bluuebunny/crossref_metadata_2025 huggingface dataset:
The space where aging acts: focus on the GABAergic synapse
Authors: Rozycka Aleksandra , Liguz‐Lecznar Monika
Published: May 2017

As it was established that aging is not associated with massive neuronal loss, as was believed in the mid‐20th Century, scientific interest has addressed the influence of aging on particular neuronal subpopulations and their synaptic contacts, which constitute the substrate for neural plasticity. Inhibitory neurons represent the most complex and diverse group of neurons, showing distinct molecular and physiological characteristics and possessing a compelling ability to control the physiology of neural circuits. This review focuses on the aging of GABAergic neurons and synapses. Understanding how aging affects synapses of particular neuronal subpopulations may help explain the heterogeneity of aging‐related effects. We reviewed the literature concerning the effects of aging on the numbers of GABAergic neurons and synapses as well as aging‐related alterations in their presynaptic and postsynaptic components. Finally, we discussed the influence of those changes on the plasticity of the GABAergic system, highlighting our results concerning aging in mouse somatosensory cortex and linking them to plasticity impairments and brain disorders. We posit that aging‐induced impairments of the GABAergic system lead to an inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond with plastic changes to environmental and cellular challenges, leaving the brain more vulnerable to cognitive decline and damage by synaptopathic diseases.
Vine copulas: modelling systemic risk and enhancing higher‐moment portfolio optimisation
Authors: Low Rand Kwong Yew
Published: May 2017

Asymmetric dependence in equities markets has been shown to have detrimental effects on portfolio diversification as assets within the portfolio exhibit greater correlations during market downturns compared to market upturns. By applying the Clayton canonical vine copula (CVC) to model asymmetric dependence, we produce a measure of systemic risk across a portfolio of assets. In addition, we use the Clayton CVC to produce estimates of expected returns in an application to higher‐moment portfolio optimisation and find evidence of an improvement in performance across a range of risk‐adjusted return measures and the indices of acceptability.
Criteria for conceptualizing behavioural addiction should be informed by the underlying behavioural mechanism
Authors: Tunney Richard J. , James Richard J. E.
Published: May 2017

Commentary to: How can we conceptualize behavioural addiction without pathologizing common behaviours?
PPAR‐gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double‐blind randomized controlled pilot trial
Authors: Schmitz Joy M. , Green Charles E. , Hasan Khader M. , Vincent Jessica , Suchting Robert , Weaver Michael F. , Moeller F. Gerard , Narayana Ponnada A. , Cunningham Kathryn A. , Dineley Kelly T. , Lane Scott D.
Published: May 2017

Background and aims

Pioglitazone (PIO), a potent agonist of PPAR‐gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance and tolerability were evaluated.

Design

Two‐arm double‐blind randomized controlled proof‐of‐concept pilot trial of PIO or placebo (PLC).

Setting

Single‐site out‐patient treatment research clinic in Houston, TX, USA.

Participants

Thirty treatment‐seeking adults, 18 to 60 years old, with CUD. Eighteen participants (8 = PIO; 10 = PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre‐/post‐treatment.

Intervention

Study medication was dispensed at thrice weekly visits along with once‐weekly cognitive behavioral therapy for 12 weeks.

Measurements

Measures of target engagement mechanisms of interest included cocaine craving assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive Drug Use Scale (OCDUS), a visual analog scale (VAS) and change in WM integrity. Feasibility measures included number completing treatment, medication compliance (riboflavin detection) and tolerability (side effects, serious adverse events).

Findings

Target engagement change in mechanisms of interest, defined as a ≥ 0.75 Bayesian posterior probability of an interaction existing favoring PIO over PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed by fractional anisotropy (FA) values. Outcomes indicated greater decrease in craving and greater increase in FA values in the PIO group. Feasibility was demonstrated by high completion rates among those starting treatment (21/26 = 80%) and medication compliance (≥ 80%). There were no reported serious adverse events for PIO.

Conclusions

Compared with placebo, patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment. Pioglitazone shows good feasibility as a treatment for cocaine use disorder.
Postoperative interventions to reduce inflammatory complications after third molar surgery: review of the current evidence
Authors: Cho H , Lynham AJ , Hsu E
Published: May 2017

Inflammatory complications such as pain, swelling, trismus, infection and alveolar osteitis have an adverse affect on the quality of life of patients after third molar removal. This review presents the current evidence on postoperative strategies to reduce these complications. A literature search was performed to identify articles published in English between 2000 to 2016 using the following keywords: third molar(s), wisdom tooth/teeth, pain, swelling, trismus, infection, alveolar osteitis and dry socket. In total, 221 papers were reviewed. Methods published included analgesics, antibiotics, corticosteroids, mouthwashes, topical gels, cryotherapy and ozone therapy. This review highlights the variability in evidence available and summarizes the findings from best‐quality evidence. In conclusion, paracetamol and ibuprofen are efficacious in managing postoperative pain. Corticosteroids and antibiotics should only be used in selected cases. Chlorhexidine reduces alveolar osteitis. The benefits of cryotherapy, postoperative irrigation and ozone gel are yet to be established.
Increased delta neutrophil index in women with severe preeclampsia
Authors: Cho Hee Young , Jung Inkyung , Kim So Jung , Park Yong Won , Kim Young Han , Kwon Ja‐Young
Published: May 2017

Problem

The pathophysiology of preeclampsia (PE) is believed to be associated with a systemic inflammatory response, but few inflammatory markers are currently available to predict PE. Therefore, the aim of this study was to compare the serum delta neutrophil index (DNI) between normal and preeclamptic women.

Methods

Sixty‐five patients with mild preeclampsia (mPE), 147 patients with severe preeclampsia (sPE), and 163 women with normal pregnancy were included in this study. Maternal laboratory values including DNI were compared among the three groups.

Results

The mean DNI was significantly higher in the sPE group, but there was no significant difference between the normal pregnancy group and mPE. The DNI also showed positive correlation with systolic and diastolic blood pressures, mean arterial pressure, proteinuria during 24 hours, proteinuria in dipstick, and ominous symptoms.

Conclusion

The serum DNI value was increased in women with severe preeclampsia compared to that in those with normal pregnancy or mild preeclampsia. Further studies are needed to evaluate application of the DNI value as a prognostic marker of preeclampsia.
Beat‐to‐beat ECG restitution: A review and proposal for a new biomarker to assess cardiac stress and ventricular tachyarrhythmia vulnerability
Authors: Fossa Anthony A.
Published: May 2017

Background

Cardiac restitution is the ability of the heart to recover from one beat to the next. Ventricular arrhythmia vulnerability can occur when the heart does not properly adjust to sudden changes in rate or in hemodynamics leading to excessive temporal and/or spatial heterogeneity in conduction or repolarization. Restitution has historically been used to study, by invasive means, the dynamics of the relationship between action potential duration (APD) and diastolic interval (DI) in sedated subjects using various pacing protocols. Even though the analogous measures of APD and DI can be obtained using the surface ECG to acquire the respective QT and TQ intervals for ECG restitution, this methodology has not been widely adopted for a number of reasons.

Methods

Recent development of more advanced software algorithms enables ECG intervals to be measured accurately, on a continuous beat‐to‐beat basis, in an automated manner, and under highly dynamic conditions (i.e., ambulatory or exercise) providing information beyond that available in the typical resting state.

Results

Current breakthroughs in ECG technology will allow ECG restitution measures to become a practical approach for providing quantitative measures of the risks for ventricular arrhythmias as well as cardiac stress in general.

Conclusions

In addition to a review of the underlying principles and caveats of ECG restitution, a new approach toward an advancement of more integrated restitution biomarkers is proposed.
Earnings Quality in a Bubble Period: The Case of Construction Activity Firms in Spain
Authors: Navarro‐García Juan Carlos , Madrid‐Guijarro Antonia
Published: May 2017

Housing bubbles may result in deep crises that affect all economic systems. This study investigates how the recent housing bubble in Spain has affected earnings quality during the whole bubble. To this end, we use data on mostly private construction activity firms in Spain, that is, construction and real estate companies. Earnings quality is studied by means of the predictive ability of earnings, conservatism, discretionary accruals and real earnings management. The results indicate a progressive decrease in the quality of financial reporting as the bubble develops, as managers try to conceal an underlying downward trend. We further show that earnings quality continues to decline even after the bubble bursts. Overall, this contribution, together with those of other environments, may suggest that, in a bubble context, we have to take care of firms’ earnings quality even some years before the crisis comes to the fore.
Conglomerate Unions and Transformations of Union Democracy
Authors: Thomas Adrien
Published: May 2017

Confronted with membership losses and declining bargaining power, trade unions have engaged in both political and organizational responses. A frequent type of organizational response has involved the creation of conglomerate unions, which bring together workers from various sectors and occupations. Pointing out a number of parallels between organizational developments in trade unions and political parties, this article analyses the emergence of conglomerate unions as a cause and consequence of changing conceptions of union democracy. Drawing on two in‐depth case studies conducted in France and Germany, the article examines how trade unions perceive their situation and how they define a reform rationale based on increasing their organizational ‘efficiency’ and ‘effectiveness’. In accordance with this rationale, unions engage in mergers and create larger conglomerates, thereby centralizing decision‐making bodies and professionalizing their staff. The reform of trade unions’ internal organization, in turn, affects unions’ capacity for interest aggregation and representation.
Ownership and Pay in Britain
Authors: Pendleton Andrew , Bryson Alex , Gospel Howard
Published: May 2017

Drawing on principal–agent perspectives on corporate governance, the article examines whether employees’ hourly pay is related to ownership dispersion. Using linked employee‐workplace data from the British Workplace Employment Relations Survey 2011, and using a variety of techniques including interval regression and propensity score matching, average hourly pay is found to be higher in dispersed ownership workplaces. The premium is broadly constant across most of the wage distribution, but falls at the 95th percentile to become statistically non‐significant. This contrasts with earlier papers which indicate that higher level employees are the primary beneficiaries of higher pay from dispersed ownership. The dispersed ownership pay premium is not readily explained by efficiency wage perspectives but is consistent with a managerial desire for a ‘quiet life’.
β2‐AR activation induces chemoresistance by modulating p53 acetylation through upregulating Sirt1 in cervical cancer cells
Authors: Chen Hongyu , Zhang Wei , Cheng Xiang , Guo Liang , Xie Shuai , Ma Yuanfang , Guo Ning , Shi Ming
Published: May 2017

It has been suggested that β2‐adrenergic receptor (β2‐AR)‐mediated signaling induced by catecholamines regulates the degradation of p53. However, the underlying molecular mechanisms were not known. In the present study, we demonstrated that catecholamines upregulated the expression of silent information regulator 1 (Sirt1) through activating β2‐AR‐mediated signaling pathway, since selective β2‐AR antagonist ICI 118, 551 and non‐selective β‐blocker proprenolol effectively repressed isoproterenol (ISO)‐induced Sirt1 expression. Catecholamines inhibited doxorubicin (DOX)‐induced p53 acetylation and transcription‐activation activities by inducing the expression of Sirt1. Knockdown of the Sirt1 expression by the specific siRNA remarkably blocked the inhibitory effects of ISO on DOX‐induced p53 acetylation. In addition, we demonstrated that catecholamines induced resistance of cervical cancer cells to chemotherapeutics both in vitro and in vivo and that β2‐AR was overexpressed in cervical cancer tissues. Our data suggest that the p53‐dependent, chemotherapeutics‐induced cytotoxicity in cervical cancer cells may be compromised by catecholamines‐induced upregulation of the Sirt1 expression through activating the β2‐AR signaling.
p62/SQSTM1 as an oncotarget mediates cisplatin resistance through activating RIP1‐NF‐κB pathway in human ovarian cancer cells
Authors: Yan Xiao‐Yu , Zhang Yu , Zhang Juan‐Juan , Zhang Li‐Chao , Liu Ya‐Nan , Wu Yao , Xue Ya‐Nan , Lu Sheng‐Yao , Su Jing , Sun Lian‐Kun
Published: May 2017

Platinum‐based therapeutic strategies have been widely used in ovarian cancer treatment. However, drug resistance has greatly limited therapeutic efficacy. Recently, tolerance to cisplatin has been attributed to other factors unrelated to DNA. p62 (also known as SQSTM1) functions as a multifunctional hub participating in tumorigenesis and may be a therapeutic target. Our previous study showed that p62 was overexpressed in drug‐resistant ovarian epithelial carcinoma and its inhibition increased the sensitivity to cisplatin. In this study, we demonstrate that the activity of the NF‐κB signaling pathway and K63‐linked ubiquitination of RIP1 was higher in cisplatin‐resistant ovarian (SKOV3/DDP) cells compared with parental cells. In addition, cisplatin resistance could be reversed by inhibiting the expression of p62 using siRNA. Furthermore, deletion of the ZZ domain of p62 that interacts with RIP1 in SKOV3 cells markedly decreased K63‐linked ubiquitination of RIP1 and inhibited the activation of the NF‐κB signaling pathway. Moreover, loss of the ZZ domain from p62 led to poor proliferative capacity and high levels of apoptosis in SKOV3 cells and made them more sensitive to cisplatin treatment. Collectively, we provide evidence that p62 is implicated in the activation of NF‐κB signaling that is partly dependent on RIP1. p62 promotes cell proliferation and inhibits apoptosis thus mediating drug resistance in ovarian cancer cells.
HBx protein‐mediated ATOH1 downregulation suppresses ARID2 expression and promotes hepatocellular carcinoma
Authors: Gao Qingzhu , Wang Kai , Chen Ke , Liang Li , Zheng Yaqiu , Zhang Yunzhi , Xiang Jin , Tang Ni
Published: May 2017

Hepatitis B virus X protein plays a crucial role in the pathogenesis of hepatocellular carcinoma. We previously showed that the tumor suppressor ARID2 inhibits hepatoma cell cycle progression and tumor growth. Here, we evaluated whether hepatitis B virus X protein was involved in the modulation of ARID2 expression and hepatocarcinogenesis associated with hepatitis B virus infection. ARID2 expression was downregulated in HBV‐replicative hepatoma cells, HBV transgenic mice, and HBV‐related clinical HCC tissues. The expression levels of HBx were negatively associated with those of ARID2 in hepatocellular carcinoma tissues. Furthermore, HBx suppressed ARID2 at transcriptional level. Mechanistically, the promoter region of ARID2 gene inhibited by HBx was located at nt‐1040/nt‐601 and contained potential ATOH1 binding elements. In addition, ectopic expression of ATOH1 or mutation of ATOH1 binding sites within ARID2 promoter partially abolished HBx‐triggered ARID2 transcriptional repression. Functionally, ARID2 abrogated HBx‐enhanced migration and proliferation of hepatoma cells, whereas depletion of ATOH1 enhanced tumorigenecity of HCC cells. Therefore, our findings suggested that deregulation of ARID2 by HBx through ATOH1 may be involved in HBV‐related hepatocellular carcinoma development.
Underinvestment in Producer‐Funded Agricultural R&D: The Role of the Horizon Problem
Authors: Xiao Zhihua , Fulton Murray
Published: May 2017

Agricultural research and development (R&D) investment has become an increasingly important policy issue as food prices increased and food security problems emerged over the last decade. An important source of agricultural R&D funding is the producer check‐off, which is increasingly being used to fund applied agricultural research. Existing studies of producer‐funded agricultural R&D indicate there are high private rates of return to agricultural R&D investment by farmers, and thus farmers are underinvesting in R&D. Since a farmer's time horizon is typically less than the period of time over which the benefits of agricultural R&D take place, the horizon problem has been identified as a possible factor in this underinvestment. This paper shows that the horizon problem is unlikely to be the only cause of the underinvestment when the internal rate of return is large. Instead, shortened producer horizons only emerge as the main source of underinvestment when the internal rate of return is low. As a result, other factors, including behavioral determinants, need to be looked at as contributors to the underfunding of agricultural R&D.

Les investissements en recherche et développement agricoles sont devenus un important enjeu politique étant donné l'augmentation des prix des aliments et les problèmes de sécurité alimentaire de la dernière décennie. Une importante source de financement pour la recherche et le développement dans le domaine agricole sont les programmes de contribution des producteurs, ces derniers étant de plus en plus sollicités pour financer la recherche agricole appliquée. Certaines études portant sur la recherche et le développement agricoles financés par les producteurs indiquent un haut taux de rendement privé des investissements en recherche et développement agricoles par les producteurs. Ces derniers y investissent donc moins. Puisque l'échéancier de l'agriculteur est typiquement moins long que celui pendant lequel les avantages liés à la recherche et au développement dans le domaine agricole s'échelonnent, le problème de l'horizon a été identifié comme facteur potentiel au sous‐investissement. Il est probable, selon cet article, que le problème de l'horizon ne soit pas la seule cause du sous‐investissement lorsque le taux interne de rendement s'avère grand. Plutôt, les échéanciers réduits des agriculteurs apparaissent seulement comme les sources principales de sous‐investissement lorsque le taux de rendement interne est bas. Il en résulte que d'autres facteurs, incluant les déterminants comportementaux, doivent être examinés à titre de contributeurs au sous‐investissement de la recherche et du développement en agriculture.
Polarizable crystals in apocrine sweat gland tumors: A series of 3 cases
Authors: Johnson Gina , Gardner Jerad M. , Shalin Sara C.
Published: May 2017

Polarizable calcium oxalate (CaOx) crystals have been well documented in breast biopsies, generally associated with benign apocrine metaplasia. In contrast, polarizable crystals are only rarely reported in skin adnexal neoplasms. We report 3 different cases of sweat gland tumors with polarizable crystals morphologically suggestive of CaOx: 1 apocrine hidrocystoma and 2 tubular apocrine adenomas. The histologic features were examined in 3 cases. Clinical presentation summary included 2 males and 1 female, ages 53 to 74 years, with lesions located on the left cheek, inferior vertex scalp and the left eyebrow. All 3 cases showed polarizable, geometric, plate‐like and fractured, colorless crystals within the lumens of the neoplasm. Of note, these crystals were seen only on the toluidine blue‐stained section of Case #1, but were not present on the corresponding permanent section. We hypothesize that polarizable crystals may be present in sweat gland neoplasms more often than previously documented, but that they may often dissolve with routine processing, accounting for their rare visibility. We highlight this rare finding, and suggest that it may be underreported. We only noted this finding in benign apocrine tumors; further investigation would be necessary to determine whether these crystals are also seen in other cutaneous adnexal neoplasms.
Optimal Pricing and Replenishment of an Expiring Inventoried Product under Heterogeneous Consumer Sensitivities
Authors: Herbon Avi
Published: May 2017

Efficient pricing and replenishment decisions have the potential to yield significant increase in revenues. A widespread assumption in existing models of expiring inventories is that consumers are homogeneous in their sensitivities towards the factors that influence demand. Yet, there are numerous scenarios in which consumers may vary in terms of their sensitivities. In addition, most of the current literature addresses expiring inventories for which the perceived quality deteriorates over time, while models of perishables for which the quality remains stable over time (e.g., electronic devices) or increases (e.g., green bananas, or wine) have rarely been suggested. We analyze a joint pricing and replenishment optimization model that aims to maximize the retailer's profit and is general enough to consider these three types of expiring inventories, as well as heterogeneity in consumer sensitivities. In particular, our model considers the effects of remaining shelf‐life, price and perceived quality on demand. We obtain the optimal price given any cycle length and derive the FOC (first order condition) for obtaining the optimal cycle length. By numerical study, we show that the seller might gain significant profits in cases where consumers are highly heterogeneous either in their sensitivity to price or in their sensitivity to perceived quality. In contrast, the results indicate that the seller might lose significant profits (up to 16%) when consumers are highly heterogeneous in their sensitivity to expiration. Unexpectedly, the optimal price consumers pay is, in general, only moderately affected by the heterogeneity in consumer sensitivity.
Children's intuitive sense of number develops independently of their perception of area, density, length, and time
Authors: Odic Darko
Published: May 2017

Young children can quickly and intuitively represent the number of objects in a visual scene through the Approximate Number System (ANS). The precision of the ANS – indexed as the most difficult ratio of two numbers that children can reliably discriminate – is well known to improve with development: whereas infants require relatively large ratios to discriminate number, children can discriminate finer and finer changes in number between toddlerhood and early adulthood. Which factors drive the developmental improvements in ANS precision? Here, we investigate the influence of four non‐numeric dimensions – area, density, line length, and time – on ANS development, exploring the degree to which the ANS develops independently from these other dimensions, from inhibitory control, and from domain‐general factors such as attention and working memory that are shared between these tasks. A sample of 185 children between the ages of 2 and 12 years completed five discrimination tasks: approximate number, area, density, length, and time. We report three main findings. First, logistic growth models applied to both accuracy and Weber fractions (w; an index of ANS precision) across age reveal distinct developmental trajectories across the five dimensions: while area and length develop by adolescence, time and density do not develop fully until early adulthood, with ANS precision developing at an intermediate rate. Second, we find that ANS precision develops independently of the other four dimensions, which in turn develop independently of the ANS. Third, we find that ANS precision also develops independently from individual differences in inhibitory control (indexed as the difference in accuracy and w between Congruent and Incongruent ANS trials). Together, these results are the first to provide evidence for domain‐specific improvements in ANS precision, and place children's maturing perception of number, space, and time into a broader developmental context.
Older people with Type 2 diabetes, including those with chronic kidney disease or dementia, are commonly overtreated with sulfonylurea or insulin therapies
Authors: Hambling C. E. , Seidu S. I. , Davies M. J. , Khunti K.
Published: May 2017

Aim

To evaluate potential overtreatment with sulfonylurea and insulin therapies amongst older people with Type 2 diabetes, including those with chronic kidney disease or dementia.

Methods

Using the ECLIPSE Live software tool, we developed a search to examine data on older people (age ≥ 70 years) with Type 2 diabetes, who were prescribed sulfonylurea or insulin therapies over the previous 90 days. Sixteen Norfolk general practices participated, representing a population of 24 661 older people, including 3862 (15.7%) with Type 2 diabetes. Of these, 1379 (35.7%) people were prescribed sulfonylurea or insulin therapies. Data extracted included age, sex, last recorded HbA1c value, renal function and dementia codes.

Results

The median age of the study cohort was 78 years. A total of 644 people (47.8%) had chronic kidney disease (estimated GFR < 60 mL/min/1.73m2) and 60 people (4.35%) had dementia. The median (interquartile range) HbA1c concentration for the entire cohort was 58 (51–69) mmol/mol [7.5 (6.8–8.5)%], with no difference in median HbA1c between those with or without either chronic kidney disease or dementia. In total, 400 older people (29.9%) had an HbA1c concentration < 53 mmol/mol (7%), of whom 162 (12.1%) had HbA1c < 48 mmol/mol (6.5%). Stratified by prescription for sulfonylurea, insulin or combined insulin and sulfonylurea therapies, 282 (35.2%), 93 (24.2%) and 25 people (16.3%), respectively, had HbA1c < 53 mmol/mol (7.0%). Treatment to an HbA1c target of < 53 mmol/mol (7.0%) was as prevalent in those with chronic kidney disease or dementia as in those without.

Conclusion

In the present cohort of older people with Type 2 diabetes prescribed sulfonylurea or insulin therapies, overtreatment was common, even in the presence of comorbidities known to increase hypoglycaemia risk.
LAPSInsulin115: A novel ultra‐long‐acting basal insulin with a unique action profile
Authors: Wronkowitz Nina , Hartmann Thorsten , Görgens Sven Wolfgang , Dietze‐Schroeder Daniela , Indrakusuma Ira , Choi In Young , Park Sung Hee , Lee Young‐Mi , Kwon Se Chang , Kang Yeonjoo , Hompesch Marcus , Eckel Jürgen
Published: May 2017

Aims

To conduct a comprehensive pre‐clinical study of the novel ultra‐long acting insulin analogue LAPSInsulin115.

Methods

Pharmacokinetic/pharmacodynamic studies comparing LAPSInsulin115 with other basal insulins were conducted in genetically diabetic (db/db) mice. Insulin signalling in the major target organs was analysed using Western blot after single subcutaneous injection in wild‐type male Wistar rats. Using in vitro assays we analysed transendothelial transport, insulin receptor (IR) interaction, and the mitogenic and metabolic properties of LAPSInsulin115. Furthermore, IR downregulation after long‐term exposure to high concentrations of LAPSInsulin115 was analysed using an in vitro desensitization/resensitization model.

Results

The novel Fc‐conjugated insulin derivative LAPSInsulin115 showed an extensively prolonged pharmacokinetic and pharmacodynamic profile in rodents. Despite its size of 59 kDa, LAPSInsulin115 passes the vascular endothelial barrier and induces insulin signalling in all major target tissues in rats. In vitro, LAPSInsulin115 showed a very slow onset of action because of its reduced IR affinity; however, after long‐term stimulation it was equipotent in respect to its metabolic potency and showed no increased mitogenic action when compared with regular insulin. Remarkably, under conditions of chronic exposure, LAPSInsulin115 does not induce irreversible desensitization of target cells, which is probably attributable to much less prominent IR downregulation.

Conclusion

Thus, LAPSInsulin115 exhibits a unique in vivo and in vitro profile and thereby represents an excellent candidate for a once‐weekly insulin analogue.
Room for manoeuvre: User participation in water resources management in Burkina Faso
Authors: Daré William's , Venot Jean‐Philippe
Published: May 2017

Participation in natural resources management is widely promoted in sub‐Saharan Africa, but faces mounting criticism from social science scholars who rarely engage with it in practice. We use the notion of room for manoeuvre to reflect on a multi‐level participatory approach designed to support the Burkinabè Integrated Water Resources Management policy and propose ways of engaging constructively with local users and policy‐makers. Within an “invited space” of participation, water users’ room for manoeuvre was enhanced through the acquisition of new knowledge on the legal Integrated Water Resources Management (IWRM) framework. This allowed them to interact with decision‐makers and to extend their networks. Power imbalances were discussed, but this did not lead to modifying existing power structures that hinge on broader societal dynamics.
Transient left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve: A stunning cause
Authors: Meuwese Christiaan L. , Boulaksil Mohamed , van Dijk Jeroen , Polad Jawed , Meijburg Huub W.
Published: May 2017

Left ventricular outflow tract obstruction (LVOTO) and systolic anterior motion (SAM) of the mitral valve may have various etiologies, of which hypertrophic cardiomyopathy is the most common. More rarely, an acute coronary syndrome, myocardial stunning, and takotsubo cardiomyopathy may give rise to LVOTO and SAM. Here, we present a 70‐year‐old female patient with a non‐ST‐elevation acute coronary syndrome treated with percutaneous coronary intervention. Echocardiography the day after, because of dyspnea and hypotension, revealed apical akinesia, LVOTO, and SAM, which proved completely reversible after treatment with a β‐blocker and a 2‐month follow‐up period. It was concluded that postischemic apical stunning had caused LVOTO and SAM.
Mitral arcade: A rare case presenting with fatigue and cough
Authors: Aydın Sahin Derya , Ceylan Ozben
Published: May 2017

An 11‐year‐old girl was admitted to pediatric emergency unit with complaints of fatigue and cough. The patient had no previous complaints. There was no history of rheumatic heart disease. The height and duration of the P‐wave was 4 mm and 0.16 seconds, respectively (p mitrale). Echocardiography showed enlarged left atrium (51×61 mm in diameter). Both the anterolateral and posteromedial papillary muscles were directly attached to the anterior and posterior mitral valve leaflets without tendinous chords. The patient was diagnosed with mitral arcade, severe mitral stenosis, and mitral regurgitation. The patient was referred to surgery for replacement of mitral valve.
Evaluation of athletes with complex congenital heart disease
Authors: Bates Benjamin A. , Richards Camille , Hall Michael , Kerut Edmund K. , Campbell William , McMullan Michael R.
Published: May 2017

As a result of improvements in congenital heart surgery, there are more adults alive today with congenital heart disease (CHD) than children. Individuals with cardiac birth defects may be able to participate in physical activities but require proper cardiovascular evaluation. The American Heart Association and American College of Cardiology released guidelines in 2015 for athletes with cardiovascular abnormalities. The guidelines express that although restriction from competitive athletics may be indicated for some, the majority of individuals with CHD can and should engage in some form of physical activity. This case study demonstrates the importance of combining all aspects of history, physical examination, ECG, and imaging modalities to evaluate cardiac anatomy and function in young athletes with complex CHD.
Epilepsia partialis continua after an anterior circulation ischaemic stroke
Authors: Bentes C. , Franco A. C. , Peralta A. R. , Viana P. , Martins H. , Morgado C. , Casimiro C. , Fonseca C. , Geraldes R. , Canhão P. , Pinho e Melo T. , Paiva T. , Ferro J. M.
Published: May 2017

Background and purpose

Although cerebrovascular disorders are the main cause of epilepsia partialis continua (EPC) in adulthood, the frequency of EPC after stroke is unknown. The aim was to prospectively ascertain its frequency 1 year after an ischaemic stroke.

Methods

This was a prospective study of consecutive acute anterior circulation ischaemic stroke patients, previously independent, with an admission National Institutes of Health Stroke Scale score ≥4, an acute ischaemic lesion on imaging and no previous epileptic seizures. During admission patients received standardized diagnostic and medical care and were submitted to a neurophysiological evaluation protocol. One year after stroke, patients were re‐evaluated by an epilepsy expert neurologist and performed a video‐electroencephalogram with electromyography co‐registration whenever myoclonus was observed during neurological examination for jerk‐locked back averaging analysis (JLBA). EPC was defined as continuously repeated fragments of epileptic seizures, with preserved consciousness, lasting at least 1 h, and representing locally restricted epileptic activity.

Results

In all, 151 acute anterior circulation stroke patients were consecutively included and prospectively evaluated, but 23 died in the first year. One year after stroke, from 127 patients alive, 117 (92.1%) underwent clinical and neurophysiological evaluation. In two (1.7%) patients, EPC diagnosis was made both by clinical and electroencephalographic criteria, namely JLBA. Both patients had a history of remote symptomatic seizures and one of them acute symptomatic seizures and non‐convulsive status epilepticus criteria during the first 7 days after stroke.

Conclusions

Despite its low frequency, the high stroke incidence makes post‐stroke EPC relevant. This study draws attention to this recognizable condition with therapeutic and eventually prognostic implications.
Low temperatures during ontogeny increase fluctuating asymmetry and reduce maternal aggression in the house mouse, Mus musculus
Authors: Benderlioglu Zeynep , Dow Eliot
Published: May 2017

Maternal aggression is behavior displayed by post‐partum lactating female mice toward unfamiliar conspecifics, presumably as a defense against infanticide. A variety of perinatal stressors can impair maternal care in adulthood. Previous studies on associations between developmental perturbations and maternal aggression have produced mixed results. To address this issue, we employed a proxy for developmental instability, namely fluctuating asymmetry (FA) to further elucidate the relationship between low temperature stress and maternal aggression. FA, small, random deviations from perfect symmetry in bilateral characters is used as a quantitative measure of stress during ontogeny. Dams were either maintained in standard laboratory temperatures (21 ± 2°C), or cold temperatures (8 ± 2°C) during gestation. During lactation, their progeny either remained in the temperature condition in which they were gestated or were transferred to the other temperature condition. Four individual measures of FA, a composite of these measures, and three measures of maternal aggression were assessed in the female progeny in adulthood. Exposure to low temperatures during both pre‐ and early post‐natal development increased composite FA and reduced all three measures of maternal aggression compared to controls. Exposure to low temperatures during the pre‐ or post‐natal period alone did not induce either high FA or altered maternal aggression. Certain measures of FA and nest defense were negatively correlated. Our results suggest that low temperatures experienced during gestation and lactation may have important fitness costs. Low maternal aggression toward infanticidal conspecifics is likely to limit the number of offspring surviving into adulthood. Overall, FA appears to be a reliable indicator of chronic developmental stress with implications for fitness.
Effect of a nitrogen pulse on ecosystem N processing at different temperatures: A mesocosm experiment with 15NO3− addition
Authors: Olsen Saara , Cao Yu , Florencia Gutierrez María , Brucet Sandra , Landkildehus Frank , Lauridsen Torben L. , Davidson Thomas A. , Søndergaard Martin , Jeppesen Erik , Risgaard‐Petersen Nils
Published: May 2017

Shallow lakes may play an important role for the nitrogen (N) balance in drainage basins by processing, transferring and retaining N inputs. An increase in the frequency of storm‐induced short‐term N pulses and increased water temperatures are both likely outcomes of climate change, potentially affecting the N processing in lakes.

An experiment with a K15NO3− pulse addition (increase in NO3− concentration from c. 0.1 to 2 mg/L) was carried out in 12 mesocosms with relatively low (applies to Danish lakes) total N (TN) and total phosphorus (TP) concentrations (c. 0.3 mg N L−1 and 0.04 mg P L−1) to assess the effects of an N pulse on N processing and storage in shallow lake ecosystems. The mesocosms have a hydraulic retention time of approximately two and a half months, and at the time of the experiment, they had been adapted to contrasting temperatures for a period of 10 years: ambient, T3 (heating according to the Intergovernmental Panel on Climate Change 2007 A2 scenario, +3.7–4.5°C, depending on season) and T5 (heating with A2 + 50%, +4.9–6.6°C).

Macrophytes and filamentous algae retained up to 40% and 30% of the added 15N, respectively, reflecting their high biomass in the mesocosms. Macrophytes and filamentous algae constituted between 70% and 80% of the biomass of all primary producers during the experiment in the T3 and ambient treatments and between 20% and 40% in T5. By comparison, less than 1% of the added 15N diffused to the sediment and less than 5% was lost to the atmosphere as N2 gas. Snails represented the long‐term storage of 15N, retaining up to 6% of the tracer and with detectable enrichment 100 days after tracer addition.

We found no significant differences among the temperature treatments in the 15N turnover after pulse dosing. However, a larger percentage of 15N was stored in macrophytes in the ambient and T3 mesocosms, reflecting higher biomasses than in T5 where filamentous algae were more abundant. Macrophytes and filamentous algae rather than temperature were therefore key controllers of N processing during the summer N pulse in these shallow, relatively low TP lakes.
From dimictic to monomictic: Empirical evidence of thermal regime transitions in three deep alpine lakes in Austria induced by climate change
Authors: Ficker Harald , Luger Martin , Gassner Hubert
Published: May 2017

Duration and timing of thermal stratification and the period of vertical mixing are crucial for internal chemical and biological processes of deep temperate lakes. Climatic changes induced a prolongation of thermal stratification in many lakes over the last decades. This study provides a comparative assessment of observed climate‐induced changes in thermal and limnological properties of three originally dimictic temperate lakes.

We analysed 41 years of vertical sampling data of Lake Irrsee (IR), Mondsee (MO) and Hallstätter See (HA) located in the Salzkammergut lake district of Austria. We examined temperatures in surface and bottom waters, quantified changes in thermal regimes and investigated the development of hypoxia, anoxia and phosphorus concentrations of the three lakes from 1975 to 2015.

Mean annual surface‐water temperatures increased substantially, whereas bottom‐water temperatures showed insignificant trends in IR and MO and a slight rising trend in HA. Resulting higher vertical temperature gradients caused stronger thermal stabilities of the lakes. Based on calculations of daily thermal stability, all three lakes showed a significant prolongation of the stratification period with +31 days (±7 days) in IR, +37 days (±7 days) in MO and +28 (±8 days) in HA. We observed greater changes in the timing of onset of stratification compared to the changes in the timing of stratification termination (IR onset −19 days versus termination +11 days, MO onset −21 days versus termination +16 days, HA onset −16 days versus termination +12 days).

We found that expanding seasonal hypoxia and anoxia were correlated to prolonged seasonal stratifications and to increasing phosphorus concentrations in bottom‐water layers. However, higher phosphorus concentrations in bottom waters did not raise the lakes′ volume‐weighted total phosphorus concentrations.

Under ongoing climate change, alterations in the thermal characteristics will inevitably lead to a transition of mixing regimes from a dimictic to a monomictic mixing pattern in originally ice‐covered temperate lakes. Our investigation revealed that this transition will be earlier in larger and deeper lakes.
Moses Mendelssohn, Germany's First Migrant
Authors: Peterson Brent O.
Published: May 2017

Germans have only recently accepted the fact that they belong to a nation of immigrants; officially, they still maintain the myth that migration to Germany began during the economic miracle of the 1950s. The claim that Moses Mendelssohn was Germany's first migrant is a deliberate intervention into the debate over the role of migrants in German culture. Mendelssohn's significance and the reason that he can function as Germany's first migrant, is that, as an early and eloquent writer on the idea of integration and belonging, he was able to write himself into the center of the discourse about what it meant to be German as that discussion was beginning. His case could leverage a new opening into still contentious and unresolved debates on issues as diverse as the history of migration, the role of religion in national cultures, the limits of tolerance vis‐à‐vis Others, and the demands that a majority culture can legitimately place on migrant minorities.
Cost of illness of non‐alcoholic liver cirrhosis in Japan: A time trend analysis and future projections
Authors: Kitazawa Takefumi , Matsumoto Kunichika , Fujita Shigeru , Seto Kanako , Wu Yinghui , Hirao Tomohiro , Hasegawa Tomonori
Published: May 2017

Aim

Liver cirrhosis is a preneoplastic condition to hepatocellular carcinoma that is an important worldwide public health concern, and its economic burden has been estimated in some countries. The objective of this study was to estimate and predict the cost of illness (COI) associated with non‐alcoholic liver cirrhosis in Japan.

Methods

Using a COI method on available data from government statistics, we estimated the economic burden in 3‐year intervals from 1996 to 2014. We then predicted the COI in 3‐year intervals from 2017 to 2029 using fixed and variable model estimations. With fixed model estimation, only the estimated future population was used as a variable. Variable model estimation considered the time trends of health‐related indicators throughout the past 18 years.

Results

The estimated COI of non‐alcoholic liver cirrhosis was ¥208.1bn in 2014. The COI of non‐alcoholic liver cirrhosis had a downward trend from 1996 to 2014. The predicted future COI of non‐alcoholic liver cirrhosis was ¥144.3–210.5bn, ¥106.0–213.8bn, ¥88.6–213.4bn, ¥76.7–215.5bn, and ¥66.4–214.3bn in 2017, 2020, 2023, 2026, and 2029, respectively.

Conclusions

The results of this study suggest that the COI of non‐alcoholic liver cirrhosis in Japan has steadily decreased and will continue to decrease. Treatment of patients with hepatitis C virus infection with newly introduced technologies has high therapeutic effectiveness, which will affect the future prevalence of non‐alcoholic liver cirrhosis. When interpreting the results of long‐term estimation, it should be noted that the results of this study were based on present conditions.
Sol‐gel preparation and properties of Ag‐containing bioactive glass films on titanium
Authors: Fu Tao , Alajmi Zafer , Shen Yaogen , Wang Lijun , Yang Shuiyun , Zhang Man
Published: May 2017

Ag‐containing bioactive glass films (Ag/Ca atomic ratios of 0, 5% and 10%) were sol‐gel prepared for bioactive and antibacterial modification of titanium. The gel powders calcined at 610°C are mainly amorphous confirmed by x‐ray diffraction, but small diffraction peaks of Ca3SiO5 and silver are detected. The film surface is porous with the pore size of ~200 nm. Silver‐rich sub‐micro particles with sizes of 100‐480 nm are present at the surface of Ag‐glass films. CaP phase, metallic silver and silica are detected by x‐ray photoelectron spectroscopy. The mean apparent bonding strength of the films is as high as 21±1 MPa measured by the pull‐off test. The potentiodynamic polarization test shows that the coated samples have better corrosion resistance than the polished sample. The Ag‐glass coatings and their wafer samples exhibit antibacterial activity against S. aureus. The coated samples are covered by apatite layer after soaked in the simulated body fluid for 2 weeks, demonstrating their bioactivity.
Analysis of solvent effects on polyphenols profile, antiproliferative and antioxidant activities of mulberry (Morus alba L.) extracts
Authors: Li Fuhua , Zhang Bin , Chen Gu , Fu Xiong
Published: May 2017

A systematic study about the solvent effect on the mulberry polyphenol (MP) profile, antioxidant and antiproliferation capacities against human hepatoma HepG2 cells was conducted. Results indicated that MP profiles showed significant differences as a function of solvents including AA/W (acetic acid/water), MeOH/AA/W (methanol/ acetic acid/water), EtOH/AA/W (ethanol/ acetic acid/water) and ME2CO/AA/W (acetone/ acetic acid/water). Among the solvents, EtOH/AA/W took advantage in obtaining MP with the highest yield (49.81 mg GAE g−1 dw), and cellular antioxidant capacity in the PBS no‐wash protocol (63.2 μmolQE/100 g), as well as low cell cytotoxicity (≥50.0 mg mL−1). ME2CO/AA/W was the best choice for extracting MP with the most various compositions (two phenolic acids, four anthocyanins and four flavonols), greatest potential in inhibiting proliferation of HepG2 cells (EC50 = 28.2 mg mL−1) and highest intracellular antioxidant activity (38.0 μmolQE/100 g). Results provide baseline information for efficient solvent extraction to obtain MP that is promising as natural antioxidants and antitumor agents.