bluuebunny/crossref_metadata_2025 huggingface dataset:
Propositional Attitudes and Embodied Skills in the Philosophy of Action
Authors: Hasselberger William
Published: July 2017

Propositionalism in the philosophy of action is the popular view that intentional actions are bodily movements caused and rationalized by certain ‘internal’ propositional attitude states that constitute the agent's perspective. I attack propositionalism's background claim that the genuinely mental/cognitive dimension of human action resides solely in some range of ‘internal’ agency‐conferring representational states that causally trigger, and thus are always conceptually disentangle‐able from, bodily activity itself. My opposing claim, following Ryle, Wittgenstein, and others, is that mentality and intentionality can be constitutively implicated in bodily actions themselves, as exercises of a distinctive form of embodied practical understanding. I attempt to show this by attending to the fine‐grained contours of various skillful actions.
Clinical studies and anti‐inflammatory mechanisms of treatments
Authors: French Jacqueline A. , Koepp Matthias , Naegelin Yvonne , Vigevano Federico , Auvin Stéphane , Rho Jong M. , Rosenberg Evan , Devinsky Orrin , Olofsson Peder S. , Dichter Marc A.
Published: July 2017

In this exciting era, we are coming closer and closer to bringing an anti‐inflammatory therapy to the clinic for the purpose of seizure prevention, modification, and/or suppression. At present, it is unclear what this approach might entail, and what form it will take. Irrespective of the therapy that ultimately reaches the clinic, there will be some commonalities with regard to clinical trials. A number of animal models have now been used to identify inflammation as a major underlying mechanism of both chronic seizures and the epileptogenic process. These models have demonstrated that specific anti‐inflammatory treatments can be effective at both suppressing chronic seizures and interfering with the process of epileptogenesis. Some of these have already been evaluated in early phase clinical trials. It can be expected that there will soon be more clinical trials of both “conventional, broad spectrum” anti‐inflammatory agents and novel new approaches to utilizing specific anti‐inflammatory therapies with drugs or other therapeutic interventions. A summary of some of those approaches appears below, as well as a discussion of the issues facing clinical trials in this new domain.
Neuroinflammation in epileptogenesis: Insights and translational perspectives from new models of epilepsy
Authors: Barker‐Haliski Melissa L. , Löscher Wolfgang , White H. Steve , Galanopoulou Aristea S.
Published: July 2017

Animal models have provided a wealth of information on mechanisms of epileptogenesis and comorbidogenesis, and have significantly advanced our ability to investigate the potential of new therapies. Processes implicating brain inflammation have been increasingly observed in epilepsy research. Herein we discuss the progress on animal models of epilepsy and comorbidities that inform us on the potential role of inflammation in epileptogenesis and comorbidity pathogenesis in rodent models of West syndrome and the Theiler's murine encephalomyelitis virus (TMEV) mouse model of viral encephalitis–induced epilepsy. Rat models of infantile spasms were generated in rat pups after right intracerebral injections of proinflammatory compounds (lipopolysaccharides with or without doxorubicin, or cytokines) and were longitudinally monitored for epileptic spasms and neurodevelopmental and cognitive deficits. Anti‐inflammatory treatments were tested after the onset of spasms. The TMEV mouse model was induced with intracerebral administration of TMEV and prospective monitoring for handling‐induced seizures or seizure susceptibility, as well as long‐term evaluations of behavioral comorbidities of epilepsy. Inflammatory processes are evident in both models and are implicated in the pathogenesis of the observed seizures and comorbidities. A common feature of these models, based on the data so far available, is their pharmacoresistant profile. The presented data support the role of inflammatory pathways in epileptogenesis and comorbidities in two distinct epilepsy models. Pharmacoresistance is a common feature of both inflammation‐based models. Utilization of these models may facilitate the identification of age‐specific, syndrome‐ or etiology‐specific therapies for the epilepsies and attendant comorbidities, including the drug‐resistant forms.
Seizure‐associated aphasia has good lateralizing but poor localizing significance
Authors: Loesch Anna Mira , Steger Hannah , Losher Claudia , Hartl Elisabeth , Rémi Jan , Vollmar Christian , Noachtar Soheyl
Published: July 2017

Objective

To investigate the occurrence of ictal and postictal aphasia in different focal epilepsy syndromes.

Methods

We retrospectively analyzed the video‐electroencephalographic monitoring data of 1,118 patients with focal epilepsy for seizure‐associated aphasia (SAA). Statistical analysis included chi‐square analysis and Fisher's exact test.

Results

We identified 102 of 1,118 patients (9.1%) in whom ictal or postictal aphasia (SAA) was part of their recorded seizures (n = 59 of 102; 57.8%) or who reported aphasia by history (n = 43; 42.2% only reported aphasia by history). Postictal aphasia was present in 18 patients (30.5%). Six of the 59 patients had both ictal and postictal aphasia (10.2%). SAA occurred either with left hemisphere seizure onset or with seizures spreading from the right to the left hemisphere. SAA was most common in patients with parieto‐occipital epilepsy (10.9%; five of 46 patients), followed by patients with temporal (6.7%; 28 of 420 patients), focal (not further localized; 4.8%; 22 of 462 patients), and frontal epilepsy (2.1%; four of 190 patients; p = 0.04). SAA was more common in parieto‐occipital epilepsy than in frontal epilepsy (p = 0.02). In contrast, there was no significant difference in SAA between temporal and parieto‐occipital epilepsy (p = 0.36).

Significance

SAA has a high lateralizing but limited localizing value, as it often reflects spread of epileptic activity into speech‐harboring brain regions.
Risk of genetic maladaptation due to climate change in three major European tree species
Authors: Frank Aline , Howe Glenn T. , Sperisen Christoph , Brang Peter , Clair J. Bradley St. , Schmatz Dirk R. , Heiri Caroline
Published: July 2017

Tree populations usually show adaptations to their local environments as a result of natural selection. As climates change, populations can become locally maladapted and decline in fitness. Evaluating the expected degree of genetic maladaptation due to climate change will allow forest managers to assess forest vulnerability, and develop strategies to preserve forest health and productivity. We studied potential genetic maladaptation to future climates in three major European tree species, Norway spruce (Picea abies), silver fir (Abies alba), and European beech (Fagus sylvatica). A common garden experiment was conducted to evaluate the quantitative genetic variation in growth and phenology of seedlings from 77 to 92 native populations of each species from across Switzerland. We used multivariate genecological models to associate population variation with past seed source climates, and to estimate relative risk of maladaptation to current and future climates based on key phenotypic traits and three regional climate projections within the A1B scenario. Current risks from climate change were similar to average risks from current seed transfer practices. For all three climate models, future risks increased in spruce and beech until the end of the century, but remained low in fir. Largest average risks associated with climate projections for the period 2061–2090 were found for spruce seedling height (0.64), and for beech bud break and leaf senescence (0.52 and 0.46). Future risks for spruce were high across Switzerland. However, areas of high risk were also found in drought‐prone regions for beech and in the southern Alps for fir. Genetic maladaptation to future climates is likely to become a problem for spruce and beech by the end of this century, but probably not for fir. Consequently, forest management strategies should be adjusted in the study area for spruce and beech to maintain productive and healthy forests in the future.
Using Training Images to Build Model Ensembles with Structural Variability
Authors: Pirot Guillaume
Published: July 2017

Article impact statement: Training images allow modelers to represent hydrogeological structure variability, improving the understanding of prediction uncertainty.
The association between patient activation and self‐care practices: A cross‐sectional study of an Australian population with comorbid diabetes and chronic kidney disease
Authors: Zimbudzi Edward , Lo Clement , Ranasinha Sanjeeva , Kerr Peter G , Polkinghorne Kevan R , Teede Helena , Usherwood Timothy , Walker Rowan G , Johnson Greg , Fulcher Greg , Zoungas Sophia
Published: July 2017

Objective

This study aimed to examine the association between performance of self‐care activities and patient or disease factors as well as patient activation levels in patients with diabetes and chronic kidney disease (CKD) in Australia.

Methods

A cross‐sectional study was conducted among adults with diabetes and CKD (eGFR <60 mL/min/1.73m2) who were recruited from renal and diabetes clinics of four tertiary hospitals in Australia. Demographic and clinical data were collected, as well as responses to the Patient Activation Measure (PAM) and the Summary of Diabetes Self‐Care Activities (SDSCA) scale. Regression analyses were performed to determine the relationship between activation and performance of self‐care activities.

Results

A total of 317 patients (70% men) with a mean age of 66.9 (SD=11.0) years participated. The mean (SD) PAM and composite SDSCA scores were 57.6 (15.5) % (range 0‐100) and 37.3 (11.2) (range 0‐70), respectively. Younger age, being male, advanced stages of CKD and shorter duration of diabetes were associated with lower scores in one or more self‐care components. Patient activation was positively associated with the composite SDSCA score, and in particular the domains of general diet and blood sugar checking (P<.05), but not specific diet, exercising and foot checking.

Conclusion

In people with diabetes and CKD, a high level of patient activation was positively associated with a higher overall level of self‐care. Our results identify subgroups of people who may benefit from tailored interventions to further improve their health outcomes. Further prospective studies are warranted to confirm present findings.
Epidemiology of tuberculosis and HIV coinfections in Singapore, 2000–2014
Authors: Nandar K , Ang LW , Tey J , James L , Kyi Win KM , Chee CBE , Ng OT , Cutter JL , Wang YT
Published: July 2017

Cross‐matching of records between Singapore's tuberculosis and HIV registries showed that 3.3% of individuals with tuberculosis (TB) were coinfected with HIV (2000−2014), the TB incidence among individuals with HIV infection was 1.65 per 100 person‐years, and 53% of coinfections were diagnosed within 1 month of each other. The findings supported joint prevention programmes for early diagnosis and treatment.
Prevalence and associations of psychological distress in Australian junior medical officers
Authors: Lau Michelle W. , Li Wenlong E. , Llewellyn Anthony , Cyna Allan M.
Published: July 2017

Background/Aims

To determine the prevalence of psychological distress in Australian junior medical officers (JMO) and investigate the determinants associated with psychological distress over a 3‐year (2014–2016) period.

Methods

JMO were surveyed using the 2014–2016 JMO Census (n = 220, 399 and 466 each year; response rate approximately 15%). Levels of psychological distress were assessed using the Kessler Psychological Distress Scale (K10). A K10 ≥ 25 was chosen to indicate high psychological distress, and this determinant was compared to various demographic and work‐related factors.

Results

Australian JMO experience a high level of psychological distress (mean: 18.1, median 16.0). There were no differences in demographical variables, such as age, gender, marital status, dependants and between postgraduate years 1 and 2. Increasing hours worked per week was associated with a higher K10, with every hour worked increasing odds by 3%. Attitudinal items, including feeling unwilling to study medicine again, feeling poorly trained and experiences of bullying, were related to high psychological distress. Coping strategies like exercise and spending time with friends correlated positively with lower distress, while time off work, frequent alcohol use, smoking and drug use were associated with increased distress levels. Of those with a high K10, 54.5% indicated that they did not use any form of professional support; 17.83% expressed that given their time again, they would not choose to study medicine.

Conclusion

A focused approach to JMO support and education regarding significant risk factors identified is likely to assist health policies that aim to improve the mental well‐being of Australian JMO.
Two‐year audit of outcomes of pituitary surgery at an Australian teaching hospital
Authors: Davis Timothy M. E. , Badshah Imran , Drinkwater Jocelyn , Kusich Emily , Latkovic Erin , Knuckey Neville
Published: July 2017

Background

There is evidence that cure rates and complications are influenced by the caseload in neurosurgical centres performing transsphenoidal pituitary surgery. Although Australian centres may perform relatively small numbers of these procedures, there have been few published audits of their performance.

Aims

To conduct an audit of surgery for pituitary tumours between 2012 and 2014 in the only public hospital neurosurgical unit in the state of Western Australia.

Methods

A retrospective chart review was conducted, with standardised extraction of data relating to indications for surgery, tumour type, procedure and postoperative endocrinological and other outcomes.

Results

Of 53 patients identified, most (91%) underwent transsphenoidal surgery. Most tumours were non‐functioning (71.7%), and most of these extended outside the sella turcica (86.8 vs 73.3% of functioning tumours). There was complete removal in 43.4% of patients and evidence of biochemical cure in 33.3% of functioning tumours, but readmission for further surgery was infrequent (5.7%). Persistent cerebrospinal fluid leakage, photophobia and deep venous thrombosis occurred in <4% of patients. There were no deaths. There was a relatively high rate of permanent diabetes insipidus (DI) (13.2 vs <5% in published series), while the frequency of new postoperative anterior pituitary dysfunction (9.4%) was within the range reported in the literature (3–14%).

Conclusion

The outcomes of pituitary surgery in this audit were largely comparable to those reported from other neurosurgical units in Australia and other countries. The increased risk of permanent postoperative DI may reflect the high proportion of non‐functioning tumours with extension outside the sella turcica.
Understanding the legacy of widespread population translocations on the post‐glacial genetic structure of the European beech, Fagus sylvatica L.
Authors: Sjölund M. Jennifer , González‐Díaz Patricia , Moreno‐Villena Jose J. , Jump Alistair S.
Published: July 2017

Aim

Human impacts have shaped species ranges throughout the Holocene. The putative native range of beech, Fagus sylvatica, in Britain was obscured by its late post‐glacial arrival and subsequent extensive management. We sought to differentiate the interacting effects of post‐glacial colonization and anthropic impacts on the current genetic structure and diversity of beech by contrasting phylogeographical signals from putatively natural and translocated populations.

Location

Samples were obtained from 42 sites throughout Great Britain.

Methods

Chloroplast and nuclear microsatellite marker data were interpreted alongside palynological, historical and anecdotal evidence. Genetic structure was analysed using individual‐based Bayesian assignment methods and colonization history was analysed using an approximate Bayesian computation framework.

Results

Phylogeographical patterns suggested contemporary forests originated from putative native south‐eastern populations. High haplotypic diversity was found near the entry point of beech into Britain. Cryptic signals of isolation‐by‐distance persisted in the putative native range, together with higher levels of gene diversity in nuclear markers. Weak regional nuclear genetic structure suggested high levels of contemporary gene flow throughout the country.

Main conclusions

Genetic patterns driven by natural colonization persist despite widespread anthropic intervention. Forests in northerly regions were established from forests in the putative native range, diminishing the credibility of any present boundary between the native and non‐native range of beech in Britain.
Electrophysiological relation between the superior vena cava and right superior pulmonary vein in patients with paroxysmal atrial fibrillation
Authors: Yoshida Kentaro , Hattori Ai , Tsuneoka Hidekazu , Tsumagari Yasuaki , Yui Yoshiaki , Kimata Akira , Ito Yoko , Ebine Mari , Uehara Yoshiko , Koda Naoya , Misaki Masako , Abe Daisuke , Takeyasu Noriyuki , Aonuma Kazutaka , Nogami Akihiko
Published: July 2017

Introduction

The superior vena cava (SVC) is a main source of nonpulmonary vein (PV) ectopies initiating atrial fibrillation (AF). Empiric SVC isolation may improve rhythm outcomes after catheter ablation of AF. Because the SVC passes immediately adjacent to the right superior PV (RSPV), an electrophysiological relation could be present between the two structures. The present study aimed to estimate the interrelation between the SVC and RSPV by evaluating arrhythmogenic activities observed during catheter ablation of AF.

Methods and results

Study subjects comprised 121 consecutive patients referred for catheter ablation of paroxysmal AF. Isoproterenol infusion was used to induce ectopies and AF. Patients were divided into two groups depending on the presence of arrhythmogenic SVC: arrhythmogenic‐SVC (A‐SVC) and nonarrhythmogenic SVC (Non‐A‐SVC) groups. The prevalence of females was higher and body surface area was smaller in the A‐SVC group (N = 22) than Non‐A‐SVC group (N = 99). Arrhythmogenic activities were observed in 60 (49%) RSPVs, 24 (20%) right inferior PVs, 72 (59%) left superior PVs, and 31 (25%) left inferior PVs. Arrhythmogenic RSPVs were more prevalent in the A‐SVC group than Non‐A‐SVC group (86% vs. 41%, P = 0.0001), whereas these prevalences in the other three PVs were not different between groups (P >0.3). In multivariable analysis, arrhythmogenic RSPV was the only independent predictor of arrhythmogenicity of the SVC (OR, 8.53; 95% CI 2.31–31.46; P = 0.001).

Conclusions

An electrophysiological interrelation may be present between the SVC and RSPV in patients with paroxysmal AF. Semiempiric SVC isolation limited to patients with an arrhythmogenic RSPV may be a more efficient treatment strategy.
Long‐term follow‐up after left atrial appendage occlusion with comparison of transesophageal echocardiography versus computed tomography to guide medical therapy and data about postclosure cardioversion
Authors: Berte Benjamin , Jost Christine Attenhofer , Maurer Dominik , Fäh‐Gunz Anja , Pillois Xavier , Naegeli Barbara , Pfyffer Monica , Sütsch Gabor , Scharf Christoph
Published: July 2017

Aims

The use of left atrial appendage (LAA) occluders in atrial fibrillation is increasing. There are few data on the comparison between transesophageal echocardiography (TEE) and computed tomography (MDCT) assessing peridevice flow and outcome of electrical cardioversion (ECV) in these patients.

Methods and results

Single‐center prospective registry from 2009 to 2015 including all LAA occluders to analyze success and complications during implantation and follow‐up. Patients having ≥1 ECV were further analyzed. TEE was performed during implantation and at 6 weeks. In a subgroup of 77 patients, we compared MDCT with TEE at 6 weeks.

Overall, 135 patients (69 ± 9 years; 70% male; CHA2DS2‐VASc score: 3.6 ± 1.4; HAS‐BLED score: 2.5 ± 0.6) received a LAA occluder (Watchman, n = 73; ACP‐1, n = 59; Amulet, n = 3; PVI + LAA occluder, n = 91; and LAA occluder only, n = 44). Device implantation was successful in 131 (97%). Eight patients (5.9%) had major periprocedural complications (ischemic stroke/transient ischemic attacks, n = 4, tamponade, n = 2, device thrombosis, n = 2, Dressler syndrome, n = 1). The periprocedural complication rate was similar between concomitant procedure and LAA occluder only (8/91 vs. 5/44; P = 0.6). Twelve patients (9%) died (procedure‐related, n = 2; 1%) during follow‐up of 44 months (IQR: 43). MDCT (n = 77) at 6 weeks showed similar peridevice flow compared to TEE (TEE: 1.5 ± 1.9 mm vs. MDCT: 1.1 ± 2.2 mm, P = 0.25). Thromboembolic events occurred in 3 patients (CVA, n = 1; TIA, n = 2) during follow‐up. In total, 41 ECV were performed in 26 patients (1.6 ± 0.9/patient), 13 months (IQR: 24) after implantation (<1 month: n = 8). No ECV‐related clinical complications were observed.

Conclusion

LAA occlusion is feasible with an acceptable safety profile and few events during long‐term follow‐up. ECV after LAA occlusion is feasible. MDCT could help to evaluate peridevice flow.
Independent Fiscal Councils: Neglected Siblings of Independent Central Banks? An EU Perspective
Authors: Larch Martin , Braendle Thomas
Published: July 2017

Governance of monetary and fiscal policy have followed diverging paths. Since the late 1980s monetary policy has been delegated to independent central banks. By contrast, fiscal stabilization remained in political hands but has progressively been constrained by rules; the Stability and Growth Pact in the EU is a prominent case in point. While delegation and independence eliminated the inflation bias, fiscal policy still suffers from a deficit bias as enforcement of rules remains difficult. A logical extension of all attempts to progressively tie the hands of politics would be to carve out the stabilization function from the broader field of fiscal policy and to delegate it to national independent fiscal councils. Apart from addressing the political economy behind the deficit bias, such a step would facilitate a better co‐ordination of macroeconomic policies in Economic and Monetary Union.
Associations Between Self‐Reported Physical Activity and Physical Performance Measures Over Time in Postmenopausal Women: The Women's Health Initiative
Authors: Laddu Deepika R. , Wertheim Betsy C. , Garcia David O. , Brunner Robert , Groessl Erik , Shadyab Aladdin H. , Going Scott B. , LaMonte Michael J. , Cannell Brad , LeBoff Meryl S. , Cauley Jane A. , Thomson Cynthia A. , Stefanick Marcia L.
Published: July 2017

Objectives

To examine prospective associations between changes in physical activity (PA) and changes in physical performance measures (PPMs) over 6 years in older women.

Design

Prospective cohort study.

Setting

Forty clinical centers in the United States.

Participants

Women aged 65 and older (mean age 69.8) enrolled in the Women's Health Initiative Clinical Trials with gait speed, timed chair stand, grip strength, and self‐reported recreational PA data assessed at baseline (1993–98) and follow‐up Years 1, 3, and 6 (N = 5,092).

Measurements

Mixed‐effects linear regression models were used to determine the association between time‐varying PA and change in each PPM. Potential interactions between time‐varying PA and age (<70, ≥70) were also tested.

Results

Significan, dose‐response associations between PA and improvements in all PPMs were observed over the 6 years of follow‐up after adjusting for important covariates. High PA groups (≥1,200 metabolic equivalent (MET)‐min/wk) had stronger grip strength (0.48 kg greater; P < .01), more chair stands (0.35 more; P < .001), and faster gait speeds (0.06 m/s faster; P < .001) than sedentary women (<100 MET‐min/wk). Higher PA levels were associated with a greater increase in chair stands over time in women aged 70 and older (P < .001) than in those younger than 70 (Pinteraction for age = .01).

Conclusion

In postmenopausal women, maintaining high PA levels over time is associated with better lower extremity function. These data support the view that regular PA plays an important role in maintaining functional status during aging in older women.
Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta‐analysis of randomised placebo‐control human clinical trials
Authors: AbuMweis S. , Jew S. , Tayyem R. , Agraib L.
Published: July 2017

Background

Over 200 clinical trials have examined the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplements on risk factors associated with cardiovascular disease. However, an updated analysis of the evidence is lacking. The aim of the present meta‐analysis was to quantify the effect of supplements containing EPA and DHA on risk factors for cardiovascular disease.

Methods

An analysis was carried on 171 clinical trials with acceptable quality (Jadad score ≥3) that were identified from a comprehensive electronic search strategy of two databases (Pubmed and Cochrane Library). A random effect model was used to obtain an overall estimate on outcomes of interest. Heterogeneity between trial results was tested for using a standard chi‐squared test.

Results

Compared with control, EPA and DHA supplements produced significant reductions of triglycerides of 0.368 mmol L−1 [95% confidence interval (CI) = −0.427 to −0.309], systolic blood pressure of 2.195 mmHg (95% CI = −3.172 to −1.217), diastolic blood pressure of 1.08 mmHg (95% CI = −1.716 to −0.444), heart rate of 1.37 bpm (95% CI = −2.41 to −0.325) and C‐reactive protein of 0.343 mg L−1 (95% CI = −0.454 to −0.232). This analysis indicates an increase in both low‐density lipoprotein cholesterol (mean difference = 0.150 mmol L−1; 95% CI = 0.058–0.243) and high‐density lipoprotein cholesterol (mean difference = 0.039 mmol L−1; 95% CI = 0.024–0.054). The triglyceride‐lowering effect was dose‐dependent.

Conclusions

The lipid‐lowering, hypotensive, anti‐arrhythmic and anti‐inflammatory actions of EPA and DHA supplements were confirmed in this analysis of randomised placebo‐control blinded clinical trials.
Insulin and leptin excite anorexigenic pro‐opiomelanocortin neurones via activation of TRPC5 channels
Authors: Qiu J. , Wagner E. J. , Rønnekleiv O. K. , Kelly M. J.
Published: July 2017

Pro‐opiomelanocortin (POMC) neurones within the hypothalamic arcuate nucleus are vital anorexigenic neurones. Both the insulin receptor and leptin receptor are coupled to activation of phosphatidylinositide‐3 kinase (PI3K) to regulate multiple functions that increase POMC neuronal excitability. Using whole‐cell recording in several mammalian species, we have found that both insulin and leptin depolarised POMC neurones via activation of transient receptor potential (TRPC)5 channels. TRPC5 channels have been rigorously characterised as the downstream effector based on their biophysical properties, pharmacological profile, and localisation by immunocytochemistry and single‐cell reverse transcriptase‐polymerase chain reaction. By contrast, insulin and leptin hyperpolarise and inhibit neuropeptide Y/agouti‐related peptide neurones via activation of KATP channels. As proof of principle, insulin given i.c.v. robustly inhibits food intake and increases O2 utilisation, CO2 production and metabolic heat production. Therefore, these findings indicate that the depolarisation/excitation of POMC neurones by insulin and leptin is preserved across mammalian species and the activation of TRPC5 channels is likely a major mechanism by which insulin and leptin regulate energy homeostasis in mammals.
The mitral‐to‐aortic flow‐velocity integral ratio in the real world echocardiographic evaluation of functional mitral regurgitation before and after percutaneous repair
Authors: Palmiero Giuseppe , Ascione Luigi , Briguori Carlo , Carlomagno Guido , Sordelli Chiara , Ascione Raffaele , Pisacane Francesca , Monda Vittorio , Severino Sergio , Caso Pio
Published: July 2017

Introduction

Percutaneous mitral valve repair (PMVR) using MitraClip system has emerged as a therapeutic option for patients with functional severe mitral regurgitation (FMR) at prohibitive risk for surgery. In this setting, the echocardiographic assessment of FMR severity is challenging because the traditional echocardiographic methods have important limitations. The aim of this study was to assess the accuracy and reliability of a simple Doppler index, the mitral/aortic flow velocity integral ratio (MAVIR), to evaluate residual FMR severity after PMVR.

Methods

Eighty‐five heart failure patients with functional MR and LV dysfunction (LVEF ≤ 40%) were included. FMR was quantified on the basis of traditional quantitative parameters of MR severity. MAVIR was expressed as the ratio of mitral and aortic time velocity integral (TVI) values. According to MR severity, 25 patients underwent MC implantation and at 6 months a complete echocardiographic follow‐up was performed.

Results

A significant linear relationship was found between MAVIR and both VC and EROA. A MAVIR ≥1.02 identified pts with severe MR with a sensitivity of 86.7% and a specificity of 90.9%. At the 6 months echocardiographic follow‐up after the MitraClip implantation, we observed a significant reduction of LAVI, LVED and LVES volume, while LVEF improved. Furthermore, MAVIR significantly decreased its decrease showed a significant linear relationship with LAVI reduction.

Conclusion

Our data show a close relationship between MAVIR and traditional indexes of MR severity in patients with FMR. This Doppler‐derived index seems applicable after PMVR where traditional echocardiographic index of MR severity shows significant limitations.
Neopuff T‐piece resuscitator mask ventilation: Does mask leak vary with different peak inspiratory pressures in a manikin model?
Authors: Maheshwari Rajesh , Tracy Mark , Hinder Murray , Wright Audrey
Published: July 2017

Aim

The aim of this study was to compare mask leak with three different peak inspiratory pressure (PIP) settings during T‐piece resuscitator (TPR; Neopuff) mask ventilation on a neonatal manikin model.

Methods

Participants were neonatal unit staff members. They were instructed to provide mask ventilation with a TPR with three PIP settings (20, 30, 40 cm H2O) chosen in a random order. Each episode was for 2 min with 2‐min rest period. Flow rate and positive end‐expiratory pressure (PEEP) were kept constant. Airway pressure, inspiratory and expiratory tidal volumes, mask leak, respiratory rate and inspiratory time were recorded. Repeated measures analysis of variance was used for statistical analysis.

Results

A total of 12 749 inflations delivered by 40 participants were analysed. There were no statistically significant differences (P > 0.05) in the mask leak with the three PIP settings. No statistically significant differences were seen in respiratory rate and inspiratory time with the three PIP settings. There was a significant rise in PEEP as the PIP increased. Failure to achieve the desired PIP was observed especially at the higher settings.

Conclusions

In a neonatal manikin model, the mask leak does not vary as a function of the PIP when the flow rate is constant. With a fixed rate and inspiratory time, there seems to be a rise in PEEP with increasing PIP.
Coumarins as potential antidiabetic agents
Authors: Li Hanbing , Yao Yuanfa , Li Linghuan
Published: July 2017

Objectives

Even with great advances in modern medicine and therapeutic agent development, the search for effective antidiabetic drugs remains challenging. Coumarins are secondary metabolites found widely in nature plants and used mainly in anticoagulation and antithrombotic therapy. Over the past two decades, however, there has been an increasing body of literatures related to the effects of coumarins and their derivatives on diabetes and its complications. This review aimed to focus on research findings concerning the effects of coumarins against diabetes and its complications using in-vitro and in-vivo animal models, and also to discuss cellular and molecular mechanisms underlying these effects.

Key findings

The search for new coumarins against diabetes and it complications, either isolated from traditional medicine or chemically synthesized, has been constantly expanding. The cellular and molecular mechanisms involved include protecting pancreatic beta cells from damage, improving abnormal insulin signalling, reducing oxidative stress/inflammation, activating AMP-activated protein kinase (AMPK), inhibiting α-glucosidases and ameliorating diabetic complications.

Conclusions

The effects and mechanisms of coumarins and their derivatives upon diabetes and its complications are discussed in current review. Further investigations remain to be carried out to develop a promising antidiabetic agent based on coumarin cores.
A comprehensive review on anticancer mechanisms of the main carotenoid of saffron, crocin
Authors: Hoshyar Reyhane , Mollaei Homa
Published: July 2017

Objectives

Crocin is derived from dried stigmas of Crocus sativus L. (saffron). It has long been used to prevent and treat various diseases. Although crocin is suggested as one of the most effective cancer therapeutic constituents of saffron stigma, its exact molecular mechanisms are not fully understood. In this study, we reviewed anticancer effects of crocin and its underlying molecular mechanisms.

Key findings

While several mechanisms may account for the antitumour activity of crocin, alteration of expression/activity of the genes and also epigenetic changes may be considered as necessary phenomena. These alternations may lead to inhibition of cancer cells' proliferation or/and induction of apoptosis through various mechanism including inhibition of synthesis of DNA and RNA, interaction with cellular topoisomerase, suppression of the telomerase activity and active STAT3, and targeting of microtubules. Moreover, this carotenoid could reverse the epithelial–mesenchymal transition and inhibit metastasis.

Conclusions

Knowing molecular mechanisms of antitumoral agents could guide us to choose the best chemotherapeutic compound especially for targeted therapy and also provide insights about possible side effects.
Adaptive maintenance of European alleles in the Brazilian Africanized honeybee
Authors: Harpur Brock A.
Published: July 2017

The Anthropocene is an epoch hallmarked by intensified human intrusion across ecosystems. One such intrusion is the movement and re‐introduction of long‐separated populations. By facilitating introgression – intraspecific genetic admixture – secondary contact can facilitate range expansion and the establishment of invasive species. The proximate mechanisms through which introgression facilitates expansion are rarely known (Bock et al., ; Rius & Darling, ), but managed species provide a useful avenue for exploration. Bee‐keepers have been interbreeding highly diverged honeybee clades for centuries, often to introduce “useful” phenotypic variation to their stocks. Across the Western honeybee's (Apis mellifera) European range, this practice has not resulted in range expansion (Moritz, Härtel, & Neumann, ). In the Americas, however, introgression of European with African subspecies resulted in a widely publicized invasive population: The Africanized honeybee (AHB). In this issue of Molecular Ecology, Nelson, Wallberg, Simões, Lawson, and Webster () have made the first step towards understanding how this invasive species successfully spread across the Americas.
Two proteases with caspase‐3‐like activity, cathepsin B and proteasome, antagonistically control ER‐stress‐induced programmed cell death in Arabidopsis
Authors: Cai Yao‐Min , Yu Jia , Ge Yuan , Mironov Aleksandr , Gallois Patrick
Published: July 2017

Programmed cell death (PCD) induced by endoplasmic reticulum (ER) stress is implicated in various plant physiological processes, yet its mechanism is still elusive. An activation of caspase‐3‐like enzymatic activity was clearly demonstrated but the role of the two known plant proteases with caspase‐3‐like activity, cathepsin B and proteasome subunit PBA1, remains to be established.

Both genetic downregulation and chemical inhibition were used to investigate the function of cathepsin B and PBA1 in ER‐stress‐induced PCD (ERSID). Transcript level and activity labelling of cathepsin B were used to assess activation. To study tonoplast rupture, a plant PCD feature, both confocal and electronic microscopies were used.

Cathepsin B downregulation reduced reactive oxygen species (ROS) accumulation and ERSID without affecting the induction of the unfolded protein response (UPR), but downregulation of PBA1 increased UPR and ERSID. Tonoplast rupture was not altered in the cathepsin B mutant and cathepsin B activation was independent of vacuolar processing enzyme (VPE). VPE activity was independent of cathepsin B.

ERSID is regulated positively by cathepsin B and negatively by PBA1, revealing a complex picture behind caspase‐3‐like activity in plants. Cathepsin B may execute its function after tonoplast rupture and works in parallel with VPE.
On the factors inducing the inhibition of diapause in the progeny of diapause females of Trichogramma telengai
Authors: Voinovich Natalia D. , Reznik Sergey Ya.
Published: July 2017

The ability to enter diapause in the progeny of Trichogramma Westw. (Hymenoptera: Trichogrammatidae) females that have undergone diapause is markedly reduced or even completely absent. This maternal inhibition of diapause can result from three types of factors: (i) environmental factors that induce maternal diapause; (ii) maternal diapause itself; and (iii) diapause‐terminating environmental factors. The present study aims to determine the factors that prevent diapause in the progeny of a Trichogramma telengai Sor. generation that has undergone diapause. Different tendencies to enter diapause in the maternal generation are induced by different photoperiods (LD 12 : 12 h, 16 : 8 h and 18 : 6 h) during development of the grandmaternal generation and different temperatures (from 10 to 15 °C) during larval development of the maternal generation. To terminate diapause, prepupae of the maternal generation are kept at 4–5 °C in the dark. To estimate the ability to enter diapause, the progeny generation is incubated at 14 °C. The results suggest that the inhibition of the tendency to enter diapause in the progeny of T. telengai females that have undergone diapause is caused by diapause itself rather than by diapause‐inducing or diapause‐terminating environmental factors. This result can be used to clarify the mechanism of the inhibition of diapause in the progeny of females that have undergone diapause.
Understanding the health of veterans who are homeless: A review of the literature
Authors: Weber Jillian , Lee Rebecca C. , Martsolf Donna
Published: July 2017

The United States Department of Housing and Urban Development estimates that almost 50,000 veterans are homeless on any given night. Homeless veterans are at greater risk of health disparities than their housed counterparts due to the multifactorial nature of their health and social needs. The Department of Veterans Affairs, in collaboration with more than a dozen other federal agencies, has concentrated efforts to improve the health of this vulnerable population while enacting a plan to eliminate veteran homelessness within the near future. Understanding the unique health needs of veterans who are homeless allows the profession of nursing to better support these efforts. The purpose of this literature review was to provide comprehensive knowledge to nurses about the health of homeless veterans for their use in clinical practice, research, and in contributing to the positive health outcomes for this vulnerable population.
EMB2738, which encodes a putative plastid‐targeted GTP‐binding protein, is essential for embryogenesis and chloroplast development in higher plants
Authors: Ye Lin‐Shan , Zhang Qin , Pan Hui , Huang Chao , Yang Zhong‐Nan , Yu Qing‐Bo
Published: July 2017

In higher plants, chloroplasts carry out many important functions, and normal chloroplast development is required for embryogenesis. Numerous chloroplast‐targeted proteins involved in embryogenesis have been identified. Nevertheless, their functions remain unclear. In this study, a chloroplast‐localized protein, EMB2738, was reported to be involved in Arabidopsis embryogenesis. EMB2738 knockout led to defective embryos, and the embryo development in emb2738 was interrupted after the globular stage. Complementation experiments identified the AT3G12080 locus as EMB2738. Cellular observation indicated that severely impaired chloroplast development was observed in these aborted embryos. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) analysis showed that chloroplast‐encoded photosynthetic genes, which are transcribed by plastid‐encoded RNA polymerase (PEP), are predominantly decreased in defective embryogenesis, compared with those in the wild‐type. In contrast, genes encoding PEP core subunits, which are transcribed by nucleus‐encoded RNA polymerase (NEP), were increased. These results suggested that the knockout of EMB2738 strongly blocked chloroplast‐encoded photosynthesis gene expression in embryos. Silencing of the EMB2738 orthologue in tobacco through a virus‐induced genome silencing technique resulted in an albinism phenotype, vacuolated chloroplasts and decreased PEP‐dependent plastid transcription. These results suggested that NtEMB2738 might be involved in plastid gene expression. Nevertheless, genetic analysis showed that the NtEMB2738 coding sequence could not fully rescue the defective embryogenesis of the emb2738 mutant, which suggested functional divergence between NtEMB2738 and EMB2738 in embryogenesis. Taken together, these results indicated that both EMB2738 and NtEMB2738 are involved in the expression of plastid genes in higher plants, and there is a functional divergence between NtEMB2738 and EMB2738 in embryogenesis.
Hip abductor muscle activity during walking in individuals with gluteal tendinopathy
Authors: Allison K. , Salomoni S. E. , Bennell K. L. , Wrigley T. V. , Hug F. , Vicenzino B. , Grimaldi A. , Hodges P. W.
Published: July 2017

The external hip adduction moment during walking is greater in individuals with gluteal tendinopathy (GT) than pain‐free controls. Although this likely represents a greater demand on the hip abductor muscles implicated in GT, no study has investigated activation of these muscles in GT. For this purpose, fine wire electrodes were inserted into the segments of the gluteus minimus and medius muscles, and surface electrodes placed on the tensor fascia lata, upper gluteus maximus, and vastus lateralis muscles of eight individuals with, and eight without, GT. Participants underwent six walking trials. Individual muscle patterns were compared between groups using a wavelet‐based linear effects model and muscle synergy analysis performed using non‐negative matrix factorization to evaluate muscle activation patterns, within‐ and between‐participant variability. Compared to controls, individuals with GT exhibited a more sustained initial burst of the posterior gluteus minimus and middle gluteus medius muscle segments. Two muscle synergies were identified; Synergy‐1 activated in early‐mid stance and Synergy‐2 in early stance. In GT participants, posterior gluteus minimus and posterior gluteus medius and tensor fascia lata contributed more to Synergy‐1 active during the period of single leg support. Participants with GT exhibited reduced within‐participant variability of posterior gluteus medius and reduced between‐participant variability of anterior gluteus minimus and medius and upper gluteus maximus. In conclusion, individuals with GT exhibit modified muscle activation patterns of the hip abductor muscles during walking, with potential relevance for gluteal tendon loading.
How did investor‐state dispute settlement get a bad rap? Blame it onNAFTA, of course
Authors: Anderson Greg
Published: July 2017

In the short history of the US bilateral investment treaty (BIT) programme, there have been no instances of dispute settlement cases initiated against the United States by firms fromBITcountries. TheNAFTAexperience changed that. Where other studies have only hinted at the reasons forNAFTAcontroversies, this paper makes clear three causal factors: (i) changing patterns and intensity ofFDI, (ii) the application of those rules to developed countries amid those changingFDIpatterns and (iii) ambiguities inISDSrules themselves. The paper explores these and traces the ways in which lessons of theNAFTAhave been instrumental in changing the pursuit of investment protection agreements.BITs used to be uncontroversial, but theNAFTAfocused attention on reforms toISDSthat maintain the utility ofBITs in the governance ofFDI, without creating a legal structure for simply challenging the state.
CFRP Reinforcement and Repair of Steel Pipe Elbows Subjected to Severe Cyclic Loading
Authors: Skarakis Ioannis , Chatzopoulou Giannoula , Karamanos Spyros A. , Tsouvalis Nicholas G. , Pournara Aglaia E.
Published: July 2017

In order to ensure safe operation and structural integrity of pipelines and piping systems subjected to extreme loading conditions, it is often necessary to strengthen critical pipe components. One method to strengthen pipe components is the use of composite materials. The present study is aimed at investigating the mechanical response of pipe elbows, wrapped with carbon fiber-reinforced plastic (CFRP) material, and subjected to severe cyclic loading that leads to low-cycle fatigue (LCF). In the first part of the paper, a set of LCF experiments on reinforced and nonreinforced pipe bend specimens are described focusing on the effects of CFRP reinforcement on the number of cycles to failure. The experimental work is supported by finite element analysis presented in the second part of the paper, in an attempt to elucidate the failure mechanism. For describing the material nonlinearities of the steel pipe, an efficient cyclic-plasticity material model is employed, capable of describing both the initial yield plateau of the stress–strain curve and the Bauschinger effect characterizing reverse plastic loading conditions. The results from the numerical models are compared with the experimental data, showing an overall good comparison. Furthermore, a parametric numerical analysis is conducted to examine the effect of internal pressure on the structural behavior of nonreinforced and reinforced elbows, subjected to severe cyclic loading.
Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery
Authors: Duffy Sandra , Sykes Melissa L. , Jones Amy J. , Shelper Todd B. , Simpson Moana , Lang Rebecca , Poulsen Sally-Ann , Sleebs Brad E. , Avery Vicky M.
Published: July 2017

Open-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open-access Pathogen Box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. We tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages
in vitro
. Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease, and leishmaniasis drug discovery efforts have been identified. Inclusive of this
in vitro
biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open-source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research.