bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between ratio indexes of body composition phenotypes and metabolic risk in Italian adults
Authors: Powell M. , Lara J. , Mocciaro G. , Prado C. M. , Battezzati A. , Leone A. , Tagliabue A. , de Amicis R. , Vignati L. , Bertoli S. , Siervo M.
Published: November 2016

The ratio between fat mass (FM) and fat‐free mass (FFM) has been used to discriminate individual differences in body composition and improve prediction of metabolic risk. Here, we evaluated whether the use of a visceral adipose tissue‐to‐fat‐free mass index (VAT:FFMI) ratio was a better predictor of metabolic risk than a fat mass index to fat‐free mass index (FMI:FFMI) ratio. This is a cross‐sectional study including 3441 adult participants (age range 18–81; men/women: 977/2464). FM and FFM were measured by bioelectrical impedance analysis and VAT by ultrasonography. A continuous metabolic risk Z score and harmonised international criteria were used to define cumulative metabolic risk and metabolic syndrome (MetS), respectively. Multivariate logistic and linear regression models were used to test associations between body composition indexes and metabolic risk. In unadjusted models, VAT:FFMI was a better predictor of MetS (OR 8.03, 95%CI 6.69–9.65) compared to FMI:FFMI (OR 2.91, 95%CI 2.45–3.46). However, the strength of association of VAT:FFMI and FMI:FFMI became comparable when models were adjusted for age, gender, clinical and sociodemographic factors (OR 4.06, 95%CI 3.31–4.97; OR 4.25, 95%CI 3.42–5.27, respectively). A similar pattern was observed for the association of the two indexes with the metabolic risk Z score (VAT:FFMI: unadjusted b = 0.69 ± 0.03, adjusted b = 0.36 ± 0.03; FMI:FFMI: unadjusted b = 0.28 ± 0.028, adjusted b = 0.38 ± 0.02). Our results suggest that there is no real advantage in using either VAT:FFMI or FMI:FFMI ratios as a predictor of metabolic risk in adults. However, these results warrant confirmation in longitudinal studies.
A national patient and public colorectal research agenda: integration of consumer perspectives in bowel disease through early consultation
Authors: McNair A. G. K. , Heywood N. , Tiernan J. , Verjee A. , Bach S. P. , Fearnhead N. S. ,   ORACLE Collaboration
Published: November 2016

Aim

There is a recognized need to include the views of patients and the public in prioritizing health research. This study aimed: (i) to explore patients’ views on colorectal research; and (ii) to prioritize research topics with patients and the public.

Method

In phase 1, 12 charitable organizations and patient groups with an interest in bowel disease were invited to attend a consultation exercise. Participants were briefed on 25 colorectal research topics prioritized by members of the Association of Coloproctology of Great Britain and Ireland. Focus groups were conducted and discussions were recorded with field notes. Analysis was conducted using principles of thematic analysis. In phase 2, a free public consultation was undertaken. Participants were recruited from newspaper advertisements, were briefed on the same research topics and were asked to rate the importance of each on a five‐point Likert scale. Descriptive statistics were used to rank the topics. Univariable linear regression compared recorded demographic details with mean topic scores.

Results

Focus groups were attended by 12 patients who highlighted the importance of patient‐centred information for trial recruitment and when selecting outcome measures. Some 360 people attended the public consultation, of whom 277 (77%) were recruited. Participants rated ‘What is the best way to treat early cancer in the back passage?’ highest, with 227 (85%) scoring it 4 or 5. There was no correlation between participant demographics and mean topic scores.

Conclusion

The present study prioritized a colorectal research agenda with the input of patients and the public. Further research is required to translate this agenda into real improvements in patient care.
Adding Some Green to the Greening: Improving the EU's Ecological Focus Areas for Biodiversity and Farmers
Authors: Pe'er Guy , Zinngrebe Yves , Hauck Jennifer , Schindler Stefan , Dittrich Andreas , Zingg Silvia , Tscharntke Teja , Oppermann Rainer , Sutcliffe Laura M.E. , Sirami Clélia , Schmidt Jenny , Hoyer Christian , Schleyer Christian , Lakner Sebastian
Published: November 2016

Ecological Focus Areas (EFAs) are one of the three new greening measures of the European Common Agricultural Policy (CAP). We used an interdisciplinary and European‐scale approach to evaluate ecological effectiveness and farmers’ perception of the different EFA options. We assessed potential benefits of EFA options for biodiversity using a survey among 88 ecologists from 17 European countries. We further analyzed data on EFA uptake at the EU level and in eight EU Member States, and reviewed socio‐economic factors influencing farmers’ decisions. We then identified possible ways to improve EFAs. Ecologists scored field margins, buffer strips, fallow land, and landscape features as most beneficial whereas farmers mostly implemented “catch crops and green cover,” nitrogen‐fixing crops, and fallow land. Based on the expert inputs and a review of the factors influencing farmers’ decisions, we suggest that EFA implementation could be improved by (a) prioritizing EFA options that promote biodiversity (e.g., reducing the weight or even excluding ineffective options); (b) reducing administrative constraints; (c) setting stricter management requirements (e.g., limiting agrochemical use); and (d) offering further incentives for expanding options like landscape features and buffer strips. We finally propose further improvements at the next CAP reform, to improve ecological effectiveness and cost‐effectiveness.
Reduced microRNA‐188‐3p expression contributes to apoptosis of spermatogenic cells in patients with azoospermia
Authors: Song Wen‐Yan , Meng Hui , Wang Xue‐Gai , Jin Hai‐Xia , Yao Gui‐Dong , Shi Sen‐Lin , Wu Liang , Zhang Xiang‐Yang , Sun Ying‐Pu
Published: November 2016

Background and aims

Human mutL homologl (MLH1) works coordinately in sequential steps to initiate repair of DNA mismatches, and aberrant MLH1 expression is related to spermatogenetic malfunction. In the present study, MLH1 expression in patients with azoospermia was investigated, and moderating effects of miR‐188‐3p on MLH1 expression and spermatogenesis were identified.

Methods

Testicular tissues from 16 patients with obstructive azoospermia (OA) and non‐obstructive azoospermia (NOA), and tissues of eight healthy patients were collected. Real‐time PCR, Western blotting and immunohistochemical staining were used to detect MLH1 expression. Chromatin immunoprecipitation assay and luciferase reporter assay were performed to evaluate histone acetylation level of miR‐188‐3p and relationships between miR‐188‐3p and MLH1.

Results

Testicular MLH1 expression at mRNA and protein levels was significantly increased, while miR‐188‐3p expression was lower in patients with OA and NOA than that in controls. Reduced histone acetylation level of miR‐188‐3p promoter was observed in patients with azoospermia. Overexpression/inhibition of HDAC1, but not HDAC2, contributed to the significant reduction/increase of miR‐188‐3p expression. miR‐188‐3p targeted 3′ UTR of MLH1 and regulated MLH1 expression. miR‐188‐3p inhibitor led to elevation of apoptotic level of spermatogenic cells in mice, while this effect was reversed by si‐MLH1.

Conclusion

Down‐regulation of miR‐188‐3p by reducing histone acetylation up‐regulated MLH1 expression and contributed to promotion of apoptosis in spermatogenic cells, in patients with azoospermia.
840. ROSA HIRTULA
Authors: Ohba Hideaki
Published: November 2016

Rosa hirtula (Regel) Nakai, a species endemic to Japan, is illustrated. It occurs in central Honshū around Mt. Fuji and Hakone and vicinity. Rosa hirtula is similar to R. roxburghii Tratt., particularly to the single‐flowered form, f. normalis Rehder & E. H. Wils., and is distinguished by its tree habit, hairy rachis, and lanceolate to narrowly oblong leaflets with acuminate to acuminate‐acute apex, serrulate margins, and hairy midvein on the lower surface.
847. FRITILLARIA KIUSIANA
Authors: Hill Laurence
Published: November 2016

Fritillaria kiusiana L. Hill, a new species from the Kyushu Central Mountains in Japan, is illustrated and described. Its ecology, genetics and conservation are discussed and instructions for its cultivation are given.
Pathogenese und Klinik der Rosazea als Schlüssel für eine symptomorientierte Therapie
Authors: Reinholz M , Ruzicka T , Steinhoff M , Schaller M , Gieler U , Schöfer H , Homey B , Lehmann P , Luger TA
Published: November 2016

Rosazea ist eine häufige chronisch‐entzündliche Hauterkrankung, die typischerweise bei Erwachsenen vorkommt und das Gesicht betrifft. Synonyme der Rosazea sind Acne rosacea, Kupferfinne, Rotfinne, Couperose und Rosacea. Die Erkrankung ist durch einen chronischen und schubartigen Verlauf gekennzeichnet und wird durch ein genetisch prädisponiertes, multifaktorielles Geschehen bedingt. Ein vermehrtes Auftreten wird bei hellem Hauttyp und positiver Familienanamnese verzeichnet. Die charakteristischen Rosazea‐Symptome manifestieren sich vorwiegend, aber nicht ausschließlich zentrofazial, wobei Stirn, Nase, Kinn und die Wangen maßgeblich betroffen sind. Dabei werden unterschiedliche Hauptsymptome voneinander unterschieden, anhand derer eine Klassifikation der verschiedenen klinischen Bilder vorgenommen werden kann. Eine Klassifizierung wird oftmals jedoch nicht der klinischen Realität gerecht, da die verschiedenen Symptome häufig gemeinsam auftreten. Diese Übersichtarbeit führt in die Pathogenese und Klinik der Rosazea ein und plädiert für einen symptomorientierten Therapieansatz.
State of the art: systemic rosacea management
Authors: Schaller M , Schöfer H , Homey B , Gieler U , Lehmann P , Luger TA , Ruzicka T , Steinhoff M
Published: November 2016

Based on numerous trials, oral tetracyclines and most commonly their second‐generation derivative doxycycline have become the main pillar in systemic rosacea treatment. However, the only preparation that has been approved so far in this setting is 40 mg doxycycline in an anti‐inflammatory dosage and with a modified release formulation. With the introduction of this once‐daily, non‐antibiotic dosing of doxycycline, oral therapy is more commonly prescribed as first‐line treatment in moderate to severe papulopustular rosacea. In addition, topical and oral strategies are often used in combination due to the more substantial improvements compared to monotherapy. Although several other non‐approved oral agents like macrolides, isotretinoin, and carvedilol have been evaluated for systemic treatment and showed promising results, yet the experience with these drugs in rosacea is limited, and thus they should be reserved for special situations.
Hepatic chemerin mRNA expression is reduced in human nonalcoholic steatohepatitis
Authors: Pohl Rebekka , Haberl Elisabeth M. , Rein‐Fischboeck Lisa , Zimny Sebastian , Neumann Maximilian , Aslanidis Charalampos , Schacherer Doris , Krautbauer Sabrina , Eisinger Kristina , Weiss Thomas S. , Buechler Christa
Published: November 2016

Background

Chemerin is associated with insulin resistance and is expressed in the liver. Nonalcoholic fatty liver disease (NAFLD) is related to impaired insulin sensitivity, but studies evaluating hepatic and serum chemerin in NAFLD resulted in discordant data.

Materials and methods

Chemerin mRNA was determined in the liver tissue obtained from 33 controls and 76 NAFLD patients. Chemerin serum levels were measured in a different cohort of patients with ultrasound‐diagnosed NAFLD and the respective controls. Hepatic stellate cells and hepatocytes were exposed to selected metabolites and nuclear receptor agonists to study the regulation of chemerin. Effect of recombinant chemerin on hepatocyte released proteins was analysed.

Results

Hepatic chemerin expression was not related to BMI, gender, type 2 diabetes and hypertension. Chemerin mRNA did not correlate with steatosis and was negatively associated with inflammation, fibrosis and nonalcoholic steatohepatitis (NASH) score. Patients with NASH had lower chemerin mRNA compared to those with borderline NASH and controls. Factors with a role in NASH mostly did not regulate chemerin in the liver cells. Of note, liver X receptor agonist reduced chemerin protein. Serum chemerin was not changed in NAFLD. Levels positively correlated with age, waist‐to‐hip ratio, systolic blood pressure, serum FGF21 and lipocalin 2, and negatively with transferrin saturation. Chemerin induced FGF21 in supernatants of primary human hepatocytes. Hepcidin, a major regulator of iron homoeostasis and lipocalin 2, were not regulated by chemerin.

Conclusion

Chemerin mRNA is reduced in the liver of NASH patients, and liver X receptor seems to have a role herein.
Bioenergetic evaluation of diel vertical migration by bull trout (Salvelinus confluentus) in a thermally stratified reservoir
Authors: Eckmann Madeleine , Dunham Jason , Connor Edward J. , Welch Carmen A.
Published: November 2016

Many species living in deeper lentic ecosystems exhibit daily movements that cycle through the water column, generally referred to as diel vertical migration (DVM). In this study, we applied bioenergetics modelling to evaluate growth as a hypothesis to explain DVM by bull trout (Salvelinus confluentus) in a thermally stratified reservoir (Ross Lake, WA, USA) during the peak of thermal stratification in July and August. Bioenergetics model parameters were derived from observed vertical distributions of temperature, prey and bull trout. Field sampling confirmed that bull trout prey almost exclusively on recently introduced redside shiner (Richardsonius balteatus). Model predictions revealed that deeper (>25 m) DVMs commonly exhibited by bull trout during peak thermal stratification cannot be explained by maximising growth. Survival, another common explanation for DVM, may have influenced bull trout depth use, but observations suggest there may be additional drivers of DVM. We propose these deeper summertime excursions may be partly explained by an alternative hypothesis: the importance of colder water for gametogenesis. In Ross Lake, reliance of bull trout on warm water prey (redside shiner) for consumption and growth poses a potential trade‐off with the need for colder water for gametogenesis.
Prediction of long‐term prognosis by heteroplasmy levels of the m.3243A>G mutation in patients with the mitochondrial encephalomyopathy, lactic acidosis and stroke‐like episodes syndrome
Authors: Fayssoil A. , Laforêt P. , Bougouin W. , Jardel C. , Lombès A. , Bécane H. M. , Berber N. , Stojkovic T. , Béhin A. , Eymard B. , Duboc D. , Wahbi K.
Published: November 2016

Background and purpose

Our aim was to determine the prognostic value of urine and blood heteroplasmy in patients with the m.3243A>G mutation.

Methods

Adults with the m.3243A>G mutation referred to our institution between January 2000 and May 2014 were retrospectively included. The relationship between their baseline clinical characteristics, their mutation load in urine and blood, and major adverse events (MAEs) during follow‐up, defined as medical complications requiring a hospitalization or complicated by death, was studied.

Results

Of the 43 patients (age 45.6 ± 13.3 years) included in the study, 36 patients were symptomatic, including nine with evidence of focal brain involvement, and seven were asymptomatic. Over a 5.5 ± 4.0 year mean follow‐up duration, 14 patients (33%) developed MAEs. Patients with MAEs had a higher mutation load than others in urine (60.1% ± 13.8% vs. 40.6% ± 26.2%, P = 0.01) and in blood (26.9% ± 18.4% vs. 16.0% ± 12.1%, P = 0.03). Optimal cutoff values for the prediction of MAEs were 45% for urine and 35% for blood. In multivariate analysis, mutation load in urine ≥45% [odds ratio 25.3; 95% confidence interval (CI) 1.1–567.8; P = 0.04], left ventricular hypertrophy (odds ratio 16.7; 95% CI 1.3– 222.5; P = 0.03) and seizures (odds ratio 48.3; 95% CI 2.5–933; P = 0.01) were associated with MAEs.

Conclusions

Patients with the m.3243A>G mutation are at high risk of MAEs, which can be independently predicted by mutation load in urine ≥45%, a personal history of seizures, and left ventricular hypertrophy.
Effects of the North Pacific Current on the productivity of 163 Pacific salmon stocks
Authors: Malick Michael J. , Cox Sean P. , Mueter Franz J. , Dorner Brigitte , Peterman Randall M.
Published: November 2016

Horizontal ocean transport can influence the dynamics of higher‐trophic‐level species in coastal ecosystems by altering either physical oceanographic conditions or the advection of food resources into coastal areas. In this study, we investigated whether variability in two North Pacific Current (NPC) indices was associated with changes in productivity of North American Pacific salmon stocks. Specifically, we used Bayesian hierarchical models to estimate the effects of the north‐south location of the NPC bifurcation (BI) and the NPC strength, indexed by the North Pacific Gyre Oscillation (NPGO), on the productivity of 163 pink, chum, and sockeye salmon stocks. We found that for salmon stocks located in Washington (WA) and British Columbia (BC), both the BI and NPGO had significant positive effects on productivity, indicating that a northward‐shifted bifurcation and a stronger NPC are associated with increased salmon productivity. For the WA and BC regions, the estimated NPGO effect was over two times larger than the BI effect for pink and chum salmon, whereas for sockeye salmon the BI effect was 2.4 times higher than the NPGO. In contrast to WA and BC stocks, we found weak effects of both horizontal ocean transport processes on the productivity of salmon stocks in Alaska. Our results indicated that horizontal transport pathways might strongly influence population dynamics of Pacific salmon in the southern part of their North American ranges, but not the northern part, suggesting that different environmental pathways may underlie changes in salmon productivity in northern and southern areas for the species under consideration.
Response of Sierra Nevada forests to projected climate–wildfire interactions
Authors: Liang Shuang , Hurteau Matthew D. , Westerling Anthony LeRoy
Published: November 2016

Climate influences forests directly and indirectly through disturbance. The interaction of climate change and increasing area burned has the potential to alter forest composition and community assembly. However, the overall forest response is likely to be influenced by species‐specific responses to environmental change and the scale of change in overstory species cover. In this study, we sought to quantify how projected changes in climate and large wildfire size would alter forest communities and carbon (C) dynamics, irrespective of competition from nontree species and potential changes in other fire regimes, across the Sierra Nevada,USA. We used a species‐specific, spatially explicit forest landscape model (LANDIS‐II) to evaluate forest response to climate–wildfire interactions under historical (baseline) climate and climate projections from three climate models (GFDL,CCSM3, andCNRM) forced by a medium–high emission scenario (A2) in combination with corresponding climate‐specific large wildfire projections. By late century, we found modest changes in the spatial distribution of dominant species by biomass relative to baseline, but extensive changes in recruitment distribution. Although forest recruitment declined across much of the Sierra, we found that projected climate and wildfire favored the recruitment of more drought‐tolerant species over less drought‐tolerant species relative to baseline, and this change was greatest at mid‐elevations. We also found that projected climate and wildfire decreased tree species richness across a large proportion of the study area and transitioned more area to a C source, which reduced landscape‐level C sequestration potential. Our study, although a conservative estimate, suggests that by late century, forest community distributions may not change as intact units as predicted by biome‐based modeling, but are likely to trend toward simplified community composition as communities gradually disaggregate and the least tolerant species are no longer able to establish. The potential exists for substantial community composition change and forest simplification beyond this century.
MYB transcription factor gene involved in sex determination in Asparagus officinalis
Authors: Murase Kohji , Shigenobu Shuji , Fujii Sota , Ueda Kazuki , Murata Takanori , Sakamoto Ai , Wada Yuko , Yamaguchi Katsushi , Osakabe Yuriko , Osakabe Keishi , Kanno Akira , Ozaki Yukio , Takayama Seiji
Published: November 2016

Dioecy is a plant mating system in which individuals of a species are either male or female. Although many flowering plants evolved independently from hermaphroditism to dioecy, the molecular mechanism underlying this transition remains largely unknown. Sex determination in the dioecious plant Asparagus officinalis is controlled by X and Y chromosomes; the male and female karyotypes are XY and XX, respectively. Transcriptome analysis of A. officinalis buds showed that a MYB‐like gene, Male Specific Expression 1 (MSE1), is specifically expressed in males. MSE1 exhibits tight linkage with the Y chromosome, specific expression in early anther development and loss of function on the X chromosome. Knockout of the MSE1 orthologue in Arabidopsis induces male sterility. Thus, MSE1 acts in sex determination in A. officinalis.
Vascular imaging for hemodialysis vascular access planning
Authors: McGill Rita L. , Ruthazer Robin , Lacson Eduardo , Meyer Klemens B. , Miskulin Dana C. , Weiner Daniel E.
Published: November 2016

Introduction: Central venous catheters (CVC) increase risks associated with hemodialysis (HD), but may be necessary until an arteriovenous fistula (AVF) or graft (AVG) is achieved. The impact of vascular imaging on achievement of working AVF and AVG has not been firmly established.

Methods: Retrospective cohort of patients initiating HD with CVC in 2010–2011, classified by exposure to venography or Doppler vein mapping, and followed through December 31, 2012. Standard and time‐dependent Cox models were used to determine hazard ratios (HRs) of death, working AVF, and any AVF or AVG. Logistic regression was used to assess the association of preoperative imaging with successful AVF or AVG among 18,883 individuals who had surgery. Models were adjusted for clinical and demographic factors.

Findings: Among 33,918 patients followed for a median of 404 days, 39.1% had imaging and 55.7% had surgery. Working AVF or AVG were achieved in 40.6%; 46.2% died. Compared to nonimaged patients, imaged patients were more likely to achieve working AVF (HR = 1.45 [95% confidence interval [CI] 1.36, 1.55], P < 0.001]), any AVF or AVG (HR = 1.63 [1.58, 1.69], P > 0.001), and less likely to die (HR = 0.88 [0.83‐0.94], P < 0.001). Among patients who had surgery, the odds ratio for any successful AVF or AVG was 1.09 (1.02–1.16, P = 0.008).

Discussion: Fewer than half of patients who initiated HD with a CVC had vascular imaging. Imaged patients were more likely to have vascular surgery and had increased achievement of working AV fistulas and grafts. Outcomes of surgery were similar in patients who did and did not have imaging.
Communication and patient participation influencing patient recall of treatment discussions
Authors: Richard Claude , Glaser Emma , Lussier Marie‐Thérèse
Published: November 2016

Context

Patient recall of treatment information is a key variable towards chronic disease (CD) management. It is unclear what communication and patient participation characteristics predict recall.

Objectives

To assess what aspects of doctor‐patient communication predict patient recall of medication information. To describe lifestyle treatment recall, in CD primary care patients.

Design

Observational study within a RCT.

Setting & participants

Community‐based primary care (PC) practices. Family physicians (n=18): practicing >5 years, with a CD patient caseload. Patients (n=159): >40 years old, English speaking, computer literate, off‐target hypertension, type II diabetes and/or dyslipidaemia.

Main variables

Patient characteristics: age, education, number of CDs. Information characteristics: length of encounter, medication status, medication class. Communication variables: socio‐emotional utterances, physician dominance and communication control scores and PACE (ask, check and express) utterances, measured by RIAS. Number of medication themes, dialogue and initiative measured by MEDICODE.

Main outcome measures

Recall of CD, lifestyle treatment and medication information.

Results

Frequency of lifestyle discussions varied by topic. Patients recalled 43% (alcohol), 52% (diet) to 70% (exercise) of discussions. Two and a half of six possible medication themes were broached per medication discussion. Less than one was recalled. Discussing more themes, greater dialogue and patient initiative were significant predictors of improved medication information recall.

Discussion

Critical treatment information is infrequently exchanged. Active patient engagement and explicit conversations about medications are associated with improved treatment information recall in off‐target CD patients followed in PC.

Conclusion

Providers cannot take for granted that long‐term off‐target CD patients recall information. They need to encourage patient participation to improve recall of treatment information.
Encapsulation of probiotic Lactobacillus acidophilus by ionic gelation with electrostatic extrusion for enhancement of survival under simulated gastric conditions and during refrigerated storage
Authors: Kim Jeong Un , Kim Bomi , Shahbaz Hafiz Muhammad , Lee Sung Hyun , Park Daseul , Park Jiyong
Published: November 2016

The probiotic Lactobacillus acidophilus was encapsulated in biodegradable and biocompatible capsules prepared by ionic gelation between phytic acid (PA) and chitosan (CS) with an electrostatic extrusion method. Calcium carbonate (CaCO3) and starch were used as co‐encapsulants for improvement of capsule stability. Capsules were characterised and evaluated for survival of encapsulated L. acidophilus cells in simulated gastric fluid (SGF) and during refrigerated storage. Loading capacity values of PA‐CS capsules, PA‐CS‐starch capsules and PA‐CS‐CaCO3 capsules were 8.20, 8.12 and 7.81 log CFU g−1 of wet capsule, respectively. Capsules showed particle sizes of 1.3–1.5 mm and a uniform spherical shape. PA‐CS‐CaCO3 capsules were the most stable vehicles for the protection of probiotic cells against acidic damage, particularly at pH 1.5 and pH 2. L. acidophilus cells from PA‐CS‐CaCO3 capsules showed only a 0.64 log CFU reduction in numbers after 2 h in pH 1.5 SGF conditions. The numbers of L. acidophilus encapsulated in PA‐CS‐CaCO3 capsules were decreased by only 0.69 log CFU g−1, while PA‐CS capsules and PA‐CS‐starch capsule numbers were reduced by more than 1.45 log CFU g−1 after 4 weeks at 4 °C. Addition of calcium carbonate to PA‐CS capsules provided protection against acid injury via antacid and buffering effects for encapsulation of L. acidophilus.
A single‐arm trial indirect comparison investigation: a proof‐of‐concept method to predict venous leg ulcer healing time for a new acellular synthetic matrix matched to standard care control
Authors: Shannon Ronald , Nelson Andrea
Published: November 2016

To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four largeUKpragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof‐of‐concept strategy to aVLUclinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plusSCfor success in future randomised, controlled clinical trials. Prospective data on chronicVLUsfrom a safety and effectiveness study on an acellular synthetic matrix conducted in one wound centre in theUK(17 patients) and three wound centres in Australia (36 patients) were compared retrospectively to propensity score‐matched data from patients with comparable leg ulcer disease aetiology, age, baseline ulcer area, ulcer duration, multi‐layer compression bandaging and majority of care completed in specialist wound centres (average of 1 visit per week), with the outcome measures at comparable follow‐up periods from patients enrolled in four prospective, multicentre, pragmatic, randomised studies of venous ulcers in theUK(the comparison group;VLUevidence network). Analysis using Kaplan–Meier survival curves showed a mean healing time of 73·1 days forASMplusSC(ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated withSCalone (Log rank test,χ25·779,P = 0·016) within 12 weeks. Sensitivity analysis indicates that an unobserved covariate would have to change the odds of healing forSCby a factor of 1·1 to impact the baseline results. Results from this study predict a significant effect on healing time when using a newASMas an adjunct toSCin the treatment of non‐healing venous ulcers in theUK, but results are sensitive to unobserved covariates that may be important in healing time comparison.
Medical Spending and Hospital Inpatient Care in England: An Analysis over Time
Authors: Aragón María José , Chalkley Martin , Rice Nigel
Published: November 2016

Health care in England is predominantly provided free at the point of service through the publicly‐funded National Health Service (NHS). Total NHS expenditure, which has risen in real terms by an average of 3.7 per cent per annum since the inception of the NHS in 1948, constituted 7.9 per cent of GDP in 2012. This paper presents a summary of the trends in medical expenditure in England together with, using detailed administrative data, an analysis of the growth over 15 years of expenditure and activity in hospital inpatient health care, which represents around 20–25 per cent of all NHS expenditure. We document the coincidence of observed trends in expenditure with reported activity, morbidity and the proximity of individuals to death. We find that: (i) expenditure for both elective and emergency inpatient care broadly follows activity, so that expenditure is mostly driven by activity rather than unit costs; (ii) expenditure is concentrated in individuals with multiple diseases, so that the prevalence and identification of complex medical conditions are important drivers of expenditure; and (iii) health care activity rises substantially for individuals in the period before death, so that expenditure is driven substantially by mortality in the population. Taken together, these findings indicate that this element of health care expenditure in England has been substantially driven by the underlying morbidity and age of the population in conjunction with improving health care technology.
Medical Spending in France: Concentration, Persistence and Evolution before Death
Authors: Gastaldi‐Ménager Christelle , Geoffard Pierre‐Yves , de Lagasnerie Grégoire
Published: November 2016

This paper studies medical spending in France from three perspectives: concentration, persistence, and evolution before death. We use claims data from a representative sample of over 500,000 individuals covered by the National Health insurance scheme, from 2008 to 2013. These data contain individual‐level information (gender, age, date of death), some clinical information and detailed information on each medical treatment (inpatient, outpatient, drugs). Medical spending in France is highly concentrated. In 2013, 10 per cent of the population accounted for 62 per cent of all health care spending. In addition, the concentration of medical expenditure increased between 2008 and 2013. The concentration of insurance reimbursement, however, is even greater, indicating that French social health insurance redistributes income from the healthy to the unhealthy. The serial correlation of health care expenditures appears relatively high between adjacent years, but not surprisingly decreases over time. Decedents have high medical expenditures – on average, eight times those of survivors – and resources devoted to health care in the last three years of life represent, on average, 22 per cent of lifetime medical spending. Decedents’ expenditures decrease with age after 55 years old.
Out‐of‐Pocket Medical Expenditures in the United States: Evidence from the Health and Retirement Study
Authors: Fahle Sean , McGarry Kathleen , Skinner Jonathan
Published: November 2016

We use data from the Health and Retirement Study (HRS) to document the distribution of out‐of‐pocket medical spending among individuals aged 55 and over in the US. The HRS data permit us to examine out‐of‐pocket spending close to the end of life and to analyse the components of spending in more detail than has been done in previous studies. We find that spending risk rises sharply at older ages and near the end of life. While the median individual spent $6,328 out‐of‐pocket in the last year of life, 5 per cent were reported to have spent over $62,040. Our results also indicate that out‐of‐pocket spending is highly concentrated, with the top 10 per cent of spenders accounting for 42 per cent of all spending, and persistent, even over periods spanning many years. Finally, while certain categories of spending are very responsive to income and wealth, we do not find overall spending to be highly concentrated along these dimensions. Viewed within the international context, our results suggest that the fraction of households facing very high out‐of‐pocket spending is substantially greater in the US than in other developed countries.
Medical Spending around the Developed World
Authors: French Eric , Kelly Elaine
Published: November 2016

We bring together estimates of patterns of medical spending in all nine countries considered in this issue – Canada, Denmark, England, France, Germany, Japan, the Netherlands, Taiwan and the United States. Comparing estimates across countries reveals three principal findings. First, medical spending in the calendar year of death accounts for 5–10 per cent of aggregate medical spending for the whole population and 9–20 per cent for those aged 65 and over. Spending in Taiwan is a little higher, at 16 per cent for the whole population and 29 per cent for the over‐65s. Second, there is a mostly negative correlation between patient income and medical spending within all countries, except Japan and Taiwan for the over‐65s and Taiwan and the US for the under‐25s. Third, medical spending in all countries is concentrated in a small share of the population and is persistent over time, although the degree of concentration and persistence varies across countries.
Renal dysfunction in patients taking fumaric acid esters – a retrospective cross‐sectional study
Authors: Menzies S. , Ismail N. , Abdalla A. , Collins P. , Kirby B. , Holian J. , Lally A.
Published: November 2016

Background

Fumaric acid esters (FAE) have been used for over 30 years in the management of psoriasis. There have been a number of case reports linking the use of FAE with nephrotoxicity, including acute renal injury and Fanconi syndrome. However, one large multicentre retrospective trial showed no evidence of renal dysfunction with FAE.

Objectives/aims

The aim of this study was to determine the number of patients in our institution being treated with FAE who developed significant proteinuria or renal dysfunction.

Methods

This was a single‐centre retrospective study assessing all patients on FAE who attended for follow‐up during an 18‐week period between February and June 2015. Demographics, comorbidities, duration and dose of treatment with FAE, proteinuria, renal function and other biochemical serum abnormalities were recorded.

Results

One hundred and twenty‐seven patients were included in the study. Eighty‐two patients had proteinuria detected at some stage during treatment with FAE, and 18 of these had persistent proteinuria (positive in at least three consecutive specimens, 12 weeks apart). Six patients (five female) developed proximal tubular dysfunction (PTD). The risk factors for the development of PTD appear to be lower bodyweight (P = 0.03), higher dose per weight (P = 0.03) and longer duration of treatment (P = 0.03). Renal dysfunction improved on discontinuation or dose reduction in FAE.

Conclusion

Fumaric acid esters are frequently associated with transient or persistent proteinuria. Significant renal dysfunction is rare and usually reversible on dose reduction or discontinuation of FAE. This study highlights the importance of screening for proteinuria. Higher doses per weight of treatment and longer duration of FAE therapy are likely risk factors for PTD.
Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: Data from the Veterans administration
Authors: Fox D Steven , McGinnis Justin J , Tonnu‐Mihara Ivy Q , McCombs Jeffrey S
Published: November 2016

Background and Aims

Data addressing real world effectiveness of direct acting antiviral agents in hepatitis C infected patients are now emerging. This study compared the sustained virologic response rates achieved 12 weeks post‐treatment in patients treated with three such agents by the Veterans Health Administration.

Methods

A retrospective cohort study was conducted using patients who terminated treatment by July 1, 2015. Data were retrieved from the Veterans Health Administration electronic medical records system. Patients were included if sufficient viral load laboratory data were available to determine sustained virologic response. Applying an intention to treat approach and logistic regression analysis, the sustained virologic response rates achieved were compared across drug regimens.

Results

A total of 11 464 patients met study selection criteria. Without controlling for other risk factors, sustained virologic response at least 12 weeks post treatment was achieved in 92% of ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and 83% of simeprevir/sofosbuvir patients. After adjusting for patient characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%) patients were statistically more likely than ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate sustained virologic response. Human immunodeficiency virus, hepatitis B infection, diabetes, obesity, previous treatment history and augmentation therapy using ribavirin did not impact sustained virologic response rates. Sustained virologic response rates were lower for patients under age 65, with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis, or a non‐genotype 1 infection. Women and Caucasian patients were more likely to achieve a sustained virologic response.

Conclusions

All three direct acting antiviral regimens appear highly effective in achieving sustained virologic response.
Peroxiredoxin‐2 up‐regulation in inflammatory bowel disease: Friend or foe?
Authors: Senhaji Nezha , Zaid Younes , El Khalfi Bouchra , Fahimi Mina , Martin Javier , Badre Wafaa , Nadifi Sellama , Soukri Abdelaziz
Published: November 2016

Background

Inflammatory bowel diseases (IBD) are chronic multi‐factorial inflammatory disorders. Accumulating investigations have provided compelling evidence that describe the interplay of a complex genetic landscape and inappropriate inflammatory response to intestinal microbes in disease etiopathogenesis but still pose challenges in diagnostic practices.

Method

In this study, comparative proteomic analysis was conducted to identify disease specific proteins underlying IBD pathogenetic mechanisms. Total blood proteins of the IBD patients and healthy subjects were analyzed with one‐dimensional electrophoresis; differentially expressed bands were excised and subjected to matrix‐assisted laser desorption ionization–time of flight mass spectrometry along with nanoflow liquid chromatography electrospray ionization‐tandem mass spectrometry analysis. Presence of glycosylation, hydroxylation, and phosphorylation post‐translational modifications was further investigated by immunoprecipitation.

Results

Peroxiredoxin‐2 (PRDX2) and hemoglobin‐subunits proteins, which are closely involved in the response to oxidative stress, were identified. PRDX2 was selected for further validation using western blot and reverse transcription–polymerase chain reaction. PRDX2 overexpression was restricted to the protein level within the membrane fraction. Immunoprecipitation identified PRDX2 to be post‐translationally glycosylated and phosphorylated.

Conclusion

Our findings demonstrate the implication of PRDX2 in IBD. Future studies are required to establish its functional role and to determine the clinical utility.
Timing of Maternal Exposure and Foetal Sex Determine the Effects of Low‐level Chemical Mixture Exposure on the Foetal Neuroendocrine System in Sheep
Authors: Bellingham M. , Fowler P. A. , MacDonald E. S. , Mandon‐Pepin B. , Cotinot C. , Rhind S. , Sharpe R. M. , Evans N. P.
Published: November 2016

We have shown that continuous maternal exposure to the complex mixture of environmental chemicals (ECs) found in human biosolids (sewage sludge), disrupts mRNA expression of genes crucial for development and long‐term regulation of hypothalamic‐pituitary gonadal (HPG) function in sheep. The present study investigated whether exposure to ECs only during preconceptional period or only during pregnancy perturbed key regulatory genes within the hypothalamus and pituitary gland and whether these effects were different from chronic (life‐long) exposure to biosolid ECs. The findings demonstrate that the timing and duration of maternal EC exposure influences the subsequent effects on the foetal neuroendocrine system in a sex‐specific manner. Maternal exposure prior to conception, or during pregnancy only, altered the expression of key foetal neuroendocrine regulatory systems such as gonadotrophin‐releasing hormone and kisspeptin to a greater extent than when maternal exposure was ‘life‐long’. Furthermore, hypothalamic gene expression was affected to a greater extent in males than in females and, following EC exposure, male foetuses expressed more ‘female‐like’ mRNA levels for some key neuroendocrine genes. This is the first study to show that ‘real‐life’ maternal exposure to low levels of a complex cocktail of chemicals prior to conception can subsequently affect the developing foetal neuroendocrine system. These findings demonstrate that the developing neuroendocrine system is sensitive to EC mixtures in a sex‐dimorphic manner likely to predispose to reproductive dysfunction in later life.
Determinants of health‐related quality of life in anti‐MAG neuropathy: a cross‐sectional multicentre European study
Authors: Delmont Emilien , Hiew Fu Liong , Cassereau Julien , Aubé‐Nathier Anne‐Catherine , Grapperon Aude‐Marie , Attarian Shahram , Rajabally Yusuf A.
Published: November 2016

Our objective was to assess determinants of quality of life (QoL) in anti‐myelin associated glycoprotein antibody (MAG) neuropathy. The SF‐36 questionnaire was assessed in 55 patients, from Marseille, Angers (France) and Birmingham (UK). Routine clinical evaluations included Medical Research Council (MRC) sum score, inflammatory neuropathy cause and treatment (INCAT) sensory score, inflammatory Rasch‐built overall disability score (I‐RODS), ataxia score, Jamar grip dynamometry, timed 10‐m walk, neuropathic pain symptom inventory (NPSI) score, and fatigue severity score (FSS). Physical component summary (PCS) and mental component summary (MCS) of the SF36 questionnaire were significantly lower than in reported normal subjects of both countries (p < 0.001). All SF‐36 domains correlated with I‐RODS, except MCS for which significance was, however, approached (p = 0.056). PCS correlated with MRC sum score, ataxia score, timed 10‐m walk, tremor, Jamar grip dynamometry, NPSI pain score, FSS and level of social support. MCS correlated exclusively with FSS and level of social support. In multivariate regression, PCS was associated independently with I‐RODS (p < 0.001) and NPSI pain score (p = 0.011), whereas MCS was associated independently with FSS (p = 0.022). QoL is accurately predicted in anti‐MAG neuropathy by the I‐RODS and FSS, lending support to their use in clinical and research settings. Effective measures to improve QoL should include tremor and neuropathic pain treatment, fatigue management, and improved social support.
Does Local Ibandronate and/or Pamidronate Delivery Enhance Osseointegration? A Systematic Review
Authors: Kellesarian Sergio Varela , Abduljabbar Tariq , Vohra Fahim , Gholamiazizi Elham , Malmstrom Hans , Romanos Georgios E. , Javed Fawad
Published: November 2016

Purpose

To our knowledge from indexed literature, the present study is the first one to systematically review the influence of local delivery of pamidronate (PAM) and/or ibandronate (IBA) on osseointegration enhancement. The aim of the present systematic review was to assess the efficacy of IBA and/or PAM local delivery (topically or coating on implants surfaces) in promoting osseointegration.

Materials and Methods

To address the focused question, “Does local IBA and/or PAM delivery enhances osseointegration?,” indexed databases were searched without time or language restrictions up to and including May 2016 using various combinations of the following keywords: “pamidronate,” “ibandronate,” “bisphosphonates,” “osseointegration,” and “topical administration.” Letters to the Editor, historic reviews, commentaries, case series, and case reports were excluded.

Results

Fifteen studies were included. Fourteen studies were performed in animals and 2 were clinical trials. One study reported an experimental model and a clinical trial in the same publication. Results from 12 experimental studies and 2 clinical studies reported improved biomechanical properties and/or osseointegration around implants with PAM and/or IBA. Two experimental studies showed that PAM and/or IBA did not improve osseointegration.

Conclusions

On experimental grounds, local IBA and/or PAM delivery seems to enhance osseointegration; however, from a clinical perspective, further randomized control trials are needed to assess the effectiveness of IBA and PAM in promoting osseointegration around dental implants.
Effect of dietary calcium level and source on mineral utilisation by piglets fed diets containing exogenous phytase
Authors: Schlegel P. , Gutzwiller A.
Published: November 2016

Calcium and phosphorus are essential minerals, closely linked in digestive processes and metabolism. With widespread use of low P diets containing exogenous phytase, the optimal dietary Ca level was verified. The 40‐day study evaluated the effects of Ca level (4, 7 and 10 g/kg diet) and Ca source (Ca from CaCO3 and from Lithothamnium calcareum) on mineral utilisation in 72 piglets (7.9 ± 1.0 kg BW) fed an exogenous phytase containing diet with 2.9 g digestible P/kg. Measured parameters were growth performance, stomach mineral solubility, bone breaking strength and urinary, serum and bone mineral concentration. The apparent total tract digestibility of minerals was also assessed in the two diets with 7 g Ca/kg, using 12 additional pigs. Regardless of Ca source, increasing dietary Ca impaired feed conversion ratio, increased urinary pH, increased serum and urinary Ca, decreased serum and urinary P, decreased serum Mg and increased urinary Mg, increased serum AP activity, decreased bone Mg increased bone Zn. Bone breaking strength was improved with 7 compared to 4 g Ca/kg. Compared to CaCO3, Ca from Lithothamnium calcareum increased serum Mg and with, 10 g Ca/kg, it limited body weight gain. The dose response of Ca in a diet with 2.9 g digestible P/kg and including exogenous phytase indicated that: (i) a low dietary Ca was beneficial for piglet growth, but was limiting the metabolic use of P; (ii) a high dietary Ca level impaired P utilisation; (iii) the optimal P utilisation and bone breaking strength was obtained with a dietary Ca‐to‐digestible P ratio of 2.1 to 2.4:1; (iv). Increasing dietary Ca reduced Mg utilisation, but not Zn status, when fed at adequate level. Finally, Ca from Lithothamnium calcareum had similar effects on Ca and P metabolism as CaCO3, but impaired growth when fed at the highest inclusion level.