bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing Preventable Hospitalizations With Two Models of Transitional Care
Authors: Morrison Jessica , Palumbo Mary Val , Rambur Betty
Published: April 2016

Purpose

Transitional care is an emerging model of health care designed to decrease preventable adverse events and associated utilization of health care through temporary follow‐up after hospital discharge. This study describes the approaches and outcomes of two distinct transitional care programs serving different populations: one is provided by master's‐prepared clinical nurse specialists (CNS) with a chronic disease self‐management focus, another by physicians specializing in palliative care (PPCs). Existing research has shown that transitional care programs with intensive follow‐up reduce hospitalizations, emergency department (ED) visits, and costs. Few studies, however, have included side‐by‐side descriptions of the efficacy of transitional care programs varying by healthcare providers or program focus.

Design

This is a retrospective cohort study comparing the number of ED visits and hospitalizations in the 120 days before and after the intervention for patients enrolled in each transitional care program. Each program included post‐hospitalization home visits, but included differences in program focus (chronic disease vs. palliative), assessment and interventions, and population (rural vs. urban). Data from participants in the CNS program (September 2014 to December 2014) were analyzed (n = 98). The average age of participants was 69 years and 65% were female. Data were collected from patients from the PPC program from September 2014 to April 2015 (n = 71). Thirty participants died within 120 days after the intervention and were excluded; the remaining 41 were included in the analysis. Participants had an average age of 81 years and 63% were female.

Methods

For the CNS program, a secondary analysis of existing data was performed. For the PPC program, a review of patient charts was done to collect data on encounters. A Wilcoxon matched‐pairs signed‐rank test was performed to test for significance.

Findings

Patients in the CNS intervention had significantly fewer ED visits (p < .005) and hospitalizations (p < .005) in the 4 months after the intervention than in the 4 months before the intervention. Patients in the PPC program had a nonsignificant reduction in ED visits (p = .327) and a significant reduction in hospitalizations postintervention (p = .03).

Conclusions

Both transitional programs have value in decreasing rehospitalizations. The CNS intervention also significantly reduced ED visits for their target population. Further study with randomized controlled trials is needed to allow for a better understanding of the healthcare workforce best fitted to enhance transitional care outcomes. Future study to examine the cost savings of each of the interventions is also needed.

Clinical Relevance

Transitional care programs have the potential to prevent unnecessary utilization of health care at the critical periods of transition that leave patients vulnerable to adverse events and poor outcomes.
Metabolic syndrome and metabolic risk profile according to polycystic ovary syndrome phenotype
Authors: Bil Enes , Dilbaz Berna , Cirik Derya Akdag , Ozelci Runa , Ozkaya Enis , Dilbaz Serdar
Published: April 2016

Aim

It is unknown which phenotype of polycystic ovary syndrome (PCOS) has a greater metabolic risk and how to detect this risk. The aim of this study was therefore to compare the incidence of metabolic syndrome (MetS) and metabolic risk profile (MRP) for different phenotypes.

Methods

A total of 100 consecutive newly diagnosed PCOS women in a tertiary referral hospital were recruited. Patients were classified into four phenotypes according to the Rotterdam criteria, on the presence of at least two of the three criteria hyperandrogenism (H), oligo/anovulation (O) and PCO appearance (P): phenotype A, H + O + P; phenotype B, H + O; phenotype C, H + P; phenotype D, O + P. Prevalence of MetS and MRP were compared among the four groups.

Results

Based on Natural Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, MetS prevalence was higher in phenotypes A and B (29.6% and 34.5%) compared with the other phenotypes (10.0% and 8.3%; P < 0.001). Although the prevalence of obesity was similar, the number of patients with homeostatic model assessment insulin resistance index (HOMA‐IR) >3.8 was significantly higher in androgenic PCOS phenotypes. After logistic regression analysis, visceral adiposity index (VAI) was the only independent predictor of MetS in PCOS (P = 0.002). VAI was also significantly higher in phenotype B, when compared with the others (P < 0.01).

Conclusion

Phenotypes A and B had the highest risk of MetS among the four phenotypes, and VAI may be a predictor of metabolic risk in PCOS women.
Keratoconjunctivitis sicca exacerbation in a dog treated with systemic atenolol
Authors: Barsotti G. , Vezzosi T.
Published: April 2016

A 6‐year‐old, intact, male English cocker spaniel was referred for treatment of chronic conjunctivitis and unilateral keratitis. The dog was diagnosed with bilateral immune‐mediated keratoconjunctivitis sicca, treated with topical cyclosporine 0·2% ointment and sodium hyaluronate eye drops and improved considerably. After 2 months, pulmonic stenosis was diagnosed, and the dog commenced treatment with oral atenolol; the ophthalmological disease worsened dramatically within a few days. The ophthalmic signs rapidly improved after discontinuation of atenolol, and there was bilateral complete remission after 3 weeks. No oral β‐blocker therapy was reintroduced, and thereafter, keratoconjunctivitis sicca was well‐controlled with topical therapy.
Polyphosphate is involved in cell cycle progression and genomic stability in Saccharomyces cerevisiae
Authors: Bru Samuel , Martínez‐Laínez Joan Marc , Hernández‐Ortega Sara , Quandt Eva , Torres‐Torronteras Javier , Martí Ramón , Canadell David , Ariño Joaquin , Sharma Sushma , Jiménez Javier , Clotet Josep
Published: April 2016

Polyphosphate (polyP) is a linear chain of up to hundreds of inorganic phosphate residues that is necessary for many physiological functions in all living organisms. In some bacteria, polyP supplies material to molecules such as DNA, thus playing an important role in biosynthetic processes in prokaryotes. In the present study, we set out to gain further insight into the role of polyP in eukaryotic cells. We observed that polyP amounts are cyclically regulated in Saccharomyces cerevisiae, and those mutants that cannot synthesise (vtc4Δ) or hydrolyse polyP (ppn1Δ, ppx1Δ) present impaired cell cycle progression. Further analysis revealed that polyP mutants show delayed nucleotide production and increased genomic instability. Based on these findings, we concluded that polyP not only maintains intracellular phosphate concentrations in response to fluctuations in extracellular phosphate levels, but also muffles internal cyclic phosphate fluctuations, such as those produced by the sudden demand of phosphate to synthetize deoxynucleotides just before and during DNA duplication. We propose that the presence of polyP in eukaryotic cells is required for the timely and accurate duplication of DNA.
CRISPR‐Cas9‐modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine‐containing compounds but potentiates artemisinin‐based combination therapy partner drugs
Authors: Ng Caroline L. , Siciliano Giulia , Lee Marcus C. S. , de Almeida Mariana J. , Corey Victoria C. , Bopp Selina E. , Bertuccini Lucia , Wittlin Sergio , Kasdin Rachel G. , Le Bihan Amélie , Clozel Martine , Winzeler Elizabeth A. , Alano Pietro , Fidock David A.
Published: April 2016

Emerging resistance to first‐line antimalarial combination therapies threatens malaria treatment and the global elimination campaign. Improved therapeutic strategies are required to protect existing drugs and enhance treatment efficacy. We report that the piperazine‐containing compound ACT‐451840 exhibits single‐digit nanomolar inhibition of the Plasmodium falciparum asexual blood stages and transmissible gametocyte forms. Genome sequence analyses of in vitro‐derived ACT‐451840‐resistant parasites revealed single nucleotide polymorphisms in pfmdr1, which encodes a digestive vacuole membrane‐bound ATP‐binding cassette transporter known to alter P. falciparum susceptibility to multiple first‐line antimalarials. CRISPR‐Cas9 based gene editing confirmed that PfMDR1 point mutations mediated ACT‐451840 resistance. Resistant parasites demonstrated increased susceptibility to the clinical drugs lumefantrine, mefloquine, quinine and amodiaquine. Stage V gametocytes harboring Cas9‐introduced pfmdr1 mutations also acquired ACT‐451840 resistance. These findings reveal that PfMDR1 mutations can impart resistance to compounds active against asexual blood stages and mature gametocytes. Exploiting PfMDR1 resistance mechanisms provides new opportunities for developing disease‐relieving and transmission‐blocking antimalarials.
Ozonated water reduces susceptibility in tomato plants to Meloidogyne incognita by the modulation of the antioxidant system
Authors: Veronico Pasqua , Paciolla Costantino , Sasanelli Nicola , De Leonardis Silvana , Melillo Maria Teresa
Published: April 2016

Few studies have been carried out on the effect of ozonated water (O3wat) on the oxidative stress of root systems and, in particular, in combination with biotic stress. The aim of this study was to determine whether aqueous ozone is effective in the control of root‐knot nematode (RKN) infection and to investigate the concomitant changes in the basal defence system. A tomato cultivar susceptible to Meloidogyne incognita was treated with O3wat as a soil drench. No negative effects were seen following ozone application in comparison with the control under the exposure conditions used. The treatment reduced significantly the nematode infection rate and induced changes in the morphology of nematode feeding sites, some of which were characterized by visible symptoms of senescence. The antioxidant response, as well as parameters of oxidative damage, were examined in untreated and O3wat‐treated galls at 2, 4 and 7 days after inoculation and compared with uninfected roots. High levels of reactive oxygen species (ROS), H2O2 and malondialdehyde were generated in galls in response to combined abiotic and biotic stresses. Throughout the experimental period, the activities and relative transcript levels of the antioxidant enzymes catalase, superoxide dismutase and ascorbate peroxidase produced different responses when exposed to ozone treatment and/or infection. The results demonstrate how O3wat protects tomato against the RKN M. incognita through the modulation of basal defence mechanisms.
The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis
Authors: Zhou Xiaofang , Li Ting , Fan Shangrong , Zhu Yuxia , Liu Xiaoping , Guo Xuedong , Liang Yiheng
Published: April 2016

To compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7–14 follow‐up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30–35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7–14 follow‐up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30–35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder.
Negating the plant apparency model: rigorous tests are the fuel of progress
Authors: Hay Mark E.
Published: April 2016

This article is a commentary on Smilanich et al., 210: 1044–1057.
Smegma Pearls in Young Uncircumcised Boys
Authors: Sonthalia Sidharth , Singal Archana
Published: April 2016

Deposition of smegma in the subpreputial region is common in young uncircumcised boys. Although the term “smegma pearls” has been used colloquially for this entity, there is an apparent lack of reference to smegma pearls and their characteristics in the extant scientific literature. We present a series of six Indian boys with smegma pearls and discuss their possible origin, course, and management.
Case Report of Focal Epithelial Hyperplasia (Heck's Disease) with Polymerase Chain Reaction Detection of Human Papillomavirus 13
Authors: Brehm Mary A. , Gordon Katie , Firan Miahil , Rady Peter , Agim Nnenna
Published: April 2016

Focal epithelial hyperplasia (FEH), or Heck's disease, is an uncommon benign proliferation of oral mucosa caused by the human papillomavirus (HPV), particularly subtypes 13 and 32. The disease typically presents in young Native American patients and is characterized by multiple asymptomatic papules and nodules on the oral mucosa, lips, tongue, and gingiva. The factors that determine susceptibility to FEH are unknown, but the ethnic and geographic distribution of FEH suggests that genetic predisposition, particularly having the human lymphocytic antigen DR4 type, may be involved in pathogenesis. We report a case of FEH with polymerase chain reaction detection of HPV13 in a healthy 11‐year‐old Hispanic girl and discuss the current understanding of disease pathogenesis, susceptibility, and treatment.
Business model innovation processes of average market players: a qualitative‐empirical analysis
Authors: Laudien Sven M. , Daxböck Birgit
Published: April 2016

Business model innovation is by now mainly understood as a strategic option for firms to enhance competitiveness. As a result, business model innovation research usually focuses on outperforming firms that deliberately innovate their business models. We enhance this rather narrow perspective by analysing business model innovation processes of average market players against the background of a multiple‐case study. Our findings show that average market players do at least initially not deliberately pursue business model innovation. Instead, they experience business model innovation as a highly emergent and very often unintended process. We identify four phases of this process and describe them in detail. Furthermore, we highlight factors that determine whether a firm is able to complete the process step or not. The results of our study are reflected in a newly developed process model that considerably enhances the understanding of business model innovation processes with regard to average market players and may serve as framework for future research.
Publicly funded R&D for public sector performance and efficiency: evidence from Europe
Authors: Maroto Andrés , Gallego Jorge , Rubalcaba Luis
Published: April 2016

Public sectors are under increasing pressure to provide better services and improve their efficiency in order to boost economic growth and social welfare. The promotion of R&D and innovation has proved to be a key determinant of economic performance of countries. However, little is known about the effect of publicly funded R&D activities on the performance and efficiency of public sectors. A better understanding behind such relationship is crucial, particularly in present times of public budget constraints. Accordingly, the article measures the public sector performance and efficiency of European countries by the construction of composite indicators. Moreover, it explores and tests the role of publicly funded R&D on public sector performance (using multivariate techniques and econometric analyses) and efficiency (by means of a non‐ parametric approach). Results indicate that publicly funded R&D should be considered a dimension of public sector performance, particularly when complementarities between private and public R&D emerge, but that it also plays a role on its efficiency.
Late‐onset noninfectious interstitial lung disease following autologous haematopoietic stem cell transplantation in paediatric patients
Authors: Lee Yoon‐Kyoung , Huh Rimm , Kim Jihyun , Ahn Kangmo , Sung Ki Woong , Cho Joongbum
Published: April 2016

Background and objective

High‐dose chemotherapy (HDCT) followed by autologous haematopoietic stem cell transplantation (HSCT) is widely used in paediatric cancer patients, but few data about noninfectious interstitial lung disease (ILD) following this treatment are available. Therefore, we aimed to evaluate the incidence, clinical features and risk factors of noninfectious ILD after HDCT in paediatric patients.

Methods

This was a retrospective cohort study of paediatric solid tumour patients who underwent HDCT and autologous HSCT between 1997 and 2012. ILD was diagnosed using clinical symptoms and radiography after excluding cardiac, renal and infectious causes. Risk factors were analysed using a Cox proportional hazard regression model.

Results

Three hundred and forty patients were enrolled, and the median age was 3 years (interquartile range 1–7). Eight patients (2.4%) were diagnosed with noninfectious ILD. The median duration of symptom onset was 30 months (range 7–74). Six (75%) of eight ILD patients died during the study period, even though steroids were administered for treatment. High‐dose cyclophosphamide use (hazard ratio = 11.37, 95% confidence interval = 1.38–93.32, P = 0.023) and sex (hazard ratio = 0.10, 95% confidence interval = 0.01–0.84, P = 0.034) were associated with late‐onset, noninfectious ILD upon multivariate analysis.

Conclusion

The incidence of noninfectious ILD after HDCT and autologous HSCT was not negligible, and the clinical features of ILD showed late onset and a poor prognosis. Female gender and high‐dose cyclophosphamide treatment may be risk factors for noninfectious ILD, but further studies with a larger number of ILD patients are suggested.
Foreign Aid and Inclusive Development: Updated Evidence from Africa, 2005–2012*
Authors: Asongu Simplice A. , Nwachukwu Jacinta C.
Published: April 2016

Objective

Motivated by the April 2015 World Bank Publication on MDGs, which reveals that poverty has been declining in all regions of the world with the exception of African countries, this study investigates the effects of a plethora of foreign aid dynamics on inequality‐adjusted human development.

Methods

Contemporary and noncontemporary OLS, fixed effects, and a system GMM technique with forward orthogonal deviations are employed. The empirical evidence is based on an updated sample of 53 African countries for the period 2005–2012.

Results

The following findings are established. First, the impacts of aid dynamics with high degrees of substitution are positive. These include aid for: social infrastructure, economic infrastructure, the productive sector, and multisectors. Second, the effect of humanitarian assistance is consistently negative across specifications and models. Third, the effects of program assistance and action on debt are ambiguous because they become positive with the GMM technique.

Conclusions

Justifications for these changes and clarifications with respect to existing literature are provided. Policy implications are discussed in light of the post‐2015 development agenda. We also provide some recommendations for a rethinking of theories and models on which development assistance is based.
Getting Short‐Changed? The Impact of Outside Money on District Representation*
Authors: Baker Anne E.
Published: April 2016

Objective

As incumbent House members increasingly recruit campaign contributions from individuals who reside outside of their districts, this raises the question of whether a dependency on outside money affects members’ responsiveness and ideological proximity to district constituents.

Method

Using data from the Cooperative Congressional Election Studies of 2006, 2008, and 2010 as well as individual contribution data corresponding to those years from the U.S. Federal Election Commission, I examine this relationship using responsiveness and proximity models of representation.

Results

I find a dependency on outside contributions decreases members’ responsiveness to their districts and increases the members’ ideological extremity. Moreover, within‐district contributions only minimally improve ideological alignment between the member and the district.

Conclusion

Donors receive additional representation from members of the House at the expense of constituents.
A Proof‐Theoretic Account of the Miners Paradox
Authors: Klev Ansten
Published: April 2016

By maintaining that a conditional sentence can be taken to express the validity of a rule of inference, we offer a solution to the Miners Paradox that leaves both modus ponens and disjunction elimination intact. The solution draws on Sundholm's recently proposed account of Fitch's Paradox.
Willingness to pay for sustainable drainage systems in a highly urbanised city: a contingent valuation study in Hong Kong
Authors: Chui Ting Fong May , Ngai Wing Yin
Published: April 2016

Sustainable drainage systems (SuDS) reduce surface runoff and pollution from developed areas using various techniques such as green roofs and porous pavements. These systems are becoming popular worldwide, except in highly urbanised cities. This study used contingent valuation to investigate city dwellers’ perceptions of SuDS and their willingness to pay (WTP). Face‐to‐face interviews were conducted with 600 respondents in Hong Kong. In general, the participants’ understanding of stormwater management was not strong, although they supported SuDS. The mean and the median WTP were 8.8 and 15.0%, respectively, of the current government spending on stormwater management for public places, and 1.8 and 2.5%, respectively, of the property price for private properties. These WTP were lower than those reported in the previous overseas studies. Respondents who were relatively younger, better educated, had higher income, and came from a previously flooded district had higher WTP. These results facilitated strategic SuDS implementation in highly urbanised cities.
On the interaction between weed and bird damage in rice
Authors: Demont M , Rodenburg J
Published: April 2016

Weeds and granivorous birds are the two major biotic constraints to rice production in sub‐Saharan Africa. Anecdotal evidence advances the hypothesis that weedy fields attract granivorous birds to the extent that the joint weed × bird impact on crops is synergistic. We develop a theoretical model, based on experimental data, of the interaction between weed and bird damage to formally test this hypothesis. We observe that the response of bird‐inflicted yield loss to weeds is unimodal and inverse‐U‐shaped. Bird‐inflicted yield loss increases from 44% in weed‐free conditions to a maximum of 55% at a critical weed infestation level of 20 g dry weight m−2. We conclude that the 11% increase in yield loss can be attributed to the synergistic interaction between weed and bird damage in rice. Our theory provides new insights into the analysis of the interaction between weeds and pests in general and supports a revision of currently accepted recommendations for weed management in rice. In areas where birds constitute an important production risk, it would be beneficial for rice farmers to remove those weeds that are tall enough to attract birds, even beyond the critical weed period.
Effects of language experience on pre-categorical perception: Distinguishing general from specialized processes in speech perception
Authors: Iverson Paul , Wagner Anita , Rosen Stuart
Published: April 2016

Cross-language differences in speech perception have traditionally been linked to phonological categories, but it has become increasingly clear that language experience has effects beginning at early stages of perception, which blurs the accepted distinctions between general and speech-specific processing. The present experiments explored this distinction by playing stimuli to English and Japanese speakers that manipulated the acoustic form of English /r/ and /l/, in order to determine how acoustically natural and phonologically identifiable a stimulus must be for cross-language discrimination differences to emerge. Discrimination differences were found for stimuli that did not sound subjectively like speech or /r/ and /l/, but overall they were strongly linked to phonological categorization. The results thus support the view that phonological categories are an important source of cross-language differences, but also show that these differences can extend to stimuli that do not clearly sound like speech.
I heart lymphatics
Authors: Thomas Susan Napier
Published: April 2016

The build-up of fluid after a heart attack is linked to cardiac lymphatic insufficiency, which can be reversed to halt fibrosis and dysfunction.
Host-Derived Sialic Acids Are an Important Nutrient Source Required for Optimal Bacterial Fitness
In Vivo
Authors: McDonald Nathan D. , Lubin Jean-Bernard , Chowdhury Nityananda , Boyd E. Fidelma
Published: April 2016

A major challenge facing bacterial intestinal pathogens is competition for nutrient sources with the host microbiota.
Vibrio cholerae
is an intestinal pathogen that causes cholera, which affects millions each year; however, our knowledge of its nutritional requirements in the intestinal milieu is limited. In this study, we demonstrated that
V. cholerae
can grow efficiently on intestinal mucus and its component sialic acids and that a tripartite ATP-independent periplasmic SiaPQM strain, transporter-deficient mutant NC1777, was attenuated for colonization using a streptomycin-pretreated adult mouse model. In
in vivo
competition assays, NC1777 was significantly outcompeted for up to 3 days postinfection. NC1777 was also significantly outcompeted in
in vitro
competition assays in M9 minimal medium supplemented with intestinal mucus, indicating that sialic acid uptake is essential for fitness. Phylogenetic analyses demonstrated that the ability to utilize sialic acid was distributed among 452 bacterial species from eight phyla. The majority of species belonged to four phyla,
Actinobacteria
(members of
Actinobacillus
,
Corynebacterium
,
Mycoplasma
, and
Streptomyces
),
Bacteroidetes
(mainly
Bacteroides
,
Capnocytophaga
, and
Prevotella
),
Firmicutes
(members of
Streptococcus
,
Staphylococcus
,
Clostridium
, and
Lactobacillus
), and
Proteobacteria
(including
Escherichia
,
Shigella
,
Salmonella
,
Citrobacter
,
Haemophilus
,
Klebsiella
,
Pasteurella
,
Photobacterium
,
Vibrio
, and
Yersinia
species), mostly commensals and/or pathogens. Overall, our data demonstrate that the ability to take up host-derived sugars and sialic acid specifically allows
V. cholerae
a competitive advantage in intestinal colonization and that this is a trait that is sporadic in its occurrence and phylogenetic distribution and ancestral in some genera but horizontally acquired in others.

IMPORTANCE
Sialic acids are nine carbon amino sugars that are abundant on all mucous surfaces. The deadly human pathogen
Vibrio cholerae
contains the genes required for scavenging, transport, and catabolism of sialic acid. We determined that the
V. cholerae
SiaPQM transporter is essential for sialic acid transport and that this trait allows the bacterium to outcompete noncatabolizers
in vivo
. We also showed that the ability to take up and catabolize sialic acid is prevalent among both commensals and pathogens that colonize the oral cavity and the respiratory, intestinal, and urogenital tracts. Phylogenetic analysis determined that the sialic acid catabolism phenotype is ancestral in some genera such as
Yersinia
,
Streptococcus
, and
Staphylococcus
and is acquired by horizontal gene transfer in others such as
Vibrio
,
Aeromonas
, and
Klebsiella
. The data demonstrate that this trait has evolved multiple times in different lineages, indicating the importance of specialized metabolism to niche expansion.
15 hz Electroacupuncture at St36 Improves Insulin Sensitivity and Reduces Free Fatty Acid Levels in Rats with Chronic Dexamethasone-Induced Insulin Resistance
Authors: Tzeng Chung-Yuh , Lee Yu-Chen , Chung Jui-Jung , Tsai Jen-Chieh , Chen Ying-I , Hsu Tai-Hao , Lin Jaung-Geng , Lee Kuan-Rong , Chang Shih-Liang
Published: April 2016

Objective

To evaluate the effect of electroacupuncture (EA) in a rat model of chronic steroid-induced insulin resistance (SIIR).

Methods

An SIIR rat model was created using daily intraperitoneal injections of clinically relevant doses of dexamethasone (1 mg/kg) for 5 days to induce chronic insulin resistance. Thirty-six SIIR rats were randomly divided into the SIIR+EA group (n=18), which received 15 Hz EA at ST36 for 60 min, and the SIIR group (n=18), which remained untreated. Plasma glucose and free fatty acid (FFA) levels were measured in serial blood samples taken without further manipulation (n=6 per group) and during insulin challenge test (ICT, n=6 per group) and intravenous glucose tolerance test (ivGTT, n=6 per group). Insulin receptor substrate (IRS)-1 and glucose transporter (GLUT)-4 were measured using Western blotting and expressed relative to β-actin.

Results

Following EA, area-under-the-curve (AUC) for glucose was reduced (7340±291 vs 10 705±1474 mg/dL/min, p=0.049) and FFA levels significantly lower at 30/60 min in the SIIR+EA versus SIIR groups. Similar effects on glucose AUC were seen during the ICT (5568±275 vs 7136±594 mg/dL/min, p<0.05) and igVTT (11 498±1398 vs 16 652±1217 mg/dL/min, p<0.01). FFA levels were lower at 30 and/or 60 min in SIIR+EA versus SIIR groups (p<0.01). Relative expression of IRS-1 and GLUT4 were significantly increased by EA (p<0.01).

Conclusions

EA decreased the FFA level and increased insulin sensitivity in SIIR rats. Further clinical studies are needed to determine whether EA is an effective alternative treatment for the reduction of insulin resistance in patients requiring chronic use of dexamethasone.
Gene of the month:HGF
Authors: Fajardo-Puerta Ana Belen , Mato Prado Mireia , Frampton Adam E , Jiao Long R
Published: April 2016

Hepatocyte growth factor (HGF) is a multifunctional cytokine with important roles in cell proliferation, survival, motility and morphogenesis. Secreted by cells of mesenchymal origin, HGF is the specific ligand for the tyrosine-kinase receptor c-MET (cellular mesenchymal-epithelial transition), also called MET, which is expressed in different types of epithelial, endothelial and haematopoietic progenitor cells. The HGF/MET axis is involved in several biological processes, such as embryogenesis, organogenesis, adult tissue regeneration (including wound healing and liver regeneration) and carcinogenesis, for both solid and haematological malignancies.1 2HGF and its particular interaction with the MET receptor have been extensively investigated in the last decades and remain the focus of numerous clinical trials.3–8This short review focuses on HGF structure and function, as well as its roles in liver regeneration and different types of tumours.
Scottish Keep Well health check programme: an interrupted time series analysis
Authors: Geue Claudia , Lewsey James D , MacKay Daniel F , Antony Grace , Fischbacher Colin M , Muirie Jill , McCartney Gerard
Published: April 2016

Background

Effective interventions are available to reduce cardiovascular risk. Recently, health check programmes have been implemented to target those at high risk of cardiovascular disease (CVD), but there is much debate whether these are likely to be effective at population level. This paper evaluates the impact of wave 1 of Keep Well, a Scottish health check programme, on cardiovascular outcomes.

Methods

Interrupted time series analyses were employed, comparing trends in outcomes in participating and non-participating practices before and after the introduction of health checks. Health outcomes are defined as CVD mortality, incident hospitalisations and prescribing of cardiovascular drugs.

Results

After accounting for secular trends and seasonal variation, coronary heart disease mortality and hospitalisations changed by 0.4% (95% CI −5.2% to 6.3%) and −1.1% (−3.4% to 1.3%) in Keep Well practices and by −0.3% (−2.7% to 2.2%) and −0.1% (−1.8% to 1.7%) in non-Keep Well practices, respectively, following the intervention. Adjusted changes in prescribing in Keep Well and non-Keep Well practices were 0.4% (−10.4% to 12.5%) and −1.5% (−9.4% to 7.2%) for statins; −2.5% (−12.3% to 8.4%) and −1.6% (−7.1% to 4.3%) for antihypertensive drugs; and −0.9% (−6.5% to 5.0%) and −2.4% (−10.1% to 6.0%) for antiplatelet drugs.

Conclusions

Any impact of the Keep Well health check intervention on CVD outcomes and prescribing in Scotland was very small. Findings do not support the use of the screening approach used by current health check programmes to address CVD. We used an interrupted time series method, but evaluation methods based on randomisation are feasible and preferable and would have allowed more reliable conclusions. These should be considered more often by policymakers at an early stage in programme design when there is uncertainty regarding programme effectiveness.
Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example
Authors: Lai Zhihong , La Noce Anna
Published: April 2016

The global development of a biosimilar product is a methodologically complex affair, lined with potential design pitfalls and operational missteps to be avoided. Without careful attention to experimental design and meticulous execution, a development programme may fail to demonstrate equivalence, as would be anticipated for a biosimilar product, and not receive regulatory approval based on current guidance. In order to demonstrate similarity of a biosimilar product versus the originator (ie, the branded product), based on regulatory guidance, a stepwise approach is usually taken, starting with a comprehensive structural and functional characterisation of the new biological moiety. Given the sequential nature of the review process, the extent and nature of the non-clinical in vivo studies and the clinical studies to be performed depend on the level of evidence obtained in these previous step(s). A clinical efficacy trial is often required to further demonstrate biosimilarity of the two products (biosimilar vs branded) in terms of comparative safety and effectiveness. Owing to the focus on demonstrating biosimilarity and not safety and efficacy de novo, designing an adequate phase III (potentially pivotal) clinical efficacy study of a biosimilar may present some unique challenges. Using adalimumab as an example, we highlight design elements that may deserve special attention.
Prevalence of rheumatic and musculoskeletal diseases and their impact on health-related quality of life, physical function and mental health in Portugal: results from EpiReumaPt– a national health survey
Authors: Branco Jaime C , Rodrigues Ana M , Gouveia Nélia , Eusébio Mónica , Ramiro Sofia , Machado Pedro M , da Costa Leonor Pereira , Mourão Ana Filipa , Silva Inês , Laires Pedro , Sepriano Alexandre , Araújo Filipe , Gonçalves Sónia , Coelho Pedro S , Tavares Viviana , Cerol Jorge , Mendes Jorge M , Carmona Loreto , Canhão Helena ,   on behalf of the EpiReumaPt study group
Published: April 2016

Objectives

To estimate the national prevalence of rheumatic and musculoskeletal diseases (RMDs) in the adult Portuguese population and to determine their impact on health-related quality of life (HRQoL), physical function, anxiety and depression.

Methods

EpiReumaPt is a national health survey with a three-stage approach. First, 10 661 adult participants were randomly selected. Trained interviewers undertook structured face-to-face questionnaires that included screening for RMDs and assessments of health-related quality of life, physical function, anxiety and depression. Second, positive screenings for ≥1 RMD plus 20% negative screenings were invited to be evaluated by a rheumatologist. Finally, three rheumatologists revised all the information and confirmed the diagnoses according to validated criteria. Estimates were computed as weighted proportions, taking the sampling design into account.

Results

The disease-specific prevalence rates (and 95% CIs) of RMDs in the adult Portuguese population were: low back pain, 26.4% (23.3% to 29.5%); periarticular disease, 15.8% (13.5% to 18.0%); knee osteoarthritis (OA), 12.4% (11.0% to 13.8%); osteoporosis, 10.2% (9.0% to 11.3%); hand OA, 8.7% (7.5% to 9.9%); hip OA, 2.9% (2.3% to 3.6%); fibromyalgia, 1.7% (1.1% to 2.1%); spondyloarthritis, 1.6% (1.2% to 2.1%); gout, 1.3% (1.0% to 1.6%); rheumatoid arthritis, 0.7% (0.5% to 0.9%); systemic lupus erythaematosus, 0.1% (0.1% to 0.2%) and polymyalgia rheumatica, 0.1% (0.0% to 0.2%). After multivariable adjustment, participants with RMDs had significantly lower EQ5D scores (β=−0.09; p<0.001) and higher HAQ scores (β=0.13; p<0.001) than participants without RMDs. RMDs were also significantly associated with the presence of anxiety symptoms (OR=3.5; p=0.006).

Conclusions

RMDs are highly prevalent in Portugal and are associated not only with significant physical function and mental health impairment but also with poor HRQoL, leading to more health resource consumption. The EpiReumaPt study emphasises the burden of RMDs in Portugal and the need to increase RMD awareness, being a strong argument to encourage policymakers to increase the amount of resources allocated to the treatment of rheumatic patients.
Reasons for Electronic Nicotine Delivery System use and smoking abstinence at 6 months: a descriptive study of callers to employer and health plan-sponsored quitlines
Authors: Vickerman K A , Schauer G L , Malarcher A M , Zhang L , Mowery P , Nash C M
Published: April 2016

Objective

Describe cigarette smoking abstinence among employer and health plan-sponsored quitline registrants who were not using Electronic Nicotine Delivery Systems (ENDS), were using ENDS to quit smoking or were using ENDS for other reasons at the time of quitline registration.

Methods

We examined 6029 quitline callers aged ≥18 years who smoked cigarettes at registration, and completed ≥1 counselling calls, baseline ENDS use questions and a 6-month follow-up survey (response rate: 52.4%). 30-day point prevalence smoking quit rates (PPQRs) were assessed at 6-month follow-up (ENDS-only users were considered quit). Data were weighted for non-response bias. Logistic regression analyses controlled for participant characteristics and programme engagement.

Results

At registration, 13.8% of respondents used ENDS (7.9% to quit smoking, 5.9% for other reasons). 30-day PPQRs were: 55.1% for callers using ENDS to quit, 43.1% for callers using ENDS for other reasons, and 50.8% for callers not using ENDS at registration. Callers using ENDS for other reasons were less likely to quit than other groups (adjusted ORs=0.65–0.77); quit rates did not significantly differ between non-ENDS users and those using ENDS to quit. Among callers using ENDS to quit at baseline, 40% used ENDS regularly at follow-up.

Conclusions

ENDS users not using ENDS to quit smoking were less successful at quitting at 6-month follow-up compared with callers using ENDS to quit smoking and callers who did not use ENDS at programme registration. Incorporating reasons for ENDS use may be important for future studies examining the role of ENDS in tobacco cessation.
Snus undermines quit attempts but not abstinence: a randomised clinical trial among US smokers
Authors: Carpenter Matthew J , Wahlquist Amy E , Burris Jessica L , Gray Kevin M , Garrett-Mayer Elizabeth , Cummings K Michael , Alberg Anthony J
Published: April 2016

Background

Observational studies and a few clinical trials suggest that use of low nitrosamine smokeless tobacco (snus) can facilitate smoking cessation. To better understand the real-world impact of snus on smoking behaviour, a large-scale, long-term clinical trial of naturalistic snus use among smokers is needed.

Study design

A nationwide clinical trial compared abstinence outcomes among smokers who were randomised to receive free samples of snus versus not. Participants (N=1236) were recruited throughout the US and assessed for 1 year following a 6-week naturalistic sampling period, with high retention throughout. Primary outcomes included self-reported quit attempts, floating abstinence (any 7-day period of non-smoking) and 7-day point-prevalence abstinence at 6 months and 12 months. Secondary outcomes were changes in smoking, motivation and confidence to quit and adverse events. No tobacco industry support was provided.

Results

Within snus group, 82% used at least once, and 16% were using regularly at end of sampling period. Compared to control participants, smokers in the snus group were less likely to make any quit attempt (RR=0.83; 95% CI 0.70 to 1.00), and any 24 h quit attempt (RR=0.77; 95% CI 0.63 to 0.95). There were no group differences on any measure of abstinence.

Conclusions

Provision of snus in a naturalistic context resulted in minimal uptake, and as a whole, undermined quit attempts and did not increase smoking abstinence. Results do not support the unguided, free provision of snus among smokers not motivated to quit as a means to facilitate quit attempts.

Trial registration number

NCT01509586, Results.
Effects of amoxicillin, ceftiofur, doxycycline, tiamulin and tulathromycin on pig humoral immune responses induced by erysipelas vaccination
Authors: Pomorska‐Mól M. , Kwit K. , Wierzchosławski K. , Dors A. , Pejsak Z.
Published: April 2016

It addition to their antimicrobial properties, antibiotics can influence the host immune system (modulation of cytokine secretion, antibody production and T‐cell proliferation). In the present study, the authors studied the effects of therapeutic doses of amoxicillin (AMX), ceftiofur (CEF), doxycycline (DOXY), tiamulin (TIAM) and tulathromycin (TUL) on the postvaccinal immune response after pigs had been vaccinated against erysipelas. Because humoral immunity is considered as the most important in the protection against swine erysipelas, the present study focused on the interactions between antibiotics and postvaccinal humoral immunity. One hundred and five, eight‐week‐old pigs of both sexes were used. Specific antibodies to the Erysipelothrix rhusiopathiae antigen were determined using a commercial ELISA test. In pigs treated with DOXY or CEF or TIAM, a significant reduction in the number of positive pigs was observed four and six weeks after the second dose of vaccine, compared with the remaining vaccinated groups. In pigs treated with CEF, the ELISA score was significantly lower than in non‐treated vaccinated pigs. While in vaccinated pigs treated with AMX or TUL, the ELISA score was significantly higher than in pigs treated with the remaining antibiotics and than in non‐treated vaccinated controls. The results of the present study indicate that vaccination of pigs against erysipelas in the presence of antibiotics may result in a decrease (CEF, DOXY, TIAM) or enhancement (AMX, TUL) in the production of specific antibodies.
The nucleosome: orchestrating DNA damage signaling and repair within chromatin
Authors: Agarwal Poonam , Miller Kyle M.
Published: April 2016

DNA damage occurs within the chromatin environment, which ultimately participates in regulating DNA damage response (DDR) pathways and repair of the lesion. DNA damage activates a cascade of signaling events that extensively modulates chromatin structure and organization to coordinate DDR factor recruitment to the break and repair, whilst also promoting the maintenance of normal chromatin functions within the damaged region. For example, DDR pathways must avoid conflicts between other DNA-based processes that function within the context of chromatin, including transcription and replication. The molecular mechanisms governing the recognition, target specificity, and recruitment of DDR factors and enzymes to the fundamental repeating unit of chromatin, i.e., the nucleosome, are poorly understood. Here we present our current view of how chromatin recognition by DDR factors is achieved at the level of the nucleosome. Emerging evidence suggests that the nucleosome surface, including the nucleosome acidic patch, promotes the binding and activity of several DNA damage factors on chromatin. Thus, in addition to interactions with damaged DNA and histone modifications, nucleosome recognition by DDR factors plays a key role in orchestrating the requisite chromatin response to maintain both genome and epigenome integrity.
Analytical, morphological, and rheological behavior of sulphur-extended-binder
Authors: Gedik Abdulgazi , Lav Abdullah Hilmi
Published: April 2016

Bituminous material is a limited natural resource mainly used in hot mix asphalt production. The high costs coupled with the large amounts required have been forcing pavement engineers to find cost effective alternative materials that can be used as extenders or partial substitutes. This prohibitive cost factor led this paper to focus on the utilization of abundant granular sulphur as an extender for the more expensive bituminous material. In this study, sulphur-extended binders were prepared by using a 50/70 grade bitumen and by increasing the amounts of granular sulphur as an extension up to a maximum 50% by weight. The samples were then exposed to short and long-term aging by performing the rolling thin film oven and pressure aging vessel tests. Aged and virgin samples were then further tested using analytical, rheological, and morphological testing methods. The promising results demonstrate that the sulphur-extended binder not only increases the performance of the neat bitumen, but can also lower overall costs.
Yield and net return from alfalfa cultivars under irrigation in Southern Alberta
Authors: Attram Jeremiah , Acharya Surya N. , Woods Shelley A. , Smith Elwin , Thomas James E.
Published: April 2016

Field studies with two types of alfalfa (Medicago sativa L.) cultivars were conducted at Lethbridge in 2012 and 2013 and at Picture Butte in 2012 to determine the effects of irrigation on the dry matter (DM) yield and on net returns. The irrigated cultivars (Longview and Blue J) and dryland cultivars (Rangelander and Rambler) were arranged on plots in a randomized complete block design with four irrigation treatments and replicated five times. For the optimal irrigation treatment (W1), soil water content was maintained between 60 and 90% of available water in the designated root zone. Other irrigation treatments received 75% (W2), 50% (W3), and 25% (W4) of the irrigation water applied to the optimal treatment. The mean DM yields of irrigated alfalfa cultivars were greater than one of the dryland cultivars in both locations. The mean total DM yields for W2and W3at Lethbridge for Blue J, Longview and Rambler were greater than those of W1, although the differences were not always significant. The net returns, calculated by using the same price for all alfalfa harvests were similar across the cultivars and irrigation treatments excepting Rangelander, where the returns were lower. The results obtained from this study indicated a trend towards comparable yields and net returns between the optimal and the 75% irrigation treatment with 40% depletion of available water at the root zone, for the irrigated alfalfa cultivars and a dryland type Rambler.