bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of sodium‐glucose co‐transporter‐2 inhibitors in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors: An Asian perspective and expert recommendations
Authors: Deerochanawong Chaicharn , Chan Siew P. , Matawaran Bien J. , Sheu Wayne H.‐H. , Chan Juliana , Man Nguyen H. , Suastika Ketut , Khoo Chin M. , Yoon Kun‐Ho , Luk Andrea , Mithal Ambrish , Linong Ji
Published: July 2019

Diabetes mellitus in Asia accounts for more than half of the global prevalence. There is a high prevalence of cardiovascular disease (CVD) in the region among people with type 2 diabetes mellitus (T2DM) and it is often associated with multiple risk factors including hypertension, renal disease and obesity. The early onset of T2DM and the eventual long disease duration portends an increasing proportion of the population to premature CVD. In addition to lowering blood glucose, sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors exert favourable effects on multiple risk factors (including blood pressure, body weight and renal function) and provide an opportunity to reduce the risk of CVD in patients with T2DM. In this article, we consolidated the existing literature on SGLT‐2 inhibitor use in Asian patients with T2DM and established contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, published data from clinical trials in the Asian population (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin and tofogliflozin), CVD outcomes trials (EMPAREG‐OUTCOME, CANVAS and DECLARE‐TIMI 58) and real‐world evidence studies (CVD‐REAL, EASEL, CVD‐REAL 2 and OBSERVE‐4D). A series of clinical recommendations on the use of SGLT‐2 inhibitors in Asian patients with T2DM was deliberated among experts with multiple rounds of review and voting. Based on the available evidence, we conclude that SGLT‐2 inhibitors represent an evidence‐based therapeutic option for the primary prevention of heart failure hospitalization and secondary prevention of CVD in patients with T2DM, and should be considered early on in the treatment algorithm for patients with multiple risk factors, or those with established CVD.
Impact of achieving primary care targets in type 2 diabetes on health outcomes and healthcare costs
Authors: Keng Mi Jun , Tsiachristas Apostolos , Leal Jose , Gray Alastair , Mihaylova Borislava
Published: July 2019

Aims

In England and Wales, the National Diabetes Audit (NDA) assesses the quality of management of type 2 diabetes (T2D) in primary care using treatment targets for HbA1c ≤58 mmol/mol, total cholesterol <5 mmol/L and blood pressure ≤140/80 mm Hg. We quantified the impact of variation in achieving these targets on health outcomes and healthcare costs across general practitioners' (GP) practices.

Methods

Summary of characteristics of T2D patients from the 2015–2016 NDA were used to generate representative populations of T2D patients. The UKPDS Outcomes Model 2 was used to estimate long‐term health outcomes and healthcare costs. The effects of achieving treatment targets on these outcomes were evaluated using regression models.

Results

Achieving more of the HbA1c, cholesterol and blood pressure targets led to a lower incidence of diabetes‐related complications. Approximately 0.5 (95% CI, 0.4‐0.6) quality‐adjusted life years (QALYs) and 0.6 (95% CI, 0.4‐0.7) years of life (LYs) were gained by T2D patients over a lifetime for each additional target met. The projected healthcare cost savings arising from fewer diabetes‐related complications as the result of achieving one, two or three targets compared to none were £859 (95% CI, £553‐£1165), £940 (95% CI, £485‐£1395) and £1037 (95% CI, £414‐£1660) over a patient's lifetime. A typical GP practice in the lowest performing decile (average, 371 T2D patients per practice, with 27% achieving all targets) is projected to gain 201 (95% CI, 123‐279) QALYs and 231 (95% CI, 133‐329) LYs, if all T2D patients achieved all three targets.

Conclusions

Substantial gains in health outcomes and reductions in healthcare costs could be achieved with further improvements in attainment of HbA1c, cholesterol and blood pressure targets for T2D patients.
Body weight management and safety with efpeglenatide in adults without diabetes: A phase II randomized study
Authors: Pratley Richard E. , Kang Jahoon , Trautmann Michael E. , Hompesch Marcus , Han OakPil , Stewart John , Sorli Christopher H. , Jacob Stephan , Yoon Kun‐Ho
Published: July 2019

Aim

To evaluate the safety of efpeglenatide, a long‐acting glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), and its effects on body weight management in adults without diabetes.

Materials and methods

In this phase II, randomized, placebo‐controlled, double‐blind trial, participants with a body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with comorbidity were randomized 1:1:1:1:1 to efpeglenatide (4 mg once weekly, 6 mg once weekly, 6 mg once every 2 wk, or 8 mg once every 2 wk; n = 237) or placebo (n = 60) in combination with a hypocaloric diet. The primary endpoint was body weight change from baseline after 20 wk of treatment, assessed using a mixed‐effect model with repeated measures with an unstructured covariance matrix over all post‐screening visits; treatment comparisons were based on least squares mean estimates.

Results

Over 20 wk, all doses of efpeglenatide significantly reduced body weight from baseline versus placebo (P < 0.0001), with placebo‐adjusted reductions ranging between −6.3 kg (6 mg once every 2 wk) and −7.2 kg (6 mg once weekly). Greater proportions of efpeglenatide‐treated participants had body weight loss of ≥5% or ≥10% versus placebo (P < 0.01, all comparisons). Efpeglenatide led to significant improvements in glycaemic variables (fasting plasma glucose and glycated haemoglobin) and lipid profiles (cholesterol, triglycerides) versus placebo. Rates of study discontinuations as a result of adverse events ranged from 5% to 19% with efpeglenatide. Gastrointestinal effects were the most common treatment‐emergent adverse events.

Conclusions

Efpeglenatide once weekly and once every 2 wk led to significant body weight reduction and improved glycaemic and lipid variables versus placebo. It was also well tolerated for weight management in adults without diabetes.
Dose‐dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial
Authors: Baker Claire , Wason Suman , Banks Phillip , Sawhney Sangeeta , Chang Anna , Danne Thomas , Gesty‐Palmer Diane , Kushner Jake A. , McGuire Darren K. , Mikell Frank , O'Neill Mark , Peters Anne L. , Strumph Paul
Published: July 2019

Aims

To assess the dose‐related effects of sotagliflozin, a novel dual inhibitor of sodium‐glucose co‐transporters‐1 and ‐2, in type 1 diabetes (T1D).

Materials and methods

In this 12‐week, multicentre, randomized, double‐blind, placebo‐controlled dose‐ranging trial, adults with T1D were randomized to once‐daily placebo (n = 36) or sotagliflozin 75 mg (n = 35), 200 mg (n = 35) or 400 mg (n = 35). Insulin was maintained at baseline doses. The primary endpoint was least squares mean (LSM) change in glycated haemoglobin (HbA1c) from baseline. Other endpoints included proportion of participants with ≥0.5% HbA1c reduction and assessments of 2‐hour postprandial glucose (PPG), weight, and urinary glucose excretion (UGE).

Results

From a mean baseline of 8.0% ± 0.8% (full study population), placebo‐adjusted LSM HbA1c decreased by 0.3% (P= .07), 0.5% (P < .001) and 0.4% (P= .006) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively, at week 12. In the placebo and sotagliflozin 75 mg, 200 mg and 400 mg groups, 33.3%, 37.1%, 80.0% and 65.7% of participants achieved an HbA1c reduction ≥0.5%. Placebo‐adjusted PPG decreased by 22.2 mg/dL (P= .28), 28.7 mg/dL (P= .16) and 50.2 mg/dL (P= .013), UGE increased by 41.8 g/d (P= .006), 57.7 g/d (P < .001) and 70.5 g/d (P < .001), and weight decreased by 1.3 kg (P= .038), 2.4 kg (P < .001) and 2.6 kg (P < .001) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively. One case of severe hypoglycaemia occurred in each sotagliflozin group and one case of diabetic ketoacidosis (DKA) occurred with sotagliflozin 400 mg.

Conclusions

Combined with stable insulin doses, sotagliflozin 200 mg and 400 mg improved glycaemic control and weight in adults with T1D. Sotagliflozin 400 mg reduced PPG levels. UGE increased with all sotagliflozin doses. Rates of severe hypoglycaemia and DKA were low (NCT02459899).
Inheriting the family farm: Generational wealth transfers in rural Kenya
Authors: Kagotho Njeri , Salim Neema N. , Patak‐Pietrafesa Michele , Kyriakakis Stavroula
Published: July 2019

Motivation

Intergenerational wealth transfers are economically important and have direct consequences on the distribution—or redistribution—of household and community wealth. In sub‐Saharan Africa, documented instances of weakly enforced statutory laws and outdated or misaligned customary laws create a space for practices that undermine the fair and smooth transition of wealth across generations.

Purpose

This study presents data drawn from a larger mixed‐methods study that evaluated a succession (inheritance) curriculum offered in a farming community in Kenya.

Approach and Methods

A sub‐set of intervention participants (n = 58) ranging in age from 20 to 78 were invited to participate in post‐test focus group discussions. Discussions followed a semi‐structured interview guide and included questions that evaluated the succession curriculum.

Findings

In addition to evaluating the intervention, emerging conversations centred on the economic and sociocultural significance of intergenerationally held family wealth. The narrative from these focus groups underscores the importance the community places on family‐held wealth and how failures in the financial socialization process have compromised the generational wealth‐transfer system. Further, both younger and older participants identified youth unemployment and substance misuse as factors that have led to a breakdown in the wealth‐transfer process. This breakdown can and has resulted in the loss of household wealth, as well as in the marginalization of vulnerable individuals including women and children.

Implications

This article concludes by identifying mutable factors that have implications for economic empowerment policies and programmes. This includes strengthening parental financial capabilities and facilitating access to legal resources to facilitate wealth transfers.
Occurrence of leaf spot disease caused by Neopestalotiopsis clavispora on Taxus chinensis in China
Authors: Wang Rongbo , Chen Shuzhun , Zheng Bowen , Liu Peiqing , Li Benjin , Weng Qiyong , Chen Qinghe
Published: July 2019

Taxus chinensis is a valuable tree with uses for timber, medicinal, ornamental and landscape purposes. Most importantly, it is a source of the anti‐cancer drug paclitaxel. In 2016, needle spot disease was observed on T. chinensis in Fujian Province of China. Five isolates of similar morphology were isolated from diseased samples. The pathogen was identified as Neopestalotiopsis clavispora based on morphological and cultural characteristics and confirmed by sequence analysis of the internal transcribed spacer region (ITS) and the large subunit ribosomal RNA gene (LSU). The pathogenicity of the isolates was confirmed by fulfilling Koch's postulates. To the best of our knowledge, this is the first report to indicate that the causal agent of needle spot disease on Chinese yew in China is N. clavispora.
Lower prepulse inhibition in clinical high‐risk groups but not in familial risk groups for psychosis compared with healthy controls
Authors: Togay Bilge , Çıkrıkçılı Uğur , Bayraktaroglu Zubeyir , Uslu Atilla , Noyan Handan , Üçok Alp
Published: July 2019

Aim

Although the lower level of prepulse inhibition (PPI) of the startle response is well known in schizophrenia, the onset of this difference is not clear. The aim of the present study was to compare PPI in individuals with clinical and familial high risk for psychosis, and healthy controls.

Methods

We studied PPI in individuals within three groups: ultra‐high risk for psychosis (UHR, n = 29), familial high risk for psychosis (FHR, n = 24) and healthy controls (HC, n = 28). The FHR group was chosen among siblings of patients with schizophrenia, whereas UHR was defined based on the Comprehensive Assessment of At‐Risk Mental States (CAARMS). We collected clinical data using the BPRS‐E, SANS and SAPS when individuals with UHR were antipsychotic‐naïve. A cognitive battery that assessed attention, cognitive flexibility, working memory, verbal learning and memory domains was applied to all participants.

Results

PPI was lower in the UHR group compared with both the FHR and HC groups. Those with a positive family history for schizophrenia had lower PPI than others in the UHR group. There was no difference in PPI between the FHR and HC groups. We found no relationship between PPI and cognitive performance in the three groups. Startle reactivity was not different among the three groups. Positive and negative symptoms were not related to PPI and startle reactivity in the UHR group.

Conclusions

Our findings suggest that clinical and familial high‐risk groups for psychosis have different patterns of PPI.
PROFIP: A Portuguese early intervention programme for first‐episode psychosis in Lisbon
Authors: Coentre Ricardo , Mendes Tiago , Rebelo Ana , Fonseca Alexandra , Levy Pedro
Published: July 2019

Aim

There is currently no national plan for early intervention in first‐episode psychosis in Portugal. Consequently, there is some heterogeneity in the evaluation and treatment of first‐episode psychosis across the country. The aim of this article is to provide a complete description of the early intervention programme Programa de Intervenção nas Fases Iniciais da Psicose (PROFIP) in Lisbon, a pioneering team in Portugal for treating first‐episode psychosis (FEP) patients. We also describe the baseline socio‐demographic and clinical data obtained from new patients over a 1‐year period. PROFIP programme accepts all cases of FEP, taking a transdiagnostic approach.

Methods

Description of PROFIP programme and baseline socio‐demographic and clinical data obtained from new patients over a 1‐year period.

Results

The team was constituted to provide early detection, treatment and support to people aged 16 to 35 years with affective and non‐affective FEP. Over a 1‐year period, 39 patients were included in the PROFIP programme. The majority of patients were young male patients with a diagnosis of non‐affective psychosis, and with 56% of patients reporting cannabis use. Patients received pharmacological and psychosocial interventions based on evidence and individual needs.

Conclusions

Our team allowed young people with early psychosis to receive effective care. We do need improvements, namely in referrals and the education of health professionals. More teams in our country should be constituted, allowing larger numbers of patients with early psychosis to be treated by specialized teams.
Victimization, violence and facial affect recognition in a community sample of first‐episode psychosis patients
Authors: Hachtel Henning , Fullam Rachael , Malone Aisling , Murphy Brendan P. , Huber Christian , Carroll Andrew
Published: July 2019

Aims

This exploratory study is the first to examine previously identified variables of increased vulnerability to victimization, the prevalence of aggression in a cohort of patients with first‐episode psychosis and the potential impact of impairments in facial affect recognition (FAR) on victimization.

Methods

Sixty‐nine male participants completed assessments of IQ, substance use, psychopathy, childhood trauma, aggressive behaviour and psychopathology. Participants were asked about violent victimization in the past year and charges for violent offences. FAR was assessed using the Animated Full Facial Comprehension Test.

Results

The victimized group (n = 25) had significantly higher psychopathy traits (P = .042) and lower recognition of sadness (P < .01) compared to the non‐victimized group (n = 44). Participants who reported charges for violent offences (n = 15) had significantly higher scores on measures of physical abuse in childhood (P < .01), substance use (P < .05 for cannabis, P < .001 for cocaine and amphetamine use), psychopathy traits (P < .01), psychopathology (P = .031) and lifetime aggressive behaviour (P < .01). The logistic regression models using FAR sadness and Psychopathic Personality Inventory‐Revised (PPI‐R) total score as predictors for victimization (χ
2 [2] = 13.81, P = .001; Nagelkerke R
2 = .30) and using physical abuse in childhood, PPI‐R total score, and psychopathology as predictors for violent offences (χ
2 [3] = 14.89, P = .002; Nagelkerke R
2 = .36) were significant.

Conclusions

These findings highlight the value of considering victimization in psychotic illness from a social information processing perspective in addition to known clinical and lifestyle factors. Based on these results, future studies could explore the use of affect recognition training early in the course of the illness as a possible intervention to reduce victimization.
The dangers of constitutional identity
Authors: Fabbrini Federico , Sajó András
Published: July 2019

This article purports to expose the dangers of the concept of constitutional identity – a doctrine shaped by apex state courts to shield areas of the national legal systems from the influence of European law. First, the article overviews the use of the concept of constitutional identity in the case law of national and supranational courts, mapping the growing expansion of this doctrine. Second, the article seeks to reconstruct the genealogy of the concept of constitutional identity, tracing its legal origins. Third, the article advances a normative criticism of the concept of constitutional identity, explaining how the doctrine suffers from an incurable lack of determinacy, which inevitably results in arbitrariness in its use. Moreover, the article points out how the practical use of a defensive concept such as constitutional identity is poised to weaken, if not undermine tout court, the process of European integration.
Gathering and evaluating innovation ideas using crowdsourcing: Impact of the idea title and the description on the number of votes in each phase of a two‐phase crowdsourcing project
Authors: Moffitt Kevin , O'Leary Daniel E.
Published: July 2019

Organizations are using crowdsourcing to capture innovation knowledge from the crowd in the form of ideas and then using the crowd to evaluate those ideas using votes. In this paper, we investigate a crowdsourcing setting in which Canada solicited information from its citizens to develop a digital transformation strategy. Canada used a two‐phase approach. Phase 1 was used to determine which ideas had the largest number of crowd votes, whereas in Phase 2, the crowd voted on the 30 leading vote‐getting ideas to determine the three winning ideas.

This research investigates the ability to use information from ideas to estimate the number of votes that the ideas generate. This approach could be used to estimate the number of ideas, before making information available to the crowd. The unstructured text information in the idea is structured by using target concept dictionaries, which are used to estimate the extent to which the dictionary words appear in the ideas (e.g., “globalism”) and are related to the number of votes. Using this approach, roughly 1% of the total words are used to explain roughly 60% of the variance in the votes. Further, we also find that the variables associated with Phase 1 votes are not the same variables associated with Phase 2 votes; that is, the decision‐making variables changed. Finally, we find that votes are statistically significantly related to the content in the idea titles and the idea statements.
New method for determining P‐S‐N curves in terms of equivalent fatigue lives
Authors: Bai Xin , Zhang Peng , Zhang Zhen‐jun , Liu Rui , Zhang Zhe‐feng
Published: July 2019

A new method for determining the P‐S‐N curves is proposed by the probabilistic analysis of the mixed samples that are composed of the testing fatigue lives and equivalent fatigue lives. The equivalent fatigue lives at each level are converted from all the testing data at all the testing levels according to the equivalent fatigue failure probability, where the life distributions are determined by the medians of logarithmic fatigue lives at respective levels and a unified coefficient of variation. Comparison results of the P‐S‐N curves of 2024‐T3 and A356.0‐T6 alloys with the different methods indicate that the new method can determine the high‐precision P‐S‐N curves with different sample sizes of the S‐N testing data, and can save testing time and improve testing efficiency, especially for the situation of large‐scatter S‐N testing data.
Genetic signatures of dominance hierarchies reveal conserved cis‐regulatory and brain gene expression underlying aggression in a facultatively social bee
Authors: Steffen Michael A. , Rehan Sandra M.
Published: July 2019

Agonistic interactions among individuals can result in the formation of dominance hierarches that can reinforce individual behavior and social status. Such dominance hierarches precede the establishment of reproductive dominance, division of labor and caste formation in highly social insect taxa. As such, deciphering the molecular basis of aggression is fundamental in understanding the mechanisms of social evolution. Assessing the proximate mechanisms of aggression in incipiently social bees can provide insights into the foundations of genomic mechanisms of social behavior. Here, we measured the effects of aggression on brain gene expression in the incipiently social bee,Ceratina australensis. We examine the brain transcriptomic differences between individuals who have experienced recurrent winning, losing, or a change in rank during repeated encounters. Using comparative analyses across taxa, we identify deeply conserved candidate genes, pathways, and regulatory networks for the formation of social hierarchies.
Relationship between blood coagulability and sense of burden among caregivers of patients with dementia
Authors: Hirano Akemi , Suzuki Yusuke , Umegaki Hiroyuki , Hayashi Toshio , Ina Koichiro , Onishi Joji , Hasegawa Jun , Kuzuya Masafumi
Published: July 2019

Aim

This study aimed to examine the relationship between blood coagulability and sense of burden among caregivers of patients with senile dementia of the Alzheimer type.

Methods

A cross‐sectional study was carried out involving healthy older caregivers who lived with their patients with senile dementia of the Alzheimer type. We evaluated the Zarit Burden Interview score, levels of von Willebrand factor antigen, D‐dimer, thrombin–antithrombin III complex, tissue plasminogen activator/plasminogen activator inhibitor type 1 complex, number of chronic diseases, body mass index and number of medications. A linear regression model was used to estimate adjusted associations.

Results

Thrombin–antithrombin III complex levels were higher in female caregivers than in male caregivers (P = 0.07). Headaches were significantly more frequent in female caregivers than in male caregivers, as assessed by a visual analog scale (P < 0.01). The number of chronic diseases and body mass index were positively associated with levels of tissue plasminogen activator/plasminogen activator inhibitor type 1 complex (P < 0.05). Similarly, the number of medications was positively associated with levels of D‐dimer (P < 0.05). However, the Zarit Burden Interview score was not associated with blood coagulability (P > 0.05).

Conclusions

The present study found that the number of chronic diseases and body mass index were associated with blood coagulability, and that female caregivers were more prone to headaches and higher blood coagulability than male caregivers. These findings highlight the essential nature of health management during caregiving. The impact of caregiver burden on blood coagulability is likely to differ depending on the long‐term or short‐term psychological stress associated with caregiving conditions. Geriatr Gerontol Int 2019; 19: 804–808.
Development of the Barthel Index 5 years after hip fracture: Results of a prospective study
Authors: Knauf Tom , Buecking Benjamin , Hack Juliana , Barthel Juliane , Bliemel Christopher , Aigner Rene , Ruchholtz Steffen , Eschbach Daphne
Published: July 2019

Aim

The importance of proximal femoral fractures is increasing due to demographic change. Despite appropriate care, these are associated with poor results. We are still lagging behind, and require information on the long‐term functional outcome of these patients and the predictive factors involved.

Methods

Between 2009 and 2011, 402 patients aged >60 years with hip fractures were included in this prospective observational study. Patients were assessed with the Barthel Index before fracture, at discharge, and 6 months, 1 year and 5 years after surgery. In addition, a variety of parameters (sex, age, fracture type, American Society of Anesthesiologists classification, Mini‐Mental State Examination, housing situation, occurrence of complications during inpatient stay and type of care) were collected to identify the possible independent predictive factors using multivariate analysis.

Results

The lowest Barthel Index was found at discharge (66 ± 24) for patients from an acute hospital. The Barthel Index improved within the first 6 months (86 ± 21) and decreased afterwards. The factors associated with a significantly higher point loss of the Barthel Index in the multivariate analysis were age (P‐value 0.020), pre‐fracture Barthel Index, (P ≤ 0.001), Mini‐Mental State Examination (P ≤ 0.001) and type II complications (P = 0.001). The other values showed no significant influence on the Barthel Index.

Conclusions

The present results showed that patients after a hip fracture have a great rehabilitation potential within the first 6 months after the event. More attention should be paid to type II complications and the occurrence of cognitive impairment. Both seem to be a surrogate parameter for the frailty of the patients. Geriatr Gerontol Int 2019; 19: 809–814.
Quality indicators and community pharmacy services: a scoping review
Authors: Alhusein Nour , Watson Margaret C
Published: July 2019

Background

Quality indicators are a commonly used improvement tool in health care. There is growing interest and activity in the use of quality indicators to improve community pharmacy practice.

Objectives

To conduct a scoping review of the use of quality indicators for community pharmacy practice, including their methods of development and evaluation.

Methods

Electronic databases (EMBASE and PubMed) were searched to identify papers published between January 2008 and April 2018. No limits were applied for language of publication or country of origin. Studies were included if they reported empirical data regarding the development or evaluation of quality indicators. All study designs were eligible for inclusion. Duplicate independent screening was undertaken of the search results. Data extraction was performed by one reviewer.

Results

Of the 988 records identified from the database search, 15 articles were included. The studies were conducted in 12 countries from six continents. Eleven studies described the development of quality indicators, eight of which included the evaluation of the psychometric properties of the indicators developed. Four studies examined the impact of quality indicators on practice all of which reported improvements in some aspects of quality, mainly with structure indicators rather than those relating to process and outcome.

Conclusions

Whilst there is a growing emphasis on promoting improvement in community pharmacy services, evidence is lacking of the effect of indicators on improving quality. Measurable process and outcome indicators are needed. The future development of quality indicators would also benefit from a multi-stakeholder approach.
Wolbachia dominate Spiroplasma in the co‐infected spider mite Tetranychus truncatus
Authors: Yang Kun , Xie Kang , Zhu Yu‐Xi , Huo Shi‐Mei , Hoffmann Ary , Hong Xiao‐Yue
Published: July 2019

Wolbachia and Spiroplasma are both maternally inherited endosymbionts in arthropods, and they can co‐infect the same species. However, how they interact with each other in the same host is not clear. Here we investigate a co‐infected Tetranychus truncatus spider mite strain that shares the same genetic background with singly infected and uninfected strains to detect the impacts of the two symbionts on their host. We found that Wolbachia‐infected and Spiroplasma‐infected mites can suffer significant fitness costs involving decreased fecundity, although with no effect on lifespan or development. Wolbachia induced incomplete cytoplasmic incompatibility in T. truncatus both in singly infected and doubly infected strains, resulting in female killing. In both females and males of the co‐infected spider mite strain, Wolbachia density was higher than Spiroplasma density. Transcriptome analysis of female adults showed that the most differentially expressed genes were found between the co‐infected strain and both the singly infected Spiroplasma strain and uninfected strain. The Wolbachia strain had the fewest differentially expressed genes compared with the co‐infected strain, consistent with the higher density of Wolbachia in the co‐infected strain. Wolbachia, therefore, appears to have a competitive advantage in host mites over Spiroplasma and is likely maintained in populations by cytoplasmic incompatibility despite having deleterious fitness effects.
Prokaryotic RNA activates endothelial cells promoting neutrophil transmigration
Authors: Castillo Luis A , Birnberg Weiss Federico , Rodriguez‐Rodrigues Nahuel , Pittaluga José R , Martire‐Greco Daiana , Milillo Maria A , Grinstein Sebastian F , Camelli María R , Mena Aybar Ana J , Landoni Verónica I , Fernández Gabriela C
Published: July 2019

Endothelial cell (EC)–neutrophil (PMN) interactions are crucial in the resolution of bacterial infections. Prokaryotic RNA (pRNA) has been reported as a pathogen‐associated molecular pattern that is released from bacteria upon death and is able to activate PMN. In this work, we studied the effects of pRNA on EC and investigated whether these effects could modulate EC–PMN interaction. For this purpose, we purified total pRNA from Escherichia coli and used it as a stimulus for Human Umbilical Vein Endothelial Cells (HUVEC). We found that the incubation of pRNA with HUVEC caused the increase of surface intercellular adhesion molecule 1 (ICAM‐1 or CD54) expression on HUVEC, and the secretion of IL‐8 and von Willebrand factor, characteristics consistent with HUVEC activation, without causing toxic effects. Moreover, pRNA‐treated HUVEC also induced PMN adhesion and the conditioned medium obtained from treated‐HUVEC was chemotactic for PMN and caused their activation, as determined by CD11b upregulation. As reported previously, the degradation products of pRNA induced similar biological effects. The treatment of HUVEC with endocytosis inhibitors revealed that the entry of pRNA partially relied on a clathrin‐dependent mechanism, whereas the effects of degradation products could not be inhibited by any of the inhibitors tested. Using a transwell system, we found that pRNA or degraded pRNA were also able to stimulate HUVEC when recognized from the basolateral side. Our results indicate that pRNA activates EC, resulting in the modulation of EC–PMN interaction by inducing PMN chemotaxis, adhesion and activation. In the context of infection, pRNA sensed by EC and PMN could favor bacterial clearance.
Effects of Holocene climate changes on alpine ecosystems: Nonequilibrium dynamics drive insect species richness on alpine islands
Authors: Marta Silvio , Lacasella Federica , Cesaroni Donatella , Sbordoni Valerio
Published: July 2019

Aim

To identify the effect of multiple, temporally close, forcing events (i.e. climate‐driven habitat fragmentations/homogenizations) in shaping current patterns of biodiversity in alpine areas. Given their spatial configuration, alpine areas have been traditionally seen as islands surrounded by an “ocean” of unsuitable lands. A quantitative assessment of the effects of Holocene climate fluctuations on islands area and inter‐island connectivity is crucial to finely reconstruct past biodiversity dynamics and forecast species responses to future changes.

Location

Italy.

Taxa

Carabidae (Ground beetles), Chrysomelidae (Leaf beetles), Elateridae (Click beetles), Orthoptera (Grasshoppers and Crickets) and Papilionoidea (Butterflies and Skippers).

Methods

A total of 1,077 species for 128,093 records were analysed and a classification based on their functional traits allowed identifying groups of good and poor dispersers within each taxon. A dynamic discrete model of ecosystem evolution provided the spatio‐temporal context to test two competing (transient equilibria vs. nonequilibrium) dynamics based on different colonization capabilities. In the transient equilibria dynamic the species are able to respond to island evolution through successful dispersal and colonization events, whereas in the nonequilibrium dynamic ineffective immigration constrains the current species richness to that generated by the strongest island contraction.

Results

With the exception of Elateridae, good dispersers (Chrysomelidae and Papilionoidea) responded to environmental changes by establishing a series of transient equilibria. In contrast, the nonequilibrium dynamic better described patterns of species richness in poor dispersers (Carabidae and Orthoptera).

Main conclusions

Our approach could be used as the basis for the development of spatially and temporally explicit models of island evolution and could be a valuable tool for quantifying the sensitivity of single taxa to climate‐driven habitat changes. It also represents a further step towards the forecasting of future responses to climate change and the accompanying development of conservation strategies that more effectively respond to the detrimental impacts of climate change on biodiversity.
Level of contact hypersensitivity response to diphencyprone and keratinocyte cancer
Authors: Bullen A. , Polcz M. , Rowe C.J. , Byrom L. , Soyer H.P. , Khosrotehrani K.
Published: July 2019

Background

Keratinocyte cancers (KC) are common and pose a significant financial burden globally. Ultraviolet radiation is a significant factor in their development, through mutagenesis promotion but also through local and systemic immunosuppression. Although systemic immunosuppression is well understood, cutaneous immunity has been more difficult to evaluate.

Objectives

This study used a contact sensitizer, diphencyprone (DPCP), which elicits a contact hypersensitivity reaction in skin, to compare the degree of reactivity to DPCP in patients with a high KC burden versus those with a low KC burden.

Methods

A prospective study was performed in immunocompetent patients aged 70 ± 5 years of age, comparing patients with a high KC burden (>10 previous KC) with those with a low KC burden (<2 previous KC). All patients were sensitized with 2% DPCP and then patch tested two weeks later with eight different concentrations of DPCP with the threshold concentration and total degree of reaction recorded.

Results

Nine patients were recruited, 5 in the ‘high cancer’ group and 4 in the ‘low cancer’ group. All patients were Fitzpatrick skin type 1 or 2. All patients developed a reaction to DPCP. Patients in the low cancer group developed a reaction at a significantly lower threshold DPCP concentration than the high cancer group (P = 0.039). The cumulative intensity of reaction was higher in the low cancer group (P = 0.087).

Conclusion

Patients with a high KC burden required a higher threshold concentration of DPCP to elicit a hypersensitivity reaction, supporting the concept of a lower skin immunity in these patients. DPCP reactivity threshold could be a useful tool in the evaluation of skin immunity and propensity to develop keratinocyte cancers.
Ex vivo confocal laser scanning microscopy for bullous pemphigoid diagnostics: new era in direct immunofluorescence?
Authors: Bağcı I.S. , Aoki R. , Krammer S. , Ruzicka T. , Sárdy M. , French L.E. , Hartmann D.
Published: July 2019

Background

Ex vivo confocal laser scanning microscopy (ex vivo CLSM) is a novel diagnostic method allowing rapid, high‐resolution imaging of excised skin samples. Furthermore, fluorescent detection is possible using fluorescent‐labelled antibodies.

Objective

To assess the applicability of ex vivo CLSM in the detection of basement membrane (BM) fluorescence in bullous pemphigoid (BP) and to compare its diagnostic accuracy with direct immunofluorescence (DIF) microscopy.

Methods

A total of 81 sections of 49 BP patients with positive DIF microscopy findings were examined using ex vivo CLSM in reflectance and fluorescence mode following staining with fluorescent‐labelled IgG and C3 antibodies.

Results

Ex vivo CLSM showed an overall performance of 65.3% in identifying BM fluorescence in BP patients. IgG and C3 deposition along the BM was detected in 50% and 45.5% of the patients, respectively. The sensitivity of ex vivo CLSM in detecting BM fluorescence was low (IgG: 50%, C3: 45.5%), but the specificity was high (IgG: 100, C3: 90%). In addition to immunoreactivity, ex vivo CLSM could display subepidermal inflammatory cells similar to histological examination in 84% of patients.

Conclusions

Basement membrane fluorescence could be identified with ex vivo CLSM in the skin sections of BP patients. Ex vivo CLSM enables simultaneous and rapid detection of histopathological and immunofluorescence findings in the same session, albeit with a lower sensitivity than DIF in detecting BM fluorescence.
Developing and psychometric testing of the anaesthesia nursing competence scale
Authors: Jeon Yunsuk , Meretoja Riitta , Vahlberg Tero , Leino‐Kilpi Helena
Published: July 2019

Rationale, aims, and objectives

The competence of nurses in anaesthesia care is important for the quality of anaesthesia nursing care and patient safety. However, there is a lack of psychometrically tested instruments to measure the competence. Therefore, this study aimed to develop and test the psychometric properties of an anaesthesia nursing competence scale (AnestComp) assessing nurses' competence in anaesthesia care.

Method

The scale development and psychometric testing had three phases: (1) based on literature reviews and the description of experts, competence areas were identified and items were created; (2) the content validity of the scale was tested by a content expert group, and the scale was pilot tested; and (3) psychometric testing of scale was tested by anaesthesia nurses' (n = 222) and nursing students' (n = 205) self‐assessments. The psychometric testing assessed the reliability when using Cronbach's α and the construct validity using factor analyses (confirmatory and exploratory) and known‐group technique. Nursing students were included for the purpose of construct validity testing.

Results

The AnestComp has 39 items and consists of seven competence areas: (a) ethics of anaesthesia care, (b) patient's risk care, (c) patient engagement with technology, (d) collaboration within patient care, (e) anaesthesia patient care with medication, (f) peri‐anaesthesia nursing intervention, and (g) knowledge of anaesthesia patient care. Cronbach's α values were high in all categories (0.83‐0.95), and factor analyses and known‐group technique supported a seven‐factor model.

Conclusion

The initial results supported the reliability and construct validity of the AnestComp. The scale is considered a promising instrument for measuring anaesthesia nursing competence among anaesthesia nurses. Further research with larger and more diverse samples is suggested to refine the current psychometric evaluation.
Index admission cholecystectomy for acute biliary pancreatitis favorably impacts outcomes of hospitalization in cirrhosis
Authors: Patel Kishan P , Mumtaz Khalid , Li Feng , Luthra Anjuli K , Hinton Alice , Lara Luis F , Conwell Darwin L , Krishna Somashekar G
Published: July 2019

Background and Aim

Despite higher rates of gallstones in patients with cirrhosis, there are no population‐based studies evaluating outcomes of acute biliary pancreatitis (ABP). Therefore, we sought to evaluate the predictors of early readmission and mortality in this high‐risk population.

Methods

We utilized the Nationwide Readmission Database (2011–2014) to evaluate all adults admitted with ABP. Multivariable logistic regression models were used to assess independent predictors for 30‐day readmission, index admission mortality, and calendar year mortality.

Results

Among 184 611 index admissions with ABP, 4344 (2.4%) subjects had cirrhosis (1649 with decompensation). Subjects with cirrhosis, when compared with those without, incurred higher rates of 30‐day readmission (20.9% vs 11.2%; P < 0.001), index mortality (2.0% vs 1.0%; P < 0.001), and calendar year mortality (4.2% vs 0.9%; P < 0.001). Decompensation in cirrhosis was associated with significantly fewer cholecystectomies (26.7% vs 60.2%; P < 0.001) and endoscopic retrograde cholangiopancreatographies (23.3% vs 29.9%; P < 0.001). Multivariate analysis revealed that severe acute pancreatitis (odds ratio [OR]: 14.8; 95% confidence interval [CI]: 5.3, 41.2), sepsis (OR: 12.6; 95% CI: 5.8, 27.4), and decompensation (OR: 3.1; 96% CI: 1.4, 6.6) were associated with increased index admission mortality. Decompensated cirrhosis (OR: 1.8; 95% CI: 1.1, 3.0) and 30‐day readmission (OR: 5.6; 95% CI: 3.3, 9.5) were predictors of calendar year mortality. However, index admission cholecystectomy was associated with decreased 30‐day readmissions (OR: 0.6; 95% CI: 0.4, 0.7) and calendar year mortality (OR: 0.44; 95% CI: 0.25, 0.78).

Conclusions

The presence of cirrhosis adversely impacts hospital outcomes of patients with ABP. Among modifiable factors, index admission cholecystectomy portends favorable prognosis by reducing risk of early readmission and consequent calendar year mortality.
Innovations in Midwifery Education: The Academic Medical Center Model
Authors: Krause Susan A. , DeJoy Susan A. , Sankey Heather Z.
Published: July 2019

Workforce analyses project a need for women's health care providers, especially in maternity care. With a stagnant number of certified nurse‐midwife/certified midwife (CNM/CM) education programs, the present production of new CNMs/CMs is not robust enough to meet the growing demand. This article describes an existing but underutilized model for CNM/CM education programs, based in an academic medical center with an existing academic affiliation. Advantages include a federal funding source through the Centers for Medicare and Medicaid Services, lower tuition costs than most current programs, and expanded job satisfaction for CNMs/CMs in clinical practice.
Identification of compounds inhibiting prion replication and toxicity by removing PrPC from the cell surface
Authors: Biggi Silvia , Pancher Michael , Stincardini Claudia , Luotti Silvia , Massignan Tania , Dalle Vedove Andrea , Astolfi Andrea , Gatto Pamela , Lolli Graziano , Barreca Maria Letizia , Bonetto Valentina , Adami Valentina , Biasini Emiliano
Published: July 2019

The vast majority of therapeutic approaches tested so far for prion diseases, transmissible neurodegenerative disorders of human and animals, tackled PrPSc, the aggregated and infectious isoform of the cellular prion protein (PrPC), with largely unsuccessful results. Conversely, targeting PrPC expression, stability or cell surface localization are poorly explored strategies. We recently characterized the mode of action of chlorpromazine, an anti‐psychotic drug known to inhibit prion replication and toxicity by inducing the re‐localization of PrPC from the plasma membrane. Unfortunately, chlorpromazine possesses pharmacokinetic properties unsuitable for chronic use in vivo, namely low specificity and high toxicity. Here, we employed HEK293 cells stably expressing EGFP‐PrP to carry out a semi‐automated high content screening (HCS) of a chemical library directed at identifying non‐cytotoxic molecules capable of specifically relocalizing PrPC from the plasma membrane as well as inhibiting prion replication in N2a cell cultures. We identified four candidate hits inducing a significant reduction in cell surface PrPC, one of which also inhibited prion propagation and toxicity in cell cultures in a strain‐independent fashion. This study defines a new screening method and novel anti‐prion compounds supporting the notion that removing PrPC from the cell surface could represent a viable therapeutic strategy for prion diseases.

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Novel shampoo reduces hair shedding by contracting the arrector pili muscle via the trace amine‐associated receptor
Authors: Kovacevic Maja , McCoy John , Goren Andy , Situm Mirna , Stanimirovic Andrija , Liu Wei , Tan Yimei , Vaño‐Galvan Sergio , Shapiro Jerry , Sinclair Rodney
Published: July 2019

Background

Approximately 40% of women experience excessive hair shedding when washing their hair. Previously, we have demonstrated that a topically applied α1 adrenergic receptor agonist can be used to contract the arrector pili muscle of the follicular unit (ie, produce “goose bumps”), increasing the force required to pluck hair by as much as 400%. Subsequently, we reported a topical cosmetic solution containing an α1 adrenergic receptor agonist that reduced hair shedding during brushing by a maximum of 77%.

Aims

In this communication, we explore a novel mechanism to contract the arrector pili muscle. Trace amine‐associated receptors (TAAR) have been shown to regulate smooth muscle tone in blood vessels, but have not been reported to be present in the skin. Here, we report on the anti‐shedding efficacy of a shampoo containing a selective TAAR agonist, tyramine hydrochloride.

Methods

A single‐blinded crossover study was designed to test the efficacy of the novel shampoo versus placebo in reducing hairs lost during brushing.

Results

In this study, the novel TAAR shampoo reduced hair shedding during brushing by 31% in a cohort of 24 women with a maximum reduction of 77%.

Conclusions

A shampoo formulated with a selective TAAR agonist was demonstrated to contract the arrector pili muscle and reduce hair shedding subsequent to washing.
Risk for Cesarean section in women of advanced maternal age under the changed reproductive policy in China: A cohort study in a tertiary hospital in southwestern China
Authors: Xie Min , Lao Terence T , Du Mingyu , Sun Qian , Qu Zaiqing , Ma Junnan , Song Xinyan , Wang Mingfang , Xu Dongqiong , Ma Runmei
Published: July 2019

Aim

To describe changed epidemiological features of advanced maternal age (AMA) and to examine the effect of AMA on the risk for Cesarean section (CS) in a Chinese pregnant population.

Methods

This retrospective single‐center cohort study investigated the changes of epidemiological features of AMA parturients with respect to the revised reproductive policy in China in 43 702 singleton deliveries with live birth at ≥28 weeks managed from January 2005 to December 2016. We also evaluated the pregnancy outcomes in different age groups and risk factors of CS with multivariate analysis.

Results

In this 12‐year study period, the average maternal age increased from 28.5 to 30.2 years, and the proportion of AMA raised from 6.5% to 17.2%. AMA was significantly associated with increased risk of adverse pregnancy outcomes, and after adjustment for confounding factors, AMA remained a significant independent risk factor for CS. Furthermore, the effect of AMA in nulliparous women on the risk of CS was more significant than in multiparous women, while the history of previous CS (adjusted odds ratio 39.85) and interdelivery interval ≥10 years (adjusted odds ratio 1.52) also increased the risk of CS in multiparous women.

Conclusion

AMA increased the risk of a number of adverse pregnancy outcomes, and was independently associated with increased risk for CS. The increasing number of AMA parturients with risk factors is likely to increase CS rate in China in the near future, thus it is imperative to reduce the rate of primary CS as a matter of policy.