bluuebunny/crossref_metadata_2025 huggingface dataset:
Diurnal variation of circulating interleukin-6 in humans: a meta-analysis
Authors: Nilsonne Gustav , Lekander Mats , Åkerstedt Torbjörn , Axelsson John , Ingre Michael
Published: March 2016

The pleiotropic cytokine interleukin-6 (IL-6) has been proposed to contribute to circadian regulation of sleepiness by increasing in the blood at night to signal for sleepiness. Earlier studies have reported diurnal variations of IL-6, but phase estimates are conflicting. We have therefore performed a meta-analysis on the diurnal variation of circulating IL-6. Studies were included if they reported circulating levels of IL-6 recorded at least twice within 24 hours in the same individual. A systematic search resulted in the inclusion of 43 studies with 56 datasets, for a total of 1100 participants. Individual participant data were available from 4 datasets with a total of 56 participants. Mixed-effects meta-regression modelling confirmed that IL-6 varied across the day, the most conspicuous effect being a trough in the morning. These results stand in contrast to earlier findings of a peak in the evening or night, and suggest that diurnal variation should be taken into account in order to avoid confounding in studies of IL-6 in plasma or serum.
Hereditary palmoplantar keratoderma “clinical and genetic differential diagnosis”
Authors: Sakiyama Tomo , Kubo Akiharu
Published: March 2016

Hereditary palmoplantar keratoderma (PPK) is a heterogeneous group of disorders characterized by hyperkeratosis of the palm and the sole skin. Hereditary PPK are divided into four groups – diffuse, focal, striate and punctate PPK – according to the clinical patterns of the hyperkeratotic lesions. Each group includes simple PPK, without associated features, and PPK with associated features, such as involvement of nails, teeth and other organs. PPK have been classified by a clinically based descriptive system. In recent years, many causative genes of PPK have been identified, which has confirmed and/or rearranged the traditional classifications. It is now important to diagnose PPK by a combination of the traditional morphological classification and genetic testing. In this review, we focus on PPK without associated features and introduce their morphological features, genetic backgrounds and new findings from the last decade.
Erythrokeratodermia variabilis et progressiva
Authors: Ishida‐Yamamoto Akemi
Published: March 2016

Erythrokeratodermia variabilis et progressiva (EKVP) is a rare inherited skin disease characterized by fixed hyperkeratotic plaques and transient erythematous patches. EKVP is most often transmitted in an autosomal dominant manner. Causal mutations were found in the GJB3, GJB4 and GJA1 genes encoding connexins 31, 30.3 and 43, respectively. Approximately 50% of affected individuals develop palmoplantar keratoderma. Connexins are components of gap junctions, which are intercellular channels that are found in almost all tissues including the skin. Treatment of EKVP usually involves use of topical keratolytics and emollients resulting in some improvement in hyperkeratosis. Low‐dose systemic retinoid may be beneficial. Novel therapies targeting connexin hemichannels and gap junctions may become available in the future.
Inherited ichthyosis: Syndromic forms
Authors: Yoneda Kozo
Published: March 2016

Among diseases that cause ichthyosis as one of the symptoms, there are some diseases that induce abnormalities in organs other than the skin. Of these, diseases with characteristic signs are regarded as syndromes. Although these syndromes are very rare, Netherton syndrome, Sjögren–Larsson syndrome, Conradi–Hünermann–Happle syndrome, Dorfman–Chanarin syndrome, ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome, and Refsum syndrome have been described in texts as representative ones. It is important to know the molecular genetics and pathomechanisms in order to establish an effective therapy and beneficial genetic counseling including a prenatal diagnosis.
Effects of environmental temperature on the gut microbial communities of tadpoles
Authors: Kohl Kevin D. , Yahn Jeremiah
Published: March 2016

Numerous studies have investigated the effects of diet, phylogeny and immune status on the gut microbial communities of animals. Most of these studies are conducted on endotherms, especially mammals, which maintain constant body temperature in the face of environmental temperature variability. However, the majority of animals and vertebrates are ectotherms, which often experience fluctuations in body temperature as a result of their environment. While there have been several studies investigating the gut microbial diversity of ectotherms, we lack an understanding of how environmental temperature affects these communities. Here, we used high‐throughput sequencing to inventory the gut microbial communities of tadpoles exposed to cool (18°C) or warm (28°C) temperature treatments. We found that temperature significantly impacted the community structure and membership of the tadpole gut. Specifically, tadpoles in the warm treatment exhibited higher abundances of the phylum Planctomycetes and the genus Mycobacterium. These results may be due to the direct effects of temperature, or mediated through changes in host physiology. Given that environmental temperatures are expected to increase due to global climate change, understanding the effects of temperature on the diversity and function of gut microbial communities is critical.
Nutrient pulses driven by internal solitary waves enhance heterotrophic bacterial growth in the South China Sea
Authors: Chen Tzong‐Yueh , Tai Jen‐Hua , Ko Chia‐Ying , Hsieh Chih‐hao , Chen Chung‐Chi , Jiao Nianzhi , Liu Hong‐Bin , Shiah Fuh‐Kwo
Published: March 2016

This study demonstrated the potential effects of internal waves (IWs) on heterotrophic bacterial activities for the first time. Nine anchored studies were conducted from 2009–2012 in the South China Sea areas with different physical conditions, i.e. areas subjected to elevation IWs, to depression IWs, and to weak/no IWs. The latter two areas were treated as the Control sites. Field survey results indicated that within the euphotic zone, the minima of the depth‐averaged bacterial production (IBP; ∼1.0 mgC m−3 d−1) and growth rate (IBμ; ∼0.1 d−1) at all sites were similar. Except for one case, the maxima of IBP (6–12 mgC m−3 d−1) and IBμ (0.55–1.13 d−1) of the elevation IWs areas were ∼fivefolds higher than those of the Control sites (IBP 1.7–2.1 mgC m−3 d−1; IBμ 0.13–0.24 d−1). Replicate surveys conducted at the north‐western area of the Dongsha atoll during spring‐to‐neap (NW1 survey) and neap‐to‐spring (NW2 survey) tide periods showed a great contrast to each other. Low variation and averages of IBμ in NW1 survey were similar to those of the Control sites, while those in NW2 were similar to the other elevation IWs sites with larger variation and higher averages of IBμ. This finding suggests that bacterial activities may be a function of the lunar fortnightly (14‐day) cycle. Enrichment experiments suggested more directly that the limiting inorganic nutrients introduced by the elevation waves (EIWs) may contribute a higher IBμ within the euphotic zone.
Esomeprazole, minocycline, metronidazole and bismuth as first‐line and second‐line regimens for Helicobacter pylori eradication
Authors: Song Zhi Qiang , Zhou Li Ya
Published: March 2016

Objective

Whether minocycline can replace tetracycline in Helicobacter pylori (H. pylori) eradication remains unclear. The aim of this study was to determine the efficacy, safety, patient compliance and risk factors of a combination regimen of esomeprazole, minocycline, metronidazole and bismuth (EMMB) for H. pylori eradication.

Methods

In this prospective single‐center study, 152 patients in the first‐line therapy group and 64 in the second‐line therapy group received EMMB therapy (esomeprazole 20 mg twice daily, minocycline 100 mg twice daily, metronidazole 400 mg four times daily and bismuth potassium citrate 110 mg four times daily) for 14 days. The eradication outcome was assessed by 13C‐urea breath test 6–12 weeks after treatment.

Results

EMMB therapy achieved eradication rates of 85.5% [95% confidence interval (CI) 79.6–91.4%] using intention‐to‐treat (ITT) analysis, 90.3% (95% CI 84.7–95.1%) using modified intention‐to‐treat (mITT) analysis and 92.6% (95% CI 88.1–96.3%) using per‐protocol (PP) analysis as the first‐line therapy; and 82.8% (95% CI 71.9–90.6%), 86.9% (95% CI 77.1–95.1%) and 89.5% (95% CI 80.7–96.5%) as the second‐line therapy, respectively. In the first‐line group, 35.6% of the patients experienced adverse effects, 4.7% discontinued medications because of adverse effects and good compliance was achieved in 91.3%, while the results were 36.5%, 3.2% and 90.5% in the second‐line therapy group. Poor compliance was identified as an independent predictor of treatment failure.

Conclusion

The efficacy of EMMB therapy for H. pylori eradication as first‐line and second‐line regimens in a region with high rates of antibiotic resistance is satisfactory with relatively good patient compliance and high safety.
Polyethylene glycol plus ascorbic acid is as effective as sodium picosulfate with magnesium citrate for bowel preparation: A randomized trial
Authors: Choi Hyun‐Seok , Chung Jun‐Won , Lee Ji Won , Lim Min Young , Park Dong Kyun , Kim Yoon Jae , Kwon Kwang Ahn , Kim Jung Ho
Published: March 2016

Objective

This study was aimed to evaluate the efficacy and safety of two low‐volume agents, polyethylene glycol (PEG)‐3350 plus ascorbic acid (PEG + Asc) and sodium picosulfate with magnesium citrate (SPMC), for bowel preparation.

Methods

We performed a prospective, endoscopist‐blinded, single‐center, randomized controlled trial comparing PEG + Asc with SPMC to evaluate the bowel cleansing efficacy of the two regimens using the modified Ottawa bowel preparation scale (OBPS) and the Aronchick scale. Patients’ taste and overall tolerance were assessed with a questionnaire.

Results

In total, 200 patients were randomized to receive either PEG + Asc (n = 98) or SPMC (n = 102). Both treatments were similarly efficacious in bowel cleansing, based on the modified OBSP (PEG + Asc 4.01 ± 2.29 vs SPMC 3.86 ± 2.47, P = 0.62) and Aronchick scale (PEG + Asc 1.96 ± 0.70 vs SPMC 1.89 ± 0.70, P = 0.42). Patient‐reported taste and tolerance of each regimen, as reported by the questionnaire, were significantly greater in the PEG + Asc group than in the SPMC group (P = 0.01). In terms of adverse events, dizziness was more frequently observed in the PEG + Asc group (P = 0.03), whereas nausea was more common in the SPMC group (P = 0.02).

Conclusions

PEG + Asc and SPMC show similar efficacy for bowel preparation. However, patient's overall tolerance is higher in the PEG + Asc group.
Finding the right coverage: the impact of coverage and sequence quality on single nucleotide polymorphism genotyping error rates
Authors: Fountain Emily D. , Pauli Jonathan N. , Reid Brendan N. , Palsbøll Per J. , Peery M. Zachariah
Published: March 2016

Restriction‐enzyme‐based sequencing methods enable the genotyping of thousands of single nucleotide polymorphism (SNP) loci in nonmodel organisms. However, in contrast to traditional genetic markers, genotyping error rates in SNPs derived from restriction‐enzyme‐based methods remain largely unknown. Here, we estimated genotyping error rates in SNPs genotyped with double digest RAD sequencing from Mendelian incompatibilities in known mother–offspring dyads of Hoffman's two‐toed sloth (Choloepus hoffmanni) across a range of coverage and sequence quality criteria, for both reference‐aligned and de novo‐assembled data sets. Genotyping error rates were more sensitive to coverage than sequence quality and low coverage yielded high error rates, particularly in de novo‐assembled data sets. For example, coverage ≥5 yielded median genotyping error rates of ≥0.03 and ≥0.11 in reference‐aligned and de novo‐assembled data sets, respectively. Genotyping error rates declined to ≤0.01 in reference‐aligned data sets with a coverage ≥30, but remained ≥0.04 in the de novo‐assembled data sets. We observed approximately 10‐ and 13‐fold declines in the number of loci sampled in the reference‐aligned and de novo‐assembled data sets when coverage was increased from ≥5 to ≥30 at quality score ≥30, respectively. Finally, we assessed the effects of genotyping coverage on a common population genetic application, parentage assignments, and showed that the proportion of incorrectly assigned maternities was relatively high at low coverage. Overall, our results suggest that the trade‐off between sample size and genotyping error rates be considered prior to building sequencing libraries, reporting genotyping error rates become standard practice, and that effects of genotyping errors on inference be evaluated in restriction‐enzyme‐based SNP studies.
Estimating fish abundance and biomass from eDNA concentrations: variability among capture methods and environmental conditions
Authors: Lacoursière‐Roussel Anaïs , Rosabal Maikel , Bernatchez Louis
Published: March 2016

Environmental DNA (eDNA) promises to ease noninvasive quantification of fish biomass or abundance, but its integration within conservation and fisheries management is currently limited by a lack of understanding of the influence of eDNA collection method and environmental conditions on eDNA concentrations in water samples. Water temperature is known to influence the metabolism of fish and consequently could strongly affect eDNA release rate. As water temperature varies in temperate regions (both seasonally and geographically), the unknown effect of water temperature on eDNA concentrations poses practical limitations on quantifying fish populations using eDNA from water samples. This study aimed to clarify how water temperature and the eDNA capture method alter the relationships between eDNA concentration and fish abundance/biomass. Water samples (1 L) were collected from 30 aquaria including triplicate of 0, 5, 10, 15 and 20 Brook Charr specimens at two different temperatures (7 °C and 14 °C). Water samples were filtered with five different types of filters. The eDNA concentration obtained by quantitative PCR (qPCR) varied significantly with fish abundance and biomass and types of filters (mixed‐design ANOVA, P < 0.001). Results also show that fish released more eDNA in warm water than in cold water and that eDNA concentration better reflects fish abundance/biomass at high temperature. From a technical standpoint, higher levels of eDNA were captured with glass fibre (GF) filters than with mixed cellulose ester (MCE) filters and support the importance of adequate filters to quantify fish abundance based on the eDNA method. This study supports the importance of including water temperature in fish abundance/biomass prediction models based on eDNA.
Bone mineral density profile among post‐menopausal women in Manipur: a hospital‐based study
Authors: Nongmaithem Romi Singh , Pertin Minggam , Chiru Chongreilen , Jotin Yengkhom
Published: March 2016

Aim

To study the bone mineral density (BMD) profile in post‐menopausal women and to examine the role of various socio‐demographic, clinical, laboratory and radiological factors in predicting fracture risk in these patients.

Methods

This cross‐sectional study recruited consenting postmenopausal women presenting with some form of pain complaints, such as joint pain, body ache, low back pain and so on. A structured questionnaire was used to collect socio‐demographic details. Height and weight were measured and BMI (body mass index) was calculated. Dual energy X‐ray absorptiometry was performed in three sites: lumbar spine (LS), femoral neck (FN) and trochanteric region (TR) to assess BMD. Serum levels of calcium, phosphorus and alkaline phosphatase were collected.

Results

There were 107 patients. Mean age was 59.70 ± 9.02 years and mean age at menopause was 46.37 ± 4.48 years. Fracture history was present in 25/107 (23.36%). Mean BMI observed was 25.34 ± 3.73. Women with fracture history had statistically significant differences in six factors, namely age, years since menopause, BMI and T‐score measurements at LS, FN and TR (P < 0.05). Multivariate logistic regression analysis for these six variables revealed that no factor was independently associated with fracture risk, but those patients who had abnormal T‐scores in all three regions had significant history of fracture (P = 0.04).

Conclusions

Age, age since menopause, BMI, and BMD T‐score measurements at LS, FN and TR individually predict fracture risk, but none remain significant when all factors are considered together. Patients with abnormal BMD T‐scores in all three sites more often gave histories of fractures. Further studies are warranted.
The effect of varicocoelectomy on the relationship of oxidative stress in peripheral and internal spermatic vein with semen parameters
Authors: Altintas R. , Ediz C. , Celik H. , Camtosun A. , Tasdemir C. , Tanbek K. , Tekin S. , Colak C. , Alan C.
Published: March 2016

The aim of this prospective controlled study was to investigate the levels of reactive oxygen species (ROS), including asymmetric dimethylarginine (ADMA), oxidative stress index (OSI) and total oxidant capacity (TOC), and antioxidants with total antioxidant capacity (TAC) in peripheral and internal spermatic veins blood, the relationship of these factors with sperm parameters in the infertile varicocoele patients, and the amelioration effect of varicocoelectomy on these outcomes. Thirty‐one primary infertile varicocoele patients and 31 fertile control patients evaluated for determining the levels of ADMA, TOC, OSI, superoxide dismutase (SOD), glutathione (GSH), TAC, and semen analysis. The patients' preoperative SOD, GSH and TAC levels, which were significantly lower than the controls, significantly increased postoperatively. Although SOD and GSH were significantly higher in spermatic vein compared to median cubital vein, TAC was significantly higher in median cubital vein. ADMA, TOC and OSI were significantly higher in the patient group. TOC and OSI were significantly higher in spermatic vein compared to median cubital vein. Postoperative TOC, OSI and ADMA reduced to the control levels. Total antioxidant capacity in the peripheral circulation and oxidative stress index in the internal spermatic vein could give an idea about the possible improvement in sperm count acquired by varicocoelectomy.
The antipsychotic story: changes in prescriptions and overdose without better safety
Authors: Berling Ingrid , Buckley Nicholas A. , Isbister Geoffrey K.
Published: March 2016

Aims

Morbidity and mortality from drug overdose has decreased over three decades. This is credited to safer drugs and therefore better outcomes in overdose. We aimed to investigate changing prescriptions of antipsychotic medications and associated changes in antipsychotic overdoses over a 26‐year period.

Methods

All antipsychotic poisoning presentations to a tertiary referral toxicology unit between 1987 and 2012 were reviewed. Data were collected prospectively on demographics, ingestion information, clinical effects, complications and treatment. Rates of antipsychotic drug use in Australia were obtained from Australian government publications for 1990–2011 and linked to overdose admissions by postcode.

Results

There were 3180 antipsychotic overdoses: 1235 first generation antipsychotics, 1695 ‘atypical’ second generation antipsychotics and 250 lithium overdoses. Over 26 years, antipsychotic overdoses increased 1.8‐fold, with first generation antipsychotics decreasing to one‐fifth of their peak (≈80/year to 16) and second generation antipsychotics increasing to double this (≈160/year), olanzapine and quetiapine accounting for 78%. All antipsychotic overdoses had a median length of stay of 18.6 h, 15.7% admitted to intensive care unit, 10.4% ventilated and 0.13% died in hospital, which was the same for first generation compared to second generation antipsychotics. There was a 2.3‐fold increase in antipsychotic prescriptions over the same period; first generation antipsychotics declined whereas there was a dramatic rise in second generation antipsychotics, mainly olanzapine, quetiapine and risperidone (79%).

Conclusion

Over 26 years there was an increase in antipsychotic prescribing associated with an increase in antipsychotic overdoses. Although the type of antipsychotics changed, the morbidity and mortality remained the same, so that antipsychotics are an increasing proportion of overdose admissions.
Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder
Authors: Samalin Ludovic , de Chazeron Ingrid , Vieta Eduard , Bellivier Frank , Llorca Pierre‐Michel
Published: March 2016

Objectives

The aims of the present study were to confirm the impact of residual symptoms on overall functioning in a large sample of euthymic patients with bipolar disorder in real‐life conditions and to explore the relationship between residual symptoms and specific areas of functional impairment.

Methods

This was a multicenter, cross‐sectional, non‐interventional study of euthymic outpatients with bipolar disorder. The Functioning Assessment Short Test was used to assess overall and specific domains of functioning (autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time). Various residual symptoms were assessed (residual mood symptoms, emotional dysregulation, sleep and sexual disorders, stigma, and perceived cognitive impairment). Logistic regression was used to determine the best model of association between functional domains and residual symptoms.

Results

Almost half of the 468 patients included (42%) had poor overall functioning. Residual depressive symptoms appeared to have an impact on overall functioning and in nearly all areas of functioning. In addition, specific residual symptoms had significantly more negative effects on some domains of functioning in euthymic patients with bipolar disorder (residual manic symptoms and occupational stigma on autonomy, emotional inhibition on occupational functioning, residual manic symptoms on financial issues, family stigma on interpersonal relationships, and sexual function and occupational stigma on leisure time).

Conclusions

Our findings highlight the importance of evaluating overall functioning in clinical practice as well as functional domains. They also indicate that some residuals symptoms in patients with bipolar disorder should be targeted in personalized treatment plans, in order to improve functioning in the domains in which the patient is most impaired.
Clinical results of ab interno trabeculotomy using the Trabectome in patients with pigmentary glaucoma compared to primary open angle glaucoma
Authors: Akil Handan , Chopra Vikas , Huang Alex , Loewen Nils , Noguchi Jonathan , Francis Brian A
Published: March 2016

Background

To evaluate outcomes of Trabectome on pigmentary glaucoma (PG) patients compared to matched controls with primary open angle glaucoma (POAG).

Design

Prospective comparison study

Participants

A total of 101 POAG cases were matched with 101 PG cases.

Methods

Data of the patients diagnosed with PG or POAG was obtained from Trabectome Study Group Database. A one‐to‐one exact matching was performed between POAG and pigmentary cases based on type of surgery, baseline IOP and baseline number of glaucoma medications. IOP and number of glaucoma medications were compared between groups by Wilcoxon test. Success was defined as IOP ≤ 21 mmHg, at least 20% IOP reduction from baseline for two consecutive visits after 3 months and no secondary surgery.

Main Outcome Measures

Success rate after Trabectome surgery in PG patients.

Results

Baseline IOP for PG is 24.4 ± 7.7 mmHg and 24.2 ± 7.5 mmHg for POAG (P = 1.0), while baseline number of glaucoma medications was 2.8 ± 1.2 mmHg for PG and 2.8 ± 1.2 mmHg for POAG (P = 1.0). Postoperative IOP values at 12 months were 17.1 ± 5.0 for PG cases and 15.9 ± 4.2 mmHg for POAG cases. Postoperative number of glaucoma medications at 12 month was 2.1 ± 1.4 in PG cases and 2.4 ± 1.3 in POAG cases. There was no statistically significant difference between groups in IOP or number of medications at any time point. Survival rate at 12 months was 92% and 86% in PG and POAG, respectively (P = 0.47). Six PG cases and nine POAG cases required secondary surgery.

Conclusion

Trabectome provides similar outcomes to PG patients and POAG patients.
Endoscopic pilonidal sinus treatment: a prospective multicentre trial
Authors: Meinero P. , Stazi A. , Carbone A. , Fasolini F. , Regusci L. , La Torre M.
Published: March 2016

Background

Pilonidal disease (PD) is a common inflammatory disease of the gluteal fold, resulting in recurrent acute/chronic infection at the level of the natal cleft. In this study, endoscopic pilonidal sinus treatment (EPSiT), a new endoscopic minimally invasive procedure, was evaluated for its effectiveness in treating PD.

Methods

Two hundred and fifty prospective patients with chronic PD were enrolled in a prospective multicentre study conducted at a secondary and tertiary colorectal surgery centre. The primary end‐point of this study was wound healing, and the short‐/long‐term outcomes such as healing time, morbidity rate and recurrence rate were analysed. The secondary end‐point of this study was quality of life (QoL).

Results

The complete wound healing rate was 94.8%, and the mean complete wound healing time was 26.7 ± 10.4 days. The incomplete healing rate (5.2%) was significantly related to the number of external openings (P = 0.01). There was no difference in the failure rate when EPSiT was performed as the first‐line treatment for PD or when it was used after unsuccessful procedures (P = n.s.). Recurrence occurred in 12 cases (5%). The QoL significantly increased from preoperative levels 15 days after the EPSiT procedure (45.3 vs 7.9; P < 0.0001).

Conclusions

The EPSiT procedure is a safe and effective technique for treating PD. It provides better short‐ and long‐term outcomes than various other techniques that are more invasive. EPSiT is a minimally invasive outpatient procedure, which is associated with a quick recovery and a good QoL outcome.
First report of Teratosphaeria gauchensis causing stem canker of Eucalyptus in Kenya
Authors: Machua J. , Jimu L. , Njuguna J. , Wingfield M. J. , Mwenje E. , Roux J.
Published: March 2016

Teratosphaeria stem canker is an important disease of Eucalyptus species in many parts of the world where these trees are intensively propagated in plantations. Symptoms similar to those of Teratosphaeria stem canker were observed on Eucalyptus grandis and a E. grandis × E. camaldulensis hybrid clone in the Central Highlands of Kenya. Symptomatic bark samples were collected from two sites and the associated fungus isolated and identified using DNA sequence analyses of multiple gene regions. The pathogen was identified as Teratosphaeria gauchensis. This represents the first report of the disease and the pathogen in Kenya.
Implementation and evaluation of a quality improvement project: carepaths for Early Psychosis Intervention Programmes in Northeastern Ontario
Authors: Bedard Terry E. , Nadin Shevaun , Zufelt Cheryl , Cheng Chiachen
Published: March 2016

Aim

This study aims to describe the implementation and evaluation of a quality improvement project, which aimed to standardize services and documentation across several district Early Psychosis Intervention Programmes in a rural region of Canada (Northeastern Ontario).

Method

A Carepath for early psychosis intervention (EPI), which outlined best practice EPI care pathways, was implemented across 12 EPI programme sites. It was hypothesized that the proportion of best practice interventions provided across the district programmes would increase after the implementation of the Carepath initiative and that documentation would be standardized. Pre‐Carepath and post‐Carepath chart audits evaluated the provision and documentation of EPI best practices that were specified in the Carepath.

Results

Pre‐audits and post‐audits were completed on 110 and 108 client files, respectively. Chi‐squared tests revealed that the post‐audit frequencies were significantly higher than the pre‐audit frequencies for two of the 12 EPI best practices that were evaluated (i.e. assessed impact on family and assessment of substance use). Standardization of documentation did not improve significantly.

Conclusions

The results are discussed in the context of barriers to implementing and evaluating the Carepaths. Various individual and agency level barriers are identified (e.g. staff resistance, resources and agency documentation parameters), and strategies to overcome them are discussed. It is concluded that, despite barriers to implementation and evaluation, Carepaths can be a useful tool for standardizing services and documentation across a network of EPI programmes and guiding programme evaluation and quality assurance.
Evaluation of a mobile team dedicated to behavioural disorders as recommended by the Alzheimer Cooperative Valuation in Europe joint action: observational cohort study
Authors: Krolak‐Salmon P. , Roubaud C. , Finne‐Soveri H. , Riolacci‐Dhoyen N. , Richard G. , Rouch I. , Leperre‐Desplanques A. , Dauphinot V.
Published: March 2016

Background and purpose

Preventing behavioural crises appears to be crucial to promote quality of life of the patient−caregiver dyad, to reduce inappropriate hospitalizations and to delay institutionalization. The Alzheimer Cooperative Valuation in Europe promotes mobile care to prevent patients from severe behavioural and psychological symptoms in dementia. This study assessed the potential efficacy of a mobile team for Alzheimer's disease on hospitalization sparing and behavioural disorder reduction.

Methods

A cohort study was set up from 1 January 2012 to 31 December 2013 by the Clinical and Research Memory Centre of Lyon (France). It included patients with behavioural and psychological symptoms living at home or in a nursing home. An interview explored the alternative patient pathways used by general practitioners (GPs) if the mobile team had not existed (hospitalization sparing). The Neuropsychiatry Inventory score was assessed at inclusion and 30 days later. The sample included 424 consecutive patients with Alzheimer's disease or related disorders and behavioural disorders at any cognitive and functional stage of the disease, taken in charge by the mobile team.

Results

Amongst the 424 patients (84.0 ± 7.2 years), 220 (51.9%) hospitalizations were considered by their GPs and 181 (82.3%) were avoided. The Neuropsychiatric Inventory score declined after mobile team intervention (45.8–29.9, P < 0.001). Sleep and appetite disorders, endangered situation and caregiver burnout were associated with higher risk of hospitalization at 30 days.

Conclusions

The mobile team for Alzheimer's disease allows a high proportion of hospitalizations related to behavioural disorders to be avoided and may help to reduce behavioural disorders.
Abnormal cognitive network interactions in Lennox‐Gastaut syndrome: A potential mechanism of epileptic encephalopathy
Authors: Warren Aaron E. L. , Abbott David F. , Vaughan David N. , Jackson Graeme D. , Archer John S.
Published: March 2016

Objective

In patients with Lennox‐Gastaut syndrome (LGS), recurrent epileptic activity is thought to contribute to impaired cognition (epileptic encephalopathy). Using concurrent electroencephalography‐functional magnetic resonance imaging (EEG‐fMRI), we recently showed that epileptiform discharges inLGSrecruit large‐scale networks that normally support key cognitive processes. InLGS, given that epileptic activity engages cognitive networks, and cognition is pervasively impaired, we hypothesized that cognitive network interactions inLGSare persistently abnormal.

Methods

We studied 15LGSpatients (mean age ± 1 standard deviation [SD] = 28.7 ± 10.6 years) and 17 healthy controls (mean age ± 1 SD = 27.6 ± 6.6 years) using task‐freeEEG‐fMRI. Four networks of interest (default‐mode, dorsal attention, executive control, and anterior salience) were defined using group‐level independent components analysis (ICA). Functional connectivity within and between networks was determined for each subject, and thenLGSnetwork interactions were compared to network behavior in the control group. To test whether group differences were present in periods without scalp‐detectable epileptiform discharges (i.e., persistent), we separately assessed discharge‐affected and discharge‐unaffected epochs in six patients with sufficient data for this analysis.

Results

InLGS, cognitive networks showed (1) reduced within‐network integration, including weaker connectivity within the default‐mode network, and (2) impaired between‐network segregation, including stronger connectivity between the default‐mode and dorsal attention networks. Abnormal interactions were present duringfMRIperiods with and without discharges, indicating that impaired network behavior may endure during periods without scalp‐detectable epileptic activity.

Significance

InLGS, cognitive network interactions are persistently abnormal. Given that cognition typically worsens with the onset ofLGS, and may improve after seizure control, our findings are consistent with the hypothesis that the epileptic process inLGSmay initiate and perhaps sustain abnormal network behavior. We propose that epileptic encephalopathy may be a consequence of persistently disrupted cognitive network interactions.
Targeting of microRNA‐199a‐5p protects against pilocarpine‐induced status epilepticus and seizure damage via SIRT1‐p53 cascade
Authors: Wang Dong , Li Zhenlu , Zhang Yukun , Wang Guangzhi , Wei Minghai , Hu Yan , Ma Shuo , Jiang Yue , Che Ningwei , Wang Xiaofeng , Yao Jihong , Yin Jian
Published: March 2016

Objective

MicroRNAs (miRNAs) are noncoding small RNAs that control gene expression at the posttranscriptional level. Some dysregulated miRNAs have been shown to play important roles in epileptogenesis. The aim of this study was to determine if miR‐199a‐5p regulates seizures and seizure damage by targeting the antiapoptotic protein silent information regulator 1 (SIRT1).

Methods

Hippocampal expression levels of miR‐199a‐5p, SIRT1, and acetylated p53 were quantified by quantitative real‐time polymerase chain reaction (RT‐PCR) and Western blotting in the acute, latent, and chronic stages of epilepsy in a rat lithium‐pilocarpine epilepsy model. Silencing of miR‐199a‐5p expression in vivo was achieved by intracerebroventricular injection of antagomirs. The effects of targeting miR‐199a‐5p and SIRT1 protein on seizure and epileptic damage post‐status epilepticus were assessed by electroencephalography (EEG) and immunohistochemistry, respectively.

Results

miR‐199a‐5p expression was up‐regulated, SIRT1 levels were decreased, and neuron loss and apoptosis were induced in epilepsy model rats compared with normal controls, as determined by up‐regulation of acetylated p53 and cleaved caspase‐3 expression. In vivo knockdown of miR‐199a‐5p by an antagomir alleviated the seizure‐like EEG findings and protected against neuron damage, in accordance with up‐regulation of SIRT1 and subsequent deacetylation of p53. Furthermore, the seizure‐suppressing effect of the antagomir was partly SIRT1 dependent.

Significance

The results of this study suggest that silencing of miR‐199a‐5p exerts a seizure‐suppressing effect in rats, and that SIRT1 is a direct target of miR‐199a‐5p in the hippocampus. The effect of miR‐199a‐5p on seizures and seizure damage is mediated via down‐regulation of SIRT1. The miR‐199a‐5p/SIRT1 pathway may thus represent a potential target for the prevention and treatment of epilepsy and epileptic damage.
Allyl‐isatin suppresses cell viability, induces cell cycle arrest, and promotes cell apoptosis in hepatocellular carcinoma HepG2 cells
Authors: Bian Weihua , An Yukuan , Qu Huiqing , Yang Yue , Yang Junhou , Xu Yanyan
Published: March 2016

The anticancer effect of the newly synthesized isatin derivative, N‐allyl‐isatin (Allyl‐I), was evaluated in vitro with human hepatocellular carcinoma HepG2 cells. Cell viability was detected by cell counting kit‐8 (CCK8) assay. Acridine orange (AO)/ethidium bromide (EB) double staining was used to observe the cell morphology. Flow cytometry was used to assess the effects of Allyl‐I on the cell cycle, apoptosis rate, and mitochondrial membrane potential (MMP). Western blot analysis was performed to detect the influence of Ally1‐I on the expression of cytochrome c (cyt c), Bax, Bcl‐2, and cleaved caspase‐3. Allyl‐I significantly inhibited HepG2 cell viability in a time‐ and dose‐dependent manner. Allyl‐I can induce cell cycle arrest in HepG2 cells at the G2/M phase. Apoptotic nuclear morphological changes were observed after AO/EB double staining. Fluorescein isothiocyanate‐conjugated Annexin V (Annexin V‐FITC) and propidium iodide (PI) double staining showed that the apoptotic rates significantly increased in the presence of Allyl‐I. Rhodamine 123 staining indicated that Allyl‐I can decrease the MMP. Allyl‐I also altered the expression of mitochondrial apoptosis‐related proteins. Protein levels of cyt c and cleaved caspase‐3 were upregulated following Allyl‐I treatment. By contrast, the Bcl‐2/Bax ratio decreased. Results suggest that Allyl‐I suppresses cell viability, induces cell cycle arrest, and promotes cell apoptosis in HepG2 cells. Furthermore, the induction of apoptosis might be correlated with the mitochondrial pathway.
Sevoflurane anesthesia induces neither contextual fear memory impairment nor alterations in local population connectivity of medial prefrontal cortex local field potentials networks in aged rats
Authors: Xu Xinyu , Zhang Qian , Tian Xin , Wang Guolin
Published: March 2016

Sevoflurane has been found to increase apoptosis and pathologic markers associated with Alzheimer disease, provoking concern over their potential contribution to postoperative cognitive dysfunction. This study aimed to determine the effects of sevoflurane on contextual fear memory of aged rats and to characterize local population connectivity of local field potentials (LFPs) in medial prefrontal cortex (mPFC) of aged rats during contextual fear memory. Eighteen‐month‐old male SD rats were implanted with one multichannel electrode array in mPFC. The aged rats were divided into control group, sevoflurane group (1 MAC sevoflurane for 2 h) and surgical group with 1.0 MAC sevoflurane for 2 h. We then assessed the effect of the anesthesia on contextual fear memory, and alterations in the local population connectivity of mPFC LFP networks by partial directed coherence (PDC). Surgery impaired contextual fear memory and reduced local population connectivity of mPFC LFP networks in aged rats at day 1 after the surgery and anesthesia. 1 MAC Sevoflurane anesthesia induced neither contextual fear memory impairment nor alterations in local population connectivity of mPFC LFP networks in aged rats when tested 1, 7, 15 and 30 days after exposure (P > 0.05). PDC values of theta band mPFC LFPs became strongly increased during contextual fear memory at 1, 7, 15, and 30 days after anesthesia. Our results suggest that 1 MAC sevoflurane anesthesia does not induce contextual fear memory impairment in aged rats and suggest that the increased local population connectivity in theta bands LFPs of mPFC plays a role in contextual fear memory.
Structural characterization of the C‐terminal coiled‐coil domains of wild‐type and kidney disease‐associated mutants of apolipoprotein L1
Authors: Sharma Alok K. , Friedman David J. , Pollak Martin R. , Alper Seth L.
Published: March 2016

Trypanosomes that cause sleeping sickness endocytose apolipoprotein L1 (APOL1)‐containing trypanolytic factors from human serum, leading to trypanolytic death through generation of APOL1‐associated lytic pores in trypanosomal membranes. The trypanosome Trypanosoma brucei rhodesiense counteracts trypanolysis by expressing the surface protein serum response‐associated (SRA), which can bind APOL1 common variant G0 to block its trypanolytic activity. However, two missense variants in the C terminal predicted coiled‐coil (CC) domains of human APOL1 G1 (S342G/I384M) and G2 (ΔN388Y389) decrease or abrogate APOL1 binding to T. brucei rhodesiense SRA, thus preserving APOL1 trypanolytic activity. These evolutionarily selected APOL1 missense variants, found at a high frequency in some populations of African descent, also confer elevated risk of kidney disease. Understanding the SRA–APOL1 interaction and the role of APOL1 G1 and G2 variants in kidney disease demands structural characterization of the APOL1 CC domain. Using CD, heteronuclear NMR, and molecular dynamics (MD) simulation on structural homology models, we report here unique and dynamic solution conformations of nephropathy variants G1 and G2 as compared with the common variant G0. Conformational plasticity in G1 and G2 CC domains led to interhelical α1–α2 approximation coupled with secondary structural changes and delimited motional properties absent in the G0 CC domain. The G1 substitutions conferred local structural changes principally along helix α1, whereas the G2 deletion altered the structure of both helix α2 and helix α1. These dynamic features of APOL1 CC variants likely reflect their intrinsic structural properties, and should help interpret future APOL1 structural studies and define the contribution of APOL1 risk variants to kidney disease.
Using models to guide field experiments: a priori predictions for the CO2 response of a nutrient‐ and water‐limited native Eucalypt woodland
Authors: Medlyn Belinda E. , De Kauwe Martin G. , Zaehle Sönke , Walker Anthony P. , Duursma Remko A. , Luus Kristina , Mishurov Mikhail , Pak Bernard , Smith Benjamin , Wang Ying‐Ping , Yang Xiaojuan , Crous Kristine Y. , Drake John E. , Gimeno Teresa E. , Macdonald Catriona A. , Norby Richard J. , Power Sally A. , Tjoelker Mark G. , Ellsworth David S.
Published: March 2016

The response of terrestrial ecosystems to rising atmospheric CO2 concentration (Ca), particularly under nutrient‐limited conditions, is a major uncertainty in Earth System models. The Eucalyptus Free‐Air CO2 Enrichment (EucFACE) experiment, recently established in a nutrient‐ and water‐limited woodland presents a unique opportunity to address this uncertainty, but can best do so if key model uncertainties have been identified in advance. We applied seven vegetation models, which have previously been comprehensively assessed against earlier forest FACE experiments, to simulate a priori possible outcomes from EucFACE. Our goals were to provide quantitative projections against which to evaluate data as they are collected, and to identify key measurements that should be made in the experiment to allow discrimination among alternative model assumptions in a postexperiment model intercomparison. Simulated responses of annual net primary productivity (NPP) to elevated Ca ranged from 0.5 to 25% across models. The simulated reduction of NPP during a low‐rainfall year also varied widely, from 24 to 70%. Key processes where assumptions caused disagreement among models included nutrient limitations to growth; feedbacks to nutrient uptake; autotrophic respiration; and the impact of low soil moisture availability on plant processes. Knowledge of the causes of variation among models is now guiding data collection in the experiment, with the expectation that the experimental data can optimally inform future model improvements.
Stress‐dependent transport properties of fractured arkosic sandstone
Authors: French M. E. , Chester F. M. , Chester J. S. , Wilson J. E.
Published: March 2016

We measure the fluid transport properties of microfractures and macrofractures in low‐porosity polyphase sandstone and investigate the controls of in situ stress state on fluid flow conduits in fractured rock. For this study, the permeability and porosity of the Punchbowl Formation sandstone, a hydrothermally altered arkosic sandstone, were measured and mapped in stress space under intact, microfractured, and macrofractured deformation states. In contrast to crystalline and other sedimentary rocks, the distributed intragranular and grain‐boundary microfracturing that precedes macroscopic fracture formation has little effect on the fluid transport properties. The permeability and porosity of microfractured and intact sandstone depend strongly on mean stress and are relatively insensitive to differential stress and proximity to the frictional sliding envelope. Porosity variations occur by elastic pore closure with intergranular sliding and pore collapse caused by microfracturing along weakly cemented grain contacts. The macroscopic fractured samples are best described as a two‐component system consisting (i) a tabular fracture with a 0.5‐mm‐thick gouge zone bounded by 1 mm thick zones of concentrated transgranular and intragranular microfractures and (ii) damaged sandstone. Using bulk porosity and permeability measurements and finite element methods models, we show that the tabular fracture is at least two orders of magnitude more permeable than the host rock at mean stresses up to 90 MPa. Further, we show that the tabular fracture zone dilates as the stress state approaches the friction envelope resulting in up to a three order of magnitude increase in fracture permeability. These results indicate that the enhanced and stress‐sensitive permeability in fault damage zones and sedimentary basins composed of arkosic sandstones will be controlled by the distribution of macroscopic fractures rather than microfractures.
Recurrence and prognosis of patients emergently hospitalized for acute esophageal variceal bleeding: A long‐term cohort study
Authors: Cho Hourin , Nagata Naoyoshi , Shimbo Takuro , Sakurai Toshiyuki , Sekine Katsunori , Okubo Hidetaka , Imbe Koh , Watanabe Kazuhiro , Mikami Shintaro , Yokoi Chizu , Kobayakawa Masao , Mizokami Masashi , Yanase Mikio , Akiyama Junichi , Uemura Naomi
Published: March 2016

Aim

To elucidate the rates of recurrence and mortality in acute esophageal variceal bleeding and the associated risk factors.

Methods

A cohort of 174 patients emergently hospitalized for esophageal variceal bleeding was analyzed. All patients underwent endoscopic variceal ligation within 3 h of arrival. Comorbidities, vital signs, drug use, laboratory data, etiology, endoscopic findings, transfusion requirement, and follow‐up endoscopy were assessed. Cox's proportional hazards model was used to estimate hazard ratios (HR).

Results

Rebleeding was identified in 49 patients with a mean follow‐up of 18 months. The cumulative rebleeding rate at 1 month, 1 year, and 5 years was 10.2%, 30.0%, and 51.0%, respectively. In multivariate analysis, independent risk factors for rebleeding were child‐Pugh class C (HR 1.94; P = 0.027), alcoholic liver cirrhosis (HR 2.32; P = 0.01), and no follow‐up endoscopy (HR 13.3; P < 0.001). During the overall mean follow‐up of 22 months, 69 patients died (17 due to bleeding), and the cumulative mortality rate at 1 month, 1 year, and 5 years was 12.2%, 26.6%, and 63.0%, respectively. In multivariate analysis, independent risk factors for mortality were child‐Pugh class C (HR 2.91; P < 0.001), coexistence of hepatocellular carcinoma (HR 1.92; P = 0.013), and no follow‐up endoscopy (HR 23.6; P < 0.001).

Conclusion

This study revealed more than 50% cumulative rebleeding and mortality in the 5‐year period after endoscopic variceal ligation for esophageal variceal bleeding in an emergency setting. Child–Pugh C, alcoholic liver cirrhosis, and no follow‐up endoscopy increased the risk of rebleeding; Child–Pugh C, coexistence of hepatocellular carcinoma, and no follow‐up endoscopy increased the risk of mortality.