bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis
Authors: Ingwersen Jens , De Santi Lorenzo , Wingerath Britta , Graf Jonas , Koop Barbara , Schneider Reiner , Hecker Christina , Schröter Friederike , Bayer Mary , Engelke Anna Dorothee , Dietrich Michael , Albrecht Philipp , Hartung Hans‐Peter , Annunziata Pasquale , Aktas Orhan , Prozorovski Tim 
Published: February 2018

AbstractMultiple sclerosis is characterised by inflammatory neurodegeneration, with axonal injury and neuronal cell death occurring in parallel to demyelination. Regarding the molecular mechanisms responsible for demyelination and axonopathy, energy failure, aberrant expression of ion channels and excitotoxicity have been suggested to lead to Ca2+ overload and subsequent activation of calcium‐dependent damage pathways. Thus, the inhibition of Ca2+ influx by pharmacological modulation of Ca2+ channels may represent a novel neuroprotective strategy in the treatment of secondary axonopathy. We therefore investigated the effects of the L‐type voltage‐gated calcium channel blocker nimodipine in two different models of mouse experimental autoimmune encephalomyelitis (EAE), an established experimental paradigm for multiple sclerosis. We show that preventive application of nimodipine (10 mg/kg per day) starting on the day of induction had ameliorating effects on EAE in SJL/J mice immunised with encephalitic myelin peptide PLP139–151, specifically in late‐stage disease. Furthermore, supporting these data, administration of nimodipine to MOG35–55‐immunised C57BL/6 mice starting at the peak of pre‐established disease, also led to a significant decrease in disease score, indicating a protective effect on secondary CNS damage. Histological analysis confirmed that nimodipine attenuated demyelination, axonal loss and pathological axonal β‐amyloid precursor protein accumulation in the cerebellum and spinal cord in the chronic phase of disease. Of note, we observed no effects of nimodipine on the peripheral immune response in EAE mice with regard to distribution, antigen‐specific proliferation or activation patterns of lymphocytes. Taken together, our data suggest a CNS‐specific effect of L‐type voltage‐gated calcium channel blockade to inflammation‐induced neurodegeneration.
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Developmental and degenerative cardiac defects in the Taiwanese mouse model of severe spinal muscular atrophy
Authors: Maxwell Gillian K. , Szunyogova Eva , Shorrock Hannah K. , Gillingwater Thomas H. , Parson Simon H. 
Published: February 2018

AbstractSpinal muscular atrophy (SMA), an autosomal recessive disease caused by a decrease in levels of the survival motor neuron (SMN) protein, is the most common genetic cause of infant mortality. Although neuromuscular pathology is the most severe feature of SMA, other organs and tissues, including the heart, are also known to be affected in both patients and animal models. Here, we provide new insights into changes occurring in the heart, predominantly at pre‐ and early symptomatic ages, in the Taiwanese mouse model of severe SMA. Thinning of the interventricular septum and dilation of the ventricles occurred at pre‐ and early symptomatic ages. However, the left ventricular wall was significantly thinner in SMA mice from birth, occurring prior to any overt neuromuscular symptoms. Alterations in collagen IV protein from birth indicated changes to the basement membrane and contributed to the abnormal arrangement of cardiomyocytes in SMA hearts. This raises the possibility that developmental defects, occurring prenatally, may contribute to cardiac pathology in SMA. In addition, cardiomyocytes in SMA hearts exhibited oxidative stress at pre‐symptomatic ages and increased apoptosis during early symptomatic stages of disease. Heart microvasculature was similarly decreased at an early symptomatic age, likely contributing to the oxidative stress and apoptosis phenotypes observed. Finally, an increased incidence of blood retention in SMA hearts post‐fixation suggests the likelihood of functional defects, resulting in blood pooling. These pathologies mirror dilated cardiomyopathy, with clear consequences for heart function that would likely contribute to potential heart failure. Our findings add significant additional experimental evidence in support of the requirement to develop systemic therapies for SMA capable of treating non‐neuromuscular pathologies.
Caring for crying babies: A mixed‐methods study to understand factors influencing nurses' and doctors' management of infant colic
Authors: McGann James , Manohar Jaqueline , Hiscock Harriet , O'Connor Denise , Hodgson Jan , Babl Franz , Sung Valerie 
Published: February 2018

AimThe aim of this study was to determine the barriers and enablers influencing the uptake of two recommendations from a tertiary paediatric hospital's clinical practice guidelines by maternal and child health nurses (MCHNs) and emergency department (ED) doctors: (i) explaining normal crying; and (ii) avoiding attributing crying to gastro‐oesophageal reflux (GOR) and limiting anti‐reflux medication use.MethodsThe study was designed as 1‐h focus group discussions, guided by the Theoretical Domains Framework, and a short questionnaire, with a purposive sample of MCHNs and ED doctors in Victoria, Australia in (March to September) 2015. Analyses were conducted by inductive content analysis to identify key barriers and enablers.ResultsA total of 53 MCHNs and 25 ED doctors participated in 11 discussions. Forexplaining normal crying,keyenablerswere: adequate experience/competency, perceiving it was their role to explain and belief it prevented over‐medicalisation. The mainbarrierswere time restriction and beliefs about parents' perceptions. For MCHNs, keybarrierstoavoid attributing crying to GORwere: lack of knowledge and confusion around their role in diagnosing GOR. For ED doctors, keybarrierstolimiting anti‐reflux medicationwere: parents requesting medication, concern about disrupting the parent–primary‐care practitioner relationship and belief it was not their role to cease anti‐reflux medication.ConclusionsOverall, MCHN and ED doctors were proficient in describing normal crying. However, several barriers to best practice were identified, including time constraints and belief about consequences of intervening. These results will be used to develop effective interventions to address the identified barriers and enablers to optimise the management of infant colic.
Effects of Diagnostic Work‐Up on Medical Decision‐Making for Canine Urinary Tract Infection: An Observational Study in Danish Small Animal Practices
Authors: Sørensen T.M. , Bjørnvad C.R. , Cordoba G. , Damborg P. , Guardabassi L. , Siersma V. , Bjerrum L. , Jessen L.R. 
Published: February 2018

BackgroundClinical signs of urinary tract disease in dogs often lead to prescription of antibiotics. Appropriate diagnostic work‐up could optimize treatment and reduce the risk of inappropriate use of antibiotics.Hypothesis/ObjectivesTo describe and evaluate the impact of diagnostic work‐up on decision to treat (DTT) and choice of antibiotic treatment (COT) for dogs presenting with clinical signs of urinary tract disease.AnimalsOne hundred and fifty‐one dogs presenting to 52 Danish veterinary practices.MethodsProspective, observational study. Clinical signs, diagnostic work‐up, and prescriptions were recorded. Urine samples were submitted to a reference laboratory for quantitative bacterial culture (QBC) and susceptibility testing. The laboratory results were used as reference for assessing the appropriateness of DTT and COT.ResultsIn the majority of dogs, veterinarians performed dipstick (99%), microscopic examination of urine (80%) and bacterial culture (56%). Fifty‐one percent of dogs had urinary tract infection (UTI) based on reference QBC. Appropriate DTT was made for 62% of the dogs, while 36% were over‐prescribed and 2% under‐prescribed. Inappropriate use of second‐line agents was found in 57% of the UTI cases. Performing microscopy—but not culture—significantly impacted DTT (P = 0.039) while no difference was seen in COT (P = 0.67). The accuracy of in‐house microscopy and culture were 64.5 and 77%, respectively.Conclusions and Clinical Importance: Over‐prescription of antibiotics was common among dogs with suspected UTI, regardless of the diagnostic work‐up performed. Test inaccuracy under practice conditions and incoherence between diagnostic test results and decision‐making both explained inappropriate and unnecessary use of antibiotics.
Immediate, short‐, and long‐term changes in tracheal stent diameter, length, and positioning after placement in dogs with tracheal collapse syndrome
Authors: Raske Matthew , Weisse Chick , Berent Allyson C. , McDougall Renee , Lamb Kenneth 
Published: February 2018

BackgroundIntraluminal tracheal stenting is a minimally invasive procedure shown to have variable degrees of success in managing clinical signs associated with tracheal collapse syndrome (CTCS) in dogs.ObjectivesIdentify immediate post‐stent changes in tracheal diameter, determine the extent of stent migration, and stent shortening after stent placement in the immediate‐, short‐, and long‐term periods, and evaluate inter‐observer reliability of radiographic measurements.AnimalsFifty client‐owned dogs.MethodsRetrospective study in which medical records were reviewed in dogs with CTCS treated with an intraluminal tracheal stent. Data collected included signalment, location, and type of collapse, stent diameter and length, and post‐stent placement radiographic follow‐up times. Radiographs were used to obtain pre‐stent tracheal measurements and post‐stent placement measurements.ResultsImmediate mean percentage change was 5.14%, 5.49%, and 21.64% for cervical, thoracic inlet, and intra‐thoracic tracheal diameters, respectively. Ultimate mean follow‐up time was 446 days, with mean percentage change of 2.55%, 15.09%, and 8.65% for cervical, thoracic inlet, and intra‐thoracic tracheal diameters, respectively. Initial mean stent length was 26.72% higher than nominal length and ultimate long‐term tracheal mean stent shortening was only 9.90%. No significant stent migration was identified in the immediate, short‐, or long‐term periods. Good inter‐observer agreement of radiographic measurements was found among observers of variable experience level.Conclusions and Clinical ImportanceUse of an intraluminal tracheal stent for CTCS is associated with minimal stent shortening with no clinically relevant stent migration after fluoroscopic placement. Precise stent sizing and placement techniques likely play important roles in avoiding these reported complications.
Comparative, multidimensional imaging of patent ductus arteriosus and a proposed update to the morphology classification system for dogs
Authors: Doocy Kelley R. , Saunders Ashley B. , Gordon Sonya G. , Jeffery Nicholas 
Published: February 2018

BackgroundAccurately assessing the morphology and shape of the patent ductus arteriosus (PDA) and obtaining measurements are important to avoid procedural complications.ObjectivesTo characterize and compare PDA morphology, shape, and dimensions with angiography and echocardiography.Animals25 client‐owned dogs with echocardiographically confirmed PDA.MethodsProspective case series. Imaging consisted of single plane angiography, transthoracic echocardiography from the right (TTE‐R) and left (TTE‐L), and two‐dimensional, biplane, and three‐dimensional transesophageal echocardiography (TEE‐2D and TEE‐3D). Measurements included angiographic minimal ductal diameter (MDD), echocardiographic pulmonary ostium in a single dimension (TTE‐R, TTE‐L, and TEE‐2D) and in perpendicular dimensions (TEE‐3D) with similar measurements of the ampulla 3 mm above the MDD or pulmonary ostium. The morphology and shape of the PDA were characterized.ResultsCatheter‐based occlusion (N = 20) and surgical ligation (N = 5) were performed without complication. Angiographic morphology was classified as type II (N = 19), type III (N = 1), and other (N = 1). Angiographic MDD and TEE‐2D pulmonary ostium measurements were significantly (P = .008) but weakly correlated (r = .56); similar relationships were found for ampulla diameter measurements (P < .0001; r = .75). In general, TEE‐2D did not correlate with other imaging modalities measurements. Based on TEE‐3D measurements, the majority of pulmonary ostium (17/24; 71%) and ampulla (19/24; 79%) were oval.Conclusions and Clinical ImportanceMeasurements using different imaging modalities are not interchangeable. TEE‐3D provided an en face view of the PDA that cannot be replicated with other echocardiographic techniques and demonstrated an oval shape in the majority of dogs. We propose an update to the current classification system to include additional PDA morphologies.
Prospective evaluation of an indwelling esophageal balloon dilatation feeding tube for treatment of benign esophageal strictures in dogs and cats
Authors: Tan Desmond K. , Weisse Chick , Berent Allyson , Lamb Kenneth E. 
Published: February 2018

BackgroundDespite multiple dilatation procedures, benign esophageal strictures (BES) remain a recurring cause of morbidity and mortality in dogs and cats.ObjectiveInvestigate the use of an indwelling Balloon Dilatation esophagostomy tube (B‐Tube) for treatment of BES in dogs and cats.AnimalsNine dogs and 3 cats.MethodsAnimals with BES were recruited for our prospective study. Endoscopic and fluoroscopic evaluation of the esophagus and balloon dilatation were performed under general anesthesia, followed by placement of an indwelling B‐Tube. The animals' owners performed twice daily at‐home inflations for approximately 6 weeks. Repeat endoscopy was performed before B‐Tube removal. Animals were reevaluated for changes in modified dysphagia score (MDS) after B‐Tube removal.ResultsThe B‐Tube management was relatively well tolerated and effective in maintaining dilatation of a BES while in place. These animals underwent a median of 2 anesthetic episodes and were monitored for a median of 472 days (range, 358‐1736 days). The mean MDS before treatment was 3.1 ± 0.5/4.0 and final follow‐up MDS were significantly (P < .0001) improved at 0.36 ± 0.65/4.0. Eleven of 12 animals (91.7%) had improved MDS at the end of the follow‐up period, with 8/12 (66.7%) having an MDS of 0/4, 2/12 (16.7%) an MDS of 1/4, and 1/12 (8.3%) an MDS of 2/4. One dog died.Conclusions and Clinical ImportanceThe B‐Tube offers an effective, and more economical method, and often decreased anesthetic time to repeated balloon dilatation procedures for the treatment of BES in dogs and cats.
Functional composition of temperate forest trees under chronic ungulate herbivory
Authors: Hedwall Per‐Ola , Churski Marcin , Jędrzejewska Bogumiła , Miścicki Stanisław , Kuijper Dries Pieter Jan 
Published: February 2018

AbstractQuestionFunctional plant traits often express consistent changes along ecological gradients and, hence, are often used as indicators of environmental change (e.g. nutrient availability, temperature changes). Besides being driven by edaphic conditions, functional plant composition is filtered by herbivory, and traits responsive to nutrient availability often coincide with those related to palatability or resistance to browsing. We hypothesized that herbivory may distort the ways in which traits are expressed along environmental gradients.LocationBiałowieża National Park, Poland.MethodsWe used a long‐term controlled, exclosure experiment in the Białowieża National Park to study tree functional trait expression and plant indicator values, with and without large ungulate browsing, along a natural soil fertility gradient.ResultsBrowsing largely reduced the functional diversity of regenerating trees, indicated by multivariate analysis and Rao's Quadratic Entropy (RQE), and altered how several traits change with increasing fertility. Browsing led to an increase in specific leaf area (SLA) on poorer sites. RQE showed a hump‐backed trend along the fertility gradient, indicating the largest functional diversity at intermediate fertility. However, this pattern was not affected by browsing. Unlike the morphological tree traits, trends of light and N plant indicator values along the gradient were unaffected by browsing.ConclusionsThese results highlight how the expression of plant traits resulting from one driver (soil fertility) can be modified by another driver (herbivory,) and stress the importance of taking herbivory into account when using plant traits as indicators of large‐scale processes (e.g. climate change). Furthermore, the results suggest that plant indicator values may be more robust towards these effects, while compiled indices such as RQE could mask considerable functional turnover. Several traits (e.g. SLA) are strongly connected to nutrient cycling. The development, driven by browsing, towards higher SLA on poorer sites may thus cause a positive feedback effect on site fertility that drives an increase in nutrient availability. This may in turn have implications for ecosystem functionality. Hence, the large reduction in functional diversity revealed at the scale of this study may in the long term have implications on multiple ecosystem processes.
The cholinergic anti‐inflammatory pathway revisited
Authors: Murray K. , Reardon C. 
Published: February 2018

AbstractInflammatory bowel disease negatively affects the quality of life of millions of patients around the world. Although the precise etiology of the disease remains elusive, aberrant immune system activation is an underlying cause. As such, therapies that selectively inhibit immune cell activation without broad immunosuppression are desired. Inhibition of immune cell activation preventing pro‐inflammatory cytokine production through neural stimulation has emerged as one such treatment. These therapeutics are based on the discovery of the cholinergic anti‐inflammatory pathway, a reflex arc that induces efferent vagal nerve signaling to reduce immune cell activation and consequently mortality during septic shock. Despite the success of preclinical and clinical trials, the neural circuitry and mechanisms of action of these immune‐regulatory circuits are controversial. At the heart of this controversy is the protective effect of vagal nerve stimulation despite an apparent lack of neuroanatomical connections between the vagus and target organs. Additional studies have further emphasized the importance of sympathetic innervation of these organs, and that alternative neural circuits could be involved in neural regulation of the immune system. Such controversies also extend to the regulation of intestinal inflammation, with the importance of efferent vagus nerve signals in question. Experiments that better characterize these pathways have now been performed by Willemze et al. in this issue of Neurogastroenterology & Motility. These continued efforts will be critical to the development of better neurostimulator based therapeutics for inflammatory bowel disease.
Melanoma cases demonstrate increased carrier frequency of phenylketonuria/hyperphenylalanemia mutations
Authors: Arbesman Joshua , Ravichandran Sairekha , Funchain Pauline , Thompson Cheryl L. 
Published: February 2018

SummaryIdentifying novel melanoma genetic risk factors informs screening and prevention efforts. Mutations in the phenylalanine hydroxylase gene (the causative gene in phenylketonuria) lead to reduced pigmentation in untreated phenylketonuria patients, and reduced pigmentation is associated with greater melanoma risk. Therefore, we sought to characterize the relationship between phenylketonuria carrier status and melanoma risk. Using National Newborn Screening Reports, we determined the United States phenylketonuria/hyperphenylalanemia carrier frequency in Caucasians to be 1.76%. We examined three publically available melanoma datasets for germline mutations in the phenylalanine hydroxylase gene associated with classic phenylketonuria and/or hyperphenylalanemia. Mutations were identified in 29/814 melanoma patients, with a carrier frequency of 3.56%. There was a twofold enrichment (p‐value = 3.4 × 10−5) compared to the Caucasian frequency of hyperphenylalanemia/phenylketonuria carriers. These data demonstrate a novel association between phenylalanine hydroxylase carrier status and melanoma risk. Further, functional investigation is warranted to determine the link between phenylalanine hydroxylase mutations and melanomagenesis.
Prevalence and duration of breast milk feeding in very preterm infants: A 3‐year follow‐up study and a systematic literature review
Authors: Rodrigues Carina , Teixeira Raquel , Fonseca Maria João , Zeitlin Jennifer , Barros Henrique ,   the Portuguese EPICE (Effective Perinatal Intensive Care in Europe) Network
Published: February 2018

AbstractBackgroundThe World Health Organization recommends exclusive breast milk feeding until 6 months and continuing up to 2 years of age; little is known about whether very preterm infants are fed in accordance with these recommendations. We aimed to describe the prevalence and duration of breast milk feeding in very preterm children and to systematically review internationally published data.MethodsWe evaluated breast milk feeding initiation and duration in very preterm children born in 2 Portuguese regions (2011‐2012) enrolled in the EPICE cohort and followed‐up to the age of 3 (n = 466). We searched PubMed® from inception to January 2017 to identify original studies reporting the prevalence and/or duration of breast milk feeding in very preterm children.Results91.0% of children received some breast milk feeding and 65.3% were exclusively breast fed with a median duration of 2 months for exclusive and 3 months for any breast milk; only 9.9% received exclusive breast milk for at least 6 months, 10.2% received any breast milk for 12 months or more, and 2.0% for up to 24 months. The literature review identified few studies on feeding after hospital discharge (n = 9); these also reported a low prevalence of exclusive breast milk feeding at 6 months (1.0% to 27.0%) and of any breast milk at 12 months (8.0% to 12.0%).ConclusionsThe duration of breast milk feeding among Portuguese very preterm infants was shorter than recommended. However, this appears to be common globally. Research is needed to inform strategies to promote continued breast milk feeding.