bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular evidence and clinical importance of β‐arrestins expression in patients with acromegaly
Authors: Coelho Maria Caroline Alves , Vasquez Marina Lipkin , Wildemberg Luiz Eduardo , Vázquez‐Borrego Mari C. , Bitana Luciana , Camacho Aline Helen da Silva , Silva Débora , Ogino Liana Lumi , Ventura Nina , Chimelli Leila , Luque Raul M. , Kasuki Leandro , Gadelha Mônica R.
Published: January 2018

β‐arrestins seem to have a role in endocytosis and desensitization of somatostatin receptor subtype 2 (sst2) and could be associated with the responsiveness to somatostatin receptor ligands (SRL) in patients with acromegaly. To investigate the in vivo correlation between β‐arrestins 1 and 2 with sst2, sst5 and dopamine receptor subtype 2 (D2) expressions, and the association of β‐arrestins with response to first‐generation SRL and invasiveness in somatotropinomas. β‐arrestins 1 and 2, sst2, sst5 and D2 mRNA expressions were evaluated by quantitative real‐time RT‐PCR on tumoral tissue of 96 patients. Moreover, sst2 and sst5 protein expressions were also evaluated in 40 somatotropinomas by immunohistochemistry. Response to SRL, defined as GH <1 μg/l and normal IGF‐I levels, was assessed in 40 patients. The Knosp‐Steiner criteria were used to define invasiveness. Median β‐arrestin 1, β‐arrestin 2, sst2, sst5 and D2 mRNA copy numbers were 478; 9375; 731; 156; and 3989, respectively. There was a positive correlation between β‐arrestins 1 and 2 (R = 0.444, P < 0.001). However, no correlation between β‐arrestins and sst2, sst5 (mRNA and protein levels) or D2 was found. No association was found between β‐arrestins expression and SRL responsiveness or tumour invasiveness. Although previous data suggest a putative correlation between β‐arrestins and sst2, our data clearly indicated that no association existed between β‐arrestins and sst2, sst5 or D2 expression, nor with response to SRL or tumour invasiveness. Therefore, further studies are required to clarify whether β‐arrestins have a role in the response to treatment with SRL in acromegaly.
Wogonoside induces depalmitoylation and translocation of PLSCR1 and N‐RAS in primary acute myeloid leukaemia cells
Authors: Li Hui , Yu Xiaoxuan , Liu Xiao , Hu Po , Shen Le , Zhou Yuxin , Zhu Yu , Li Zhiyu , Hui Hui , Guo Qinglong , Xu Jingyan
Published: January 2018

Acute myeloid leukaemia (AML) comprises a range of disparate genetic subtypes, involving complex gene mutations and specific molecular alterations. Post‐translational modifications of specific proteins influence their translocation, stability, aggregation and even leading disease progression. Therapies that target to post‐translational modification of specific proteins in cancer cells represent a novel treatment strategy. Non‐homogenous subcellular distribution of PLSCR1 is involved in the primary AML cell differentiation. However, the nuclear translocation mechanism of PLSCR1 remains poorly understood. Here, we leveraged the observation that nuclear translocation of PLSCR1 could be induced during wogonoside treatment in some primary AML cells, despite their genetic heterogeneity that contributed to the depalmitoylation of PLSCR1 via acyl protein thioesterase 1 (APT‐1), an enzyme catalysing protein depalmitoylation. Besides, we found a similar phenomenon on another AML‐related protein, N‐RAS. Wogonoside inhibited the palmitoylation of small GTPase N‐RAS and enhanced its trafficking into Golgi complex, leading to the inactivation of N‐RAS/RAF1 pathway in some primary AML cells. Taken together, our findings provide new insight into the mechanism of wogonoside‐induced nuclear translocation of PLSCR1 and illuminate the influence of N‐RAS depalmitoylation on its Golgi trafficking and RAF1 signalling inactivation in AML.
MicroRNA‐99a is a novel regulator of KDM6B‐mediated osteogenic differentiation of BMSCs
Authors: Tang Yin , Zhang Lan , Tu Tianchi , Li Yijia , Murray Dana , Tu Qisheng , Chen Jake Jinkun
Published: January 2018

Skeletal tissue originates from mesenchymal stem cells (MSCs) with differentiation potential into the osteoblast lineage regulated by essential transcriptional and post‐transcriptional mechanisms. Recently, miRNAs and histone modifications have been identified as novel key regulators of osteogenic differentiation of MSCs. Here, we identified miR‐99a and its target lysine (K)‐specific demethylase 6B (KDM6B) gene as novel modulators of osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Microarray profiling and further validation by quantitative real‐time RT‐PCR revealed that miR‐99a was up‐regulated during osteoblastic differentiation of BMSCs, and decreased in differentiated osteoblasts. Transfection of miR‐99a mimics inhibited osteoblastic commitment and differentiation of BMSCs, whereas inhibition of miR‐99a by inhibitors enhances these processes. KDM6B was determined as one of important targets of miR‐99a, which was further confirmed by luciferase assay of 3′‐UTR of KDM6B. Moreover, HOX gene level decreased after transfection of miR‐99a mimics in BMSCs, which indicated that KDM6B is a bona fide target of miR‐99a. Furthermore, in a model of in vivo bone regeneration, osteoblast‐specific gain‐ and loss‐of‐function experiments performed using cranial bone defects revealed that miR‐99a mimics‐transfected BMSCs reduced bone formation, and conversely, miR‐99a inhibitors‐transfected BMSCs increased in vivo bone formation. Tissue‐specific inhibition of miR‐99a may be a potential novel therapeutic approach for enhancing BMSCs‐based bone formation and regeneration.
Overexpression of geranylgeranyl diphosphate synthase contributes to tumour metastasis and correlates with poor prognosis of lung adenocarcinoma
Authors: Wang Xiaoxia , Xu Wujian , Zhan Ping , Xu Tianxiang , Jin Jiajia , Miu Yingying , Zhou Zejun , Zhu Qingqing , Wan Bing , Xi Guangmin , Ye Liang , Liu Yafang , Gao Jianwei , Li Huijuan , Lv Tangfeng , Song Yong
Published: January 2018

This study aimed to evaluate the biological role of geranylgeranyl diphosphate synthase (GGPPS) in the progression of lung adenocarcinoma. GGPPS expression was detected in lung adenocarcinoma tissues by qRT‐PCR, tissue microarray (TMA) and western blotting. The relationships between GGPPS expression and the clinicopathological characteristics and prognosis of lung adenocarcinoma patients were assessed. GGPPS was down‐regulated in SPCA‐1, PC9 and A549 cells using siRNA and up‐regulated in A549 cells using an adenoviral vector. The biological roles of GGPPS in cell proliferation, apoptosis, migration and invasion were determined by MTT and colony formation assays, flow cytometry, and transwell and wound‐healing assays, respectively. In addition, the regulatory roles of GGPPS on the expression of several epithelial‐mesenchymal transition (EMT) markers were determined. Furthermore, the Rac1/Cdc42 prenylation was detected after knockdown of GGPPS in SPCA‐1 and PC9 cells. GGPPS expression was significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Overexpression of GGPPS was correlated with large tumours, high TNM stage, lymph node metastasis and poor prognosis in patients. Knockdown of GGPPS inhibited the migration and invasion of lung adenocarcinoma cells, but did not affect cell proliferation and apoptosis. Meanwhile, GGPPS inhibition significantly increased the expression of E‐cadherin and reduced the expression of N‐cadherin and vimentin in lung adenocarcinoma cells. In addition, the Rac1/Cdc42 geranylgeranylation was reduced by GGPPS knockdown. Overexpression of GGPPS correlates with poor prognosis of lung adenocarcinoma and contributes to metastasis through regulating EMT.
Association of NRG1 and AUTS2 genetic polymorphisms with Hirschsprung disease in a South Chinese population
Authors: Zhang Yan , Xie Xiaoli , Zeng Jixiao , Wu Qiang , Zhang Ruizhong , Zhu Deli , Xia Huimin
Published: January 2018

Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of enteric ganglia. There are more than 15 genes identified as contributed to HSCR by family‐based or population‐based approaches. However, these findings were not fulfilled to explain the heritability of most sporadic cases. In this study, using 1470 HSCR and 1473 control subjects in South Chinese population, we replicated two variants in NRG1 (rs16879552, P = 1.05E‐04 and rs7835688, P = 1.19E‐07), and further clarified the two replicated SNPs were more essential for patients with short‐segment aganglionosis (SHSCR) (P = 2.37E‐05). We also tried to replicate the most prominent signal (rs7785360) in AUTS2, which was a potential susceptibility gene with HSCR. In our results, in terms of individual association, marginal effect was observed to affect the HSCR patients following recessive model (P = 0.089). Noteworthy, significant intergenic synergistic effect between rs16879552 (NRG1) and rs7785360 (AUTS2) was identified through cross‐validation by logistic regression (P = 2.45E‐03, OR = 1.53) and multifactor dimensionality reduction (MDR, P < 0.0001, OR = 1.77). Significant correlation was observed between expression of these two genes in the normal segments of the colons (P = 0.018), together with differential expression of these genes between aganglionic colonic segments and normal colonic segments of the HSCR patients (P value for AUTS2 <0.0001, P value for NRG1 = 0.0243). Although functional evaluation is required, we supply new evidence for the NRG1 to HSCR and raised up a new susceptibility gene AUTS2 to a specific symptom for the disease.
Maternal diabetes up‐regulates NOX2 and enhances myocardial ischaemia/reperfusion injury in adult offspring
Authors: Zhang Lili , Wang Xiaoyan , Wu Yan , Lu Xiangru , Chidiac Peter , Wang Guoping , Feng Qingping
Published: January 2018

Offspring of diabetic mothers are at risk of cardiovascular diseases in adulthood. However, the underlying molecular mechanisms are not clear. We hypothesize that prenatal exposure to maternal diabetes up‐regulates myocardial NOX2 expression and enhances ischaemia/reperfusion (I/R) injury in the adult offspring. Maternal diabetes was induced in C57BL/6 mice by streptozotocin. Glucose‐tolerant adult offspring of diabetic mothers and normal controls were subjected to myocardial I/R injury. Vascular endothelial growth factor (VEGF) expression, ROS generation, myocardial apoptosis and infarct size were assessed. The VEGF‐Akt (protein kinase B)‐mammalian target of rapamycin (mTOR)‐NOX2 signalling pathway was also studied in cultured cardiomyocytes in response to high glucose level. In the hearts of adult offspring from diabetic mothers, increases were observed in VEGF expression, NOX2 protein levels and both Akt and mTOR phosphorylation levels as compared to the offspring of control mothers. After I/R, ROS generation, myocardial apoptosis and infarct size were all significantly higher in the offspring of diabetic mothers relative to offspring of control mothers, and these differences were diminished by in vivo treatment with the NADPH oxidase inhibitor apocynin. In cultured cardiomyocytes, high glucose increased mTOR phosphorylation, which was inhibited by the PI3 kinase inhibitor LY294002. Notably, high glucose‐induced NOX2 protein expression and ROS production were inhibited by rapamycin. In conclusion, maternal diabetes promotes VEGF‐Akt‐mTOR‐NOX2 signalling and enhances myocardial I/R injury in the adult offspring. Increased ROS production from NOX2 is a possible molecular mechanism responsible for developmental origins of cardiovascular disease in offspring of diabetic mothers.
Clinical relevance of integrin alpha 4 in gastrointestinal stromal tumours
Authors: Pulkka Olli‐Pekka , Mpindi John‐Patrick , Tynninen Olli , Nilsson Bengt , Kallioniemi Olli , Sihto Harri , Joensuu Heikki
Published: January 2018

The molecular mechanisms for the dissemination and metastasis of gastrointestinal stromal tumours (GIST) are incompletely understood. The purpose of the study was to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in GIST. GIST transcriptomes were first compared with transcriptomes of other types of cancer and histologically normal gastrointestinal tract tissue in the MediSapiens in silico database. ITGA4 was identified as an unusually highly expressed gene in GIST. Therefore, the effects of ITGA4 knock‐down and selective integrin alpha 4 beta 1 (VLA‐4) inhibitors on tumour cell proliferation and invasion were investigated in three GIST cell lines. In addition, the prognostic role of ITGA4 expression in cancer cells was investigated in a series of 147 GIST patients with immunohistochemistry. Inhibition of ITGA4‐related signalling decreased GIST cell invasion in all investigated GIST cell lines. ITGA4 protein was expressed in 62 (42.2%) of the 147 GISTs examined, and expression was significantly associated with distant metastases during the course of the disease and several adverse prognostic features. Patients whose GIST expressed strongly ITGA4 had unfavourable GIST‐specific survival and overall survival compared to patients with low or no ITGA4 expression. Taken together, ITGA4 is an important integrin in the molecular pathogenesis of GIST and may influence their clinical behaviour.
Licensing and innovation with imperfect contract enforcement
Authors: Gilbert Richard , Kristiansen Eirik Gaard
Published: January 2018

Licensing promotes technology transfer and innovation, but enforcement of licensing contracts is often imperfect. We model contract enforcement as a game with perfect information but probabilistic enforcement and explore the implications of weak enforcement on the design of licensing contracts, the conduct of firms, and market performance. An upstream firm develops a technology that it can license to downstream firms using a fixed fee and a per‐unit royalty. Strictly positive per‐unit royalties maximize the licensor's profit if competition among licensees limits joint profits. With imperfect enforcement, the licensor lowers variable royalties to avoid cheating. Although imperfect contract enforcement reduces the profits of the licensor, weak enforcement lowers prices, increases downstream innovation, and in some circumstances can increase total economic welfare.
The Five Attributes of a Supportive Midwifery Practice Climate: A Review of the Literature
Authors: Thumm E. Brie , Flynn Linda
Published: January 2018

Introduction

A supportive work climate is associated with decreased burnout and attrition, and increased job satisfaction and employee health. A review of the literature was conducted in order to determine the unique attributes of a supportive practice climate for midwives.

Methods

The midwifery literature was reviewed and synthesized using concept analysis technique guided by literature from related professions. The search was conducted primarily in PubMed, CINAHL, Web of Science, and Google Scholar. Articles were included if they were conducted between 2006 and 2016 and addressed perceptions of the midwifery practice climate as it related to patient, provider, and organizational outcomes.

Results

The literature identified 5 attributes consistent with a supportive midwifery practice climate: effective leadership, adequate resources, collaboration, control of one's work, and support of the midwifery model of care. Effective leadership styles include situational and transformational, and 9 traits of effective leaders are specified. Resources consist of time, personnel, supplies, and equipment. Collaboration encompasses relationships with all members of the health care team, including midwives inside and outside of one's practice. Additionally, the patients are considered collaborating members of the team. Characteristics of effective collaboration include a shared vision, role clarity, and respectful communication. Support for the midwifery model of care includes value congruence, developing relationships with women, and providing high‐quality care.

Discussion

The attributes of a supportive midwifery practice climate are generally consistent with theoretical models of supportive practice climates of advanced practice nurses and physicians, with the exception of a more inclusive definition of collaboration and support of the midwifery model of care. The proposed Midwifery Practice Climate Model can guide instrument development, determining relationships between the attributes of the practice climate and outcomes, and creating interventions to improve the practice climate, workforce stability, and patient outcomes.
Maternal thyroid hormone is required for parvalbumin neurone development in the anterior hypothalamic area
Authors: Harder L. , Dudazy‐Gralla S. , Müller‐Fielitz H. , Hjerling Leffler J. , Vennström B. , Heuer H. , Mittag J.
Published: January 2018

Thyroid hormone (TH) is crucial for brain development and function. This becomes most evident in untreated congenital hypothyroidism, leading to irreversible mental retardation. Likewise, maternal hypothyroxinaemia, a lack of TH during pregnancy, is associated with neurological dysfunction in the offspring, such as autism and reduced intellectual capacity. In the brain, TH acts mainly through TH receptor α1 (TRα1). Consequently, mice heterozygous for a dominant‐negative mutation in TRα1 display profound neuroanatomical abnormalities including deranged development of parvalbumin neurones. However, the exact timing and orchestration of TH signalling during parvalbumin neurone development remains elusive. In the present study, we dissect the development of parvalbumin neurones in the anterior hypothalamic area (AHA) in male mice using different mouse models with impaired pre‐ and postnatal TH signalling in combination with bromodeoxyuridine birth dating and immunohistochemistry. Our data reveal that hypothalamic parvalbumin neurones are born at embryonic day 12 and are first detected in the AHA at postnatal day 8, reaching their full population number at P13. Interestingly, they do not require TH postnatally because their development is not impaired in mice with impaired TH signalling after birth. By contrast, however, these neurones crucially depend on TH through TRα1 signalling in the second half of pregnancy, when the hormone is almost exclusively provided by the mother. For the first time, our findings directly link a maternal hormone to a neuroanatomical substrate in the foetal brain, and underline the importance of proper TH signalling during pregnancy for offspring mental health. Given the role of hypothalamic parvalbumin neurones in the central control of blood pressure, the present study advocates the inclusion of cardiovascular parameters in the current discussion on possible TH substitution in maternal hypothyroxinaemia.
Neonatal exposure to oestradiol increases dopaminergic transmission in nucleus accumbens and morphine‐induced conditioned place preference in adult female rats
Authors: Bonansco C. , Martínez‐Pinto J. , Silva R. A. , Velásquez V. B. , Martorell A. , Selva M. V. , Espinosa P. , Moya P. R. , Cruz G. , Andrés M. E. , Sotomayor‐Zárate R.
Published: January 2018

Steroid sex hormones produce physiological effects in reproductive tissues and also in nonreproductive tissues, such as the brain, particularly in cortical, limbic and midbrain areas. Dopamine (DA) neurones involved in processes such as prolactin secretion (tuberoinfundibular system), motor circuit regulation (nigrostriatal system) and driving of motivated behaviour (mesocorticolimbic system) are specially regulated by sex hormones. Indeed, sex hormones promote neurochemical and behavioural effects induced by drugs of abuse by tuning midbrain DA neurones in adult animals. However, the long‐term effects induced by neonatal exposure to sex hormones on dopaminergic neurotransmission have not been fully studied. The present study aimed to determine whether a single neonatal exposure with oestradiol valerate (EV) results in a programming of dopaminergic neurotransmission in the nucleus accumbens (NAcc) of adult female rats. To answer this question, electrophysiological, neurochemical, cellular, molecular and behavioural techniques were used. The data show that frequency but not amplitude of the spontaneous excitatory postsynaptic current is significantly increased in NAcc medium spiny neurones of EV‐treated rats. In addition, DA content and release are both increased in the NAcc of EV‐treated rats, caused by an increased synthesis of this neurotransmitter. These results are functionally associated with a higher percentage of EV‐treated rats conditioned to morphine, a drug of abuse, compared to controls. In conclusion, neonatal programming with oestradiol increases NAcc dopaminergic neurotransmission in adulthood, which may be associated with increased reinforcing effects of drugs of abuse.
Which Europeans Like Nudges? Approval and Controversy in Four European Countries
Authors: Loibl Cäzilia , Sunstein Cass R. , Rauber Julius , Reisch Lucia A.
Published: January 2018

Policy makers show an increasing interest in “nudges”—behaviorally motivated interventions that steer people in certain directions but maintain freedom of consumer choice. Despite this interest, little evidence has surfaced about which population groups support nudges and nudging. We report the results of nationally representative surveys in Denmark, Hungary, Italy, and the United Kingdom. Individual, household, and geographic characteristics served as predictors of nudge approval, and the count of significant predictors as measures of controversy. Less high approval rates of nudges in Denmark and Hungary were reflected in higher controversy about “System 1” nudges, whereas the United Kingdom and Italy were marked by higher controversy about “System 2” nudges, despite high approval rates. High‐controversy nudges tended to be associated with current public policy concerns, for example, meat consumption. The results point to means for effective targeting and increase knowledge about the types of nudges likely to obtain public support.
Assessment of a training programme on detection of temporomandibular joint osseous changes applying pre‐defined 2D multiplane cone beam computed tomography reconstructions
Authors: Iskanderani D. , Alstergren P. , Hellén‐Halme K.
Published: January 2018

Objectives

Osseous changes in temporomandibular joint disorders (TMD) are common indications for cone beam computed tomography (CBCT). The number of such cases is increasing while a number of qualified oral radiologists is limited. This study investigated the usefulness of a training programme for general dental practitioners (GDPs) regarding temporomandibular joint (TMJ) osseous changes detection in CBCT images.

Methods

We selected CBCT images of 35 TMD cases and chose 5 of them to use in training 7 GDPs on detecting osseous changes in the TMJ. In evaluation directly following training, GDPs assessed the 30 remaining cases. Three qualified radiologists served as reference standard. A 2‐month follow‐up of training comprising evaluation of the same cases. The cases are assessed according to Ahmad et al (Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 107, 2009, 844) protocol of TMJ osseous changes in CBCT images.

Results

Sensitivity and specificity of the CBCT protocol were high, except for some criteria that did not appear in the cases. Average observer sensitivity was 65% while specificity was 87%. Average correct individual response rate was 84%. Mean agreement among the GDPs was 73%. Observer performance had improved at the 2‐month follow‐up.

Conclusion

The present educational programme could be a helpful material on recognising possible osseous changes of TMJ and it can be used as a part of a training programme for GDP and for specialist candidates.
Supporting young researchers in food texture studies
Authors: Kohyama Kaoru
Published: January 2018

I learned about food texture by reading many articles in the Journal of Texture Studies (JTS) and Prof. Bourne's textbook Food Texture and Viscosity, Concept and Measurement. I present here his great contributions as both the Editor‐in‐Chief of JTS and as the author of a superior textbook in the cultivation of future food texture researchers. Prof. Bourne has provided significant guidance to those in the industry using his textbook to suggest appropriate approaches to measure, evaluate, and alter the textures of agro‐products and processed foods. I began my career in food rheology, learned the physiological techniques necessary for measuring mastication, and developed relationships with good sensory scientists along the way. I am happy to offer advice to agriculture and food scientists, researchers, and engineers in the food industry regarding food texture. I would like to be a follower of Prof. Bourne and support young food texture scientists in the 21st century.

Practical applications

Food texture studies conducted during the last century are beginning to evolve. Based on previous publications in the Journal of Texture Studies, I believe that several areas can be further examined in this century. First, methods to evaluate the textures of heterogeneous materials, such as fruits and vegetables, require improvements. Second, the monitoring of rapid changes in food texture during oral processing should be considered during the design of food products. Third, a new instrumental method that mimics the movement and breakdown of soft foods by the tongue is being developed. The optimization of food processing to reduce the loss of agro‐products and production of high‐quality foods both require more attention according to the Sustainable Development Goals adopted by the United Nations in 2015.
Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory Disease Complex
Authors: Shoemake B.M. , Vander Ley B.L. , Newcomer B.W. , Heller M.C.
Published: January 2018

Background

The prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations.

Objective

Determine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/iodide (LPO/H2O2/I−) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo.

Animals

Sixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd.

Methods

In vitro viral and bacterial assays were performed to determine susceptibility to the LPO/H2O2/I− system at varying concentrations of NaI. Sixteen randomly selected, healthy crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a blinded, placebo‐controlled trial. Blood and nasal secretions were collected for 72 hours and analyzed for I− concentration.

Results

Bovine herpesvirus‐1, parainfluenza‐3, Mannheimia haemolytica and Bibersteinia trehalosi were all inactivated or inhibited in vitro by the LPO/H2O2/I− reaction. Oral administration of NaI caused a marked increase in nasal fluid I concentration with a Cmax = 181 (1,420 μM I), T12, a sufficient concentration to inactivate these pathogens in vitro.

Conclusions and Clinical Importance

In vitro, the LPO/H2O2/I− system inactivates and inhibits common pathogens associated with BRD. The administration of oral NaI significantly increases the I concentration of nasal fluid indicating that this system might be useful in preventing bovine respiratory infections.
Rapid Diagnosis of Babesia gibsoni by Point‐of‐Need Testing by Insulated Isothermal PCR in Dogs at High Risk of Infection
Authors: Cooke K.L. , Frenzer P. , Tucker S.J. , Crawford P.C. , Kirk S.K. , Levy J.K.
Published: January 2018

Background

Dogs seized by law enforcement agencies during dogfighting investigations are at increased risk of Babesia gibsoni infection. A rapid and cost‐effective diagnostic test would increase the feasibility of mass screening of dogs for infection and monitoring treatment efficacy in B. gibsoni‐infected dogs.

Objective

To determine the performance of a point‐of‐need insulated isothermal PCR (iiPCR) test for diagnosis of B. gibsoni in dogs rescued in dogfighting investigations.

Animals

Two hundred and thirty‐three dogs seized in dogfighting investigations.

Methods

Cross‐sectional study. Whole blood samples were tested for B. gibsoni and Babesia spp. by iiPCR. Results were compared to a reference standard comprised of concordant results from real‐time PCR in a commercial diagnostic laboratory and antibody titers.

Results

The iiPCR system was quick to learn, portable, and had a short processing time of <2 hours. Sensitivity and specificity of the iiPCR assay for B. gibsoni were 90% (95% confidence interval [CI] 81–95%) and 99% (CI, 95–100%), respectively. Sensitivity and specificity of the iiPCR assay for Babesia spp. were 87% (CI, 78–93%) and 98% (CI, 0.94–99%), respectively.

Conclusions and Clinical Importance

The iiPCR system produced few false‐positive results, indicating that positive results are likely to represent true infections when used in high‐risk animals. The iiPCR system can fail to identify 10–15% of truly infected dogs. However, the portability, speed, and economy of the iiPCR system compared to testing through a reference laboratory can allow rescue groups to screen and identify infection in more dogs.
Gallbladder Agenesis in 17 Dogs: 2006–2016
Authors: Sato K. , Sakai M. , Hayakawa S. , Sakamoto Y. , Kagawa Y. , Kutara K. , Teshima K. , Asano K. , Watari T.
Published: January 2018

Background

Gallbladder agenesis (GBA) is extremely rare in dogs.

Hypothesis/Objectives

To describe the history, clinical signs, diagnosis, treatment, and outcomes of dogs with GBA.

Animals

Seventeen client‐owned dogs with GBA.

Methods

Medical records from 2006 through 2016 were retrospectively reviewed. Dogs were included when GBA was suspected on abdominal ultrasonography and confirmed by gross evaluation. Signalment, clinical signs, clinicopathological data, diagnostic imaging, histopathology, treatment, and outcome were recorded.

Results

Dogs were of 6 different breeds, and Chihuahuas (10 of 17) were most common. Median age at presentation was 1.9 (range, 0.7–7.4) years. Clinical signs included vomiting (5 of 17), anorexia (2 of 17), ascites (2 of 17), diarrhea (1 of 17), lethargy (1 of 17), and seizures (1 of 17). All dogs had increased serum activity of at least 1 liver enzyme, most commonly alanine aminotransferase (15 of 17). Fifteen dogs underwent computed tomography (CT) cholangiography; common bile duct (CBD) dilatation was confirmed in 12, without evidence of bile duct obstruction. Gross evaluation confirmed malformation of the liver lobes in 14 of 17 dogs and acquired portosystemic collaterals in 5 of 17. Ductal plate malformation was confirmed histologically in 16 of 17 dogs. During follow‐up (range, 4–3,379 days), 16 of 17 dogs remained alive.

Conclusions and Clinical Importance

Dogs with GBA exhibit clinicopathological signs of hepatobiliary injury and hepatic histopathological changes consistent with a ductal plate abnormality. Computed tomography cholangiography was superior to ultrasound examination in identifying accompanying nonobstructive CBD distention. Computed tomography cholangiography combined with laparoscopic liver biopsy is the preferable approach to characterize the full disease spectrum accompanying GBA in dogs.
Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism
Authors: Peterson M.E. , Varela F.V. , Rishniw M. , Polzin D.J.
Published: January 2018

Background

Hyperthyroidism can complicate (mask) the diagnosis of chronic kidney disease (CKD) because it increases glomerular filtration rate and decreases body muscle mass, both of which can lower serum creatinine concentrations. Currently, there is no clinical test that can reliably predict which hyperthyroid cats have concurrent azotemicCKDthat will become apparent after treatment of the hyperthyroidism.

Objectives

To investigate serum symmetric dimethylarginine (SDMA) concentration as a potential marker of masked azotemia in untreated hyperthyroid cats.

Animals

Two hundred and sixty‐two hyperthyroid cats and 206 aged‐matched, clinically normal cats.

Methods

Prospective study. We measured creatinine, urea nitrogen,SDMA, T4, andTSHconcentrations before and 1, 3, and 6 months after treatment with radioiodine (131I) and classified131I‐treated cats as azotemic or nonazotemic based on persistent, post‐treatment creatinine concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and diagnostic accuracy was determined by receiver operating characteristic analysis and logistic regression.

Results

No hyperthyroid cats were azotemic before treatment, but 42 (16%) became azotemic when rechecked at 4–8 months (median, 6 months) after131I treatment; of these, 14 had highSDMAconcentrations before treatment. As a diagnostic test for pre‐azotemic (masked)CKDin untreated hyperthyroid cats,SDMAshowed a sensitivity of 33.3% and specificity of 97.7%.

Conclusions and Clinical Importance

Finding a high serumSDMAconcentration in a hyperthyroid cat can help predict development of azotemia after treatment. The test has high diagnostic test specificity (few false‐positive results) but relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats).
Re‐Os isotope systematics and fractionation of siderophile elements in metal phases from CBa chondrites
Authors: Nakanishi Nao , Yokoyama Tetsuya , Okabayashi Satoki , Usui Tomohiro , Iwamori Hikaru
Published: January 2018

We report Os isotope compositions of metal grains in two CBa chondrites (Bencubbin and Gujba) determined using a micromilling sampling coupled with thermal ionization mass spectrometry, together with the abundances of major and trace siderophile elements obtained by electron probe microanalysis and femtosecond laser ablation inductively coupled plasma–mass spectrometry. The CBa metal grains presented 187Os/188Os ratios akin to carbonaceous chondrites with limited variations (0.1257–0.1270). Most of the CBa metal grains were scattered along a 187Re‐187Os reference isochron of IIIAB iron meteorites, indicating that the CBa metals experienced limited Re‐Os fractionation at the time of their formation. The Re/Os ratios of sampling spots for the CBa metals, recast from the observed 187Os/188Os ratios, had a positive correlation with their Os/Ir ratios. In addition, the metal grains showed a positive correlation in a Pd/Fe versus Ni/Fe diagram. These correlations suggest that the CBa metal grains have formed via equilibrium condensation or evaporation from a gaseous reservoir at ~10−4 bar with enhanced metal abundances. Compared to the Bencubbin metals, the Gujba metals are characterized by having systematically lower Pd/Fe and Ni/Fe ratios that span subchondritic values. Such a difference was most likely induced by the compositionally heterogeneous impact plume from which the metals were condensed.
Nurses’ competence in genetics: An integrative review
Authors: Wright Helen , Zhao Lin , Birks Melanie , Mills Jane
Published: January 2018

The aim of this integrative review was to update a mixed method systematic review by Skirton, O'Connor, and Humphreys (2012) that reported on nurses’ levels of competence in using genetics in clinical practice. Three electronic databases were searched using selected key words. Research studies published in English between January 2011 and September 2017 reporting levels of nurse competence in genetics or genomics were eligible for inclusion. The selected studies were subjected to thematic analysis. Three main themes were identified: (i) genomic knowledge and utilization, (ii) perceived relevance to practice, and (iii) genomic education. While the reviewed papers produced varied findings, many nurses were shown to have poor genomic knowledge and/or competency, and yet there was a consensus that most nurses believe genomics is important to their practice. The present review indicated that in the past 5 years nurses have made minimal progress toward achieving the core genomic competencies appropriate for clinical practice.
Nurse and midwifery prescribing in Ireland: A scope‐of‐practice development for worldwide consideration
Authors: Wilson Donna M. , Murphy Jill , Nam Mavis A. , Fahy Anne , Tella Susanna
Published: January 2018

For 10 years, select Irish nurses and midwives who pass a rigorous 6 month theory and practical program can prescribe medications and other medicinal products. Given the need for timely, accessible, and affordable health‐care services in all countries, this nursing/midwifery education and practice development is worthy of examination. Irish nurse/midwife prescribing occurred following long‐term deliberative nursing profession advocacy, nursing education planning, nursing administration and practice planning, interdisciplinary health‐care team support and complementary efforts, and government action. A review of documents, research, and other articles was undertaken to examine this development process and report evaluative information for consideration by other countries seeking to improve their health‐care systems. Nurse/midwife prescribing was accomplished successfully in Ireland, with the steps taken there to initiate and establish nurse/midwife prescribing of value internationally.
Patterns of diversity, endemism and specialization in the root symbiont communities of alder species on the island of Corsica
Authors: Pozzi Adrien C. , Roy Mélanie , Nagati Mélissande , Schwob Guillaume , Manzi Sophie , Gardes Monique , Moreau Pierre‐Arthur , Fernandez Maria P.
Published: January 2018

We investigated whether the diversity, endemicity and specificity of alder symbionts could be changed by isolation in a Mediterranean glacial refugium. We studied both ectomycorrhizal (EM) fungi and nitrogen‐fixing actinobacteria associated with alders, and compared their communities in Corsica and on the European continent.

Nodules and root tips were sampled on the three alder species present in Corsica and continental France and Italy. Phylogenies based on internal transcribed spacer (ITS) and a multilocus sequence analysis approach were used to characterize fungal and Frankia species, respectively. Patterns of diversity, endemism and specialization were compared between hosts and regions for each symbiont community.

In Corsica, communities were not generally richer than on the mainland. The species richness per site depended mainly on host identity: Alnus glutinosa and Alnus cordata hosted richer Frankia and EM communities, respectively. Half of the Frankia species were endemic to Corsica against only 4% of EM species.

Corsica is not a hotspot of diversity for all alder symbionts but sustains an increased frequency of poor‐dispersers such as hypogeous fungi. Generalist EM fungi and host‐dependent profusely sporulating (Sp+) Frankia were abundantly associated with Corsican A. cordata, a pattern related to a more thermophilic and xerophylic climate and to the co‐occurrence with other host trees.
A novel HD‐ZIP IV/MIXTA complex promotes glandular trichome initiation and cuticle development in Artemisia annua
Authors: Yan Tingxiang , Li Ling , Xie Lihui , Chen Minghui , Shen Qian , Pan Qifang , Fu Xueqing , Shi Pu , Tang Yueli , Huang Huayi , Huang Yiwen , Huang Youran , Tang Kexuan
Published: January 2018

Glandular trichomes and cuticles are both specialized structures that cover the epidermis of aerial plant organs. The former are commonly regarded as ‘biofactories’ for producing valuable natural products. The latter are generally considered as natural barriers for defending plants against abiotic and biotic stresses. However, the regulatory network for their formation and relationship remains largely elusive.

Here we identify a homeodomain‐leucine zipper (HD‐ZIP) IV transcription factor, AaHD8, directly promoting the expression of AaHD1 for glandular trichome initiation in Artemisia annua.

We found that AaHD8 positively regulated leaf cuticle development in A. annua via controlling the expression of cuticle‐related enzyme genes. Furthermore, AaHD8 interacted with a MIXTA‐like protein AaMIXTA1, a positive regulator of trichome initiation and cuticle development, forming a regulatory complex and leading to enhanced transcriptional activity in regulating the expression of AaHD1 and cuticle development genes.

Our results reveal a molecular mechanism by which a novel HD‐ZIP IV/MIXTA complex plays a significant role in regulating epidermal development, including glandular trichome initiation and cuticle formation.
Clinical trials for myasthenia gravis: a historical perspective
Authors: Kaminski Henry J. , Alnosair Eman , Algahtani Rami M.
Published: January 2018

Symposia dedicated to myasthenia gravis and related disorders date back to 1947 and serve as markers of the progress for the field. We provide a brief historical review of therapy development through the lens of the publications that arose from the close to quinquennial meetings that have been supported nearly since their inception by the Myasthenia Gravis Foundation of America and the New York Academy of Sciences. One can appreciate great advances, false starts, and dead ends that are found in all fields of medicine. We tally up the score card for MG and find points scored, but the win is not yet close.
Piecing together the puzzle of pancreatic islet adaptation in pregnancy
Authors: Banerjee Ronadip R.
Published: January 2018

Pregnancy places acute demands on maternal physiology, including profound changes in glucose homeostasis. Gestation is characterized by an increase in insulin resistance, counterbalanced by an adaptive increase in pancreatic β cell production of insulin. Failure of normal adaptive responses of the islet to increased maternal and fetal demands manifests as gestational diabetes mellitus (GDM). The gestational changes and rapid reversal of islet adaptations following parturition are at least partly driven by an anticipatory program rather than post‐factum compensatory adaptations. Here, I provide a comprehensive review of the cellular and molecular mechanisms underlying normal islet adaptation during pregnancy and how dysregulation may lead to GDM. Emerging areas of interest and understudied areas worthy of closer examination in the future are highlighted.
Pathophysiological mechanisms of autoimmunity
Authors: Sudres Muriel , Verdier Julien , Truffault Frédérique , Le Panse Rozen , Berrih‐Aknin Sonia
Published: January 2018

Autoimmune diseases (AIDs) are chronic disorders characterized by inflammatory reactions against self‐antigens that can be either systemic or organ specific. AIDs can differ in their epidemiologic features and clinical presentations, yet all share a remarkable complexity. AIDs result from an interplay of genetic and epigenetic factors with environmental components that are associated with imbalances in the immune system. Many of the pathogenic mechanisms of AIDs are also implicated in myasthenia gravis (MG), an AID in which inflammation of the thymus leads to a neuromuscular disorder. Our goal here is to highlight the similarities and differences between MG and other AIDs by reviewing the common transcriptome signatures and the development of germinal centers and by discussing some unresolved questions about autoimmune mechanisms. This review will propose hypotheses to explain the origin of regulatory T (Treg) cell defects and the causes of chronicity and specificity of AIDs.
Distinct patterns of gene expression in human cardiac fibroblasts exposed to rapamycin treatment or methionine restriction
Authors: Azar Ashley , Lawrence Ibiyonu , Jofre Sebastian , Mell Joshua , Sell Christian
Published: January 2018

Both methionine restriction and rapamycin treatment are robust longevity‐enhancing regimens for which the mechanisms remain unclear. Cellular senescence is a major contributor to the aging process, and we find that both the methionine and rapamycin regimens delay or prevent activation of the senescence program in human cells. Using a transcriptome‐wide analysis, we examined the impact of methionine restriction and rapamycin treatment on senescence‐associated gene expression in human cardiac fibroblasts. Our findings have been integrated into gene expression data sets from human lung and skin fibroblasts during senescence. The data demonstrate both common and tissue‐specific aspects to the senescent phenotype in these cell types. For example, cardiac fibroblasts express brain naturetic peptide, a clinically relevant marker for cardiac failure, whereas senescent cells from all three tissues express at least one of the insulin‐like growth factor (IGF)‐binding proteins. The IGF‐binding proteins are tissue‐specific mediators of IGF‐1, a growth factor required for proliferation of all tissues. These data suggest that senescent cells serve tissue‐specific roles. Moreover, the prolongevity regimens produce distinct patterns of gene expression.
Update on management of diabetic foot ulcers
Authors: Everett Estelle , Mathioudakis Nestoras
Published: January 2018

Diabetic foot ulcers (DFUs) are a serious complication of diabetes that results in significant morbidity and mortality. Mortality rates associated with the development of a DFU are estimated to be 5% in the first 12 months, and 5‐year morality rates have been estimated at 42%. The standard practices in DFU management include surgical debridement, dressings to facilitate a moist wound environment and exudate control, wound off‐loading, vascular assessment, and infection and glycemic control. These practices are best coordinated by a multidisciplinary diabetic foot wound clinic. Even with this comprehensive approach, there is still room for improvement in DFU outcomes. Several adjuvant therapies have been studied to reduce DFU healing times and amputation rates. We reviewed the rationale and guidelines for current standard of care practices and reviewed the evidence for the efficacy of adjuvant agents. The adjuvant therapies reviewed include the following categories: nonsurgical debridement agents, dressings and topical agents, oxygen therapies, negative pressure wound therapy, acellular bioproducts, human growth factors, energy‐based therapies, and systemic therapies. Many of these agents have been found to be beneficial in improving wound healing rates, although a large proportion of the data are small, randomized controlled trials with high risks of bias.
A presynaptic congenital myasthenic syndrome attributed to a homozygous sequence variant in LAMA5
Authors: Maselli Ricardo A. , Arredondo Juan , Vázquez Jessica , Chong Jessica X. , Bamshad Michael J. , Nickerson Deborah A. , Lara Marian , Ng Fiona , Lo Victoria Lee , Pytel Peter , McDonald Craig M.
Published: January 2018

We report a severe defect of neuromuscular transmission in a consanguineous patient with a homozygous variant in the laminin α5 subunit gene (LAMA5). The variant c.8046C > T (p.Arg2659Trp) is rare and has a predicted deleterious effect. The affected individual, who also carries a rare homozygous sequence variant in LAMA1, had normal cognitive function, but magnetic resonance brain imaging showed mild volume loss and periventricular T2 prolongation. Repetitive nerve stimulation at 2 Hz showed 50% decrement of compound muscle action potential amplitudes but 250% facilitation immediately after exercise, similar to that seen in Lambert–Eaton myasthenic syndrome. Endplate studies demonstrated a profound reduction of the endplate potential quantal content but normal amplitudes of miniature endplate potentials. Electron microscopy showed endplates with increased postsynaptic folding that were denuded or only partially occupied by small nerve terminals. Expression studies revealed that p.Arg2659Trp caused decreased binding of laminin α5 to SV2A and impaired laminin‐521 cell adhesion and cell projection support in primary neuronal cultures. In summary, this report describing severe neuromuscular transmission failure in a patient with a LAMA5 mutation expands the list of phenotypes associated with defects in genes encoding α‐laminins.