bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of the effects of oleoylethanolamide, a high‐affinity endogenous ligand of PPAR‐α, on the management and prevention of obesity
Authors: Tutunchi Helda , Saghafi‐Asl Maryam , Ostadrahimi Alireza
Published: December 2019

Along with an increase in overweight and obesity among all age groups, the development of efficacious and safe anti‐obesity strategies for patients, as well as health systems, is critical. Oleoylethanolamide (OEA), a high‐affinity endogenous ligand of nuclear receptor peroxisome proliferator‐activated receptor alpha (PPAR‐α), plays important physiological and metabolic actions. OEA is derived from oleic acid, a monounsaturated fatty acid, which has beneficial effects on body composition and regional fat distribution. The role of OEA in the modulation of food consumption and weight management makes it an attractive molecule requiring further exploration in obesogenic environments. This systematic review was conducted to assess the effects of OEA on the obesity management, with emphasizing on its physiological roles and possible mechanisms of action in energy homeostasis. We searched PubMed/Medline, Google Scholar, ScienceDirect, Scopus, ProQuest, and EMBASE up until September 2019. Out of 712 records screened, 30 articles met the study criteria. The evidence reviewed here indicates that OEA, an endocannabinoid‐like compound, leads to satiation or meal termination through PPAR‐α activation and fatty acid translocase (FAT)/CD36. Additionally, the lipid‐amide OEA stimulates fatty acid uptake, lipolysis, and beta‐oxidation, and also promotes food intake control. OEA also exerts satiety‐inducing effects by activating the hedonic dopamine pathways and increasing homeostatic oxytocin and brain histamine. In conclusion, OEA may be a key component of the physiological system involved in the regulation of dietary fat consumption and energy homeostasis; therefore, it is suggested as a possible therapeutic agent for the management of obesity.
Effects of hydrogen sulphide on oxidative stress, inflammatory cytokines, and vascular remodelling in l‐NAME‐induced hypertension
Authors: Abd Allah Eman S. H. , Ahmed Marwa A. , Makboul Rania , Abd El‐Rahman Mona A.
Published: December 2019

This study was designed to evaluate the protective effects of hydrogen sulphide (H2S) against NG‐Nitro l‐Arginine Methyl Ester (l‐NAME)‐induced hypertension and its possible effects on the inflammatory process, oxidative stress, and vascular remodelling in rats. Forty male Wistar Albino rats were assigned to four equal groups: the control group, the H2S control group, the hypertensive group, and the treated group, which received concomitant treatment with sodium hydrosulphide (NaHS) and l‐NAME. Systolic blood pressure (SBP) was measured weekly. Serum levels of nitric oxide (NO), total peroxide, and total antioxidant capacity (TAC) were measured and the oxidative stress index (OSI) was calculated. Aortic weight and length were measured and the aortic weight/length ratio determined. Aortic fold expression of interferon‐γ (IFN‐γ) and vascular cell adhesion molecule‐1 (VCAM‐1) mRNA was measured using qPCR. Aortic media thickness and elastin content were measured morphometrically. l‐NAME administration increased SBP, serum levels of total peroxide and OSI, but reduced serum levels of NO and TAC. Aortic fold expression of IFN‐γ and VCAM‐1 mRNA, aortic weight, aortic weight/length ratio, aortic media thickness, and elastin area percentage were increased in the hypertensive group. Concurrent administration of l‐NAME and H2S attenuated these changes. Thus, H2S could attenuate the increase in ABP through restoration of the NO level, reduction in the oxidative state, and attenuation of the inflammatory process, thereby reduced vascular remodelling.
Environmental conditions steer phenotypic switching in acute hepatopancreatic necrosis disease‐causing Vibrio parahaemolyticus, affecting PirAVP/PirBVP toxins production
Authors: Kumar Vikash , Roy Suvra , Baruah Kartik , Van Haver Delphi , Impens Francis , Bossier Peter
Published: December 2019

Bacteria in nature are widely exposed to differential fluid shears which are often a trigger for phenotypic switches. The latter mediates transcriptional and translation remodelling of cellular metabolism impacting among others virulence, antimicrobial resistance and stress resistance. In this study, we evaluated the role of fluid shear on phenotypic switch in an acute hepatopancreatic necrosis disease (AHPND)‐causing Vibrio parahaemolyticus M0904 strain under both in vitro and in vivo conditions. The results showed that V. parahaemolyticus M0904 grown at lower shaking speed (110 rpm constant agitation, M0904/110), causing low fluid shear, develop cellular aggregates or floccules. These cells increased levan production (as verified by concanavalin binding) and developed differentially stained colonies on Congo red agar plates and resistance to antibiotics. In addition, the phenotypic switch causes a major shift in the protein secretome. At 120 rpm (M0904/120), PirAVP/PirBVP toxins are mainly produced, while at 110 rpm PirAVP/PirBVP toxins production is stopped and an alkaline phosphatase (ALP) PhoX becomes the dominant protein in the protein secretome. These observations are matched with a very strong reduction in virulence of M0904/110 towards two crustacean larvae, namely, Artemia and Macrobrachium. Taken together, our study provides substantial evidence for the existence of two phenotypic forms in AHPND V. parahaemolyticus strain displaying differential phenotypes. Moreover, as aerators and pumping devices are frequently used in shrimp aquaculture facilities, they can inflict fluid shear to the standing microbial agents. Hence, our study could provide a basis to understand the behaviour of AHPND‐causing V. parahaemolyticus in aquaculture settings and open the possibility to monitor and control AHPND by steering phenotypes.
Anammox and beyond
Authors: Kuenen J. Gijs
Published: December 2019

When looking back and wonder how we did it, I became even more aware of how my wanderings in microbiology are all linked, from the start of my PhD with Hans Veldkamp on sulphur‐oxidizing bacteria in chemostats. My interests broadened from obligate chemolithoautotrophic bacteria to facultative organisms and the question about the ecological niches of these different metabolic types. The sulphide oxidizing bacteria also may be used to produce elemental sulphur, which can easily be removed from wastewater. This fitted in a long‐standing collaboration with Dimitry Sorokin on the ecophysiology and application of alkaliphilic sulphur bacteria. Then came the denitrifying sulphur‐oxidizing bacteria and their application to remove sulphide from wastewater, which lead to our interest in nitrate, nitrite and ammonium removal in general. The big surprise was the serendipitous discovery of the ‘anammox’‐process, whereby ammonium is anaerobically oxidized to dinitrogen gas with nitrite as electron acceptor. The early days of our anammox research are the main focus of this article, which describes the struggle of growing and identifying the most peculiar bacteria we ever came across. A specialized organelle, the anammoxosome was shown to be responsible for the key ammonium oxidation, whereby a rocket fuel, hydrazine, turned out to be an intermediate. Soon after we became aware that anammox is everywhere and in the marine environment makes up a major portion of the nitrogen cycle. The intense scientific collaboration with Mike Jetten and Mark van Loosdrecht and colleagues led to our further understanding and application of this fascinating process, which is briefly summarized in this article. My broader interest in environmental microbiology and microbial ecology has been a regularly returning theme, taking me all over the world to great collaborations lasting to this very day.
Biological inhibition of soil nitrification by forest tree species affects Nitrobacter populations
Authors: Laffite Amandine , Florio Alessandro , Andrianarisoa Kasaina Sitraka , Creuze des Chatelliers Charline , Schloter‐Hai Brigitte , Ndaw Sidy M. , Periot Charlotte , Schloter Michael , Zeller Bernd , Poly Franck , Le Roux Xavier
Published: December 2019

Some temperate tree species are associated with very low soil nitrification rates, with important implications for forest N dynamics, presumably due to their potential for biological nitrification inhibition (BNI). However, evidence for BNI in forest ecosystems is scarce so far and the nitrifier groups controlled by BNI‐tree species have not been identified. Here, we evaluated how some tree species can control soil nitrification by providing direct evidence of BNI and identifying the nitrifier group(s) affected. First, by comparing 28 year‐old monocultures of several tree species, we showed that nitrification rates correlated strongly with the abundance of the nitrite oxidizers Nitrobacter (50‐ to 1000‐fold changes between tree monocultures) and only weakly with the abundance of ammonia oxidizing archaea (AOA). Second, using reciprocal transplantation of soil cores between low and high nitrification stands, we demonstrated that nitrification changed 16 months after transplantation and was correlated with changes in the abundance of Nitrobacter, not AOA. Third, extracts of litter or soil collected from the low nitrification stands of Picea abies and Abies nordmanniana inhibited the growth of Nitrobacter hamburgensis X14. Our results provide for the first time direct evidence of BNI by tree species directly affecting the abundance of Nitrobacter.
Feasibility study for implementation of resuscitative balloon occlusion of the aorta in peri‐arrest, exsanguinating trauma at an adult level 1 Australian trauma centre
Authors: Fitzgerald Mark , Lendrum Robbie , Bernard Stephen , Moloney John , Smit De Villiers , Mathew Joseph , Kim Yesul , Nickson Chris , Lin Richard M‐H , Yeung Meei , Bystrzycki Adam , Niggemeyer Louise , Hendel Simon , Mitra Biswadev
Published: December 2019

Objective

This prospective, observational, interventional study sought to determine if the introduction of resuscitative balloon occlusion of the aorta (REBOA) at an Australian adult major trauma centre would improve survival for major trauma patients.

Methods

Patients aged 18–60 years, transported directly from scene with exsanguinating, sub‐diaphragmatic haemorrhage and hypovolaemic shock (systolic BP <70 mmHg or hypovolaemic cardiac arrest) were eligible for recruitment and followed up until hospital discharge (ACTRN12618000550202).

Results

During the 14‐month study period (17 January 2015 to 12 March 2016) 3032 patients were admitted direct from scene with an overall mortality of 97 (3.71%). Of these patients 3019 had trauma centre vital signs recorded in the data set (99.57%) and 1523 were between the ages of 18–60, including 143 patients with a shock index of >1.0 (4.74%). There were 13 (0.43%) patients with a systolic BP <70 mmHg and/or cardiorespiratory arrest on arrival. The mortality in this group was six out of 13 (46.15%). Of these 13 patients, there were two (0.07% of the total cohort) where REBOA was attempted. There were no eligible patients for whom REBOA was achieved. None of the six patients who died would have benefited from REBOA deployment.

Conclusions

Despite considerable training and resource allocation to ensure 24‐h availability, the introduction of REBOA failed to effectively demonstrate any impact on patient outcome. Despite retrospective literature supporting the introduction of REBOA, in this 14‐month prospective study there was no evidence of benefit. Further studies may define indications and subgroups of patients who may benefit.
Carbohydrate counting accuracy in adults with cystic fibrosis related diabetes
Authors: Stonestreet Jenna , AR Ashmitha , Herd Karen , Matson Angela , Bell Jack
Published: December 2019

Aim

Poorly controlled Cystic Fibrosis‐Related Diabetes (CFRD) is associated with adverse impacts on lung function and nutritional status. Insulin therapy is the only recommended medical treatment. Carbohydrate Counting (CC) is used to guide insulin doses and can assist in achieving optimal postprandial blood glucose levels. This study aimed to determine the prevalence of individuals with CFRD who carbohydrate count, explore barriers to its use and assess the accuracy of CC in hospitalised patients.

Methods

A cross‐sectional, mixed‐methods, descriptive study recruited individuals with CFRD hospitalised at an Australian tertiary hospital. Consenting patients completed a questionnaire. Patients were asked to estimate the carbohydrate content of their ordered meals provided by hospital foodservices. The study dietitian assessed each meal's estimation against the actual content.

Results

17 individuals were recruited to this study and five declined. Seven had a fixed insulin regimen, and ten had a flexible insulin regimen and used CC. Patients in the fixed insulin group reported lower levels of confidence in their ability to carbohydrate count (P < .001) and placed less importance on CC (P < .001). 53% of the fixed insulin group's and 41.7% of the flexible insulin group's estimations of the carbohydrate content of the hospital food items were accurate.

Conclusion

Of those patients recruited to this study, 59% used CC as a tool to guide insulin dosing, and patients estimated accurate carbohydrate values in only 46% of meals. Further research is warranted to investigate the most suitable method to assist accurate carbohydrate content estimations in a hospital setting.
Early removal of senescent cells protects retinal ganglion cells loss in experimental ocular hypertension
Authors: Rocha Lorena Raquel , Nguyen Huu Viet Anh , Palomino La Torre Claudia , Xu Qianlan , Jabari Mary , Krawczyk Michal , Weinreb Robert N. , Skowronska‐Krawczyk Dorota
Published: December 2019

Experimental ocular hypertension induces senescence of retinal ganglion cells (RGCs) that mimics events occurring in human glaucoma. Senescence‐related chromatin remodeling leads to profound transcriptional changes including the upregulation of a subset of genes that encode multiple proteins collectively referred to as the senescence‐associated secretory phenotype (SASP). Emerging evidence suggests that the presence of these proinflammatory and matrix‐degrading molecules has deleterious effects in a variety of tissues. In the current study, we demonstrated in a transgenic mouse model that early removal of senescent cells induced upon elevated intraocular pressure (IOP) protects unaffected RGCs from senescence and apoptosis. Visual evoked potential (VEP) analysis demonstrated that remaining RGCs are functional and that the treatment protected visual functions. Finally, removal of endogenous senescent retinal cells after IOP elevation by a treatment with senolytic drug dasatinib prevented loss of retinal functions and cellular structure. Senolytic drugs may have the potential to mitigate the deleterious impact of elevated IOP on RGC survival in glaucoma and other optic neuropathies.
Foetal growth restriction has negative influence on narrative skills in 8–10‐year‐old children
Authors: Partanen Lea , Korkalainen Noora , Mäkikallio Kaarin , Olsén Päivi , Heikkinen Hanna , Yliherva Anneli
Published: December 2019

Aim

The risk for neurocognitive difficulties is increased in children born with foetal growth restriction (FGR), but no data exist yet on their narrative skills. The narrative skills of 8‐ to 10‐year‐old children born with FGR between 24 and 40 weeks were compared with those of children born with appropriate growth for gestational age (AGA).

Methods

A prospectively collected cohort of 36 children with FGR was recruited prenatally at a Finnish tertiary hospital from 1998‐2001, and 31 children with AGA served as controls. Narrative skills were assessed using a standardised test, and correlations between narrative, communication, reading and spelling skills were studied.

Results

Children born with FGR produced significantly less information and shorter utterances in their narratives than the AGA group. Children born preterm with FGR performed significantly more poorly in their narratives than the preterm AGA group. Poor narrative skills correlated with poor communication, reading and spelling skills.

Conclusion

Children born with FGR had poorer narrative skills compared with their AGA peers at the age of 8‐10 years, and narrative skills were linked to other language‐based skills, which underlines the importance of early detection and preventive measures to optimise the educational outcome of children born with FGR.
BOARD GOVERNANCE: DOES OWNERSHIP MATTER?
Authors: HIDETO DATO Muluneh , HUDON Marek , MERSLAND Roy
Published: December 2019

Good governance is crucial to achieving an organization's mission. Nevertheless, little is known about how the structure of governance is influenced by the nonprofit (NPO) or for‐profit ownership (FPO) structure of an organization, partly because they tend to be active in different sectors. In this paper we overcome this challenge by using data from a global sample of 392 microfinance institutions. The results show that the average NPO has a larger board, more female directors, and a higher number of board meetings than the average FPO. Moreover, where there are larger boards and more frequent board meetings, this has a positive effect on the financial performance of NPOs. It is thus confirmed that ownership structures influence boards’ characteristics and that some board mechanisms are more efficient in some ownership structures than in others. An effective board design should thus be based on a firm's ownership structure.
Negotiating Chineseness: Incorporating critical reflection into workplace research on Chinese investment in Ethiopia
Authors: Fei Ding
Published: December 2019

Critical geographic reflection on researcher subjectivity is inadequately practised by scholars studying workplaces, especially those involving emerging powers from the global south. In the context of growing Chinese investment in Africa, this paper reflects on the negotiation of my Chineseness during multi‐sited research on capital–labour and expatriate–local relations in three Chinese companies in Ethiopia. It examines the nexus of identity, power, and place to shape my fieldwork process at three stages: seeking access to the enclosed space of companies, building credibility in front of different groups of participants, and arranging interviews in the particular socio‐spatial contexts of the workplace. Specifically, I explain the enabling and problematic nature of my Chinese identity when intersectioned with my multiple subjective positions as a US‐based female student‐researcher. I elaborate how my engagements with expatriates and locals are influenced by the existing system of power relations in Chinese companies. I demonstrate that the place of interview can generate crucial insights into management practices and work relations, and facilitate researcher autonomy and employee agency to momentarily revert the power relations in the workplace. My field experiences highlight the importance of critical reflection to assist researchers to navigate the layered complexity and unexpectancy of doing fieldwork.
Incidence, cause, outcome and possible risk factors associated with facial nerve paralysis in dogs in a Sydney population (2001–2016): a retrospective study
Authors: Chan MK , Toribio J‐ALML , Podadera JM , Child G
Published: December 2019

Objective

This study aims to assess the incidence and causes of facial nerve paralysis (FNP) in dogs in the Sydney region. Its outcome and possible risk factors are investigated to prognosticate and aid design of diagnostic and treatment plans.

Design

Retrospective case study.

Methods

Client‐owned dogs presented to the University Veterinary Teaching Hospital, Sydney (UVTHS), between 2001 and 2016 with FNP were included (n = 122). The incidence of each cause of FNP was investigated. A reference population of noncases seen at the UVTHS during the same time period was used to study the association between idiopathic facial nerve paralysis (IFNP) and gender, age and breed.

Results

IFNP (29.5%) was the most common diagnosis. Male dogs (odds ratio [OR], 2.3) had increased odds of IFNP compared with female dogs. Age was a significant risk factor for both the occurrence of FNP and IFNP. There was higher occurrence of IFNP among middle‐aged dogs (5–13 years) and reduced risk in juvenile dogs (less than 2 years). Cavalier King Charles Spaniels were over‐represented for FNP (OR, 6.9) and IFNP (OR, 17.5). For IFNP, 6 of 16 dogs with known follow‐up showed definitive resolution within 3 years of diagnosis. Concurrent vestibular signs were common in dogs with middle/inner ear abnormality and intracranial disease; and were also seen in 50% of dogs with IFNP.

Conclusion

The results of this study demonstrate statistical predilections in age, gender and breed for IFNP. Guarded prognosis for recovery should be given to dogs diagnosed with IFNP and supportive management instigated.
The efficacy and safety of fingolimod in patients with relapsing multiple sclerosis: A meta‐analysis
Authors: Yang Ting , Tian Xin , Chen Chao‐Yang , Ma Ling‐Yun , Zhou Shuang , Li Min , Wu Ye , Zhou Ying , Cui Yi‐Min
Published: December 2019

Aims

The aim of the present meta‐analysis was to evaluate the efficacy and safety of fingolimod in patients with relapsing multiple sclerosis (RMS).

Methods

PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were searched for relevant studies. Two authors independently selected the studies, assessed the risk of bias, and extracted the data. The meta‐analysis was performed in RevMan 5.3 provided by the Cochrane Collaboration.

Results

Ten studies met the inclusion criteria. In patients with RMS, fingolimod demonstrated a significantly lower annualized relapse rate (0.5 mg/d: mean difference [95% confidence interval] = −0.22 [−0.29 to −0.14]; 1.25 mg/d: −0.26 [−0.36 to −0.16]; 5 mg/d: −0.41 [−0.72 to −0.10]) than placebo. Fingolimod also exhibited a favorable performance on other magnetic resonance imaging outcomes and improved the quality of life in patients. No significant difference was noted in the prevalence of adverse events between the fingolimod treatment group and the placebo/disease‐modifying therapy groups.

Conclusions

Fingolimod may offer benefits for RMS patients and presents an acceptable safety profile.
A unified evaluation of differential vaccine efficacy
Authors: Gabriel Erin E. , Sachs Michael C. , Follmann Dean A. , Andersson Therese M‐L.
Published: December 2019

Many infectious diseases are well prevented by proper vaccination. However, when a vaccine is not completely efficacious, there is great interest in determining how the vaccine effect differs in subgroups conditional on measured immune responses postvaccination and also according to the type of infecting agent (eg, strain of a virus). The former is often called correlate of protection (CoP) analysis, while the latter has been called sieve analysis. We propose a unified framework for simultaneously assessing CoP and sieve effects of a vaccine in a large Phase III randomized trial. We use flexible parametric models treating times to infection from different agents as competing risks and estimated maximum likelihood to fit the models. The parametric models under competing risks allow for estimation of both cumulative incidence‐based contrasts and instantaneous rates. We outline the assumptions with which we can link the observable data to the causal contrasts of interest, propose hypothesis testing procedures, and evaluate our proposed methods in an extensive simulation study.
T cell reconstitution after lymphocyte depletion features a different pattern of inhibitory receptor expression in ABO- versus HLA-incompatible kidney transplant recipients
Authors: Del Bello A , Kamar N , Treiner E
Published: December 2019

Chronic antigen stimulation can lead to immune exhaustion (a state of T cell dysfunction). Several phenotypical signatures of T cell exhaustion have been described in various pathological situations, characterized by aberrant expression of multiple inhibitory receptors (IR). This signature has been barely studied in the context of allogenic organ transplantation. We undertook a cross-sectional analysis of the expression of IR [CD244, CD279, T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) and CD57] and their correlation with cytokine-producing functions in T cells reconstituting after lymphocyte depletion in patients transplanted from living donors, with preformed donor-specific antibodies. After ABO incompatible transplantation, T cells progressively acquired a phenotype similar to healthy donors and the expression of several IR marked cells with increased functions, with the exception of TIGIT, which was associated with decreased cytokine production. In stark contrast, T cell reconstitution in patients with anti-human leukocyte antigen (HLA) antibodies was characterized with an increased co-expression of IR by T cells, and specifically by an increased expression of TIGIT. Furthermore, expression of these receptors was no longer directly correlated to cytokine production. These results suggest that T cell alloreactivity in HLA-incompatible kidney transplantation drives an aberrant T cell reconstitution with respect to IR profile, which could have an impact on the transplantation outcome.
The influence of the gastrointestinal microbiome on colorectal metastasis: a narrative review
Authors: Stakelum A. , Zaborowski A. , Collins D. , Winter D. C.
Published: December 2019

Introduction

The gastrointestinal microbiome has been suggested to contribute to the development of both primary and secondary colorectal cancer. Despite advances in understanding the prognostic and predictive value of clinico‐pathological parameters, the underlying mechanisms that result in progression to metastatic disease have yet to be defined. The metastatic cascade involves a number of sequential steps, including detachment of tumour cells from the primary site, intravasation and dissemination within the circulatory and lymphatic systems, with extravasation and proliferation at a secondary site.

Objective

An analysis of the literature relating to the gastrointestinal microbiome and its role in colorectal metastasis was conducted. This review aims to examine the current evidence supporting a role for the microbiome in colorectal metastasis and to describe the mechanisms by which it may contribute to metastatic progression.

Conclusion

The invasive pathways utilized by bacteria and how they may be manipulated by tumour cells for migration and metastasis are presented and the potential of the intestinal microbiome as a therapeutic target in colorectal carcinogenesis and metastasis is detailed here.
BRAT1 encephalopathy: a recessive cause of epilepsy of infancy with migrating focal seizures
Authors: Scheffer Ingrid E , Boysen Katja E , Schneider Amy L , Myers Candace T , Mehaffey Michele G , Rochtus Anne M , Yuen Yuet‐Ping , Ronen Gabriel M , Chak Wai Km , Gill Deepak , Poduri Annapurna , Mefford Heather C
Published: December 2019

Epilepsy of infancy with migrating focal seizures (EIMFS), one of the most severe developmental and epileptic encephalopathy syndromes, is characterized by seizures that migrate from one hemisphere to the other. EIMFS is genetically heterogeneous with 33 genes. We report five patients with EIMFS caused by recessive BRAT1 variants, identified via next generation sequencing. Recessive pathogenic variants in BRAT1 cause the rigidity and multifocal seizure syndrome, lethal neonatal with hypertonia, microcephaly, and intractable multifocal seizures. The epileptology of BRAT1 encephalopathy has not been well described. All five patients were profoundly impaired with seizure onset in the first week of life and focal seizure migration between hemispheres. We show that BRAT1 is an important recessive cause of EIMFS with onset in the first week of life, profound impairment, and early death. Early recognition of this genetic aetiology will inform management and reproductive counselling.
Human regular U‐500 insulin via continuous subcutaneous insulin infusion versus multiple daily injections in adults with type 2 diabetes: The VIVID study
Authors: Grunberger George , Bhargava Anuj , Ly Trang , Zisser Howard , Ilag Liza L. , Malone James , Fan Ludi , Zhang Shuyu , Johnson Jennal
Published: December 2019

Aim

To compare the safety and efficacy of U500‐R delivered by a novel, specifically designed U500‐R insulin pump with U‐500R delivered by multiple daily injections (MDI).

Methods

The phase 3 VIVID study randomized people with type 2 diabetes to U‐500R by continuous subcutaneous insulin infusion (CSII) or MDI. Participants (aged 18–85 years) had HbA1c ≥7.5% and ≤12.0% and a total daily dose of insulin >200 and ≤600 U/day. After a 2‐week transition to three times daily injections of U‐500R, participants were treated for 24 weeks with U‐500R by CSII or MDI. Treatment arms were compared using mixed model repeated measures analysis.

Results

The study randomized 420 participants (CSII: 209, MDI: 211) with 365 completers. Mean changes from baseline were: HbA1c, −1.27% (−13.9 mmol/mol) with CSII and −0.85% (−9.3 mmol/mol) with MDI (difference − 0.42% [−4.6 mmol/mol], P <0.001); fasting plasma glucose, −33.9 mg/dL (−1.9 mmol/L) with CSII and 1.7 mg/dL (0.09 mmol/L) with MDI (difference − 35.6 mg/dL [−2.0 mmol/L], P <0.001); total daily dose, 2.8 U with CSII and 51.3 U with MDI (P < 0.001). Weight changes and rates of documented symptomatic and severe hypoglycaemia were similar between groups; the CSII group had a higher rate of nocturnal hypoglycaemia.

Conclusions

In type 2 diabetes requiring high doses of insulin, both methods of U‐500R delivery lowered HbA1c. However, the CSII group attained greater HbA1c reduction with significantly less insulin. Individualized dose titration will be important to balance glycaemic control with hypoglycaemia risk.
Annexin A6 improves anti‐migratory and anti‐invasive properties of tyrosine kinase inhibitors in EGFR overexpressing human squamous epithelial cells
Authors: Hoque Monira , Elmaghrabi Yasmin A. , Köse Meryem , Beevi Syed S. , Jose Jaimy , Meneses‐Salas Elsa , Blanco‐Muñoz Patricia , Conway James R. W. , Swarbrick Alexander , Timpson Paul , Tebar Francesc , Enrich Carlos , Rentero Carles , Grewal Thomas
Published: December 2019

Annexin A6 (AnxA6), a member of the calcium (Ca2+) and membrane binding annexins, is known to stabilize and establish the formation of multifactorial signaling complexes. At the plasma membrane, AnxA6 is a scaffold for protein kinase Cα (PKCα) and GTPase‐activating protein p120GAP to promote downregulation of epidermal growth factor receptor (EGFR) and Ras/mitogen‐activated protein kinase (MAPK) signaling. In human squamous A431 epithelial carcinoma cells, which overexpress EGFR, but lack endogenous AnxA6, restoration of AnxA6 expression (A431‐A6) promotes PKCα‐mediated threonine 654 (T654)–EGFR phosphorylation, which inhibits EGFR tyrosine kinase activity. This is associated with reduced A431‐A6 cell growth, but also decreased migration and invasion in wound healing, matrigel, and organotypic matrices. Here, we show that A431‐A6 cells display reduced EGFR activity in vivo, with xenograft analysis identifying increased pT654‐EGFR levels, but reduced tyrosine EGFR phosphorylation compared to controls. In contrast, PKCα depletion in A431‐A6 tumors is associated with strongly reduced pT654 EGFR levels, yet increased EGFR tyrosine phosphorylation and MAPK activity. Moreover, tyrosine kinase inhibitors (TKIs; gefitinib, erlotinib) more effectively inhibit cell viability, clonogenic growth, and wound healing of A431‐A6 cells compared to controls. Likewise, the ability of AnxA6 to inhibit A431 motility and invasiveness strongly improves TKI efficacy in matrigel invasion assays. This correlates with a greatly reduced invasion of the surrounding matrix of TKI‐treated A431‐A6 when cultured in 3D spheroids. Altogether, these findings implicate that elevated AnxA6 scaffold levels contribute to improve TKI‐mediated inhibition of growth and migration, but also invasive properties in EGFR overexpressing human squamous epithelial carcinoma.
Guns and Homicides: A Multiscale Geographically Weighted Instrumental Variables Approach
Authors: Bilgel Firat
Published: December 2019

This article assesses the locally varying effects of gun ownership levels on total and gun homicide rates in the contiguous United States using cross‐sectional county data for the period 2009–2015. Employing a multiscale geographically weighted instrumental variables regression that takes into account spatial nonstationarity in the processes and the endogenous nature of gun ownership levels, estimates show that gun ownership exerts spatially monotonically negative effects on total and gun homicide rates, indicating that there are no counties supporting the “more guns, more crime” hypothesis for these two highly important crime categories. The number of counties in the contiguous United States where the “more guns, less crime” hypothesis is confirmed is limited to at least 1258 counties (44.8% of the sample) with the strongest total homicide‐decreasing effects concentrated in southeastern Texas and the deep south. On the other hand, stricter state gun control laws exert spatially monotonically negative effects on gun homicide rates with the strongest effects concentrated in the southern tip of Texas extending toward the deep south.
Oxidation and microstructure of SiCf/SiC composites in moist air up to 1600°C by X‐ray tomographic characterization
Authors: Lu Zilong , Bie Bixiong , Pang Aimin , Li Wei , Yue Jianling , Huang Xiaozhong , Yang Haitang
Published: December 2019

SiCf/SiC composites that possess PyC or BN interface layers were fabricated and then oxidized in moist air at 1000, 1200, 1400, and 1600°C. High‐resolution CT was used for capturing 3D images and quantifying the SiC phase, mesophase, and voids. The oxidation behavior and microstructural evolution of SiCf/SiC with PyC or BN interface are discussed in this study. The microstructure of the SiCf/SiC with a PyC layer was seriously damaged in moist air at high temperature, whereas the BN interface layer enhanced the oxidation resistance of the SiCf/SiC. These results are also confirmed by using XRD, oxidation mass gain, tensile testing, and SEM measurements. The results of the oxidation behavior and microstructural evolution for SiCf/SiC oxidized in dry air are also compared with the results of this study. Comparing the SiCf/SiC with a PyC interface layer, the composite with a BN interface layer oxidized in moist air exhibits a high void growth rate and a low SiO2 grain growth rate from 1000 to 1600°C. This work will provide guidance for predicting the service life of SiCf/SiC for multiscale damage rate models of materials at a local scale and will also provide guidance on the life service design of SiCf/SiC materials.
Developmental outcomes of infants adopted from foster care: Predictive associations from perinatal and preplacement risk factors
Authors: Tung Irene , Christian‐Brandt Allison S. , Langley Audra K. , Waterman Jill M.
Published: December 2019

Infants adopted domestically from foster care often present with prenatal substance exposure and risky birth outcomes such as prematurity and low birthweight. Because few longitudinal studies of foster‐adoptive infants exist, it is unclear how these preplacement risk factors influence development over time. The present study examined associations between perinatal risk factors and developmental outcomes among an ethnically/racially diverse sample of 97 infants in foster care (56% boys) placed into adoptive homes at ages 0–19 months. Relative to population norms, foster‐adoptive infants showed comparable cognitive but lower language and motor functioning at baseline and 1‐year follow‐up. Age‐adjusted language scores significantly improved 1 year following placement, consistent with a developmental “catch‐up” effect. Low birthweight uniquely predicted lower language scores at baseline, but this association was no longer significant at follow‐up. Prenatal substance exposure was associated with lower baseline cognitive scores, but only for infants placed after 6 months of age. In contrast, infants with low birthweight and later placement age (>12 months) showed the most accelerated motor development. Sex differences emerged at follow‐up when predicting motor and language outcomes, suggesting potential sex‐specific pathways of risk. Overall, results support adoption as an early intervention that may buffer vulnerability to perinatal risk on development.
Comparison between haplotype‐based and individual snp‐based genomic predictions for beef fatty acid profile in Nelore cattle
Authors: Feitosa Fabieli Loise Braga , Pereira Angélica Simone Cravo , Amorim Sabrina Thaise , Peripolli Elisa , Silva Rafael Medeiros de Oliveira , Braz Camila Urbano , Ferrinho Adrielle Matias , Schenkel Flavio Schramm , Brito Luiz Fernando , Espigolan Rafael , de Albuquerque Lucia Galvão , Baldi Fernando
Published: December 2019

The aim of this study was to evaluate the genomic predictions using the single‐step genomic best linear unbiased predictor (ssGBLUP) method based on SNPs and haplotype markers associated with beef fatty acids (FAs) profile in Nelore cattle. The data set contained records from 963 Nelore bulls finished in feedlot (±90 days) and slaughtered with approximately 24 months of age. Meat samples from the Longissimus dorsi muscle were taken for FAs profile measurement. FAs were quantified by gas chromatography using a SP‐2560 capillary column. Animals were genotyped with the high‐density SNP panel (BovineHD BeadChip assay) containing 777,962 markers. SNPs with a minor allele frequency and a call rate lower than 0.05 and 0.90, respectively, monomorphic, located on sex chromosomes, and with unknown position were removed from the data set. After genomic quality control, a total of 469,981 SNPs and 892 samples were available for subsequent analyses. Missing genotypes were imputed and phased using the FImpute software. Haplotype blocks were defined based on linkage disequilibrium using the Haploview software. The model to estimate variance components and genetic parameters and to predict the genomic values included the random genetic additive effects, fixed effects of the contemporary group and the age at slaughter as a linear covariate. Accuracies using the haplotype‐based approach ranged from 0.07 to 0.31, and those SNP‐based ranged from 0.06 to 0.33. Regression coefficients ranged from 0.07 to 0.74 and from 0.08 to 1.45 using the haplotype‐ and SNP‐based approaches, respectively. Despite the low to moderate accuracies for the genomic values, it is possible to obtain genetic progress trough selection using genomic information based either on SNPs or haplotype markers. The SNP‐based approach allows less biased genomic evaluations, and it is more feasible when taking into account the computational and operational cost underlying the haplotypes inference.
Xenotransfusion of canine blood to cats: a review of 49 cases and their outcome
Authors: Le Gal A. , Thomas E. K. , Humm K. R.
Published: December 2019

Objectives

To describe the use of a xenotransfusion protocol, the outcome of xenotransfusion in recipient cats and to assess owner memory of the xenotransfusion.

Materials and Methods

Cats administered xenotransfusions in two hospitals between January 2016 and July 2018 were included. Adherence to xenotransfusion protocol, cause of anaemia, blood type, packed cell volume (PCV), transfusion volume, transfusion reactions, PCV 12 hours after transfusion and survival to discharge were recorded. Owners of surviving cats were questioned to assess if they remembered that a xenotransfusion had been performed.

Results

Forty‐nine cats underwent the xenotransfusion protocol. The most common causes of anaemia were surgical blood loss (n = 17), immune‐mediated haemolytic anaemia (n = 14) and neoplasia (n = 14). Median PCV before transfusion was 10%. Six cats (12%) had febrile non‐haemolytic transfusion reactions. Median PCV 12 hours after transfusion was 25%. Ten cats (20%) died or were euthanased within 24 hours of xenotransfusion. A delayed haemolytic transfusion reaction occurred in 25 of 39 (64%) cats manifesting as icterus in 15 cats after a median of 1.9 days and haemolytic serum in 19 cats after a median of 2 days. Of the 18 cats alive at 1 week after discharge, 15 (83%) were still alive at a median of 173 days after xenotransfusion. All owners contacted remembered that their cats had received a xenotransfusion.

Clinical Significance

Xenotransfusion of canine packed red blood cells to cats is possible but haemolysis should be expected between 1 and 6 days after transfusion.
Fire and hydrologically mediated diversity change in subalpine forests through the Holocene
Authors: Rust Robert A. , Minckley Thomas A.
Published: December 2019

Questions

We consider whether: (a) fire frequency and hydrologic trends drive changes in subalpine forest community diversity and; (b) if there are cumulative effects on diversity when frequent fire and hydrologic drying occur synchronically?

Location

We use three high elevation sites from Wyoming, USA to investigate the response and resiliency of subalpine forests in the Rocky Mountains to centennial‐to‐millennial drought and fire disturbances in regards to shifts in pollen richness, evenness and diversity.

Methods

‘We examine ecological changes measured by pollen richness, evenness and diversity between subalpine communities under drying and wetting conditions to determine if there is an amplified effect when differing fire frequencies are considered. Using the inverse Simpson index of pollen diversity on pollen percentages as an estimate of biodiversity.

Results

Periods of frequent fire display significantly higher diversity (p < 0.05) than periods of infrequent or intermediate fire return intervals regardless of hydrologic trends at Little Windy Hill Pond. Further, sites in the northern and southern Rocky Mountains appear to operate under differing fire regimes with sites in the northern Rocky Mountains not recording periods of frequent fire (>225 year mean fire return interval) through the Holocene.

Conclusions

Changes in past pollen abundance and diversity have the ability to capture past landscape structure and ecosystem turnover prior to European settlement of the Americas. If fire regimes in subalpine forests of the Rocky Mountains continue trending towards higher frequencies there is the potential for these areas to experience an increase in vegetation diversity.
A case study on the challenges of learning and teaching English spelling: insights from eight Australian students and their teachers
Authors: Daffern Tessa , Mackenzie Noella Maree
Published: December 2019

Spelling is a key transcription skill for writing. While little is understood about the particular challenges some students experience when learning to spell, explicit instruction is known to improve spelling performance. The study reported in this article draws on eight case studies from a larger Australian mixed‐methods study examining spelling acquisition, as represented by a stratified random sample of Australian students aged 8 to 12 years (n=1,198). This case study utilised Triple Word Form Theory for the spelling error analysis of dictated words, narrative and expository writing, as well as semi‐structured interview data from a randomly selected sample of low‐achieving spellers. Analyses of phonological, orthographic and morphological spelling errors revealed students' common and unique challenges in learning to spell. Qualitative analysis of semi‐structured interview data identified that the students lacked confidence in spelling, used limited strategies for spelling unknown words, and displayed constrained metalanguage associated with spelling. Interview data from the respective classroom teachers revealed that the teachers had inadequate strategies for teaching spelling and lacked confidence in their ability to teach spelling. The findings highlight the need for improved ways to support those students beyond the first few years of schooling who find learning to spell challenging.
Prevalence and correlates of the composite index of anthropometric failure among children under 5 years old in Bangladesh
Authors: Islam Md. Saimul , Biswas Tuhin
Published: December 2019

The prevalence of stunting, wasting, and underweight are reported separately. However, the data of the multiple anthropometric failures combinations of these conventional indicators are scant. This study attempted to estimate the overall burden of undernutrition among children under 5 years old, using the composite index of anthropometric failure (CIAF), and to explore the correlates. The study used secondary data from the Bangladesh demographic and health surveys (BDHS), undertaken in 2014. CIAF provides an overall prevalence of undernutrition, which gives six mutually exclusive anthropometric measurements of height‐for‐ age, height‐for‐weight, and weight‐for‐age. Multivariable logistic regression was used to explore the correlates of CIAF. The overall prevalence of undernutrition using the CIAF was 48.3% (95% CI [47.1%, 49.5%]) among the children under 5 years old. The prevalence of anthropometric failure due to a combination of both stunting and underweight was 18.2%, wasting and underweight was 5.5%, and wasting, underweight, and stunting was 5.7%. The odds of CIAF were higher among young maternal age, having the poorest socio‐economic status, living in rural areas, higher order of birth, and received no vaccination compared with other counterparts. In Bangladesh, one out of two children has undernutrition, which is preventing the potential of the millions of children. Mothers who gave birth before age 20 living in the rural areas with belonging to lower socio‐economic status and whose children had a higher order of birth and receive no vaccination were observed as the main determinants of undernutrition. Nutrition sensitive interventions along with social protection programmes are crucial to deal the underlying causes of undernutrition.
Incompleteness, regularity, and collective preference
Authors: Cato Susumu
Published: December 2019

This paper examines the incompleteness of collective preference. We provide a series of Arrovian impossibility theorems without completeness. First, we consider the notion of regularity introduced by Eliaz and Ok (2006, Games and Economic Behavior 56, 61–86); it is an appropriate richness property for strict preference when preference is allowed to be incomplete. We examine the implication of imposing regularity on collective preference. Second, we propose responsiveness, a variation of positive responsiveness. This axiom requires that some changes in individual preferences make an alternative weakly better than another. Third, we consider coherency conditions for collective preferences; this conditionally requires the existence of comparable pairs in a certain manner. We prove an impossibility result for each condition using Arrovian axioms.
Time for change: Overcoming perpetual feelings of inadequacy and silenced struggles in medicine
Authors: Atherley Anique , Meeuwissen Stephanie N E
Published: December 2019

Focusing on support of psychological wellness in medical students, residents and physicians, this commentary highlights the need for cultural change and the accompanying importance of leadership.