bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of intact IgE and the mechanism of ligelizumab revealed by electron microscopy
Authors: Jensen Rasmus K. , Jabs Frederic , Miehe Michaela , Mølgaard Brian , Pfützner Wolfgang , Möbs Christian , Spillner Edzard , Andersen Gregers R.
Published: February 2020

Background

IgE is the central antibody isotype in TH2‐biased immunity and allergic diseases. The structure of intact IgE and the impact of IgE‐targeting molecules on IgE however remain elusive. In order to obtain insights into IgE biology and the clinical impact, we aimed for structure determination of IgE and the complex of IgE with the anti‐IgE antibody ligelizumab.

Methods

Structures of two distinct intact IgE with specificity for cross‐reactive carbohydrate determinants and Der p 2 as well as complexes of ligelizumab‐Fab with IgE and IgE Fc were assessed by negative stain electron microscopy and solution scattering. Inhibition of IgE binding and displacement of receptor‐bound IgE were assessed using cellular assays, basophil activation testing and ELIFAB assays.

Results

Our data reveal that the investigated IgE molecules share an overall rigid conformation. In contrast to the IgE Fc fragment, the IgE Fc in intact IgE is significantly less asymmetrically bent. The proximal and the distal Fabs are rigidly tethered to the Fc. Binding of ligelizumab to IgE in a 2:1 stoichiometry induces an extended and twofold symmetrical conformation of IgE, which retains a rigid Fab‐Fc architecture. Analyses of effector cell activation revealed that ligelizumab inhibits IgE binding without displacing receptor‐bound IgE. Together with an interference of CD23 binding, the data underline a functional activity similar to omalizumab.

Conclusions

Our data reveal the first structures of intact IgE suggesting that the IgE Fab is fixed relative to the Fc. Furthermore, we provide a structural rationale for the inhibitory mechanism of ligelizumab.
Peri‐articular infiltration analgesia for shoulder surgery: a systematic review and meta‐analysis
Authors: Yung E. M. , Patel N. , Brull R. , Abdallah F. W.
Published: February 2020

Effective analgesic alternatives to interscalene brachial plexus block are sought for shoulder surgery. Peri‐articular infiltration analgesia is a novel, less invasive technique, but evidence surrounding its use is unclear. This systematic review and meta‐analysis aims to evaluate the utility of peri‐articular infiltration analgesia in shoulder surgery. We searched literature for trials comparing peri‐articular infiltration analgesia with control or with interscalene brachial plexus block. Control groups received no intervention, placebo or systemic opioids. The primary outcome was cumulative oral morphine equivalent consumption during the first 24 h postoperatively. Secondary outcomes included: rest pain scores up to 48 h; risk of side‐effects; and durations of post‐anaesthetic care unit and hospital stay. Data were pooled with random‐effects modelling. Seven trials (383 patients) were included. Compared with control, peri‐articular infiltration analgesia reduced 24‐h oral morphine consumption by a mean difference (95%CI) of −38.0 mg (−65.5 to −10.5; p = 0.007). It also improved pain scores up to 6 h, 36 h and 48 h, with the greatest improvement observed at 0 h (−2.4 (−2.7 to −1.6); p < 0.001). Peri‐articular infiltration analgesia decreased postoperative nausea and vomiting by an odds ratio (95%CI) of 0.3 (0.1–0.7; p = 0.006). In contrast, peri‐articular infiltration analgesia was not different from interscalene brachial plexus block for analgesic consumption, pain scores or side‐effects. This review provides moderate evidence supporting peri‐articular infiltration for postoperative analgesia following shoulder surgery. The absence of difference between peri‐articular infiltration analgesia and interscalene brachial plexus block for analgesic outcomes suggests that these interventions are comparable, but further trials are needed to support this conclusion and identify the optimal peri‐articular infiltration technique.
Pre‐ and postnatal growth failure with microcephaly due to two novel heterozygous IGF1R mutations and response to growth hormone treatment
Authors: Gkourogianni Alexandra , Andrade Anenisia C. , Jonsson Björn‐Anders , Segerlund Emma , Werner‐Sperker Antje , Horemuzova Eva , Dahlgren Jovanna , Burstedt Magnus , Nilsson Ola
Published: February 2020

Aim

To explore the phenotype and response to growth hormone in patients with heterozygous mutations in the insulin‐like growth factor I receptor gene (IGF1R).

Methods

Children with short stature, microcephaly, born SGA combined with biochemical sign of IGF‐I insensitivity were analysed for IGF1R mutations or deletions using Sanger sequencing and Multiple ligation‐dependent probe amplification analysis.

Results

In two families, a novel heterozygous non‐synonymous missense IGF1R variant was identified. In family 1, c.3364G > T, p.(Gly1122Cys) was found in the proband and co‐segregated perfectly with the phenotype in three generations. In family 2, a de novo variant c.3530G > A, p.(Arg1177His) was detected. Both variants were rare, not present in the GnomAD database. Three individuals carrying IGF1R mutations have received rhGH treatment. The average gain in height SDS during treatment was 0.42 (range: 0.26‐0.60) and 0.64 (range: 0.32‐0.86) after 1 and 2 years of treatment, respectively.

Conclusion

Our study presents two heterozygous IGF1R mutations causing pre‐ and postnatal growth failure and microcephaly and also indicates that individuals with heterozygous IGF1R mutations can respond to rhGH treatment. The findings highlight that sequencing of the IGF1R should be considered in children with microcephaly and short stature due to pre‐ and postnatal growth failure.
Haematological reference intervals of wild southern Australian koalas (Phascolarctos cinereus)
Authors: Fabijan J , Speight N , Boardman WSJ , Hemmatzadeh F , Trott DJ , Woolford L
Published: February 2020

Objective

Current haematology reference intervals (RIs) for koalas were developed in northern Australian koalas, using low numbers and/or individuals of unknown Chlamydia pecorum and koala retrovirus (KoRV) status. This study developed haematological RIs for wild, clinically healthy southern Australian koalas of known C. pecorum and KoRV infection status and investigated the effects of population, age and sex.

Methods

Haematological RIs were determined for 138 clinically healthy South Australian koalas (Mount Lofty Ranges [MLR], n = 68; Kangaroo Island, n = 70) examined in April 2016 and February 2017, respectively. C. pecorum and KoRV status were determined by PCR.

Results

RIs for southern koala haematological parameters were established for all koalas based on the finding that there were limited differences in haematological values in koalas with subclinical C. pecorum or KoRV infections (P > 0.05), except KoRV‐infected koalas had a lower haematocrit than noninfected koalas. MLR koalas had significantly lower erythrocyte mass and leucocyte counts than Kangaroo Island koalas. Young koalas had significantly lower haemoglobin, haematocrit and higher mean cellular haemoglobin concentration and lymphocyte counts than adult koalas. MLR male koalas had elevated erythrocyte, leucocyte and neutrophil counts compared with MLR females.

Conclusion

The haematological RIs developed in this study are based on a large number of clinically healthy koalas, where subclinical C. pecorum and KoRV infections had no effect on haematological values and will be a valuable tool during clinical examination and disease investigation by veterinarians and researchers Australia‐wide.
Protective effects of doxepin cream on radiation dermatitis in breast cancer: A single arm double‐blind randomized clinical trial
Authors: Shariati Laleh , Amouheidari Alireza , Naji Esfahani Hajar , Abed Alireza , Haghjooy Javanmard Shaghayegh , Laher Ismail , Ghasemi Ahmad , Vaseghi Golnaz
Published: February 2020

Aims

Breast cancer is the most frequently occurring cancer in women. Lumpectomy followed by radiotherapy is suggested to be as effective as a total mastectomy. Radiation‐induced dermatitis often occurs as a result of breast radiotherapy. Recent studies suggest that doxepin has promising anti‐inflammatory properties. This study was undertaken to evaluate the effects of doxepin therapy on radiation dermatitis.

Methods

A double‐blind randomized clinical trial was launched from 2016 to 2017, with a total of 48 patients who had undergone breast‐conserving surgery and received postoperative radiation therapy. Radiotherapy was applied 5 days per week for 5 weeks. Adverse dermatological effects were evaluated by a physician at the beginning of the fifth week of radiotherapy and the patients were then randomly assigned (1:1 ratio) to receive either doxepin (5%) or placebo cream for 7 days.

Results

There were no significant differences in the dermatitis grade between doxepin and placebo groups at baseline (P > .5). The occurrence of acute dermatitis (grade 2 or higher) was significantly lower with the use of doxepin than with placebo (P ≤ .0001, Zα = 1.96 at 95% confidence interval).

Conclusion

Doxepin cream prevents dermatitis grade 2 or higher during post‐operative breast irradiation. Doxepin cream is easy to use, affordable and prevents pain and irritation.
P7C3‐A20 alleviates fatty liver by shaping gut microbiota and inducing FGF21/FGF1, via the AMP‐activated protein kinase/CREB regulated transcription coactivator 2 pathway
Authors: Hua Xia , Sun Di‐Yang , Zhang Wen‐Jie , Fu Jiang‐Tao , Tong Jie , Sun Si‐Jia , Zeng Fei‐Yan , Ouyang Shen‐Xi , Zhang Guo‐Yan , Wang Shu‐Na , Li Dong‐Jie , Miao Chao‐Yu , Wang Pei
Published: February 2020

Background and Purpose

Non‐alcoholic fatty liver disease (NAFLD) is a worldwide public health problem with no established pharmacological therapy. Here, we explored the potential benefit of P7C3‐A20, a novel aminopropyl carbazole compound with neuroprotective activity, in a NAFLD model, induced in mice by a high‐fat diet (HFD).

Experimental Approach

C57BL/6J mice were given a HFD (42% fat content) for 16 weeks to induce NAFLD. P7C3‐A20 (20 mg·kg−1·day−1) was given by gavage for 2 weeks. Indirect calorimetry, histological analysis, immunoblotting, immunohistochemistry, and biomedical examinations were performed. Gut microbiota were determined using a 16S ribosomal RNA sequencing analysis.

Key Results

P7C3‐A20 treatment reduced body weight gain/adiposity, improved insulin resistance, promoted energy expenditure (O2 consumption/CO2 production), inhibited lipid oxidation, suppressed hepatic inflammation (Kupffer cell number and pro‐inflammatory factors), decreased necroptosis/apoptosis (receptor‐interacting protein kinase 3, cleaved caspase‐3, and TUNEL), and alleviated liver fibrosis and injury. Mechanistically, P7C3‐A20 stimulated FGF21 and FGF1 via activating liver kinase B1 (LKB1) and AMP‐activated protein kinase (AMPK), which further resulted in a reduced nuclear translocation of CREB‐regulated transcription coactivator 2 (CRTC2). In AMPKα2 knockout mice, the protection of P7C3‐A20 against HFD‐induced metabolism abnormalities and fat accumulation, as well as the elevation of blood FGF21 and FGF1, was abolished. P7C3‐A20 increased the gut microbiota species richness. Moreover, it enhanced the proportions of Akkermansia, Lactobacillus, and Prevotellaceae, while reducing the proportions of Enterobacteriaceae, Escherichia, and Parasutterella.

Conclusions and Implications

P7C3‐A20 increased levels of NAD+ and alleviated NAFLD through stimulating FGF21 and FGF1 in an LKB1/AMPK/CRTC2‐dependent manner and shaping gut microbiota.

LINKED ARTICLES

This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc
The feasibility of a multi‐professional training to improve how health care professionals deliver different news to families during pregnancy and at birth
Authors: Mugweni Esther , Lowenhoff Catherine , Walker Melita , Jaswal Sabrena , Emrys‐Jones Angela , Adams Cheryll , Kendall Sally
Published: February 2020

Background

In the United Kingdom, pregnant women are offered foetal anomaly screening to assess the chance of their baby being born with eleven different conditions. How health care professionals (HCPs) deliver news about a child having a congenital anomaly affects how it is received and processed by parents. We refer to this news as different news.

Methods

We conducted a mixed methods evaluation of a training intervention to improve how HCPs deliver different news. Twenty‐six HCPs self‐completed pretraining and posttraining questionnaires on skills, knowledge, and attitudes related to delivering different news. Qualitative interviews were conducted with eight HCPs. Quantitative data were analysed using descriptive statistics, the paired t test to compare the pre and post scores and estimate the difference between pre and post scores, and the 95% confidence interval. Qualitative data were analysed using framework analysis guided by the Theoretical Domains Framework (TDF).

Results

The training intervention was both feasible and acceptable. HCPs indicated that it enhanced or consolidated their knowledge and skills, covered topics relevant to their practice, and that they would recommend it to colleagues. Participants particularly valued integration of the voice of parents with lived experience in the training. Significant increase in mean scores were observed in confidence to deliver different news (2.81, 95% CI [2.43, 3.19] to 4.28, 95% CI [4.09, 4.47]; p < .001) and skills to deliver different news (3.00, 95% CI [2.64, 3.36] to 4.36, 95% CI [4.13, 4.59]; p < .001). HCPs reported feeling more confident in their ability to provide sensitive, responsive, balanced care to families.

Conclusions

The significant improvements in confidence and skills reported by HCPs suggest that the training may be effective in equipping HCPs to minimize the distress, anxiety, and depression associated with receiving different news. This represents a key aspect of the prevention of mental ill health across the life course.
Institutions and the financial development–economic growth nexus in sub‐Saharan Africa
Authors: Aluko Olufemi A. , Ibrahim Muazu
Published: February 2020

Using a sample splitting approach that does not impose an exogenous quadratic term, we examine the effect of financial development on economic growth in sub‐Saharan Africa by allowing the link to be mediated by the level of institutions. Our findings reveal a disproportionate growth‐enhancing effect of finance, given countries’ distinct level of institutional quality. More specifically, when the International Country Risk Guide‐based measure of institutions is used as the threshold variable, below the optimal level of institutional quality, financial development does not significantly promote economic growth. For countries with institutional quality above the threshold, higher finance is associated with growth. However, when institutions are measured by World Governance Indicators proxy, we find a significant effect of financial development, irrespective of whether a country is below or above the threshold. Interestingly, the growth‐enhancing effect of finance is greater for low‐institution countries relative to high‐institution countries. Thus, through its ability to provide some crucial roles, the well‐developed financial sector may also perform the function of sound institutions in influencing economic growth.
First detection of Bursaphelenchus mucronatus (Nematoda: Aphelenchoididae) on Monochamus sutor (Coleoptera: Cerambycidae) in Romania
Authors: Mitrea‐Calin Monica , Inácio Maria L. , Cean Mirela , Costache Claudia , Rusinque Leidy , Paraschiv Marius , Camacho Maria J. , Vieira Paulo , Cristea Stelica , Nóbrega Filomena
Published: February 2020

As a result of the detection of the pinewood nematode Bursaphelenchus xylophilus in Portugal, and its subsequent spread to Spain, intense surveys were conducted to screen for the presence of Bursaphelenchus species in Romania. Herein, we report recent surveys of insects potentially vectoring Bursaphelenchus species collected using trap trees or pheromone‐baited traps placed in the forest. Trap felled spruce trees (Picea abies) and pheromone‐baited traps were installed in six different counties in Romania (Brașov, Sibiu, Suceava, Hunedoara, Timiș and Dâmbovița). Ten different species of insects distributed among Curculionidae and Cerambycidae were obtained. Nematodes were extracted from insects and observed to validate the presence of Bursaphelenchus specimens. One female identified as Monochamus sutor was the only specimen carrying nematodes in the genus Bursaphelenchus. Nematodes were identified as B. mucronatus based on morphological and molecular features. This is the first detection and report of natural spread of B. mucronatus in Romania. The absence of B. xylophilus was confirmed in the areas of Romania surveyed in this work.
Medical interventions suppressed progression of advanced Alzheimer's disease more than mild Alzheimer's disease
Authors: Honjo Yasuyuki , Ide Kazuki , Takechi Hajime
Published: February 2020

Aim

Alzheimer's disease (AD) is the most common neurodegenerative disease. In 2000, Mendiondo et al. reported on a model predicting that AD progresses at an accelerating rate and cognitive function worsens rapidly. Recently, anti‐AD drugs and non‐pharmacological intervention have been established, but the effect of intervention is unclear and might depend on the stage of AD progression. Here, we examined the prediction of Mendiondo's model in patients with different severities of AD.

Methods

A total of 163 new outpatients with AD at four memory clinics were retrospectively analyzed. The Revised Hasegawa Dementia Scale (HDS‐R) and Mini‐Mental State Examination (MMSE) were administered to all AD patients at the first visit and after approximately 12 months. We divided the patients into three groups according to scores at the first visit: mild, moderate and moderate‐to‐severe. We compared the scores at the first visit with those obtained after 12 months of anti‐AD drug and non‐pharmacological interventions.

Results

The HDS‐R score improved from 14.5 to 15.0, and the MMSE score improved from 18.8 to 19.1 after 12 months of intervention. Also, the HDS‐R and MMSE scores at the first visit were significantly associated with the annual change in the scores. Among the three groups, lower HDS‐R and MMSE scores at the first visit were associated with significantly greater annual improvement in the scores after 12 months of intervention.

Conclusions

Contrary to the prediction of Mendiondo's model, mild or moderate AD progressed more rapidly than moderate‐to‐severe AD under pharmacological and non‐pharmacological interventions. Geriatr Gerontol Int 2020; 20: 324–328.
Blended professionals, technology and online learning: Identifying a socio‐technical third space in higher education
Authors: White Steven , White Su , Borthwick Kate
Published: February 2020

The idea of a ‘third space’ located between academic and professional domains has proven useful in exploring changing academic and professional roles in higher education, including in online learning. However, the role of technology in accounts of third space activity remains under‐explored. Drawing on research into the introduction of Massive Open Online Courses (MOOCs) at three UK higher education institutions, it is argued that both social and technical factors must be considered to understand, plan for and manage the third space roles and structures which emerge in such initiatives. This study focuses on learning designers, confirming that they act as third space ‘blended professionals’ in the somewhat distinctive case of MOOC development. However, it also proposes the concept of a socio‐technical third space in which blended professionals act as hubs in a metaphorical network of activity, using social and technical means to shape their own roles and those of others.
Executive functioning and disinhibited eating in children and adolescents
Authors: Kelly Nichole R. , Jaramillo Manuela , Ramirez Sophie , Altman Deborah R. , Rubin Sarah G. , Yang Shanna B. , Courville Amber B. , Shank Lisa M. , Byrne Meghan E. , Lemay‐Russell Sarah , Brady Sheila M. , Broadney Miranda M. , Tanofsky‐Kraff Marian , Yanovski Jack A.
Published: February 2020

Background

Executive functioning (EF) difficulties may be associated with problems regulating eating behaviours. Few studies have evaluated this question in youth using diverse measures of EF or objective measures of energy intake.

Methods

The current study used neuropsychological tasks and a laboratory test meal to evaluate the links between EF and youth's disinhibited eating patterns. Two‐hundred‐five nontreatment seeking youth (M age = 13.1 ± 2.8 years; M BMIz = 0.6 ± 1.0; 33.2% overweight; 54.1% female) completed tasks measuring decision making, general and food‐specific behavioural disinhibition, willingness to delay gratification for food and money, cognitive flexibility, and working memory. Age (children vs adolescents) was examined as a moderator. All analyses adjusted for demographic factors, pubertal status, lean mass (kg), fat mass (%), height, general intellectual functioning, and depressive symptoms.

Results

After adjusting for multiple comparisons, more general behavioural disinhibition was associated with greater total energy intake (P = .02), and poorer cognitive flexibility was associated with more fat intake (P = .03) across all ages. Poorer decision making in children (P = .04), but not adolescents (P = .24), was associated with greater fat intake. Food‐specific behavioural disinhibition, the ability to delay gratification for both food and monetary rewards, and working memory were not significantly associated with youth's disinhibited eating patterns during a single meal.

Conclusions

Most domains of EF were not associated with youth's disinhibited eating. Significant associations may highlight the need to target specific cognitive processes, particularly behavioural disinhibition, decision making, and cognitive flexibility, in potential intervention strategies for children's disinhibited eating.
ACTN2 (rs6656267) and MPPED2 (rs11031093 and rs536007) polymorphisms in primary dentition caries: A case‐control study
Authors: Katifelis Hector , Sioziou Anna , Gazouli Maria , Emmanouil Dimitris
Published: February 2020

Background

Dental caries represents one of the most common human diseases which can lead to pulpitis, pain, and tooth loss and can negatively affect growth and well‐being. Although dietary and environmental factors have been extensively studied towards their contribution of the disease, genetic factors that contribute one's susceptibility over caries development remain rather clouded.

Aim

To investigate the possible contribution of ACTN2 (rs6656267) and MPPED2 (rs11031093 and rs536007) polymorphisms in primary dentition caries.

Design

Samples from children (5‐12 years old) were collected and genotyped for ACTN2 (rs6656267) and MPPED2 (rs11031093 and rs536007) polymorphisms. With regard to dmfs index and socio‐economic status, an association between these polymorphisms and primary dentition caries was investigated.

Results

ACTN2 (rs6655267) and MPPED2 (rs536007) are not associated with primary dentition caries. MPPED2 (rs11031093, G Allele) is marginally associated.

Conclusions

MPPED2 (rs11031093, G Allele) is marginally associated with caries susceptibility on primary dentition.
The MAAPE score in intermediate and advanced hepatocellular carcinoma treated with Yttrium‐90 resin microsphere radioembolization
Authors: Wallace Michael C , Samuelson Shaun , Khoo Tiffany , Ooi Jacob , Tibballs Jonathan , Ferguson John , Preen David B , Knuiman Matthew , Garas George , MacQuillan Gerry , Adams Leon A , Jeffrey Gary P
Published: February 2020

Background and Aim

Yttrium‐90 resin microsphere radioembolization (RE) is not recommended for routine use in intermediate or advanced hepatocellular carcinoma (HCC) by recent guidelines. This study aims to establish pre‐treatment variables which predict survival in HCC patients treated with RE to identify those who will benefit most from it, and to inform patient selection for future trials.

Methods

Single center, retrospective study of consecutive patients with HCC treated with RE from 2007 to 2018. Patients included if undergoing their first RE treatment for intermediate or advanced HCC; a Child–Pugh score of B7 or less; and a performance status of 1 or less. Multivariable Cox regression identified variables that were significantly associated with survival. A predictive score was developed based upon coefficients from the fitted Cox regression model, and cubic spline regression was used to identify prognostic groups.

Results

One hundred thirteen patients with intermediate (53.1%) and advanced HCC (45.1%) followed for a median of 13.2 months were included. Variables associated with superior survival used to derive the MAAPE score were lower Model for End‐Stage Liver Disease score (≤ 7), lower Alpha‐fetoprotein (≤ 150 IU/L), higher serum Albumin (> 37 g/L), absence of Portal vein tumor thrombus, and better performance status (Eastern Cooperative Oncology Group = 0). Three survival prognostic groups were identified: good (median overall survival 25.0 months), average (15.3 months), and poor (6.3 months) (overall log–rank test, P < 0.001).

Conclusion

The MAAPE score accurately identifies HCC patients in whom RE is safe and effective. This will allow for optimal patient selection for future trials of RE versus systemic therapy.
Differences in Caregiver Reports of the Quality of Hospice Care Across Settings
Authors: Quigley Denise D. , Parast Layla , Haas Ann , Elliott Marc N. , Teno Joan M. , Anhang Price Rebecca
Published: February 2020

OBJECTIVES

To examine variation in reported experiences with hospice care by setting.

DESIGN

Consumer Assessment of Healthcare Providers and Systems Hospice (CAHPS®) Survey data from 2016 were analyzed. Multivariate linear regression analysis was used to examine differences in measure scores by setting of care (home, nursing home [NH], hospital, freestanding hospice inpatient unit [IPU], and assisted living facility [ALF]).

SETTING

A total of 2636 US hospices.

PARTICIPANTS

A total of 311 635 primary caregivers of patients who died in hospice.

MEASUREMENTS

Outcomes were seven hospice quality measures, including five composite measures that assess aspects of hospice care important to patients and families, including hospice team communication, timeliness of care, treating family member with respect, symptom management, and emotional and spiritual support, and two global measures of the overall rating of the hospice and willingness to recommend it to friends and family. Analyses were adjusted for mode of survey administration and differences in case‐mix between hospices.

RESULTS

Caregivers of decedents who received hospice care in a NH reported significantly worse experiences than caregivers of those in the home for all measures. ALF scores were also significantly lower than home for all measures, except providing emotional and spiritual support. Differences in NH and ALF settings compared to home were particularly large for hospice team communication (ranging from −11 to −12 on a 0‐100 scale) and getting help for symptoms (ranging from −7 to −10). Consistently across all care settings, hospice team communication, treating family member with respect, and providing emotional and spiritual support were most strongly associated with overall rating of care.

CONCLUSIONS

Important opportunities exist to improve quality of hospice care in NHs and ALFs. Quality improvement and regulatory interventions targeting the NH and ALF settings are needed to ensure that all hospice decedents and their family receive high‐quality, patient‐ and family‐centered hospice care. J Am Geriatr Soc 68:1218–1225, 2020.
The Community‐Academic Aging Research Network: A Pipeline for Dissemination
Authors: Mahoney Jane E. , Pinzon Maria Mora , Myers Shannon , Renken Jill , Eggert Erin , Palmer Will
Published: February 2020

BACKGROUND/OBJECTIVES

The Community‐Academic Aging Research Network (CAARN) was created to increase the capacity and effectiveness of Wisconsin's Aging Network and the University of Wisconsin to conduct community‐based research related to aging. The purpose of this article is to describe CAARN's infrastructure, outcomes, and lessons learned.

DESIGN

Using principles of community‐based participatory research, CAARN engages stakeholders to participate in the design, development, and testing of older adult health interventions that address community needs, are sustainable, and improve health equity.

SETTING

Academic healthcare and community organizations.

PARTICIPANTS

Researchers, community members, and community organizations.

INTERVENTION

CAARN matches academic and community partners to develop and test evidence‐based programs to be distributed by a dissemination partner.

MEASUREMENTS

Number of partnerships and funding received.

RESULTS

CAARN has facilitated 33 projects since its inception in 2010 (30 including rural populations), involving 46 academic investigators, 52 Wisconsin counties, and 1 tribe. These projects have garnered 52 grants totaling $20 million in extramural and $3 million in intramural funding. Four proven interventions are being prepared for national dissemination by the Wisconsin Institute for Healthy Aging: one to improve physical activity; one to reduce bowel and bladder incontinence; one to reduce sedentary behavior; and one to reduce falls risk among Latinx older adults. Additionally, one intervention to improve balance using a modified tai chi program is being disseminated by another organization.

CONCLUSION

CAARN's innovative structure creates a pipeline to dissemination by designing for real‐world settings through inclusion of stakeholders in the early stages of design and by packaging community‐based health interventions for older adults so they can be disseminated after the research has been completed. These interventions provide opportunities for clinicians to engage with community organizations to improve the health of their patients through self‐management. J Am Geriatr Soc 68:1325–1333, 2020.
Disentangling aggregation‐prone proteins: a new method for isolating α‐synuclein species
Authors: Nichols Michael R.
Published: February 2020

Protein aggregation plays a central role in numerous neurodegenerative diseases. The key proteins in these diseases are of significant importance, but their investigation can be challenging due to unique properties of protein misfolding and oligomerization. Alpha‐synuclein protein (α‐Syn) is the predominant component of Lewy Bodies in Parkinson’s disease (PD) and is a member of this class of proteins. Many α‐Syn studies are limited by the inability to separate various monomeric, oligomeric, and fibrillar forms of the protein from heterogeneous mixtures. This Editorial Highlight summarizes the impact of a study published in the current issue of Journal of Neurochemistry, in which Lashuel and colleagues developed a simple, rapid centrifugation‐ and filter‐based method for separating, isolating, and quantifying different forms of α‐Syn. The researchers used electron microscopy, SDS‐PAGE, circular dichroism, and protein assays to carefully validate the method and quantitate α‐Syn yields and loss. The publication of this new method will not only aid in future studies of α‐Syn, but will likely extend to other proteins that underlie a variety of neurodegenerative diseases.

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From “Time is Brain” to “Imaging is Brain”: A Paradigm Shift in the Management of Acute Ischemic Stroke
Authors: Puig Josep , Shankar Jai , Liebeskind David , Terceño Mikel , Nael Kambiz , Demchuk Andrew M , Menon Bijoy , Dowlatshahi Dar , Leiva‐Salinas Carlos , Wintermark Max , Thomalla Götz , Silva Yolanda , Serena Joaquin , Pedraza Salvador , Essig Marco
Published: February 2020

Arterial recanalization to restore the blood supply and limit the brain damage is the primary goal in the management of acute ischemic stroke (AIS). Since the publication of pivotal randomized clinical trials in 2015, endovascular thrombectomy has become part of the standard of care in selected cases of AIS from large‐vessel occlusions up to 6 hours after the onset of symptoms. However, the association between endovascular reperfusion and improved functional outcome is not strictly time dependent. Rather than on rigid time windows, candidates should be selected based on vascular and physiologic information. This approach places imaging data at the center of treatment decisions. Advances in imaging‐based management of AIS provide crucial information about vessel occlusion, infarct core, ischemic penumbra, and degree of collaterals. This information is invaluable in identifying patients who are likely to benefit from reperfusion therapies and excluding those who are unlikely to benefit or are at risk of adverse effects. The approach to reperfusion therapies continues to evolve, and imaging is acquiring a greater role in the diagnostic work‐up and treatment decisions as shown in recent clinical trials with extended time window. The 2018 American Heart Association/American Stroke Association guidelines reflect a paradigm shift in the management of AIS from “Time is Brain” to “Imaging is Brain.” This review discusses the essential role of multimodal imaging developing from recent trials on therapy for AIS.
Gadolinium causes M1 and M2 microglial apoptosis after intracerebral haemorrhage and exerts acute neuroprotective effects
Authors: Ohnishi Masatoshi , Kai Takao , Shimizu Yuki , Yano Yukino , Urabe Yuui , Tasaka Shunpei , Akagi Marina , Yamaguchi Yasunori , Inoue Atsuko
Published: February 2020

Objectives

Gadolinium (Gd) affects microglial polarization during remyelination. We previously reported that the suppression of proinflammatory microglia was neuroprotective in intracerebral haemorrhage (ICH). The objective of the present study was to investigate the effects of Gd on microglial polarization and neuronal injury after ICH.

Methods

Gadolinium was intraperitoneally administered to ICH mice prepared by an intrastriatal microinjection of collagenase type VII. The polarization of M1, 2a, b and c microglia was evaluated by real-time PCR using the respective markers. Changes in representative mRNAs were also confirmed by immunological methods. Neuroprotective effects were evaluated by counting NeuN-positive cells and a behavioural analysis.

Key findings

One day after ICH, the mRNA levels of proinflammatory M1 microglial markers, such as inducible nitric oxide synthase (iNOS), and anti-inflammatory M2 microglial markers, such as arginase1 (M2a, c), Ym1 (M2a), and transforming growth factor-β (M2c), increased, while those of chemokine CCL1 (M2b) only increased after 3 days. Gd decreased the levels of all M1 and M2 markers. Arginase1 and iNOS protein levels also increased, and Gd reduced them due to apoptotic cell death. Gadolinium attenuated oedema, neuron loss, neurological deficits and the mortality rate without affecting haematoma sizes.

Conclusions

Gadolinium induced M1 and M2 microglial apoptosis and exerted acute neuroprotective effects after ICH.
The adaptation and implementation of the Health Improvement Profile to Australian standards in public mental health settings
Authors: Brown Trudy , May Alexis , Beverley‐Stone Matthew
Published: February 2020

Accessible Summary

What is known on the subject?

The Health Improvement Profile (HIP) is a one‐page form developed in the United Kingdom as a tool for mental health nurses to assess service user's physical health needs.

The HIP screens service users’ physical health and provides recommendations that clinicians can provide service users with in order to improve their physical health.

There was evidence supporting the effectiveness of the HIP; however, the majority of HIP studies to date involve the screening tool being completed by nurses. In Australia, a large proportion of mental health clinicians providing case management to service users in community settings are not nurses.

What the paper adds to existing knowledge?

This paper shows that the HIP can be adjusted to suit the needs of Australian service users and can be utilized by clinicians from a variety of disciplines.

It also shows that both clinicians and Australian service users find the HIP helpful and argues for it being made available for all service users.

It has clearly shown a need to target flu vaccine programmes at service users.

What are the implications for practice?

The HIP has been shown to be a suitable and acceptable screening tool for different clinicians to assess multiple lifestyle risk factors at once, which can be used across different diagnoses and settings. This study, for example, demonstrated a need to focus on promoting the flu vaccine and smoking cessation, as well as encouraging service users to visit eye and dental health services.

Introduction

Health Improvement Profile (HIP) studies to date primarily focused on the screening tool being completed by nurses. This paper explores the HIP in two different settings, with an emphasis on expanding physical health roles for all mental health clinicians.

Aim

The aim of the present study was to adapt the HIP to Australian standards and implement it at a large mental health service.

Method

This is an evaluation of the implementation of the HIP over a two‐month pilot period. Clinicians and service users were surveyed on their experience of the HIP.

Results

The community team completed the HIP with 34 (15%) service users. The inpatient unit completed the HIP with 137 (54%) service users. Results from the HIP clearly show priority areas for health interventions. Feedback from clinicians and service users was predominately positive.

Discussion

We found the HIP to be an acceptable screening tool that encompasses multiple lifestyle risk factors.

Implications for practice

This study clearly demonstrates the utility of the HIP as a workable and acceptable screening tool with real world applicability. In our pilot, for example, we identified the need for the promotion of influenza vaccinations amongst service users, as well as the ongoing need to target smoking cessation and substance use.
McCune–Albright syndrome and type 1 diabetes mellitus: a novel presentation
Authors: Chatty Prerana , Khattab Ahmed , Marshall Ian
Published: February 2020

McCune–Albright syndrome (MAS) is caused by postzygotic somatic activating mutations of GNAS and is classically characterized by the clinical triad of peripheral precocious puberty, café‐au‐lait pigmentation, and polyostotic fibrous dysplasia. It can also present with other hyperfunctioning endocrinopathies, including growth hormone excess, hyperprolactinemia, hypercortisolemia, hyperthyroidism, and renal phosphate wasting due to excess fibroblast growth factor 23. We review the clinical, biochemical, radiological, and genetic findings in a 7‐year‐old girl diagnosed with MAS at age 4 and then with autoimmune type 1 diabetes mellitus at age 7. While MAS is associated with hyperglycemia secondary to growth hormone excess and hypercortisolemia, an association with diabetes mellitus has not been demonstrated. We review the unique presentation of a patient with these two rare conditions.
Can the 12‐lead ECG distinguish RVOT from aortic cusp PVCs in pediatric patients?
Authors: Clark Bradley C. , Ceresnak Scott R. , Pass Robert H. , Nappo Lynn , Sumihara Kohei , Dubin Anne M. , Motonaga Kara , Moak Jeffrey P.
Published: February 2020

Background

The ability to differentiate right ventricular outflow tract (RVOT) from coronary cusp (CC) site of origin (SOO) by 12‐lead ECG in pediatric patients may impact efficacy and procedural time. The objective of this study was to predict RVOT versus CC SOO by ECG in pediatric patients.

Methods

Pediatric patients (<21 years) without structural heart disease with RVOT or CC premature ventricular contraction (PVC) ablations performed (2014‐2018) were evaluated through multi‐institution retrospective review. Demographics, ECG PVC parameters, ablation site, recurrence, and repeat procedures were collected.

Results

Thirty‐seven patients were evaluated (mean age 14.6 years, weight 60.6 kg): 11 CC and 26 RVOT PVC SOO. CC PVCs were less likely to exhibit left bundle branch block (64% vs 100%, P = .005), had larger R‐wave amplitude in V1 (0.27 vs 0.11 mV, P = .03), larger R/S ratio in V1 (0.37 vs 0.09, P = .003), and had precordial transition in V3 or earlier (73% vs 15%, P = .002). A composite score was created with the following variables: isodiphasic or positive QRS in V1, R/S ratio in V1 > 0.05, S wave in V1 < 0.9 mV, and precordial transition at or before V3. Composite score ≥ 2 was associated with a CC SOO (OR 42.0, P = .001, and AUC 0.86).

Conclusions

12‐lead ECG of PVCs from the CC was associated with larger V1 R‐wave amplitude, larger R/S ratio in V1, and precordial transition at or before V3. A composite score may help predict PVC/VT arising from the CC.
Anesthetic management of catheter‐based patent ductus arteriosus closure in neonates weighing <3 kg: A Retrospective Observational Study
Authors: Hubbard Richard , Edmonds Kayla , Rydalch Eric , Pawelek Olga , Griffin Evelyn , Gautam Nischal
Published: February 2020

Background

The patent ductus arteriosus is a cardiac lesion commonly found in premature neonates. Though surgical closure via thoracotomy is the most definitive treatment option, it is associated with significant morbidity. New catheter‐based closure options offer a potentially safer alternative treatment, even in premature neonates. However, no literature reports the anesthetic techniques, challenges, and risks associated with this procedure in this population.

Aim

This study documents the anesthetic challenges and potential complications associated with the management of catheter‐based closure of the ductus arteriosus in neonates under 3 kg.

Methods

This single‐center, retrospective study examined patients who underwent catheter‐based ductus arteriosus closure between August 2015 and February 2019. A clinical protocol for anesthetic management of these patients was utilized throughout the study period. Clinical outcomes considered were new hemodynamic instability or vasoactive medication requirements, hypothermia, prolonged intubation (>3 days postoperatively), postprocedure acute kidney injury, perioperative red blood cell transfusion, and accidental extubation.

Results

Seventy‐six neonates underwent 78 procedures. No patient developed perioperative hemodynamic instability, vasoactive medication requirements, or acute kidney injury. Four patients (5%) required red blood cell transfusion, two (3%) became hypothermic, and one (1%) was accidentally extubated. Closure was achieved in 73 patients (96%) on the first attempt. However, 17 patients (40%) required prolonged periods of mechanical ventilation following the procedure.

Conclusion

Despite multiple clinical and logistical challenges, anesthetic risk associated with catheter‐based PDA closure in small neonates can be effectively managed through standardized and multidisciplinary care.
Direct Versus Indirect: Control, Moral Responsibility, and Free Action
Authors: Mele Alfred R.
Published: February 2020

This article has two primary aims. The first is to identify relationships among direct control, direct moral responsibility for an action, and directly free action. The second is to provide a partial map depicting the bearing of some familiar competing views about moral responsibility and free action – traditional compatibilism, semicompatibilism, and event‐causal libertarianism – on differences in conceptions of direct and indirect species of moral responsibility and free action.
Peripheral venous access devices for apheresis: 16‐gauge is not always needed
Authors: Mustieles María‐Jesús , Acosta Maria , Cid Joan , Jiménez María , Mateo Dolors , Andreu Bienvenida , Alba Cristina , Perea Dolores , Lozano Miquel
Published: February 2020

BACKGROUND

Peripheral venous access (PVA) devices for apheresis should be selected to provide enough flow with the least vein damage, but little information is available about PVA devices blood flow rates. The aim of this study was to know the blood flow rates provided by the most frequent PVA devices used in apheresis procedures.

STUDY DESIGN AND METHODS

An experimental study was designed to simulate a plasma exchange procedure using citrated whole blood (WB). Two steel needles (16‐ and 17‐gauge [G]) and six plastic cannulas (16G, 17G, two 18G, 20G, and 22G) were analyzed. The hematocrit of the WB was adjusted to 45%, 40%, 35%, 30%, and 25%. The separated plasma from the WB was used as replacement fluid.

RESULTS

Blood flow rate (inlet/return, mL/min) for 16G and 17G devices with a hematocrit of 45% was 142/142 (maximum admitted by separator); one of the 18G cannulas reached 142/142 and the other one reached 117/140; the 20G cannula reached 78/94; and the 22G reached 45/55. A hematocrit reduction from 45% to 25% increased the flow rate (when possible) over 22% (range: 14%‐30%).

CONCLUSIONS

PVA devices with a size of 16‐18G provided the maximum flow admitted by the apheresis system. The 20G provided flow rates for a significant number of procedures, and 22G could be used in some procedures. The hematocrit should be taken into account when selecting the PVA device since, at hematocrit of 25%, the flow can be from 14% to 30% higher than flow rates reached with blood at hematocrit of 45%.
Application of the Naturally Optimised Revenue Demand in Communities NORDIC Model to Improve the Workforce in Sweden
Authors: Stenis Jan
Published: February 2020

The Naturally Optimised Revenue Demand in Communities (NORDIC) model was employed to improve the workforce. The proposed model produced constructed shadow costs to be inserted into the public accounts to induce economic incentives to increase the employment-to-population ratio. The resulting shadow cost, and its impact on the PSBR, constitutes a single key factor that by one digit only, expresses how successful the labour policy is over time. The launched model considered and promoted the health of the workforce and reduced the costs of non-employment. This case study showed how the workforce in the Swedish society could be improved by application of the NORDIC model, that is the system of cooperation between workers and employers. The results point at a promising methodology for improving the health of the workforce and increasing the employment-to-population ratio by using economic instruments. The study concludes that the versatile NORDIC model could be used to improve the Swedish workforce and its quality of life, particularly for seniors. Possible end users include labour authorities and politicians that want a comprehensive tool to redesign the labour policy. The NORDIC model is recommended to apply to labour issues, and employ to improve the health of the workforce. Further research should focus on developing algorithms for certain sections of the workforce.
Globalization in Trade or Trade Restrictions? A Study of Post-War and Recent Trends
Authors: Monadjemi Mehdi , Lodewijks John
Published: February 2020

Despite all of the advantages of free trade and WTO effort to discourage trade restrictions, in July 2018, the President of the United States decided that he is going to impose tariffs on certain goods imported from China. The Chinese government retaliated by levying tariffs on goods and services imported from the United States. This trade war is opposite of the trend ininternational trade during the Post-war period. While the trade deficit figures have improved this has occurred at considerable cost. Tariffs on imported goods are a tax on domestic consumers.