bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxychloroquine sulphate therapy of erosive oral lichen planus
Authors: Yeshurun Algit , Bergman Reuven , Bathish Naji , Khamaysi Ziad
Published: November 2018

Background/Objectives

Erosive oral lichen planus (LP) may be painful and debilitating. Symptomatic oral LP has been treated with a wide spectrum of topical and systemic therapies, but few have been evaluated in large series. Hydroxychloroquine is suggested to be effective in oral LP.

Methods

Twenty‐one consecutive patients with erosive, biopsy‐confirmed oral LP were prescribed. hydroxychloroquine sulphate 400 mg/day. Symptomatic improvement was evaluated by means of a visual analogue scale into three groups: no change, moderate to marked improvement and complete remission.

Results

Five (24%) patients obtained complete remission, 12 (57%) patients showed moderate to marked improvement, 3 (14%) patients did not improve at all and in one patient therapy was terminated after 1 month due to side effects. Response to therapy was observed after 2–4 months. Side effects which ultimately led to termination of therapy in three patients were elevated creatinine serum levels (after 1 month), visual field defects (after 8 months) and hyperpigmentation (after 24 months). Among six patients who responded to therapy, three flared on stopping.

Conclusions

Hydroxychloroquine sulphate may be effective and relatively safe treatment for erosive oral LP.
Clinical and financial evaluation of carbetocin as postpartum haemorrhage prophylaxis at caesarean section: A retrospective cohort study
Authors: Wohling Jemma , Edge Nicole , Pena‐Leal David , Wang Rui , Mol Ben Willem , Dekker Gustaaf
Published: November 2018

Background

The long‐acting oxytocic agent; carbetocin, has been consistently shown to reduce the need for additional uterotonics at caesarean section, but not postpartum haemorrhage (PPH). While promising, current evidence is limited by heterogenicity in study design and findings.

Aims

To examine whether carbetocin confers clinical or economic benefit compared to oxytocin at caesarean section in an all‐risk Australian population.

Materials and Methods

A retrospective cohort study was undertaken of all singleton caesarean sections at a public tertiary hospital from 2008 to 2010 (n = 2499). From 1 January 2008 to 24 March 2009 all women received prophylactic oxytocin 5–10 units slow push intravenously at delivery, after which all patients received 100 μg intravenous carbetocin. Outcomes were PPH (≥1000 mL) and the requirement of secondary uterotonics. A post hoc cost analysis was also performed.

Results

A total of 1467 and 1024 patients received carbetocin and oxytocin, respectively. Incidence of PPH ≥1000 mL was 7.8% for carbetocin compared to and 9.7% for oxytocin (odds ratio (OR) 0.79, 95% CI 0.59–1.05). Moderate blood loss >500 mL was significantly reduced with carbetocin; occurring in 27.3% versus 39.4% (OR 0.57, 95% CI 0.49–0.68). There was a 20.0% reduction in secondary uterotonic treatment with carbetocin (OR 0.42, 95% CI 0.35–0.49). Average drug costs were lower with oxytocin at $4.74 versus $36.42/patient. However, the 1.9% reduction in PPH with carbetocin resulted in a $63.46 reduction in cost per patient, with a cost‐effectiveness ratio of $1667 to prevent one case of PPH ≥1000 mL.

Conclusions

Carbetocin reduced moderate blood loss >500 mL, but not PPH ≥1000 mL. Carbetocin conferred a 20% reduction in secondary uterotonic treatment, as well as lowering direct medical costs.
Maternal smoking during pregnancy and the risk of strabismus in offspring: a meta‐analysis
Authors: Yang Yudi , Wang Chao , Gan Yong , Jiang Heng , Fu Wenning , Cao Shiyi , Lu Zuxun
Published: November 2018

The effect of maternal smoking during pregnancy on strabismus in offspring remains unclear. We conducted a meta‐analysis to summarize epidemiological evidences on the association between maternal smoking during pregnancy and the risk of offspring strabismus. Eligible studies were searched from the PubMed, Ovid, Embase and CNKI databases up to May 2018. The qualities of included articles were assessed with the Newcastle–Ottawa Scale and the assessment scale recommended by the Agency for Healthcare Research and Quality. Odds ratios (ORs) corresponding with its 95% confidence intervals (CIs) were pooled to estimate the effects of maternal cigarette smoking on the risk of offspring strabismus. Subgroup analyses and meta‐regression were performed to explore the potential sources of heterogeneity. The Begg's test and Egger's test were used to assess the publication bias. Eleven articles involving 4,833 patients with strabismus were included. The pooled OR showed that maternal smoking during pregnancy was significantly associated with strabismus in offspring (OR = 1.46, 95% CI = 1.32–1.60). Compared with less than 10 cigarettes per day (OR = 1.17, 95% CI = 1.06–1.29), maternal smoking 10 cigarettes or more per day during pregnancy significantly increased the risk of offspring strabismus (OR = 1.79, 95% CI = 1.39–2.31). The risk of developing esotropia and exotropia for smoking pregnant women, respectively, increased by 65% (OR = 1.65, 95% CI = 1.31–2.09 and OR = 1.65, 95% CI = 1.24–2.19) than those who did not smoke during pregnancy. Additionally, the increased risk of maternity smoking associated with offspring strabismus was stable across all subgroup analyses. Overall, maternal smoking during pregnancy was associated with a significantly increased risk of offspring strabismus and the result was persistent in subgroup analyses, suggesting the importance in changing smoking habit or smoking cessation for women who are pregnant or preparing to.
Vertical and horizontal mismatches and career mobility: evidence from female college graduates
Authors: Park Kihong
Published: November 2018

Using panel data from the 2010 Graduates Occupational Mobility Survey, this paper estimates the incidence and impact of horizontal and vertical mismatches on labour mobility among Korean female college graduates at the early stages of their careers. Unlike most previous studies, this study proposes three types of educational mismatch status: (1) vertically mismatched only; (2) horizontally mismatched only; and (3) both vertically and horizontally mismatched. The findings show that the share of educationally mismatched workers is non‐negligible in the Korean labour market (approximately 30 per cent). However, the data also points to an improvement in job matching over time. Regardless of the type of educational mismatch, the results provide evidence consistent with many previous studies: educational mismatch is significantly and positively associated with job turnover. In particular, vertically and horizontally mismatched workers are more likely to switch jobs than their vertically or horizontally mismatched counterparts. These findings indicate that educationally mismatched graduates are more likely to change jobs—suggesting that educational mismatch can be viewed as an investment in human capital at the beginning of a career.
Systematic review: the consequences of psychosocial effects of inflammatory bowel disease on patients′ reproductive health
Authors: Purewal Satvinder , Chapman Sarah , Czuber‐Dochan Wladyslawa , Selinger Christian , Steed Helen , Brookes Matthew J.
Published: November 2018

Background

High levels of voluntary childlessness and pregnancy‐related fears have been reported amongst inflammatory bowel disease (IBD) patients.

Aims

To investigate what factors determine IBD patients’ childbearing decisions; and to examine psychosocial consequences of IBD on various aspects of patients' reproductive health.

Methods

Six electronic databases were searched in a pre‐specified and structured manner.

Results

A total of 41 articles with data on 7122 patients were included. Between one‐fifth to one‐third of IBD patients had chosen voluntary childlessness. Around 50% of all IBD patients have poor knowledge of pregnancy‐related issues in IBD. Poor knowledge of pregnancy‐related issues in IBD was associated with voluntary childlessness. Observational studies have found preconception counselling is associated with patients choosing parenthood. Pregnancy‐related fears and concerns are multifaceted, stemming partly from lack of knowledge of pregnancy‐related issues in IBD. Many female patients are considered at increased risk for pregnancy because between one‐fifth to one‐third of patients do not use contraception. Research evidence for sexual dysfunction after disease diagnosis and treatment is inconsistent. There are limited data on patients’ pregnancy, postpartum and parenting experiences. A few shortcomings of the literature are evident; sample sizes were small, participation rates were low, use of non‐validated questionnaires was common, and few studies included men and/or ethnic minority groups. The design of intervention studies is also weak.

Conclusion

This review recommends pre‐conception counselling for all IBD patients of childbearing age to tackle poor knowledge and allow patients to make an informed decision on their reproductive health.
Operative outcomes after laparoscopic splenectomy with special reference to prophylactic antibiotics
Authors: Matsuda Tsunemi , Kubo Shoji , Ueno Masaki , Takifuji Katsunari , Yamaue Hiroki , Takemura Shigekazu , Tanaka Shogo , Shinkawa Hiroji , Yamada Koichi , Kakeya Hiroshi
Published: November 2018

Introduction

We conducted a retrospective study to investigate the progress of the operative outcome after laparoscopic splenectomy (LS), with a special reference to the administration of prophylactic antibiotics (PA).

Methods

The study included 123 patients who underwent elective LS. Operative outcomes before and after the operative procedure was standardized and the impact of treatment with PA on surgical‐site infection were investigated.

Results

With regard to complications, wound infection developed in one (0.8%), portal trunk thrombosis in one (0.8%), pancreatic fistula in one (0.8%), postoperative bleeding in two (1.6%), pleural effusion in one (0.8%), and reoperation because of bowel injury in one (0.8%). Although morbidity did not differ between patients in the early (until the end of 2010) and late (after the beginning of 2011) periods, intraoperative blood loss was lower in patients in the late period. During the late period, no patients required conversion to open surgery. The proportion of patients with surgical‐site infection did not differ between those who received PA 1 h before the start of surgery and every 3 h during surgery and those who received PA 1 h before the start of surgery, every 3 h during surgery, and twice a day for 24–72 h after surgery.

Conclusion

Operative outcomes after LS improved after the standardization of the operative procedure. The administration of PA 1 h before surgery and every 3 h during surgery seems to be sufficient to prevent surgical‐site infection during LS.
Microvascular anatomy of testes in the adult pipid frog, Xenopus laevis Daudin: A scanning electron microscopic study of vascular corrosion casts
Authors: Lametschwandtner Alois , Minnich Bernd
Published: November 2018

The three‐dimensional microvascular anatomy of the testes of adult Xenopus laevis was studied by scanning electron microscopy of vascular corrosion casts. Results showed that testicular arteries branch off from urogenital arteries and approach the testes via the mesorchium. At the dorsal surface of testes, arteries course towards the medial and lateral surfaces of the ovoid testes, pierce the tunica albuginea and run in the subalbugineal space and then penetrate the testicular parenchyma. In the parenchyma, they branch in all directions. At sites where larger branches arise, sphincters are present. Intimal cushions are found at the origin of smaller branches. Terminal arterioles capillarize and form a wide‐meshed capillary network around convoluted seminiferous tubules. Inter‐ and peritubular capillaries cannot be differentiated reliably. Arterio‐venous transition distances are short. Arterio‐arterial anastomoses and veno‐venous anastomoses are present. Testicular venules empty into a venous subalbugineal plexus which shows veno‐venous anastomoses of different lengths and calibres. Signs of the ongoing non‐sprouting angiogenesis, particularly intussusceptive branch remodelling, reflect the dynamics of the testicular parenchyma. The present study is the first that demonstrates the testicular microvascular anatomy in an anuran species and shows that X. laevis and men share the intricate convoluted seminiferous tubules with associated vascular patterns as a feature in common.
Maternity care hospital trends in providing postdischarge breastfeeding supports to new mothers—United States, 2007‐2015
Authors: Beauregard Jennifer L. , Nelson Jennifer M. , Hamner Heather C.
Published: November 2018

Background

Hospitals that provide maternity care can play an important role in providing or directing mothers to postdischarge breastfeeding support, which improves breastfeeding duration especially when providing multiple support modes. This study described 2007‐2015 national trends in postdischarge breastfeeding supports among United States maternity care hospitals.

Methods

Data were from the Maternity Practices in Infant Nutrition and Care survey, a biennial census of maternity care hospitals in the United States and territories. Hospitals reported whether they provided nine support types, which we categorized into three support modes: physical contact (eg, return visits), active reaching out (eg, telephone calls), and referrals (eg, to lactation consultants). We calculated prevalence of each support type, each support mode, and providing all three support modes for each survey year and examined trends over 2007‐2015. For 2015, we assessed differences by hospital‐ and area‐level characteristics.

Results

Prevalence of providing all three support modes increased from 24% (2007) to 31% (2015). Nearly all (99%) hospitals provided referrals in each survey year. Fewer offered physical contact and active reaching out. However, from 2007 to 2015, the prevalence of physical contact increased from 39% to 46%; active reaching out increased from 54% to 64%. In 2015, smaller and rural hospitals were more likely to provide all three discharge supports.

Conclusions

Prevalence of offering referrals was high, but there is room for improvement in providing physical contact and active reaching out to ensure multiple modes of support are available to help mothers reach their breastfeeding goals.
Clinical and radiographic peri‐implant variables around short dental implants in type 2 diabetic, prediabetic, and non‐diabetic patients
Authors: Mokeem Sameer , Alfadda Sara Abdulaziz , Al‐Shibani Nouf , Alrabiah Mohammed , Al‐Hamdan Rana Sulaiman , Vohra Fahim , Abduljabbar Tariq
Published: November 2018

Background

Clinical and radiographic status around short dental implants in patients with different glycemic levels remains unexplored.

Purpose

To determine the clinical and radiographic bone level (RBL) around short dental implants in type‐2 diabetes mellitus (T2DM), prediabetic, and non‐diabetic patients.

Materials and Methods

Participants were grouped into three groups based on HbA1c levels: T2DM (Group‐1); prediabetic patients (Group‐2); and non‐diabetic subjects (Group‐3). Clinical recordings included the assessment of peri‐implant plaque index (PI), bleeding on probing (BOP), probing depth (PD). Radiographic analysis included evaluation of standardized periapical digital radiographs using specialized software and image analyzer.

Results

Clinical peri‐implant parameters including PI and BOP were statistically significantly higher in group‐1 (P < .01) and group 2 (P < .05) as compared to group‐3. Mean PD was statistically significantly higher in group‐1 patients compared to group‐3 (P < .01). Radiographic bone loss was significantly higher in both group‐1 (P < .01) and group‐2 (P < .05) patients as compared to patients in group 3. RBL showed statistically significant difference among T2DM patients even after adjusting for HbA1c, total cholesterol, and body mass index (P < .05) and statistically significant difference in prediabetic patients after adjusting for only HbA1c (P < .05).

Conclusion

Clinical and radiographic peri‐implant parameters are compromised around short dental implants in type‐2 diabetes mellitus patients. Further longitudinal studies are needed to compare clinical performance of short dental implants with standard dental implants placed in patients with different glycemic level.
Oncological outcomes before and after the extralevator abdominoperineal excision era in rectal cancer patients treated with abdominoperineal excision in a single centre, high volume unit
Authors: Lehtonen T. , Räsänen M. , Carpelan‐Holmström M. , Lepistö A.
Published: November 2018

Aim

The extralevator abdominoperineal excision (ELAPE) has been expected to reduce the risk of positive circumferential resection margins (CRMs) and local recurrence in locally advanced distal rectal cancer. The aim was to determine whether there is any difference in local recurrence rates between patients who were operated on for distal rectal cancer before and after the introduction of ELAPE in our unit.

Patients and methods

In all, 206 patients with distal rectal cancer without distant metastases (T1‐4N0‐2M0) were treated with curative intent. The patients were divided into two cohorts operated in 2000–2007 (A) and 2008–2014 (B). The ELAPE procedure was introduced in 2008. Since then, it has been used in cases of T4 and T3 tumours with threatened margins. In T1–T3 tumours without threatened margins a conventional abdominal perineal excision has been performed.

Results

There was no significant difference in overall survival or cancer‐specific survival between the two time periods. The local recurrence rate was 15.5% in group A and 6.7% in group B (P = 0.048), although there was no significant difference in the cumulative local recurrence rate. Intra‐operative tumour perforation occurred significantly more often during the earlier period when ELAPE was not in use: group A 15/71 (21.1%) vs group B 11/135 (8.1%), P = 0.01. CRM was positive more often in group A (16.4%) vs group B (7.4%), P = 0.054.

Conclusion

The local recurrence rate, intra‐operative tumour perforation and positive CRM rate were significantly lower during the later period when more extensive surgery (ELAPE) was performed for locally advanced T3–T4 rectal cancer with threatened margins.
High risk of permanent stoma after anastomotic leakage in anterior resection for rectal cancer
Authors: Jutesten H. , Draus J. , Frey J. , Neovius G. , Lindmark G. , Buchwald P. , Lydrup M. L.
Published: November 2018

Aim

This study investigates how often bowel continuity was restored after anastomotic leakage in anterior resection for rectal cancer and assesses the clinical factors associated with permanent stoma.

Method

The Swedish Colorectal Cancer Registry was used to identify cases of anastomotic leakage registered in southern Sweden between January 2001 and December 2011. Patient characteristics, surgical details and clinical information about the anastomotic leakages were retrieved from medical records.

Results

Of the 1442 patients operated on with anterior resection in 11 hospitals, 144 (10%) were diagnosed with anastomotic leakage after anterior resection for rectal cancer. After a median follow‐up of 87 months (range 21–165), the overall rate of permanent stoma among patients with anastomotic leakage was 65%. Age ≥ 70 years (P = 0.02) and re‐laparotomy (P < 0.001) were independently related to permanent stoma. Compared with nondefunctioned patients with anastomotic leakage, defunctioned patients with anastomotic leakage at the index procedure less often required re‐laparotomy at some point during the entire clinical course (P < 0.001), but nondefunctioned and defunctioned patients with anastomotic leakage both had permanent stoma to the same extent (67% and 62%, respectively).

Conclusion

Anastomotic leakage is highly associated with permanent stoma after anterior resection, especially in patients aged ≥ 70 years. In this cohort of patients with anastomotic leakage, 65% had permanent stoma at long‐term follow‐up. A defunctioning stoma ameliorates the clinical course but does not affect the end result of bowel continuity in established anastomotic leakage after anterior resection.
Feeding and swallowing impairment in children with stroke and unilateral cerebral palsy: a systematic review
Authors: Sherman Victoria , Greco Elissa , Moharir Mahendranath , Beal Deryk , Thorpe Kevin , Martino Rosemary
Published: November 2018

Aim

This systematic review targeted frequency estimates of dysphagia (feeding and swallowing problems), related health outcomes, and caregiver burden in children with stroke or unilateral cerebral palsy (CP).

Method

Six electronic databases were searched from their inception to November 2017 along with a manual search of eight relevant journals. Two blinded raters assessed abstracts and full articles for eligibility. Discrepancies were resolved by consensus. Accepted articles were evaluated for quality. Data were extracted and analysed descriptively.

Results

Of 1660 abstracts, five met inclusion criteria, of which three focused on stroke and two unilateralCP. Across studies, operational definitions of feeding and swallowing varied. Insufficient details were provided on assessment methods and timing. Reported frequencies of dysphagia ranged from 24.2% to 88.6%. One study reported dysphagia‐related health outcomes and none reported caregiver burden.

Interpretation

These results suggest that dysphagia is common in children with stroke and unilateralCP; however, its frequency is yet unknown as is its impact on health and caregiver burden. Availability of a standardized tool to identify dysphagia in these children accurately is a recommended first step to address this evidence gap.

What this paper adds

There is limited data on the incidence of dysphagia after childhood stroke and unilateral cerebral palsy.

Available evidence shows reported dysphagia frequencies from 24.2% to 88.6%.

Only one study reported on dysphagia‐related health outcomes.

No study reported on caregiver burden.
Prevalence and predictors of gestational diabetes mellitus: a nationwide multicentre prospective study
Authors: Aydın H. , Çelik Ö. , Yazıcı D. , Altunok Ç. , Tarçın Ö. , Deyneli O. , Sancak S. , Kıyıcı S. , Aydın K. , Yıldız B.O. ,   the TURGEP Study Group
Published: November 2018

Aim

Prevalence rates of gestational diabetes mellitus (GDM) show considerable variation among different countries and regions of the world. The primary aim of this study was to determine the nationwide prevalence and predictors of GDM in Turkey.

Methods

We conducted prospective nationwide screening among pregnant women. Between August 2016 and November 2017, a total of 2643 pregnant women from 51 centres in 12 different regions were enrolled. A two‐step screening method and Carpenter and Coustan criteria were used in the diagnosis of GDM. Clinical and biochemical data were obtained using electronic database software.

Results

The national prevalence of GDM was found to be 16.2% [95% confidence intervals (CI) 15.0% to 17.4%] without a significant difference between urban and rural regions. Women with GDM were older (mean age: 32 ± 5 vs. 28 ± 5 years, P < 0.001) and heavier (mean BMI: 27.2 ± 5.1 vs. 24.7 ± 4.7 kg/m2, P < 0.001) than their counterparts without GDM. The prevalence of GDM tended to increase with age (< 25 years, 6.9%; 26–35 years, 15.6%; and 36–45 years, 32.7%; P < 0.001). Maternal age, maternal BMI, history of previous GDM and family history of diabetes mellitus were independent predictors of developing GDM (P < 0.05 for all). Low‐risk women (age < 25 years, BMI < 25 kg/m2, no family history of diabetes) comprised 10.7% of the total population and the prevalence of GDM in these women was 4.5% (95% CI 2.4% to 7.8%).

Conclusion

The results of this nationwide study indicate that GDM is very common, affecting one in seven pregnancies in Turkey. Implementation of international guidelines on screening and management of this public health problem is required.
Evidence‐based diabetes care for older people with Type 2 diabetes: a critical review
Authors: Sinclair A. J. , Abdelhafiz A. H. , Forbes A. , Munshi M.
Published: November 2018

In our ageing society diabetes imposes a significant burden in terms of the numbers of people with the condition, diabetes‐related complications including disability, and health and social care expenditure. Older people with diabetes can represent some of the more complex and difficult challenges facing the clinician working in different settings, and the recognition that we have only a relatively small (but increasing) evidence base to guide us in diabetes management is a limitation of our current approaches. Nevertheless, in this review we attempt to explore what evidence there is to guide us in a comprehensive scheme of treatment for older adults, often in a high‐risk clinical state, in terms of glucose lowering, blood pressure and lipid management, frailty care and lifestyle interventions. We strive towards individualized care and make a call for action for more high‐quality research using different trial designs.
Two‐dimensional speckle tracking to image ventricular‐arterial coupling in uremia
Authors: Ye Fu‐Yong , Liang Yin‐Ting , Lin Xiao‐Chun
Published: November 2018

Objective

To study ventricular‐arterial coupling(VAC) in uremic patients by application of two‐dimensional speckle tracing imaging (2DSTI).

Methods

One hundred uremic patients were divided into two groups based on left ventricular ejection fraction (LVEF): group 1 with LVEF ≥ 5%, and group 2 with LVEF < 55%. Forty healthy subjects were recruited as a control group. Conventional echocardiography was performed; VAC components and myocardial performance index were calculated. Longitudinal strain (LS) of 17 segments was measured using 2DSTI. Mean base (LSBA), papillary muscle (LSPM), and apex values (LSAP) were calculated.

Results

Compared to subjects in the control group and group 1, subjects in group 2 exhibited decreased LV end‐diastolic volume (EDV), end‐systolic volume (ESV), LV mass index (LVMI), and VAC (P < 0.05). EF, fractional shortening (FS), end‐systolic elastance (Ees) were significantly higher in group 2 (P < 0.05). SLBA, SLPM, and SLAP differed significantly among the groups (all P < 0.05). SLBA, SLPM, and SLAP correlated positively with Ees, EF, and FS (all P < 0.05) but negatively with arterial elastance (Ea), VAC, systemic vascular resistance index (SVRI), and rate‐pressure product (RPP) (all P < 0.05). Multiple regression analysis revealed that relative wall thickness (RWT), LVMI, LSAP, and stroke works (SW) were independent predictors of VAC (b′ = −0.443, 0.537, −0.470, and −0.491, all P < 0.05).

Conclusions

In patients with uremia, LV myocardial LS gradually decreased as LV systolic dysfunction decreased. VAC correlated negatively with left ventricular LS, and LSAP was an independent predictor for VAC.
Periodicity, repression, and the molecular architecture of the mammalian circadian clock
Authors: Rosensweig Clark , Green Carla B.
Published: November 2018

Large molecular machines regulate daily cycles of transcriptional activity and help generate rhythmic behavior. In recent years, structural and biochemical analyses have elucidated a number of principles guiding the interactions of proteins that form the basis of circadian timing. In its simplest form, the circadian clock is composed of a transcription/translation feedback loop. However, this description elides a complicated process of activator recruitment, chromatin decompaction, recruitment of coactivators, expression of repressors, formation of a repressive complex, repression of the activators, and ultimately degradation of the repressors and reinitiation of the cycle. Understanding the core principles underlying the clock requires careful examination of molecular and even atomic level details of these processes. Here, we review major structural and biochemical findings in circadian biology and make the argument that shared protein interfaces within the clockwork are critical for both the generation of rhythmicity and timing of the clock.
Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol‐dependent and polysubstance‐dependent individuals
Authors: Nestor Liam J. , Paterson Louise M. , Murphy Anna , McGonigle John , Orban Csaba , Reed Laurence , Taylor Eleanor , Flechais Remy , Smith Dana , Bullmore Edward T. , Ersche Karen D. , Suckling John , Elliott Rebecca , Deakin Bill , Rabiner Ilan , Lingford Hughes Anne , Sahakian Barbara J. , Robbins Trevor W. , Nutt David J. ,   ICCAM Consortium
Published: November 2018

Identifying key neural substrates in addiction disorders for targeted drug development remains a major challenge for clinical neuroscience. One emerging target is the opioid system, where substance‐dependent populations demonstrate prefrontal opioid dysregulation that predicts impulsivity and relapse. This may suggest that disturbances to the prefrontal opioid system could confer a risk for relapse in addiction due to weakened ‘top‐down’ control over impulsive behaviour. Naltrexone is currently licensed for alcohol dependence and is also used clinically for impulse control disorders. Using a go/no‐go (GNG) task, we examined the effects of acute naltrexone on the neural correlates of successful motor impulse control in abstinent alcoholics (AUD), abstinent polysubstance‐dependent (poly‐SUD) individuals and controls during a randomised double blind placebo controlled fMRI study. In the absence of any differences on GNG task performance, the AUD group showed a significantly greater BOLD response compared to the control group in lateral and medial prefrontal regions during both placebo and naltrexone treatments; effects that were positively correlated with alcohol abstinence. There was also a dissociation in the positive modulating effects of naltrexone in the orbitofrontal cortex (OFC) and anterior insula cortex (AIC) of the AUD and poly‐SUD groups respectively. Self‐reported trait impulsivity in the poly‐SUD group also predicted the effect of naltrexone in the AIC. These results suggest that acute naltrexone differentially amplifies neural responses within two distinct regions of a salience network during successful motor impulse control in abstinent AUD and poly‐SUD groups, which are predicted by trait impulsivity in the poly‐SUD group.
Rare copy number variation in extremely impulsively violent males
Authors: Vevera Jan , Zarrei Mehdi , Hartmannová Hana , Jedličková Ivana , Mušálková Dita , Přistoupilová Anna , Oliveriusová Petra , Trešlová Helena , Nosková Lenka , Hodaňová Kateřina , Stránecký Viktor , Jiřička Václav , Preiss Marek , Příhodová Kateřina , Šaligová Jana , Wei John , Woodbury‐Smith Marc , Bleyer Anthony J. , Scherer Stephen W. , Kmoch Stanislav
Published: November 2018

The genetic correlates of extreme impulsive violence are poorly understood, and there have been no studies that have systematically characterized a large group of affected individuals both clinically and genetically. We performed a genome‐wide rare copy number variant (CNV) analysis in 281 males from four Czech prisons who met strict clinical criteria for extreme impulsive violence. Inclusion criteria included age ≥ 18 years, an ICD‐10 diagnosis of Dissocial Personality Disorder, and the absence of an organic brain disorder. Participants underwent a structured psychiatric assessment to diagnose extreme impulsive violence and then provided a blood sample for genetic analysis. DNA was genotyped and CNVs were identified using Illumina HumanOmni2.5 single‐nucleotide polymorphism array platform. Comparing with 10851 external population controls, we identified 828 rare CNVs (frequency ≤ 0.1% among control samples) in 264 participants. The CNVs impacted 754 genes, with 124 genes impacted more than once (2‐25 times). Many of these genes are associated with autosomal dominant or X‐linked disorders affecting adult behavior, cognition, learning, intelligence, specifically expressed in the brain and relevant to synapses, neurodevelopment, neurodegeneration, obesity and neuropsychiatric phenotypes. Specifically, we identified 31 CNVs of clinical relevance in 31 individuals, 59 likely clinically relevant CNVs in 49 individuals, and 17 recurrent CNVs in 65 individuals. Thus, 123 of 281 (44%) individuals had one to several rare CNVs that were indirectly or directly relevant to impulsive violence. Extreme impulsive violence is genetically heterogeneous and genomic analysis is likely required to identify, further research and specifically treat the causes in affected individuals.
Soil aggregates as biogeochemical reactors and implications for soil–atmosphere exchange of greenhouse gases—A concept
Authors: Wang Bin , Brewer Paul E. , Shugart Herman H. , Lerdau Manuel T. , Allison Steven D.
Published: November 2018

Soil–atmosphere exchange significantly influences the global atmospheric abundances of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O). These greenhouse gases (GHGs) have been extensively studied at the soil profile level and extrapolated to coarser scales (regional and global). However, finer scale studies of soil aggregation have not received much attention, even though elucidating the GHG activities at the full spectrum of scales rather than just coarse levels is essential for reducing the large uncertainties in the current atmospheric budgets of these gases. Through synthesizing relevant studies, we propose that aggregates, as relatively separate micro‐environments embedded in a complex soil matrix, can be viewed as biogeochemical reactors of GHGs. Aggregate reactivity is determined by both aggregate size (which determines the reactor size) and the bulk soil environment including both biotic and abiotic factors (which further influence the reaction conditions). With a systematic, dynamic view of the soil system, implications of aggregate reactors for soil–atmosphere GHG exchange are determined by both an individual reactor's reactivity and dynamics in aggregate size distributions. Emerging evidence supports the contention that aggregate reactors significantly influence soil–atmosphere GHG exchange and may have global implications for carbon and nitrogen cycling. In the context of increasingly frequent and severe disturbances, we advocate more analyses of GHG activities at the aggregate scale. To complement data on aggregate reactors, we suggest developing bottom‐up aggregate‐based models (ABMs) that apply a trait‐based approach and incorporate soil system heterogeneity.
Disability studies and development geography: Empirical connections, theoretical resonances, and future directions
Authors: Jampel Catherine , Bebbington Anthony
Published: November 2018

Scholarship that jointly considers disability and development has advanced over the past decade to include greater attention to the shared histories of colonialism, racism, and the disability category and the relationships among developmental states, ideas about disability, and development projects. A handful of geographers have also directly addressed disability and development or disability in the “developing world” context. This paper reviews current scholarship and highlights three areas where disability studies and development geography share under‐explored empirical connections and theoretical resonances: the disability–poverty nexus, interventions in the name of improvement and cure, and mobility and migration. Yet bringing greater attention to disability in development must be done carefully, given the fraught nature of the disability category. As such, this paper also considers how development geographers might contribute to the literature while accounting for the ways in which ideas about what constitutes “disability” and what constitutes “development” emerge through sets of processes and relationships.
Concizumab restores thrombin generation potential in patients with haemophilia: Pharmacokinetic/pharmacodynamic modelling results of concizumab phase 1/1b data
Authors: Eichler Hermann , Angchaisuksiri Pantep , Kavakli Kaan , Knoebl Paul , Windyga Jerzy , Jiménez‐Yuste Victor , Harder Delff Philip , Chowdary Pratima
Published: November 2018

Introduction

Concizumab enhances thrombin generation (TG) potential in haemophilia patients by inhibiting tissue factor pathway inhibitor (TFPI). In EXPLORER3 (phase 1b), a dose‐dependent pharmacokinetic/pharmacodynamic (PK/PD) relationship was confirmed between concizumab dose, free TFPI and TG potential.

Aim

Determine the association between concizumab exposure, PD markers (free TFPI; peak TG) and bleeding episodes to establish the minimum concizumab concentration for achieving sufficient efficacy.

Methods

Free TFPI predictions were generated using an estimated concizumab‐free TFPI exposure‐response (Emax) model based on concizumab phase 1/1b data for which simultaneously collected concizumab and free TFPI samples were available. Concizumab concentration at the time of a bleed was predicted using a PK model, based on available data for concizumab doses >50 μg/kg to ≤9 mg/kg. Peak TG vs concizumab concentration analyses and an Emax model were constructed based on EXPLORER3 observations.

Results

The Emax model showed a tight PK/PD relationship between concizumab exposure and free TFPI; free TFPI decreased with increasing concizumab concentration. A strong correlation between concizumab concentration and peak TG was observed; concizumab >100 ng/mL re‐established TG potential to within the normal reference range. Estimated EC50 values for the identified concizumab‐free TFPI and concizumab‐TG potential models were very similar, supporting free TFPI as an important biomarker. A correlation between bleeding episode frequency and concizumab concentration was indicated; patients with a concizumab concentration >100 ng/mL experienced less frequent bleeding. The PK model predicted that once‐daily dosing would minimize within‐patient concizumab PK variability.

Conclusion

Concizumab phase 2 trials will target an exposure ≥100 ng/mL, with a once‐daily regimen.
Comparison of biocompatibility in polysulfone dialysis membranes with different sterilization
Authors: Togo Konomi , Yamamoto Masahito , Ono Takahisa , Imai Motoyuki , Akiyama Keiichi , Ebine Kunio , Yamashita Akihiro C.
Published: November 2018

Introduction: Polysulfone (PSf) membrane has been widely used for hemodialysis. A few studies have been reported in which a method of sterilization may affect biocompatibility. In this study, the comparison was made between two PSf membranes in order to evaluate the effect of sterilization from the biocompatibility point of view.

Methods: We investigated the biocompatibility of the following two dialyzers, that is, APS‐11SA (Asahi Kasei medical Co., Tokyo, Japan), sterilized by gamma‐ray irradiation, and RENAK PS‐1.0 (Kawasumi laboratories, Tokyo, Japan), sterilized by autoclave. Heparin of 40 units/mL was put in a syringe, and test blood was collected from healthy volunteers. Then, the dialyzer and blood circuit were filled with the test blood. Subsequently, the blood was circulated by a roller pump at the rate of 200 mL/min. We measured the platelet counts, CD41 and CD42b platelet surface markers, beta‐thromboglobulin (beta‐TG) and platelet factor 4 (PF4) at 30, 120, and 240 minutes, respectively.

Findings: The platelet counts at 30, 120, and 240 minutes decreased significantly from the initiation of blood circulation in both dialyzers. The average beta‐TG and PF4 increased from 61.3 ± 22.1 and 17.0 ± 6.4 ng/mL to 680.7 ± 217.1 and 550.7 ± 116.7 ng/mL with APS‐11SA and to 454.3 ± 85.6 and 402.0 ± 58.0 ng/mL with RENAK PS‐1.0, respectively. The average expression of CD41 and CD42b in APS‐11SA and RENAK PS‐1.0 was similar.

Discussion: There are some reports that the gamma‐ray irradiation changes the membrane structure of the PSf membrane, crosslinking the polyvinylpyrrolidone (PVP), a hydrophilic agent, on to the membrane. On the other hand, excess amount of PVP may have been eluted during the rinsing procedure in RENAK PS‐1.0 because it was sterilized with autoclave. Because both these factors influenced on our results, APS‐11SA and RENAK PS‐1.0 dialyzers showed excellent blood compatibility.
Recruitment of CCR6+ Foxp3+ regulatory gastric infiltrating lymphocytes in Helicobacter pylori gastritis
Authors: Wu Yi‐Ying , Hsieh Chin‐Tung , Tsay Gregory J. , Kao Jung‐Ta , Chiu Ying‐Ming , Shieh Dong‐Chen , Lee Yi‐Ju
Published: November 2018

Helicobacter pylori (H. pylori) infection is associated with an inflammatory response in the gastric mucosa, leading to chronic gastritis, peptic ulcers, and gastric cancer. Increased T‐cell infiltration is found at sites of H. pylori infection. The CCR6+ subset of CD4+ regulatory T cells (Tregs), a newly characterized subset of Tregs, has been reported to contribute to local immune inhibition. However, whether CCR6+ Tregs are present in H. pylori gastritis, and what their relationship is to disease prognosis, remains to be elucidated. In this study, gastric infiltrating lymphocytes were isolated from endoscopic biopsy specimens of H. pylori gastritis patients and analyzed. We found that in gastric infiltrating lymphocytes, CCR6+ CD4+ CD25high Tregs, which express high levels of CD45RO, are positively associated with more severe inflammation in gastric mucosa during H. pylori infection. Furthermore, the frequency of CCR6+ Tregs in gastric infiltrating lymphocytes, but not CCR6− Tregs, is significantly increased in inflamed gastric tissues, which is inversely correlated with significantly lower expression of IFN‐γ+ CD8+ T cells. We also found that the frequency of CCR6+ Tregs is positively correlated with the frequency of CD4+ IFN‐γ+ T cells. In addition, the frequency of CCR6+ Tregs, but not that of CCR6− Tregs, is significantly correlated with increased inflammation in H. pylori gastritis. This study demonstrates that immunosuppression in H. pylori gastritis might be related to the activity of CCR6+ Tregs, which could influence disease prognosis.
Evaluation of the potential use of discard species for fish silage and assessment of its oils for human consumption
Authors: Özyurt Gülsün , Özkütük Ali Serhat , Uçar Yılmaz , Durmuş Mustafa , Ozogul Yesim
Published: November 2018

Waste or by‐products contains a substantial amount of nutrients. Fish silage is an alternative way for assessment of fish discards and waste generated in the fish processing industries. The aim of the study was to evaluate the potential use of discard species (Equulites klunzingeri, marine fish and Carassius gibelio, freshwater fish) for fish silage and chemical quality of fish oil extracted from fish silages prepared with acid and fermented methods. Lipid quality of fish oils extracted from fish silages with LAB strains was evaluated in terms of thiobarbituric acid (TBA), peroxide value (PV), p‐Anisidine (AV), totox values and fatty acid composition. The results showed that PV, TBA, AV and totox values of all extracted fish oils were within the acceptable limits for edible oils. Recovered fish oils from silage contained high level of polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), serving as a source of good quality fish oil for human consumption.
Effects of green tea powder on the quality attributes of hard red winter wheat flour and Chinese steamed bread
Authors: Ning Jingming , Hou Gary G. , Sun Jingjing , Zhang Zhengzhu , Wan Xaiochun
Published: November 2018

The effects of green tea powder (GTP) on the properties of hard red winter (HRW) flour and Chinese steamed bread were investigated. GTP was blended with HRW flour at levels of 0.00, 1.00, 2.00, 3.00 and 4.00 g GTP/100 g wheat flour. With the addition of GTP, the maximum torque of flour became stronger. The resilience and degree of green colour of steamed bread increased, while hardness and chewiness decreased, with the addition of GTP. The addition of 1.00% GTP did not significantly affect the specific volume, but remarkably influenced the hardness and resilience of steamed bread. In steamed bread formulated with GTP, the antioxidant activity was 0.84 mm TE per g at 1.00% of GTP and increased with GTP levels. The steamed bread had a pleasant flavour, and the degree of overall liking of steamed bread increased with GTP levels to the maximum used in this work.
Recommendations for the use of pegylated interferon‐α in the treatment of classical myeloproliferative neoplasms
Authors: Forsyth Cecily J. , Chan Wai‐Hoong , Grigg Andrew P. , Cook Nathalie C. , Lane Steven W. , Burbury Kate L. , Perkins Andrew C. , Ross David M.
Published: November 2018

The classical myeloproliferative neoplasms (MPN) are uncommon clonal haemopoietic malignancies characterised by excessive production of mature blood cells. Clinically, they are associated with thrombosis, haemorrhage, varying degrees of constitutional disturbance and a risk of progression to myelofibrosis or acute myeloid leukaemia. Many of the disease manifestations may be ameliorated by treatment with interferon‐α (IFN), but its use in Australian MPN patients has been limited due to the inconvenience of frequent injections and side‐effects. The pegylated form of IFN is a long‐acting preparation, which is better tolerated, and its Pharmaceutical Benefits Scheme listing is likely to lead to increased usage. We review the literature on risks and benefits of IFN treatment for MPN, suggest criteria for patient selection in each of these diseases and discuss strategies to manage the side‐effects of pegylated IFN.
Characteristics and outcomes of oncology unit patients requiring admission to an Australian intensive care unit
Authors: Tan Aaron C. , Jacques Sarah K. , Oatley Meredith , Guminski Alexander D.
Published: November 2018

Background

Patients with advanced malignancies have historically been considered poor candidates for admission to the intensive care unit (ICU); however, prognosis is continually improving, and requirements for ICU access are increasing.

Aim

To understand the characteristics and outcomes of oncology unit patients admitted to an Australian ICU and identify potential prognostic factors.

Methods

A single‐centre, retrospective, cohort study conducted at a tertiary public hospital with a quaternary ICU in Sydney, Australia. All patients admitted under the medical oncology team requiring ICU admission between June 2014 and June 2016 were evaluated. Clinical outcomes were determined including mortality, ICU requirements (ventilation, dialysis, vasopressors, infection) and prognostic scores (Acute Physiologic and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) score).

Results

There were 96 patients with mean age 61 years, 58% were male and 76% had metastatic disease. Most were receiving palliative treatment (89%), with recent chemotherapy (43%), immunotherapy (10%) and other therapies (5%). Of the 10 patients with recent immunotherapy, three (all with melanoma) required ICU admission due to immunotoxicity; 13% were admitted due to an oncological emergency. Mean APACHE II score was 17 (standard deviation (SD) 5.33), mean SOFA score was 3.99 (SD 2.70), ICU mortality was 5% and hospital mortality was 22%. Using multivariate logistic regression analysis, cancer stage, infection during ICU admission, intracranial mass effect on ICU admission and SOFA score were associated with 30‐day mortality.

Conclusion

Our patient population had good short‐term survival outcomes despite most receiving palliative treatment. Cancer patients can achieve positive outcomes after ICU admission, and appropriate selection of patients is crucial.