic cardiomyopathy (NICM) (22% female), and 46 with arrhythmogenic right ventricular cardiomyopathy (ARVC) (17% female). Women with CAD and NICM were younger than men at first ablation (63 years vs. 68 years, P = 0.05; resp. 53 years vs. 59 years, P = 0.026) with no other significant differences in baseline characteristics. Age, LVEF, NYHA‐class, and VT‐recurrence but not gender were independently associated with increased mortality in CAD and NICM. Mortality rates in patients with no SHD and ARVC are low in men (0%, 2.6%) and women (1.8%, 0%).

Conclusions

Although heart disease tends to present later in women, our data do not suggest that women are referred later than men. Women with CAD or NICM and VT present for ablation at younger age with disease severity comparable to men. VT ablation in women can be accomplished with success‐ and complication rates comparable to male patients in both those with and without SHD.
Feeding ecology and trophic segregation of two sympatric mesopredatory sharks in the heavily exploited coastal ecosystem of the Adriatic Sea
Authors: Gračan R. , Zavodnik D. , Krstinić P. , Dragičević B. , Lazar B.
Published: November 2016

The ecological roles and trophic interactions of two commercially important mesopredatory shark species, Squalus acanthias and Mustelus punctulatus that co‐occur on the continental shelf of the north‐central Adriatic Sea were investigated. Both shark species are dietary specialists, with a significant dietary overlap recorded only during the spring season. They showed different patterns of feeding as they grew: S. acanthias extended its trophic niche with an increase in size, while M. punctulatus developed a more specialized diet. These two sharks partition food resources and reduce niche overlap by foraging at different trophic levels. Mustelus punctulatus is a crustacean feeder, specialized in foraging on scavenging malacostracans frequently found along trawl tracks or on discards in the Adriatic fishing zone. Conversely, S. acanthias prefers small pelagic fishes, which are commercially exploited and in decline. The different foraging strategies adopted by these two species suggest that they should be managed separately. Dietary specialization, direct competition with humans for prey and their higher intrinsic vulnerability make S. acanthias particularly susceptible to the effects of anthropogenic perturbations.
Spawning in a cold bath: reproduction of polar and deep‐sea fish family Psychrolutidae
Authors: Laptikhovsky V. , Reid B. , Brickle P.
Published: November 2016

This study describes the spawning of the fatheads Psychrolutes marmoratus and Cottunculus granulosus, two psychrolutid species that inhabit the shelf edge and continental slope of the south‐west Atlantic. Females lay large eggs of c. 2·5 mm (P. marmoratus) and 4·5–5·0 mm (C. granulosus); fecundity is from the hundreds (C. granulosus) to a few thousand eggs (P. marmoratus). Egg maturation is synchronous in P. marmoratus with an autumn–winter peak of spawning and group‐synchronous in C. granulosus, which reproduces all year round. In the fishery, females predominate among adult fish in both species, possibly indicating male nest guarding on hard grounds inaccessible to fishing vessels. The reproductive strategy of representatives of the Psychrolutidae is similar to that of other sculpins of the superfamily Cottoidea.
A randomized two-way crossover bioequivalence study in healthy adult volunteers of paediatric zidovudine/lamivudine/nevirapine fast-disintegrating fixed-dose combination tablet
Authors: Joshi Anjali , Gbadero Daniel , Esseku Fredrick , Adesanya Olufikayo J , Adeyeye Moji C
Published: November 2016

Objective

The bioequivalence study was conducted to compare the developed paediatric fixed-dose combination (FDC) zidovudine/lamivudine/nevirapine (60/30/50 mg) tablet – the test formulation – with the combined mixture of single-entity innovator products (reference product).

Methods

A single-dose open-label randomized two-way crossover study was conducted in healthy adult African volunteers after an informed consent was obtained. The 24 volunteers, divided into two groups, were administered the products after an overnight fast on two treatment days with 14 days of washout period. Blood samples were collected for 96 h and analysed using a validated RP-HPLC-UV assay method. Pharmacokinetic (PK) parameters (non-compartmental model) were assessed with WinNonlin® software. Analysis of variance (ANOVA) and FDA bioequivalence statistical criterion of 90% CI or 80% to 125% range (set at P < 0.05) of least square geometric means (LSGM) ratios of test: reference product for Cmax, AUC0–t, and AUC0–∞ were determined.

Results

ANOVA indicated that the period, sequence and formulation had no significant effect on the PK parameters (P > 0.05). The 90% CIs for all the drugs were within the 80% to 125% range.

Conclusion

The developed FDC tablet is bioequivalent to the reference product.
Effect of soaking, fermentation with lactobacillus and enzyme treatment on nitrogen‐corrected apparent metabolizable energy values of wheat in cockerels and quails
Authors: Alahyari‐Shahrasb M. , Moravej H. , Kianfar R. , Kim W. K.
Published: November 2016

An experiment was carried out to determine nitrogen‐corrected apparent metabolizable energy (AMEn) values of processed wheat products with two levels of enzyme (0 and 0.5 g/kg) and five processing methods [control (C), water‐soaking for 12 h (SO12h), 24 h (SO24h) and 48 h (SO48h) and fermentation with lactobacillus (FL)] in two species of poultry (cockerel and Japanese quail). In this study, each processing method group had six replications with two cockerels or four quails per replication. The results showed that the calculated AMEn values of processed wheat by different methods were as follows: C‐12.61 and 12.60; SO12h‐12.75 and 12.73; SO24h‐12.80 and 12.79; SO48h‐12.97 and 12.96; and FL‐13.36 and 13.33 MJ/kg for cockerels and quails, respectively, indicating that fermentation improved AMEn values compared with the others. The mean AMEn of processed wheat with enzyme (13.12 MJ/kg) was significantly higher than that of processed wheat without enzyme (12.64 MJ/kg). However, there were no significant differences in the AMEn of processed wheat between cockerels and quails. The interaction between species and levels of enzyme in AMEn values was not significant. There was no significant difference (p > 0.05) in three‐way interactions among species, levels of enzyme and wheat processing methods for AMEn values. In conclusion, the results of the experiment suggest that the FL was more effective processing method of wheat to obtain high level of AMEn values than the others, and the combination of enzyme and processing methods can increase the AMEn values compared with processing methods alone.
Plane of nutrition affects growth rate, organ size and skeletal muscle satellite cell activity in newborn calves
Authors: MacGhee M. E. , Bradley J. S. , McCoski S. R. , Reeg A. M. , Ealy A. D. , Johnson S. E.
Published: November 2016

Plane of nutrition effects on body, tissue and cellular growth in the neonatal calf are poorly understood. The hypothesis that a low plane of nutrition (LPN) would limit skeletal muscle size by reducing fibre growth and muscle progenitor cell activity was tested. At birth, calves were randomly assigned to either a LPN (20% CP, 20% fat; GE=1.9 Mcal/days) or a high plane of nutrition (HPN; 27% CP, 10% fat, GE = 3.8 Mcal/days) in a 2 × 3 factorial design to test the impact of diet on neonatal calf growth, organ weight and skeletal muscle morphometry with time. Groups of calves (n = 4 or 5) were euthanised at 2, 4 and 8 week of age and organ and empty carcass weights were recorded. Body composition was measured by DXA. Longissimus muscle (LM) fibre cross‐sectional area (CSA), fibre/mm2 and Pax7 were measured by immunohistology. Satellite cells were isolated at each time point and proliferation rates were measured by EdU incorporation. Calves fed a HPN had greater (p < 0.05) BW, ADG and hip height than those fed a LPN for 2, 4 or 8 weeks. HPN calves contained a greater (p < 0.05) percentage of fat tissue than LPN calves. Liver, spleen and thymus weights were less (p < 0.05) in LPN calves than HPN animals. Calves fed HPN had larger (p < 0.05) LM CSA at 8 weeks than LPN fed animals with no differences between the groups in numbers of satellite cells per fibre. Proliferation rates of satellite cells isolated from HPN fed calves were greater (p < 0.05) at 2 weeks than LPN fed animals, which exhibited greater (p < 0.05) proliferation rates at 4 weeks than HPN fed calves. We conclude a LPN diet reduces body growth and organ size and metabolically reprograms satellite cell activity.
Effect of particle size and partial replacement of alfalfa hay by soya bean hulls on nutrient intake, total tract digestibility and rumen degradability of diets by Holstein steers
Authors: Behgar M. , Valizadeh R. , Naserian A. A. , Ghasemi S. , Vahmani P.
Published: November 2016

This study examined the effect of alfalfa hay (AH) particle size and the replacement of soya bean hull (SH) for AH within the diet of restricted fed Holstein steers on dry matter intake (DMI), total tract digestion, ruminal digestion, ruminal pH and ammonia nitrogen content, and faecal pH. Four rumen‐cannulated Holstein steers averaging 353 ± 9.6 kg of BW were assigned to a 4 × 4 Latin square experiment with four periods and a 2 × 2 factorial arrangement of treatments. Factor A was AH particle size (fine vs. coarse) and factor B was diet SH content (0% vs. 10%; substituted for AH). Steers were fed at 1% of body weight of TMR containing 400 g/kg forage and 600 g/kg concentrate. Chopping of AH to fine particles decreased (p = 0.01) amount of dietary materials retained on the medium sieve (8 mm). The inclusion of SH significantly increased (p = 0.01) materials retained on the 1.18‐mm sieve and tended to decrease (p = 0.07) materials on 19‐mm sieves. The inclusion of SH increased (p = 0.01) ether extract (EE) intake and increased (p = 0.07) DMI. Inclusion of SH increased (p = 0.01) EE digestion and decreased (p < 0.01) faecal pH. Neither AH particle size nor SH inclusion in diets affected (p > 0.10) the in situ ruminal degradability coefficients of DM (‘a’, ‘b’, ‘c’ or ‘a+b’). No interaction of AH×SH was seen on nutrient intake, digestibility and in situ ruminal degradability of Holstein steers.
Zinc methionine and laminarin have growth‐enhancing properties in newly weaned pigs influencing both intestinal health and diarrhoea occurrence
Authors: Bouwhuis M. A. , Sweeney T. , Mukhopadhya A. , Thornton K. , McAlpine P. O. , O'Doherty J. V.
Published: November 2016

Three experiments were conducted to investigate the interaction between zinc methionine (ZnM) and laminarin (LAM) on piglet growth performance and intestinal health post‐weaning. Experiment 1 was designed as 2 × 2 factorial with four treatments [n = 8, weaning age (WA) 24 days, live weight (LW) 7.15 kg]: (i) basal diet (BD); (ii) BD + 500 mg/kg ZnM; (iii) BD + 300 mg/kg LAM; and (iv) BD + 500 mg/kg ZnM + 300 mg/kg LAM. There was an interaction (p < 0.05) between LAM and ZnM. Pigs that were offered the LAM diet had a similar performance to the BD. However, when combining LAM with ZnM, pigs had reduced average daily gain (ADG), gain‐to‐feed ratio (G:F) and LW at slaughter at day 8 post‐weaning compared to the ZnM. Both LAM and ZnM improved the small intestinal morphology of the pigs at day 8 post‐weaning. Experiment 2 was designed as 2 × 2 factorial with four dietary treatments (n = 9, WA 24 days, LW 7.32 kg): (i) BD; (ii) BD + 500 mg/kg ZnM; (iii) BD + 175 mg/kg LAM; and (iv) BD + 500 mg/kg ZnM + 175 mg/kg LAM. The ADG and average daily feed intake were improved between day 0 and 31 PW when pigs were offered a LAM diet (p < 0.01). Faecal scores were reduced between day 0 and day 31 post‐weaning with ZnM (p < 0.001). Experiment 3 consisted of four dietary treatments (n = 10, WA 24 days, LW 7.32 kg): (i) BD; (ii) BD + 3300 mg/kg zinc oxide (ZnO); (iii) BD + 500 mg/kg ZnM; and (iv) BD + 175 mg/kg LAM. Pigs that were offered the ZnO diet had an increased ADG compared to the BD or ZnM diets (p < 0.01). Pigs that were offered the LAM diet had increased ADG compared to the ZnM diet (p < 0.05). Faecal scores were reduced between day 0 and day 31 PW with ZnM or ZnO supplementation (p < 0.001). In conclusion, the inclusion of 175 mg/kg LAM and ZnO improved ADG while both ZnO and ZnM reduced the faecal scores post‐weaning.
Hepatitis B infection is associated with an increased incidence of thrombocytopenia in healthy adults without cirrhosis
Authors: Joo E.‐J. , Chang Y. , Yeom J.‐S. , Lee Y.‐G. , Ryu S.
Published: November 2016

The association between HBV infection and incident thrombocytopenia among subjects without cirrhosis or splenomegaly is unknown. Therefore, we sought to elucidate the association between HBV infection and the development of thrombocytopenia in a large cohort of apparently healthy men and women. A cohort study was performed in 122 200 participants without liver cirrhosis or splenomegaly who underwent comprehensive health examinations and were followed until December 2014. HBV infection was defined by the presence of hepatitis B surface antigen (HBsAg) at baseline. Thrombocytopenia was defined as a platelet count <150 000/μL. Cox proportional hazard models were used to estimate adjusted hazard ratios with 95% confidence intervals (CIs) for incident thrombocytopenia. HBsAg was positive in 4857 of 122 200 subjects (4.0%) at baseline. During 883 983 person‐years of follow‐up, 2037 incident cases of thrombocytopenia were identified (incident rate 2.3 per 1000 person‐years). HBsAg–positive subjects had a higher incidence of thrombocytopenia than did healthy controls (11.2 vs 1.9 per 1000 person‐years, respectively). The multivariate‐adjusted hazard ratio (95% CI) for incident thrombocytopenia comparing HBsAg‐positive to HBsAg‐negative subjects was 5.71 (5.10‐6.38). Strong associations between HBsAg positivity and thrombocytopenia were consistently observed across prespecified subgroups. In this large cohort study of an apparently healthy population, HBsAg positivity was strongly and independently associated with incident thrombocytopenia, indicating that mechanisms of thrombocytopenia other than portal hypertension may exist in healthy HBV carriers.
A Prospective, Randomized, Masked, Placebo‐Controlled Clinical Study of Capromorelin in Dogs with Reduced Appetite
Authors: Zollers B. , Wofford J.A. , Heinen E. , Huebner M. , Rhodes L.
Published: November 2016

Background

Reduced appetite is a common clinical sign in dogs. This study evaluated the effectiveness and safety of capromorelin oral solution, (ENTYCE®, Aratana Therapeutics, Leawood, KS) a new drug that is a ghrelin receptor agonist, for stimulation of appetite in dogs with reduced appetite.

Hypothesis/Objectives

Capromorelin will increase appetite, as measured by the owner's evaluation, over 4 days. An additional objective was to evaluate the safety of capromorelin at the labeled dose.

Animals

A total of 244 client‐owned dogs reported by owners to be inappetent for at least 2 days were enrolled, with 177 cases in the effectiveness analysis.

Methods

In this prospective, randomized, masked, placebo‐controlled study, dogs were treated daily with capromorelin (3 mg/kg) oral solution (n = 121) or placebo oral solution (n = 56). Owners completed an evaluation of appetite at days 0 and 3 ± 1. Success was defined as improvement in appetite at day 3. Safety was evaluated by physical examination, clinical pathology, and monitoring adverse events and owner observations.

Results

Capromorelin treatment improved appetite compared to placebo (68.6% and 44.6% treatment successes with 95% CI 59.7, 76.3 and 32.2, 57.8, respectively, P = .008). Mean body weight in capromorelin‐treated dogs increased compared to placebo‐treated dogs (1.8% with 95% CI 1.3, 2.3, and 0.1% with 95% CI 0.9, 1.1, respectively, P < .001). Adverse reactions occurring in >5% of either group were diarrhea and vomiting.

Conclusions and Clinical Importance

Capromorelin oral solution is an effective treatment for stimulation of appetite in dogs and represents the first ghrelin receptor agonist shown to be effective for this indication.
Digestive Enzyme Activity during Initial Ontogeny and after Feeding Diets with Different Protein Sources in Zebra Cichlid, Archocentrus nigrofasciatus
Authors: Mente Eleni , Solovyev Mikhail M. , Vlahos Nikolaos , Rotllant Guiomar , Gisbert Enric
Published: November 2016

This study aims to describe changes in the activity of digestive enzymes of the zebra cichlid, Archocentrus nigrofasciatus, from hatching until 30 d after hatch (d.a.h.), and to evaluate the effects of feeding diets with different levels of fishmeal (FM) substitution with alternative nonanimal protein sources from 30 d.a.h. up to the age of 60 d.a.h. Results indicated that the developmental patterns of digestive enzymes from the exocrine pancreas and intestine are similar to those of other phylogenetically close cichlids, although they seemed to develop faster than other species as indicated by the peaks in enzyme activity, which were detected at younger stages of development. The 100% FM replacement with different alternative nonanimal protein sources had a negative impact on the growth performance of A. nigrofasciatus juveniles, whereas fish fed the diet with a 50% FM replacement showed similar results to those fed the 100% FM diet. Fish showing the lowest growth rate had also the lowest enzyme activity, especially in relation to the intestinal brush border enzymes. This study assesses the digestive capabilities and nutritional condition of the zebra cichlid fish and provides knowledge on the potential for FM substitution in their feeds.
Microglia and brain macrophages: An update
Authors: Sasaki Atsushi
Published: November 2016

Current immunohistochemical techniques have made the identification of microglia possible in routinely processed tissue sections from human brains. Previous studies have indicated that almost no neurological diseases exist without microglial activation. Activated microglia often secrete inflammatory cytokines in various diseases, including Alzheimer's disease, but microglial activation is not always associated with inflammation. The equation microglial activation means “neuroinflammation” is absurd and misleading. Neuropathologists are in the best position to provide clarity to end the existing confusion. The functions of microglia in the non‐diseased brain probably include a role in synaptic maintenance, but defects in the expression of specific molecules on microglia can also cause leukoencephalopathy, such as Nasu‐Hakola disease (NHD) and hereditary leukoencephalopathy with spheroids (HDLS). “Microgliopathies” is a new term used to designate conditions where microglial dysfunction is primary and at the center of the disease process. The molecules responsible are DAP12 or TREM2 in NHD and CSF1R in HDLS, respectively, but further studies are needed to clarify how exactly these microglial molecules influence the pathogenesis of axonal and myelin loss. Diffusely infiltrating glial tumors showing microglial differentiation (true microglioma) are exceedingly rare but recent evidence suggests that they indeed exist, although their molecular genetic characterization is still lacking. Participation of the expert neuropathology community will be required to identify additional cases and provide the latter. A large number of tumor‐associated macrophages (TAMs), which are partly derived from microglia, have been observed in glioblastomas. In TAMs, the expression of M2‐like molecules is higher than that of M1‐like molecules, but the number and differentiation state of TAMs vary in the intratumoral area and with the type of macrophage markers used. In future studies, we should focus on the morphological and molecular alterations of the microglia that are specific to the disease where they are observed.
Evaluation of the Sensitivity and Accuracy of Birth Defects Indicators on the 2003 Revision of the U.S. Birth Certificate: Has Data Quality Improved?
Authors: Salemi Jason L. , Tanner Jean Paul , Sampat Diana P. , Rutkowski Rachel E. , Anjohrin Suzanne B. , Marshall Jennifer , Kirby Russell S.
Published: November 2016

Background

The 2003 revision of the U.S. Birth Certificate was restricted to birth defects readily identifiable at birth. Despite being the lone source of birth defects cases in some studies, we lack population‐based information on the quality of birth defects data from the most recent revision of the birth certificate.

Methods

We linked birth certificate data to confirmed cases from the Florida Birth Defects Registry (FBDR) to assess the sensitivity and positive predictive value (PPV) of birth defects indicators on the birth certificate. Descriptive statistics and log‐binomial regression were used to examine variation in data quality measures by defect type and other characteristics. We also evaluated the contribution of birth certificates as a case ascertainment source for the FBDR.

Results

Sensitivity of the birth certificate was poor (19.1%) with variation across defects ranging from 55% for anencephaly and 54% for gastroschisis, to <10% for other defects. PPV was better (87.1%) and ranged from >93% for orofacial clefts and gastroschisis to <55% for anencephaly and limb reduction defects. We also observed variation in data quality across maternal, infant, and hospital characteristics. Of cases identified by the birth certificate and not any other FBDR data source, 54.9% were false‐positive diagnoses.

Conclusions

Efforts to restrict the 2003 revision of the birth certificate to defects identifiable at birth have not improved the likelihood that birth certificates will identify infants born with those defects. We do not recommend the use of birth certificates as a source of birth defects data without case verification strategies.