bluuebunny/crossref_metadata_2025 huggingface dataset:
The orexin-1 receptor antagonist SB-334867 reduces motivation, but not inhibitory control, in a rat stop signal task
Authors: Wiskerke Joost , James Morgan H. , Aston-Jones Gary
Published: November 2018

There is considerable clinical interest in the neuropeptide orexin/hypocretin for its ability to regulate motivation and reward as well as arousal and wakefulness. For instance, antagonists for the orexin-1 receptor (OxR1) are thought to hold great promise for treating drug addiction and disorders associated with overeating, as these compounds repeatedly have been found to suppress seeking of various drugs of abuse as well as highly palatable foods in preclinical models. Given the hypothesized role of OxR1 signaling in cue-driven motivation, an outstanding question is whether pharmacologically blocking this receptor affects cognitive functioning. Response inhibition – the ability to cancel ongoing behavior – is one aspect of cognitive control that may be particularly relevant. Response inhibition deficits are commonly associated with a range of psychiatric disorders and neurological diseases, including substance use disorders and obesity. Moreover, OxR1 signaling recently has been implicated in waiting impulsivity, another aspect of inhibitory control. Here, we investigated the effects of the OxR1 antagonist SB-334867 on response inhibition in a rat version of the stop signal reaction time task. Results show that acutely blocking OxR1 had minimal effects on response inhibition or attentional functioning. In contrast, this manipulation reduced motivation to perform the task and earn food rewards. These results add to the growing body of literature implicating OxR1 in the regulation of motivation and suggest that effects of pharmacological compounds such as SB-334867 on drug seeking behavior are not related to effects on response inhibition.

Highlights

Orexin-1 receptor antagonists hold great promise for treatment of drug addiction

These compounds are thought to reduce motivation for drug seeking

Less is known about effects of orexin-1 receptor blockade on cognitive functioning

We tested the orexin-1 receptor antagonist SB-334867 in a rat stop signal task

SB-334867 reduced task motivation but had little effect on executive control as measured with response inhibition
Anti-NMDA receptor encephalitis in mice induced by active immunization with conformationally-stabilized holoreceptors
Authors: Jones Brian E. , Tovar Kenneth R , Goehring April , Okada Nana J. , Gouaux Eric , Westbrook Gary L.
Published: November 2018

Autoimmunity to membrane proteins in the central nervous system has been increasingly recognized as a cause of neuropsychiatric disease. A key recent development was the discovery of antibodies to NMDA receptors in limbic encephalitis, characterized by cognitive changes, memory loss, seizures and sometimes long-term morbidity or mortality. Treatment approaches and experimental studies have largely focused on the pathogenic role of these autoantibodies. Passive antibody transfer to mice has provided useful insights, but does not produce the full spectrum of the human disease. Here we describe ade novoautoimmune mouse model of anti-NMDA receptor encephalitis. Active immunization of immune competent mice with conformationally-stabilized, native-like NMDA receptors induced a fulminant encephalitis that was strikingly similar to the behavioral and pathologic characteristics of human cases. Our results provide evidence of neuroinflammation and immune cell infiltration as early and robust features of the autoimmune response. Use of transgenic mice indicated that mature T cells as well as antibody-producing cells were required for disease induction. Our results provide new insights into disease pathogenesis as well as a platform for testing mechanisms of disease initiation and therapeutic approaches.

One Sentence Summary

We report an active immunization model of anti-NMDA receptor encephalitis in mice that recapitulates the features of the clinical disease, provides new insights into the pathophysiology, and offers a platform for investigation of new therapeutic interventions.
Unbiased genome-scale identification ofcis-regulatory modules in the human genome by GRAMc
Authors: Guay Catherine L. , Nam Jongmin
Published: November 2018

Although significant advances have been made toward functionally identifying human regulatory elements, existing genome-scale reporter methods preferentially detect either enhancers or promoters. Here we develop GRAMc, a highly reproducible unbiased Genome-scale Reporter Assay Method forcis-regulatory modules (CRMs). GRAMc combines the versatility of traditional reporter constructs and the scalability of DNA barcode reporters, and unites the complementary advantages of several currently available high-throughput reporter assays. We demonstrate that GRAMc can reliably measurecis-regulatory activity of nearly 90% of the human genome in 200 million HepG2 cells with randomly fragmented ~800bp inserts. By using the GRAMc-identified CRMs, we show that CRMs identified in one cell type are useful for predicting gene regulatory programs not only within that cell type but also between cell types or conditions separated in time and space. In addition, the GRAMc-identified CRMs support the hypothesis that SINE/Alu elements are rich sources of regulatory evolution. Finally, the observation that the majority of experimentally identified regulatory elements do not overlap with computationally predicted elements underscores the necessity of an efficient and unbiased genome-scale reporter assay.
Gender in management: differences in male and female evaluations in leadership
Authors: Dutton Kelly
Published: November 2018

Purpose

This paper aims to review the latest management developments across the globe and pinpoint practical implications from cutting-edge research and case studies.

Design/methodology/approach

This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context.

Findings

Gender equality is increasing; however, in the higher management levels of organizations, there persists a bias toward male management. Investigating how bosses and peers rated managers showed that males provide lower job evaluations than females, regardless of sex, but at the same time, male peers provided higher ratings toward their own gender. Bosses were indifferent to gender in their ratings. Affecting the evaluation could be factors of social homophily and interpersonal familiarity. Lower performance ratings and a gender bias could hold back female career progression and create an overall atmosphere of gender perception within the workplace.

Practical implications

The paper provides strategic insights and practical thinking that have influenced some of the world’s leading organizations.

Originality/value

The briefing saves busy executives and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.
Optimization of Ultrasound‐Assisted Extraction of Monoterpene Glycoside from Oil Peony Seed Cake
Authors: Deng Rui‐xue , Yang Xiao , Wang Yi‐xiang , Du Ming‐zhu , Hao Xu‐ting , Liu Pu
Published: November 2018

Ultrasound‐assisted extraction (UAE) of total monoterpene glycosides extract (TMGE) from oil peony seed cakes was investigated. The extraction yield was optimized using response surface methodology (RSM). The chemical constituents of the monoterpene glycosides extract were isolated by repeated column chromatography, and the contents of the main isolated monoterpene glycosides in the oil peony seed cakes were determined by HPLC. The optimum conditions were as follows: a liquid‐to‐solid ratio of 27 mL/g, ultrasonic extraction time of 16 min, ultrasonic extraction temperature of 26 °C, and ethanol concentration of 67%. Under these conditions, the extraction yield of TMGE was 10.24%. Twenty monoterpene glycosides were isolated from the oil peony seed cakes, and compounds 11‐12, 16 and 20 showed strong inhibitory activities on NO production. TMGE from oil peony seed cakes can also to be used as promising immunosuppressive drug due to its high content of monoterpene glycosides and immune‐inhibitory activity.

Practical Aapplication

The peony seed oil was authorized as a new food by the Ministry of Health of the People's Republic of China. Peony seed cake is one of the most important by‐products in the preparation of peony seed oil, and accounts for approximately 40% of the total mass of the peony seed. Total monoterpene glycosides are the main active ingredient of oil peony seed cake. This research has optimized the extraction conditions of total monoterpene glycoside from seeds cake of Paeonia ostii, which will provide useful reference information for further studies, and offer related industries with helpful guidance in practice.
Application of Physical Gas Absorbers in Manipulating the CO2 Pressure of Kimchi Package
Authors: Jaisan Chalalai , An Duck Soon , Lee Dong Sun
Published: November 2018

Physical gas absorption and release of activated carbon or zeolite were used to attain the desired CO2 concentration profile inside a package of kimchi for its dynamic storage and consumption environment. The CO2 adsorption/desorption behavior of different combinations of physical scavengers in the microporous Tyvek sachet was measured at 0, 10 and 20 °C. A combination of highly permeable microporous Tyvek and much less permeable nylon/polyethylene laminate was also examined as a variable to help control the access of CO2 to the physical CO2 absorber. The composition of the absorber and its packing density in the sachet affected the CO2 absorption rate and capacity. Increased zeolite in the Tyvek sachet showed higher CO2 absorption followed by higher CO2 release concomitant with moisture sorption, while activated carbon itself had low CO2 absorption and little subsequent CO2 desorption. Lower temperatures increased the capacity of CO2 absorption and release along with lower CO2 absorption and release rates. A reduction in Tyvek area could decrease the absorption and release rates. An application of a physical CO2 absorber to the kimchi package was tested at 10 °C to show potential for keeping the desired CO2 pressure profile for carbonic cool flavor under tolerable pressure during storage and use.

Practical Applications

Physical carbon dioxide absorbers consisting of zeolite and activated carbon inside the gas‐permeable sachet can be placed in kimchi packages for time‐dependent absorption and release of carbon dioxide, which responds in harmony with the fermentation profile of kimchi. Its practical potential is both to provide a carbonic cool taste of the product and to avoid excessive overpressure in the package through its shelf life when used in kimchi packaging. Its intelligent use may resolve the problem of a dull kimchi taste, which occurs when incorporating calcium hydroxide as the chemical scavenger in the package.
The analysis of human leukocyte antigen‐G level in patients with endometrial cancer by Western blot technique
Authors: Walentowicz‐Sadlecka Małgorzata , Dziobek Konrad , Grabiec Marek , Sadlecki Pawel , Walentowicz Pawel , Mak Paweł , Szymankiewicz Maria , Kwinta Przemko , Dutsch‐Wicherek Magdalena
Published: November 2018

Problem

Aberrant expression of human leukocyte antigen‐G (HLA‐G) in various malignancies has been shown to participate in tumour development by suppressing immune regulation within the tumour microenvironment. The detection of HLA‐G has reportedly been correlated with certain clinicopathological parameters in several neoplasms. Both the soluble and membranous forms of HLA‐G are biologically active, and therefore, we aimed to evaluate the HLA‐G level by Western blot technique.

Method of study

The total amount of HLA‐G protein was analyzed in the primary tumour in 113 tissue samples derived from patients with endometrial cancer. The HLA‐G protein level was measured by Western Blot technique and was analyzed with respect to the clinicopathological parameters.

Results

Human leukocyte antigen‐G protein levels were statistically significantly higher in the cancerous tissues derived from the women with advanced endometrial cancer than those from women with early stage disease. Moreover, we showed that endometrial cancer patients with lymph node metastases had statistically significantly higher HLA‐G levels in the primary uterine tumour.

Conclusion

The aberrant expression of HLA‐G antigens by malignant cells could be one of the strategies tumour cells use to escape immune surveillance. The presence of HLA‐G within the cancer nest and its microenvironment would seem to be linked to disease progression.
Usefulness of platelet to lymphocyte ratio for predicting recurrence of atrial fibrillation after direct current cardioversion
Authors: Dereli Seçkin , Bayramoğlu Adil , Yontar Osman Can
Published: November 2018

Objective

Atrial fibrillation (AF) is the most common cardiac rhythm disorder with the associated risks of stroke and mortality. The usefulness of platelet to lymphocyte ratio (PLR), a recently described inflammatory marker, in predicting adverse cardiovascular events has been demonstrated in several studies. In the current study, we investigated the role of PLR in predicting recurrence after successful electrical cardioversion (ECV) in patients with non‐valvular persistent AF.

Methods

A total of 287 patients with non‐valvular persistent AF achieving restoration of the sinus rhythm after successful ECV were included in this study. At study entry, complete blood count, routine biochemistry tests, and transthoracic echocardiography (TTE) were performed routinely in all subjects. Patients were followed up for 6 months following the procedure and comparisons were performed between patients who recurred and who maintained the sinus rhythm (SR).

Results

At 6 months of follow‐up, AF recurred in 108 patients, corresponding to a recurrence rate of 39%. Mean PLR values in the “AF recurrence group” (mean age 57.4 ± 12.0 years, 47.6% [n = 80] female) and in “SR maintenance” group (mean age 65.0 ± 9.4 years, 55.6% [n = 60] female) were 184.8 ± 44.2 and 103.3 ± 44.2, respectively, with a significant difference between the two groups (p < 0.001). In multiple regression analyses, PLR emerged as a risk factor associated with AF recurrence during the 6‐month follow‐up period after successful ECV (odds ratio [OR]: 3.029 (1.013–9.055 95% confidence interval [CI]), p = 0.047). When a cutoff value of 147 was used, the sensitivity and specificity of PLR for predicting AF recurrence were 83.3% and 84.5%, respectively.

Conclusion

Elevated PLR is a marker of increased inflammation and may serve as a practical and inexpensive predictor for recurrence during 6 months of follow‐up in patients with non‐valvular persistent AF who had restoration of the sinus rhythm after successful ECV.
Randomized controlled trial of probiotic use for post‐colonoscopy symptoms
Authors: Mullaney Tamara G. , Lam David , Kluger Roman , D'Souza Basil
Published: November 2018

Background

Symptoms of bloating, discomfort and altered bowel function persist post‐colonoscopy in up to 20% of patients. A previous randomized controlled trial of probiotics for post‐colonoscopy symptoms has demonstrated a reduction in duration of pain with the use of probiotics. This was performed with air insufflation and the question was asked whether the effect would persist with the use of carbon dioxide to insufflate the colon.

Methods

Eligible patients were recruited and randomized to receive either probiotic or placebo capsules post colonoscopy. A questionnaire was completed documenting the presence of pre‐procedural and post‐procedural symptoms for the following 2 weeks. The results were entered into a database and processed by an independent statistician. The primary outcome was mean pain score and incidence of bloating over the first 7 days and at 14 days post procedure. The secondary outcome was the time to return of normal bowel function.

Results

Two hundred and forty participants were recruited and randomized (120 probiotic and 120 placebo). Data were available for 75 patients in the probiotic and 75 in the placebo group. There was no significant difference between groups in post‐procedural discomfort, bloating nor time to return of normal bowel function. Subgroup analysis of the patients with preexisting symptoms showed a reduction in incidence of bloating with the use of probiotics.

Conclusion

There may be a role for the use of probiotics in the subgroup of patients with preexisting symptoms; however, routine use of probiotics to ameliorate post‐procedural symptoms of carbon dioxide insufflation colonoscopy cannot be advocated.
Emergency presentations of acute biliary pain: changing patterns of management in a tertiary institute
Authors: Cox Daniel R. A. , Fong Jonathan , Liew Chon Hann , Goh Su Kah , Yeoh Michael , Fink Michael A. , Jones Robert M. , Mukkadayil Jude , Nikfarjam Mehrdad , Perini Marcos V. , Rumler Greg , Starkey Graham , Christophi Chris , Muralidharan Vijayaragavan
Published: November 2018

Background

Acute biliary pain is the most common presentation of gallstone disease. Untreated patients risk recurrent pain, cholecystitis, obstructive jaundice, pancreatitis and multiple hospital presentations. We examine the outcome of implementing a policy to offer laparoscopic cholecystectomy on index presentation to patients with biliary colic in a tertiary hospital in Australia.

Methods

This is a retrospective cohort study of adult patients presenting to the emergency department (ED) with biliary pain during three 12‐month periods. Outcomes in Group A, 3 years prior to policy implementation, were compared with groups 2 and 7 years post implementation (Groups B and C). Primary outcomes were representations to ED, admission rate and time to cholecystectomy.

Results

A total of 584 patients presented with biliary colic during the three study periods. Of these, 391 underwent cholecystectomy with three Strasberg Type A bile leaks and no bile duct injuries. The policy increased admission rates (A = 15.8%, B = 62.9%, C = 29.5%, P < 0.001) and surgery on index presentation (A = 12.0%, B = 60.7%, C = 27.4%, P < 0.001). There was a decline in time to cholecystectomy (days) (A = 143, B = 15, C = 31, P < 0.001), post‐operative length of stay (days) (A = 3.6, B = 3.2, C = 2.0, P < 0.05) and representation rates to ED (A = 42.1%, B = 7.1%, C = 19.9%, P < 0.001). There was a decline in policy adherence in the later cohort.

Conclusion

Index hospital admission and cholecystectomy for biliary colic decrease patient representations, time to surgery, post‐operative stay and complications of gallstone disease. This study demonstrates the impact of the policy with initial improvement, the dangers of policy attrition and the need for continued reinforcement.
Monitoring of avulsion channel evolution and river morphology changes using UAV photogrammetry: Case study of the gravel bed Ondava River in Outer Western Carpathians
Authors: Rusnák Miloš , Sládek Ján , Pacina Jan , Kidová Anna
Published: November 2018

This paper presents results from monitoring the chute cutoff in the meander bend of the Ondava River in Eastern Slovakia. An avulsion channel was formed in the central part of the meander neck during 2010 flood events, and here we describe the mechanism of evolution and post‐cutoff avulsion channel adjustment using drones, unmanned aerial vehicle (UAV) photogrammetry and field survey. Monitoring by UAV images began on 15 June 2012 with 78 processed images, followed by 259 images during April 2014 and 375 from 18 July 2014. The majority of UAV digital elevation model (DEM) errors in the study area were associated with vegetation cover, with the average vertical root mean square error (RMSE) of the UAV‐DEM on bare ground at 0.209 m compared with 0.673 m in vegetated areas. The chute cutoff was formed by floodplain headcutting during meander neck overflow and headcut migration was directed by floodplain sediment structure and land use. Although low river discharge after the 2010 floods stabilised the avulsion channel by vegetation succession, recurrent two‐yearly interval flooding increased the avulsion channel bank erosion from 36.9 m3/month (June 2012–April 2014) to 425.6 m3/month (April 2014–July 2014).
Clinicopathologic features of anaplastic myxopapillary ependymomas
Authors: Lee Julieann C. , Sharifai Nima , Dahiya Sonika , Kleinschmidt‐DeMasters Bette K. , Rosenblum Marc K. , Reis Gerald F. , Samuel David , Siongco Aleli M. , Santi Mariarita , Storm Phillip B. , Ferris Sean P. , Bollen Andrew W. , Pekmezci Melike , Solomon David A. , Tihan Tarik , Perry Arie
Published: November 2018

Myxopapillary ependymomas (MPE) are considered benign (World Health Organization (WHO) grade I) neoplasms with favorable prognosis. However, malignant behavior occurs in a small subset. To our knowledge, only five anaplastic MPEs have been reported without consensus on diagnostic criteria. We retrieved 14 anaplastic MPEs from the pathology archives of six institutions. Each tumor included at least two of the following features: ≥5 mitoses per 10 high power fields, Ki‐67 labeling index (LI) ≥10%, microvascular proliferation (MVP) and spontaneous necrosis. These features were typically encountered in the foci of hypercellularity and reduced mucin. There were eight male and six female patients (age range 6–57 years, median = 16.5). Ten tumors displayed anaplasia at initial resection, and 4 were anaplastic at a second surgery for recurrence (ranging from 9 months to 14 years following initial resection). The Ki‐67 LI ranged between 8% and 40% in the anaplastic foci and <3% in the foci of classic MPE. There was documented cerebrospinal fluid (CSF) dissemination in seven cases, recurrence following an anaplastic diagnosis in three cases and bone or soft tissue invasion in two cases. One patient suffered lung metastases. Two cases evaluated by targeted next‐generation sequencing and one evaluated by fluorescence in situ hybridization (FISH) showed nonspecific chromosomal gains. We conclude that although rare, anaplastic MPE occurs in both pediatric and adult patients, similar to other ependymomas. At a minimum, closer follow‐up is recommended, given the concern for aggressive biologic potential. Further study is needed to determine WHO grading criteria and genetic indicators of tumor progression.
Histamine receptors and cancer pharmacology: an update
Authors: Massari Noelia A , Nicoud Melisa B , Medina Vanina A
Published: November 2018

In the present review, we will discuss the recent advances in the understanding of the role of histamine and histamine receptors in cancer biology. The controversial role of the histaminergic system in different neoplasias including gastric, colorectal, oesophageal, oral, pancreatic, liver, lung, skin, blood and breast cancers will be reviewed. The expression of histamine receptor subtypes, with special emphasis on the histamine H4receptor, in different cell lines and human tumours, the signal transduction pathways and the associated biological responses as well as thein vivotreatment of experimental tumours with pharmacological ligands will be described. The presented evidence demonstrates that histamine regulates cancer‐associated biological processes during cancer development in multiple cell types, including neoplastic cells and cells in the tumour micro‐environment. The outcome will depend on tumour cell type, the level of expression of histamine receptors, signal transduction associated with these receptors, tumour micro‐environment and histamine metabolism, reinforcing the complexity of cancer disease. Findings show the pivotal role of H4receptors in the development and progression of many types of cancers, and considering its immunomodulatory properties, the H4receptor appears to be the most promising molecular therapeutic target for cancer treatment within the histamine receptor family. Furthermore, the H4receptor is differentially expressed in tumours compared with normal tissues, and in most cancer types in which data are available, H4receptor expression is associated with clinicopathological characteristics, suggesting that H4receptors might represent a novel cancer biomarker.

Linked Articles

This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc
Pharmacokinetic and Pharmacodynamic Considerations in the Design of Therapeutic Antibodies
Authors: Leipold Douglas , Prabhu Saileta
Published: November 2018

The design and development of therapeutic monoclonal antibodies (mAbs) through optimizing their pharmacokinetic (PK) and pharmacodynamic (PD) properties is crucial to improve efficacy while minimizing adverse events. Many of these properties are interdependent, which highlights the inherent challenges in therapeutic antibody design, where improving one antibody property can sometimes lead to changes in others. Here, we discuss optimization approaches for PK/PD properties of therapeutic mAbs.
Angiotropism in recurrent cutaneous squamous cell carcinoma: Implications for regional tumor recurrence and extravascular migratory spread
Authors: Fedda Faysal , Migden Michael R. , Curry Jonathan L. , Torres‐Cabala Carlos A. , Tetzlaff Michael T. , Aung Phyu P. , Prieto Victor G. , Ivan Doina , Myers Jeffrey N. , Nagarajan Priyadharsini
Published: November 2018

Extravascular migratory metastasis is a form of cancer metastasis in which tumor cells spread by tracking along the abluminal aspect of vessel walls without breaking the vascular endothelial lining or intraluminal invasion. This phenomenon has been extensively described in melanoma and is being increasingly recognized in other neoplasms. Various modalities of treatment, including radiation‐, chemo‐, targeted‐, and immune‐ therapies may potentially induce angiotropic behavior in neoplastic cells. Although there is a risk for tumor recurrence and metastasis, angiotropism may be under‐recognized and is rarely reported. Here, we report a case of recurrent poorly‐differentiated acantholytic squamous cell carcinoma of the scalp with extensive perineural invasion, previously treated with multiple therapies. There was multifocal extravascular cuffing of neoplastic cells around and focally involving the walls of small to medium‐caliber blood vessels within and surrounding the tumor, without obvious tumor intravasation. In addition, small subtle nests of neoplastic keratinocytes were noted along the abluminal aspect of a large‐caliber deep dermal blood vessel in an en‐face margin, away from the main tumor mass. Such involvement can be difficult to identify; and thus, may be missed particularly during intra‐operative frozen section evaluation, leading to false‐negative margins and is therefore, a diagnostic pitfall.
Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers
Authors: Heerspink Hiddo J. L. , Sjöström C. David , Inzucchi Silvio E. , Hallow Melissa K. , Cain Valerie A. , Rossing Peter , Stefansson Bergur V. , Sartipy Peter
Published: November 2018

The sodium glucose co‐transporter‐2 inhibitor dapagliflozin has been shown to decrease urinary albumin‐to‐creatinine ratio (UACR). This effect, however, varies among individual patients. In this study, we assessed the baseline characteristics and concurrent changes in other cardiovascular risk markers that might be associated with UACR response to dapagliflozin. A pooled analysis of 11 phase 3 randomized, controlled clinical trials was performed. UACR change from baseline after 24 weeks treatment with dapagliflozin 10 mg/d in 531 patients with type 2 diabetes and UACR ≥30 mg/g at baseline was determined. UACR response was defined as >30% reduction from baseline at 24 weeks, whereas UACR non‐response was defined as ≤30% reduction at 24 weeks. A total of 288 (54%) patients were classified as responders and 243 (46%) as non‐responders. At 24 weeks, the UACR‐adjusted mean change from baseline was −71.2% and 25.9% in responders and non‐responders, respectively. Baseline characteristics were similar between both groups. Changes in HbA1c and body weight were comparable across groups. Responders showed a numerically larger reduction in estimated glomerular filtration rate and systolic blood pressure versus non‐responders. UACR reduction to dapagliflozin is an individual characteristic that cannot be predicted by baseline clinical features or changes in metabolic variables. Whether UACR response would improve long‐term renal and cardiovascular outcomes remains to be determined.
The Balancing Act in a Military‐Dominated Transition to Democracy in Egypt After the Arab Spring
Authors: Zohny Ahmed Y.
Published: November 2018

This article genealogically traces the historical development of democracy in Egypt and the military and Islamists’ involvement in politics since the British occupation in Egypt in 1882, following the semi‐independence in 1922, through the 1952 revolution, and up to the revolutionary waves of the Arab Spring of January 25, 2011 and June 30, 2013. In this article, the author provides perceptual and analytical insight into the outcome of the Arab Spring of 2011 within the complicated realities of Egypt's politics during the transition to democracy, where the military and Islamists are competing to retain power in order to shape Egypt's future. The author argues that it is too early to make a judgmental argument that the transition to democracy has failed since the process of democratization is long and not linear, with periods of political trajectories while adapting in response to national, regional, and international events, dynamics, and forces. The research concludes that the coping models of democracy from outside of the Egyptian context may not work. Egypt should develop its own model of democracy based on an all stakeholders consensus accompanied by an incremental process of demilitarizing and desecuritizing the nation.
Living in protracted communal conflict: Socioeconomic trends and household poverty in Ghana's Yendi area
Authors: Adonteng‐Kissi Obed , Adonteng‐Kissi Barbara , Jibril Mohammed Kamal , Kwesi Osei Samuel
Published: November 2018

Motivation

The conflict in Yendi, which dates to the colonial period, was one of the major sources of conflict in northern Ghana. The conflict was partly attributed to the contention on whether it is a convention that succession to the Yendi throne must essentially rotate between the two warring royal factions or revert to the primogenital tradition of unilateral royal family succession to the Ya Na Skin.

Purpose

This article provides a critical synthesis of the impact of communal conflict on household poverty and economic empowerment of the poor to achieve decent standards of living in Ghana's Yendi area. It is therefore necessary to answer the research question, what is the impact of the Yendi communal conflict on socioeconomic trends and household poverty?

Methods

We aimed to ascertain the impact of the Yendi conflict on 20 local government officials, NGO representatives, traders, parents, teachers, students, farmers, nurses, members of the traditional authority and security personnel. The average age of participants was 35. Unstructured interviews were conducted with key informants using in‐depth interview techniques to gather the necessary data and purposively sampled across Ghana's Yendi. Interviews were recorded, transcribed using a framework approach

Results

The article finds that families that were rich in landed assets and had sufficient income but were most impacted by the conflict have seen their economic conditions deteriorate. This study further reveals that conflict impacts negatively on the welfare of families in different ways. Families endowed with more assets and higher education are identified as having better capacity to withstand economic shocks.

Conclusion

There is a need for agricultural industrialization to offer spin‐offs and the generation of backward and forward linkages. To create strong linkages within the agriculture industry, it must become a resourceful business environment that offers a steady supply of quality raw materials at low costs. Government must help transform the rural environment from its subsistence structure to a commercially appealing, feasible and active sector, one which is critical for the accomplishment of sustained equitable growth.
Association of serum galectin‐3 with risks of death and vascular events in acute ischaemic stroke patients: the role of hyperglycemia
Authors: Zeng N. , Wang A. , Zhong C. , Zheng X. , Zhu Z. , Xu T. , Peng Y. , Peng H. , Li Q. , Ju Z. , Geng D. , Zhang Y. , He J.
Published: November 2018

Background and purpose

Whether the association between galectin‐3 and stroke outcome is modified by fasting plasma glucose (FPG) is unknown. The aim was to evaluate the prognostic effect of galectin‐3 amongst ischaemic stroke patients stratified by FPG.

Methods

In all, 3082 ischaemic stroke patients were included in this study and serum galectin‐3 was tested at baseline. The primary outcome was a composite outcome of death and vascular events, and secondary outcomes were death, stroke recurrence and vascular events within 1 year after stroke.

Results

Increased galectin‐3 was significantly associated with the primary outcome, stroke recurrence and vascular events in the patients with hyperglycemia but not in those with normoglycemia (P for interaction < 0.05 for all). The multivariate‐adjusted hazard ratios (95% confidence intervals) were 1.72 (1.05–2.84), 2.64 (1.14–6.12) and 2.68 (1.33–5.38) for the primary outcome, stroke recurrence and vascular events, respectively. A linear association between galectin‐3 and the primary outcome was observed in hyperglycemic patients (P for linearity = 0.007).

Conclusion

Increased galectin‐3 was associated with the primary outcome, stroke recurrence and vascular events within 1 year after stroke in the patients with hyperglycemia, suggesting that galectin‐3 may be an important prognostic factor for ischaemic stroke patients with hyperglycemia.
Hemorrhagic transformation after stroke: inter‐ and intrarater agreement
Authors: Guenego A. , Lecler A. , Raymond J. , Sabben C. , Khoury N. , Premat K. , Botta D. , Boisseau W. , Maïer B. , Ciccio G. , Redjem H. , Smajda S. , Ducroux C. , Di Meglio L. , Davy V. , Olivot J. M. , Wang A. , Duplantier J. , Roques M. , Krystal S. , Koskas P. , Collin A. , Ben Maacha M. , Hamdani M. , Zuber K. , Blanc R. , Piotin M. , Fahed R. ,   the Aspiration versus STEnt‐Retriever (ASTER) trial investigators
Published: November 2018

Background and purpose

Hemorrhagic transformation (HT) is a complication of stroke that can occur spontaneously or after treatment. We aimed to assess the inter‐ and intrarater reliability of HT diagnosis.

Methods

Studies assessing the reliability of the European Cooperative Acute Stroke Study (ECASS) classification of HT or of the presence (yes/no) of HT were systematically reviewed. A total of 18 raters independently examined 30 post‐thrombectomy computed tomography scans selected from the Aspiration versus STEnt‐Retriever (ASTER) trial. They were asked whether there was HT (yes/no), what the ECASS classification of the particular scan (0/HI1/HI2/PH1/PH2) (HI indicates hemorrhagic infarctions and PH indicates parenchymal hematomas) was and whether they would prescribe an antiplatelet agent if it was otherwise indicated. Agreement was measured with Fleiss’ and Cohen's κ statistics.

Results

The systematic review yielded four studies involving few (≤3) raters with heterogeneous results. In our 18‐rater study, agreement for the presence of HT was moderate [κ = 0.55; 95% confidence interval (CI), 0.41–0.68]. Agreement for ECASS classification was only fair for all five categories, but agreement improved to substantial (κ = 0.72; 95% CI, 0.69–0.75) after dichotomizing the ECASS classification into 0/HI1/HI2/PH1 versus PH2. The inter‐rater agreement for the decision to reintroduce antiplatelet therapy was moderate for all raters, but substantial among vascular neurologists (κ = 0.70; 95% CI, 0.57–0.84).

Conclusion

The ECASS classification may involve too many categories and the diagnosis of HT may not be easily replicable, except in the presence of a large parenchymal hematoma.
MitochondrialDNAhaplogroups and age at onset of Machado–Joseph disease/spinocerebellar ataxia type 3: a study in patients from multiple populations
Authors: Ramos A. , Planchat M. , Vieira Melo A. R. , Raposo M. , Shamim U. , Suroliya V. , Srivastava A. K. , Faruq M. , Morino H. , Ohsawa R. , Kawakami H. , Bannach Jardim L. , Saraiva‐Pereira M. L. , Vasconcelos J. , Santos C. , Lima M.
Published: November 2018

Background and purpose

Mitochondrial dysfunction has been implicated in the pathogenesis of several neurodegenerative disorders, including Machado–Joseph disease (MJD), an autosomal dominant late‐onset polyglutamine ataxia that results from an unstable expansion of a CAG tract in theATXN3gene. The size of the CAG tract only partially explains age at onset (AO), highlighting the existence of disease modifiers. Mitochondrial DNA (mtDNA) haplogroups have been associated with clinical presentation in other polyglutamine disorders, constituting potential modifiers of MJD phenotype.

Methods

A cross‐sectional study, using 235 unrelated patients from Portugal, Brazil, India and Japan, was performed to investigate if mtDNA haplogroups contribute to AO of MJD. mtDNA haplogroups were obtained after sequencing the mtDNA hypervariable region I. Patients were classified in 15 phylogenetically related haplogroup clusters.

Results

The AO was significantly different among populations, implying the existence of other non‐CAG factors, which seem to be population specific. In the Portuguese population, patients classified as belonging to haplogroup JT presented the earliest onset (estimated onset 34.6 years of age). Haplogroups W and X seem to have a protective effect, causing a delay in onset (estimated onset 47 years of age). No significant association between haplogroup clusters and AO was detected in the other populations or when all patients were pooled. Although haplogroup JT has already been implicated in other neurodegenerative disorders, no previous reports of an association between haplogroups W and X and disease were found.

Conclusions

These findings suggest that haplogroups JT, W and X modify AO in MJD. Replication studies should be performed in European populations, where the frequency of the candidate modifiers is similar.
Clinical course of multiple sclerosis and labour‐force absenteeism: a longitudinal population‐based study
Authors: Castelo‐Branco A. , Landfeldt E. , Svedbom A. , Löfroth E. , Kavaliunas A. , Hillert J.
Published: November 2018

Background and purpose

Multiple sclerosis (MS) is a chronic neurological disease associated with substantial disability and morbidity. The objective of our study was to assess the long‐term consequences of MS clinical course on sick leave and disability pension.

Methods

Patients with relapsing‐remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS) were identified through the Swedish Multiple Sclerosis Registry. We calculated the mean annual prevalence and number of sick leave and disability pension days by clinical course, age and year pre‐ and post‐diagnosis, and compared outcomes using Welch's t‐tests and ANOVA models, mixed‐effects regression and survival analysis.

Results

The sample included 5371 patients (4568 with RRMS, 390 with SPMS and 413 with PPMS). The mean annual number of days with sick leave and disability pension ranged from 101 at 1 year after diagnosis to 164 after 11 years for patients with RRMS. Corresponding estimates for PPMS were 188 and 311 days. Higher levels of absenteeism were observed in patients with PPMS versus RRMS 7 years before diagnosis for sick leave (P < 0.025) and 10 years before diagnosis for disability pension (P < 0.034). Differences between SPMS and PPMS were minor.

Conclusions

Patients with RRMS had substantially lower levels of sick leave and disability pension over time compared with their counterparts with SPMS and PPMS, whereas labour‐force absenteeism was similar for patients with SPMS and PPMS. These findings contribute to the understanding of the impact of MS on socioeconomic outcomes and help inform the discussion on the clinical classification of different courses of the disease.
Inhibition of dentin matrix‐bound cysteine cathepsins by potassium fluoride
Authors: Altinci Pinar , Mutluay Murat , Tjäderhane Leo , Tezvergil‐Mutluay Arzu
Published: November 2018

Matrix metalloproteinases (MMPs) and cysteine cathepsins (CCs) can break down unprotected type I collagen fibrils in dentin matrix. This study investigated the use of potassium fluoride (KF) as a potential inhibitor of MMPs and CCs in dentin. Demineralized dentin beams were divided into groups (n = 10 in each group) and incubated in artificial saliva (AS, control), either alone or with one of seven concentrations of KF (6–238 mM fluoride) for 1, 7, and 21 d. After 21 d, all groups were further aged in AS for 6 months. Total MMP activity was screened using the colorimetric MMP assay. The activities of MMP‐2 and MMP‐9 were investigated using gelatin zymography. At the end of each incubation, changes in loss of dry mass and CC‐mediated or total dissolution of collagen peptides were measured via precision weighing, C‐terminal crosslinked telopeptide of type I collagen (CTX), and hydroxyproline (HYP) assays. The beams were examined using scanning electron microscopy. After 21 d, total MMP activities, dry mass loss, and CTX release for the groups exposed to 179 and 238 mM fluoride were significantly lower compared with the control group. After 6 months, all groups showed similar total MMP activity, dry mass loss, and HYP release, and CTX levels were significantly lower when the fluoride concentration was ≥24 mM. Calcium fluoride (CaF2)‐like precipitates were observed over the beams. In summary, KF significantly inhibited the catalytic activity of dentin matrix‐bound CCs but did not seem to be effective for MMP‐mediated activity.
Factors associated with survival, laminitis and insulin dysregulation in horses diagnosed with equine pituitary pars intermedia dysfunction
Authors: Horn R. , Bamford N. J. , Afonso T. , Sutherland M. , Buckerfield J. , Tan R. H. H. , Secombe C. J. , Stewart A. J. , Bertin F. R.
Published: November 2018

Background

Pituitary pars intermedia dysfunction (PPID) is a commonly described endocrine disorder in higher latitudes of the Northern hemisphere but the description of the disease at lower latitudes and in the Southern hemisphere is limited.

Objectives

Document the clinical features ofPPIDat different Australian latitudes and climates, and investigate factors associated with survival, laminitis and insulin dysregulation (ID).

Study design

Retrospective study of 274 equids from eight institutions across Australia.

Methods

A diagnosis ofPPIDwas based on endogenousACTH, overnight dexamethasone suppression test, thyrotropin‐releasing hormone stimulation test or necropsy. Clinical and clinicopathologic characteristics ofPPIDand therapeutic responses were investigated. Laminitis was diagnosed by radiographic or histologic changes andIDwas diagnosed based on endogenous insulin, an oral glucose test or a 2‐step insulin‐response test.

Results

Being a pony, having a higher body condition score and pergolide administration were associated with survival. The clinical presentation ofPPIDchanged with latitude and climate, with anhidrosis and polyuria/polydipsia more commonly recognised at lower latitudes. Laminitis was diagnosed in 89.9% of cases andIDwas present in 76.5% of cases in which they were investigated.

Main limitations

Despite the sample size, the lack of uniform testing at all locations (primary or referral cases) and the incompleteness of data sets limited the power of the statistical analyses.

Conclusions

PPIDcan present with variable signs at different latitudes and climates, andIDshould be investigated in equids diagnosed withPPID. Adequate body condition and administration of pergolide are fundamental inPPIDmanagement.
A Phenomenological Study on the Experience of Syrian Asylum‐Seekers and Refugees in the United States
Authors: Utržan Damir S. , Wieling Elizabeth A.
Published: November 2018

Violence in Syria has displaced an unprecedented number of people from their homes. While couple/family therapy (C/MFT) scholars have explored migration experiences, particularly among refugees, there is still limited research using a bioecological framework. This exploratory study examined the experiences of Syrian asylum‐seekers and refugees living in the United States using a qualitative phenomenological approach. Twelve Syrians (n = 8 men, n = 4 women) between 20 and 52 years of age (M = 35.8, SD = 10.7) were interviewed about their experiences across three stages of resettlement: (1) pre‐resettlement, (2) resettlement/migration, and (3) post‐resettlement. Findings suggest that the effects of conflict‐induced displacement and resettlement permeate across multiple ecologies. These range from the individual and his or her interpersonal relationships to their larger community and society. C/MFTs should account for contextual factors while becoming familiar with the sociopolitical impact of displacement and resettlement in their clinical work with this population.
nanoDSF as screening tool for enzyme libraries and biotechnology development
Authors: Magnusson Anders O. , Szekrenyi Anna , Joosten Henk‐Jan , Finnigan James , Charnock Simon , Fessner Wolf‐Dieter
Published: November 2018

Enzymes are attractive tools for synthetic applications. To be viable for industrial use, enzymes need sufficient stability towards the desired reaction conditions such as high substrate and cosolvent concentration, non‐neutral pH and elevated temperatures. Thermal stability is an attractive feature not only because it allows for protein purification by thermal treatment and higher process temperatures but also due to the associated higher stability against other destabilising factors. Therefore, high‐throughput screening (HTS) methods are desirable for the identification of thermostable biocatalysts by discovery from nature or by protein engineering but current methods have low throughput and require time‐demanding purification of protein samples. We found that nanoscale differential scanning fluorimetry (nanoDSF) is a valuable tool to rapidly and reliably determine melting points of native proteins. To avoid intrinsic problems posed by crude protein extracts, hypotonic extraction of overexpressed protein from bacterial host cells resulted in higher sample quality and accurate manual determination of several hundred melting temperatures per day. We have probed the use of nanoDSF for HTS of a phylogenetically diverse aldolase library to identify novel thermostable enzymes from metagenomic sources and for the rapid measurements of variants from saturation mutagenesis. The feasibility of nanoDSF for the screening of synthetic reaction conditions was proved by studies of cosolvent tolerance, which showed protein melting temperature to decrease linearly with increasing cosolvent concentration for all combinations of six enzymes and eight water‐miscible cosolvents investigated, and of substrate affinity, which showed stabilisation of hexokinase by sugars in the absence of ATP cofactor.

Enzymes

Alcohol dehydrogenase (NADP+) (EC 1.1.1.2), transketolase (EC 2.2.1.1), hexokinase (EC 2.7.1.1), 2‐deoxyribose‐5‐phosphate aldolase (EC 4.1.2.4), fructose‐6‐phosphate aldolase (EC 4.1.2.n).