bluuebunny/crossref_metadata_2025 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

Multiple 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

Spinal 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

Aim

The 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.

Methods

The 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.

Results

A 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.

Conclusions

Overall, 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.
Borrelia burgdorferiInfection and Lyme Disease in North American Horses: A Consensus Statement
Authors: Divers T.J. , Gardner R.B. , Madigan J.E. , Witonsky S.G. , Bertone J.J. , Swinebroad E.L. , Schutzer S.E. , Johnson A.L.
Published: February 2018

Borrelia burgdorferiinfection is common in horses living in Lyme endemic areas and the geographic range for exposure is increasing. Morbidity afterB. burgdorferiinfection in horses is unknown. Documented, naturally occurring syndromes attributed toB. burgdorferiinfection in horses include neuroborreliosis, uveitis, and cutaneous pseudolymphoma. Although other clinical signs such as lameness and stiffness are reported in horses, these are often not well documented. Diagnosis of Lyme disease is based on exposure toB. burgdorferi, cytology or histopathology of infected fluid or tissue and antigen detection. Treatment of Lyme disease in horses is similar to treatment of humans or small animals but treatment success might not be the same because of species differences in antimicrobial bioavailability and duration of infection before initiation of treatment. There are no approved equine label Lyme vaccines but there is strong evidence that proper vaccination could prevent infection in horses.
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

Background

Clinical 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/Objectives

To 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.

Animals

One hundred and fifty‐one dogs presenting to 52 Danish veterinary practices.

Methods

Prospective, 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.

Results

In 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

Background

Intraluminal 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.

Objectives

Identify 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.

Animals

Fifty client‐owned dogs.

Methods

Retrospective 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.

Results

Immediate 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 Importance

Use 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

Background

Accurately assessing the morphology and shape of the patent ductus arteriosus (PDA) and obtaining measurements are important to avoid procedural complications.

Objectives

To characterize and compare PDA morphology, shape, and dimensions with angiography and echocardiography.

Animals

25 client‐owned dogs with echocardiographically confirmed PDA.

Methods

Prospective 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.

Results

Catheter‐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 Importance

Measurements 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

Background

Despite multiple dilatation procedures, benign esophageal strictures (BES) remain a recurring cause of morbidity and mortality in dogs and cats.

Objective

Investigate the use of an indwelling Balloon Dilatation esophagostomy tube (B‐Tube) for treatment of BES in dogs and cats.

Animals

Nine dogs and 3 cats.

Methods

Animals 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.

Results

The 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 Importance

The 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

Question

Functional 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.

Location

Białowieża National Park, Poland.

Methods

We 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.

Results

Browsing 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.

Conclusions

These 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

Inflammatory 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

Identifying 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

Background

The 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.

Methods

We 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.

Results

91.0% 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%).

Conclusions

The 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.
Timing of seeding after herbicide application influences rates of germination and seedling biomass of native plants used for grassland restoration
Authors: McManamen Christine , Nelson Cara R. , Wagner Viktoria
Published: February 2018

Natural resource managers commonly use herbicides to control invasive weeds. This practice, however, can lead to secondary invasion by other invasive plants, unless measures such as seeding are taken to promote natives. Although there is evidence that seeding immediately after herbicide treatment adversely affects germination, there is little information on optimal timing between spraying and seeding or variation among species in herbicide sensitivity. We investigated effects of picloram and aminopyralid on seed performance of 10 native plants. We separated the herbicide application and seeding by 0, 3, 6, 9, and 11 months in a greenhouse, and recorded the rates of germination and germinant biomass after 6 weeks. In addition, we installed 72 field plots to test the effects of fall‐ and spring‐treated plots on seed performance. In the greenhouse, herbicides negatively impacted germination of four species over the entire 11‐month trail whereas six showed less sensitivity over time. Results from spring‐treated field plots were largely consistent with those from the greenhouse: rates of germination and biomass were lower in herbicide‐treated plots than those in control plots for 75% of seeded species. In fall‐sprayed plots, however, the adverse effects of herbicides were only apparent for 25% of seeded species. Results from greenhouse and field studies combined indicate that herbicides can have strong adverse effects on germination, but that actual effects in field settings will be based on complex interactions between species traits, field conditions, and management choices. Thus, site‐specific trials will ultimately be the best method for making inference to particular restoration sites.
Geology and Isotope Geochemistry of the Dongzhongla Pb–Zn Deposit in Tibet: Implications for the Origin of the Ore‐Forming Fluids and Storage Condition of Certain Metals
Authors: Fei Guang Chun , Zhou Yu , Deng Yun , Chen Xu , Wen Chun Qi , Yu Qinglin , Ding Feng , Zhou Xiong , Huo Yan
Published: February 2018

As a newly discovered medium‐sized deposit (proven Pb + Zn resources of 0.23 Mt, 9.43% Pb and 8.73% Zn), the Dongzhongla skarn Pb–Zn deposit is located in the northern margin of the eastern Gangdese, central Lhasa block. Based on the geological conditions in this deposit of ore‐forming fluids, H, O, C, S, Pb, Sr, and noble gas isotopic compositions were analyzed. Results show that δ18OSMOW of quartz and calcite ranged from −9.85 to 4.17‰, and δDSMOW ranged from −124.7 to −99.6‰ (where SMOW is the standard mean ocean water), indicating magma fluids mixed with meteoric water in ore‐forming fluids. The δ13CPDB and δ18OSMOW values of calcite range from −1.4 to −1.1‰ and from 5.3 to 15.90‰, respectively, show compositions consistent with the carbonate limestone in the surrounding rocks, implying that the carbon was primarily sourced from the dissolution of carbonate strata in the Luobadui Formation. The ore δ34S composition varied in a narrow range of 2.8 to 5.7‰, mostly between 4‰ and 5‰. The total sulfur isotopic value δ34S was 4.7‰ with characteristics of magmatic sulfur. The 3He/4He values of pyrite and galena ranged from 0.101 to 5.7 Ra, lower than those of mantle‐derived fluids (6 ± 1 Ra), but higher than those of the crust (0.01–0.05 Ra), and therefore classified as a crust–mantle mixed source. The Pb isotopic composition for 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb values of the ores were in the ranges of 18.628–18.746, 15.698–15.802, and 39.077–39.430, respectively, consistent with the Pb isotopic composition of magmatic rocks in the deposit, classified as upper‐crust lead. The ore lead was likely sourced partially from the crustal basement of the Lhasa Terrane. The initial (87Sr/86Sr)i value from five sulfide samples ranged from 0.71732 to 0.72767, and associated ore‐forming fluids were mainly sourced from the partial melting of the upper‐crust materials. Pb isotopic compositions of ore sulfides from the Dongzhongla deposit are similar to that of the Yuiguila and Mengya'a deposit, indicating that they have similar sources of metal‐rich ore‐forming solution. According to basic skarn mineralogy, the economic metals, and the origin of the ore‐forming fluids, the Dongzhongla deposit was classified as a skarn‐type Pb–Zn deposit.
The Relation between Descriptive Norms, Suicide Ideation, and Suicide Attempts among Adolescents
Authors: Reyes‐Portillo Jazmin A. , Lake Alison M. , Kleinman Marjorie , Gould Madelyn S.
Published: February 2018

This study examined the relationship between adolescents' beliefs about the prevalence of youth suicide ideation (ideation descriptive norms) and suicide attempts (attempt descriptive norms) with self‐reported suicide ideation and attempts. Descriptive norms, suicide ideation, and suicide attempts as well as gender, race/ethnicity, and exposure to family, peer, and others' suicide were assessed in 2,109 students at six suburban New York State high schools. After controlling for demographic variables and exposure to suicide, elevated ideation descriptive norms and attempt descriptive norms were associated with higher rates of suicide ideation and lifetime suicide attempts among adolescents. Adolescents who believed suicide ideation and attempts to be more widespread among peers (i.e., elevated ideation and attempt descriptive norms) were more likely to endorse suicide ideation and attempts. Correcting these descriptive norms may be a worthwhile goal for school‐based suicide prevention programs.
The mechanism of photosystem‐II inactivation during sulphur deprivation‐induced H2 production in Chlamydomonas reinhardtii
Authors: Nagy Valéria , Vidal‐Meireles André , Podmaniczki Anna , Szentmihályi Klára , Rákhely Gábor , Zsigmond Laura , Kovács László , Tóth Szilvia Z.
Published: February 2018

Sulphur limitation may restrain cell growth and viability. In the green alga Chlamydomonas reinhardtii, sulphur limitation may induce H2 production lasting for several days, which can be exploited as a renewable energy source. Sulphur limitation causes a large number of physiological changes, including the inactivation of photosystem II (PSII), leading to the establishment of hypoxia, essential for the increase in hydrogenase expression and activity. The inactivation of PSII has long been assumed to be caused by the sulphur‐limited turnover of its reaction center protein PsbA. Here we reinvestigated this issue in detail and show that: (i) upon transferring Chlamydomonas cells to sulphur‐free media, the cellular sulphur content decreases only by about 25%; (ii) as demonstrated by lincomycin treatments, PsbA has a significant turnover, and other photosynthetic subunits, namely RbcL and CP43, are degraded more rapidly than PsbA. On the other hand, sulphur limitation imposes oxidative stress early on, most probably involving the formation of singlet oxygen in PSII, which leads to an increase in the expression of GDP‐L‐galactose phosphorylase, playing an essential role in ascorbate biosynthesis. When accumulated to the millimolar concentration range, ascorbate may inactivate the oxygen‐evolving complex and provide electrons to PSII, albeit at a low rate. In the absence of a functional donor side and sufficient electron transport, PSII reaction centers are inactivated and degraded. We therefore demonstrate that the inactivation of PSII is a complex and multistep process, which may serve to mitigate the damaging effects of sulphur limitation.
Trade, productivity and profitability: On profit levels and profit margins
Authors: van den Berg Marcel , van Marrewijk Charles , Tamminen Saara
Published: February 2018

Do firms engaging in international trade have higher or lower profit margins? It is well established that more productive firms engage in trading activities and as a result have higher profit levels. We use two theoretical models (the Melitz model and the Egger–Kreickemeier model) to clarify the relationship between productivity, trade activity, and profit margins and derive three hypotheses: (I) profit margins rise as productivity rises for domestic firms; (II) profit margins rise as productivity rises for trading firms; and (III) profit margins are not higher for trading firms than for domestic firms. We test these hypotheses using detailed micro‐data for Finland (2005–10) and the Netherlands (2002–10). We find strong support for Hypothesis I (in favour of the Melitz model), Hypothesis II (in favour of both models) and Hypothesis III (in favour of the Egger–Kreickemeier model). A propensity score matching analysis provides further support for Hypothesis III.
The effects of vegetation distribution pattern on overland flow
Authors: Zhang Shengtang , Zhang Jingzhou , Liu Yuanchen , Liu Ying , Wang Zhikai
Published: February 2018

Soil erosion is a major environmental problem. Vegetation, on the other hand, plays an important role in controlling soil erosion. The goal of the study is to examine the effects of the distribution pattern of vegetation on water flow. The vegetation parameters involved included the direction of plant rows, plant stem diameter and row spacing. To study how vegetation affects the flow of water on slopes, flume simulation experiments were conducted using three different plant row directions, three different plant diameters and three row spacing. Experimental slope is fixed, slope ratio of 1.0%. The hydraulic characteristics of the slope under the three vegetation distribution patterns are explored. The results showed that the pattern of vegetation distribution significantly affected the resistance of vegetation to water flow and pattern on this slope. When the angle (θ) between plant row and water flow directions decreased, the plant diameter (d) increased, or the row spacing (a × a) decreased, the Darcy–Weisbach resistance coefficient (f) for water flow became larger. Simultaneously, the Reynolds and Froude numbers (Re and Fr) both became smaller. In experimental procedure condition, the change rate of f, Re and Fr were analysed by linear regression, the θ decreased every 10°, the average increase rate of f was 6.6%, the average decrease rate of Re and Fr were 2.0 and 3.0%. The d increased every 0.001 m, the average increase rate of f was 41.6%, the average decrease rate of Re and Fr were 11.2 and 12.2%. The a × a decreased every 0.01 m, the average increase rate of f was 45.2%, the average decrease rate of Re and Fr were 11.7 and 10.7%. The flow depth h increased every 0.01 m, the average increase rate of f and Re were 13.6 and 25.2%, and the average decrease rate of Fr was 10.4%. The experimental procedure results will be valuable for not only revealing the hydraulic characteristics of flow over vegetation land, but also the optimisation of the distribution of vegetation on a slope.
Numerical Analysis of a Vessel-Shaped Offshore Fish Farm
Authors: Li Lin , Jiang Zhiyu , Vangdal Høiland Andreas , Chen Ong Muk
Published: February 2018

The aquaculture industry is aiming to move fish farms from nearshore areas to open seas because of many attractive advantages in the open water. However, one major challenge is to design the structure to withstand the environmental loads due to wind, waves, and currents. The purpose of this paper is to study a vessel-shaped fish farm concept for open sea applications. The structure includes a vessel-shaped hull, a mooring system, and fish cages. The shape of the hull minimizes the wave loads coming from the bow, and the single-point mooring system is connected to the turret at the vessel bow. Such a system allows the whole fish farm to rotate freely about the turret, reduces the environmental loads on the structure and increases the spread area of fish wastes. A basic geometry of the vessel hull was considered and the hydrodynamic properties were obtained from the frequency-domain (FD) analysis. A mooring system with six mooring lines was designed to avoid possible interactions with the fish cages. Time-domain (TD) simulations were performed by coupling the hull with the mooring system. A simplified rigid model of the fish cages was considered. The global responses of the system and the mooring line loads were compared under various wave and current conditions. The effects due to misalignment of wave and current directions on the responses were discussed. Finally, the responses using flexible and rigid net models were compared under steady current conditions.
Nitric Oxide-Mediated Induction of Dispersal in Pseudomonas aeruginosa Biofilms Is Inhibited by Flavohemoglobin Production and Is Enhanced by Imidazole
Authors: Zhu Xinyi , Oh Hyun-Suk , Ng Yu Chiu Beverly , Tang Pei Yi Peggy , Barraud Nicolas , Rice Scott A.
Published: February 2018

The biological signal molecule nitric oxide (NO) was found to induce biofilm dispersal across a range of bacterial species, which led to its consideration for therapeutic strategies to treat biofilms and biofilm-related infections. However, biofilms are often not completely dispersed after exposure to NO. To better understand this phenomenon, we investigated the response of
Pseudomonas aeruginosa
biofilm cells to successive NO treatments. When biofilms were first pretreated with a low, noneffective dose of NO, a second dose of the signal molecule at a concentration usually capable of inducing dispersal did not have any effect. Amperometric analysis revealed that pretreated
P. aeruginosa
cells had enhanced NO-scavenging activity, and this effect was associated with the production of the flavohemoglobin Fhp. Further, quantitative real-time reverse transcription-PCR (qRT-PCR) analysis showed that
fhp
expression increased by over 100-fold in NO-pretreated biofilms compared to untreated biofilms. Biofilms of mutant strains harboring mutations in
fhp
or
fhpR
, encoding a NO-responsive regulator of
fhp
, were not affected in their dispersal response after the initial pretreatment with NO. Overall, these results suggest that FhpR can sense NO to trigger production of the flavohemoglobin Fhp and inhibit subsequent dispersal responses to NO. Finally, the addition of imidazole, which can inhibit the NO dioxygenase activity of flavohemoglobin, attenuated the prevention of dispersal after NO pretreatment and improved the dispersal response in older, starved biofilms. This study clarifies the underlying mechanisms of impaired dispersal induced by repeated NO treatments and offers a new perspective for improving the use of NO in biofilm control strategies.
The Amphibian Antimicrobial Peptide Temporin B Inhibits
In Vitro
Herpes Simplex Virus 1 Infection
Authors: Marcocci M. E. , Amatore D. , Villa S. , Casciaro B. , Aimola P. , Franci G. , Grieco P. , Galdiero M. , Palamara A. T. , Mangoni M. L. , Nencioni L.
Published: February 2018

The herpes simplex virus 1 (HSV-1) is widespread in the population, and in most cases its infection is asymptomatic. The currently available anti-HSV-1 drugs are acyclovir and its derivatives, although long-term therapy with these agents can lead to drug resistance. Thus, the discovery of novel antiherpetic compounds deserves additional effort. Naturally occurring antimicrobial peptides (AMPs) represent an interesting class of molecules with potential antiviral properties. To the best of our knowledge, this study is the first demonstration of the
in vitro
anti-HSV-1 activity of temporin B (TB), a short membrane-active amphibian AMP. In particular, when HSV-1 was preincubated with 20 μg/ml TB, significant antiviral activity was observed (a 5-log reduction of the virus titer). Such an effect was due to the disruption of the viral envelope, as demonstrated by transmission electron microscopy. Moreover, TB partially affected different stages of the HSV-1 life cycle, including the attachment and the entry of the virus into the host cell, as well as the subsequent postinfection phase. Furthermore, its efficacy was confirmed on human epithelial cells, suggesting TB as a novel approach for the prevention and/or treatment of HSV-1 infections.
Deletion of
sll1541
in Synechocystis sp. Strain PCC 6803 Allows Formation of a Far-Red-Shifted
holo
-Proteorhodopsin
In Vivo
Authors: Chen Que , van der Steen Jeroen B. , Arents Jos C. , Hartog Aloysius F. , Ganapathy Srividya , de Grip Willem J. , Hellingwerf Klaas J.
Published: February 2018

In many pro- and eukaryotes, a retinal-based proton pump equips the cell to drive ATP synthesis with (sun)light. Such pumps, therefore, have been proposed as a plug-in for cyanobacteria to artificially increase the efficiency of oxygenic photosynthesis. However, little information on the metabolism of retinal, their chromophore, is available for these organisms. We have studied the
in vivo
roles of five genes (
sll1541
,
slr1648
,
slr0091
,
slr1192
, and
slr0574
) potentially involved in retinal metabolism in
Synechocystis
sp. strain PCC 6803. With a gene deletion approach, we have shown that
Synechocystis apo-
carotenoid-15,15-oxygenase (SynACO), encoded by gene
sll1541
, is an indispensable enzyme for retinal synthesis in
Synechocystis
, presumably via asymmetric cleavage of β-
apo
-carotenal. The second carotenoid oxygenase (SynDiox2), encoded by gene
slr1648
, competes with SynACO for substrate(s) but only measurably contributes to retinal biosynthesis in stationary phase via an as-yet-unknown mechanism.
In vivo
degradation of retinal may proceed through spontaneous chemical oxidation and via enzyme-catalyzed processes. Deletion of gene
slr0574
(encoding CYP120A1), but not of
slr0091
or of
slr1192
, causes an increase (relative to the level in wild-type
Synechocystis
) in the retinal content in both the linear and stationary growth phases. These results suggest that CYP120A1 does contribute to retinal degradation. Preliminary data obtained using
13
C-labeled retinal suggest that conversion to retinol and retinoic acid and subsequent further oxidation also play a role. Deletion of
sll1541
leads to deficiency in retinal synthesis and allows the
in vivo
reconstitution of far-red-absorbing
holo
-proteorhodopsin with exogenous retinal analogues, as demonstrated here for all-
trans
3,4-dehydroretinal and 3-methylamino-16-nor-1,2,3,4-didehydroretinal.

IMPORTANCE
Retinal is formed by many cyanobacteria and has a critical role in most forms of life for processes such as photoreception, growth, and stress survival. However, the metabolic pathways in cyanobacteria for synthesis and degradation of retinal are poorly understood. In this paper we identify genes involved in its synthesis, characterize their role, and provide an initial characterization of the pathway of its degradation. This led to the identification of
sll1541
(encoding SynACO) as the essential gene for retinal synthesis. Multiple pathways for retinal degradation presumably exist. These results have allowed us to construct a strain that expresses a light-dependent proton pump with an action spectrum extending beyond 700 nm. The availability of this strain will be important for further work aimed at increasing the overall efficiency of oxygenic photosynthesis.
Prostaglandin E2Induction Suppresses the Th1 Immune Responses in Cattle with Johne's Disease
Authors: Sajiki Yamato , Konnai Satoru , Okagawa Tomohiro , Nishimori Asami , Maekawa Naoya , Goto Shinya , Ikebuchi Ryoyo , Nagata Reiko , Kawaji Satoko , Kagawa Yumiko , Yamada Shinji , Kato Yukinari , Nakajima Chie , Suzuki Yasuhiko , Murata Shiro , Mori Yasuyuki , Ohashi Kazuhiko
Published: February 2018

Johne's disease, caused byMycobacterium aviumsubsp.paratuberculosis, is a bovine chronic infection that is endemic in Japan and many other countries. The expression of immunoinhibitory molecules is upregulated in cattle with Johne's disease, but the mechanism of immunosuppression is poorly understood. Prostaglandin E2(PGE2) is immunosuppressive in humans, but few veterinary data are available. In this study, functional and kinetic analyses of PGE2were performed to investigate the immunosuppressive effect of PGE2during Johne's disease.In vitroPGE2treatment decreased T-cell proliferation and Th1 cytokine production and upregulated the expression of immunoinhibitory molecules such as interleukin-10 and programmed death ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMCs) from healthy cattle. PGE2was upregulated in sera and intestinal lesions of cattle with Johne's disease.In vitrostimulation with Johnin purified protein derivative (J-PPD) induced cyclooxygenase-2 (COX-2) transcription, PGE2production, and upregulation of PD-L1 and immunoinhibitory receptors in PBMCs from cattle infected withM. aviumsubsp.paratuberculosis. Therefore, Johnin-specific Th1 responses could be limited by the PGE2pathway in cattle. In contrast, downregulation of PGE2with a COX-2 inhibitor promoted J-PPD-stimulated CD8+T-cell proliferation and Th1 cytokine production in PBMCs from the experimentally infected cattle. PD-L1 blockade induced J-PPD-stimulated CD8+T-cell proliferation and interferon gamma productionin vitro. Combined treatment with a COX-2 inhibitor and anti-PD-L1 antibodies enhanced J-PPD-stimulated CD8+T-cell proliferationin vitro, suggesting that the blockade of both pathways is a potential therapeutic strategy to control Johne's disease. The effects of COX-2 inhibition warrant further study as a novel treatment of Johne's disease.
Impact of Acupuncture on Antihistamine Use in Patients Suffering Seasonal Allergic Rhinitis: Secondary Analysis of Results from a Randomised Controlled Trial
Authors: Adam Daniela , Grabenhenrich Linus , Ortiz Miriam , Binting Sylvia , Reinhold Thomas , Brinkhaus Benno
Published: February 2018

Background

Seasonal allergic rhinitis (SAR) is a common disease that has detrimental effects on the quality of life (QoL) of affected individuals. Approximately 18% of patients try to alleviate their symptoms through acupuncture. The ACUSAR (ACUpuncture in Seasonal Allergic Rhinitis) study (ClinicalTrials.gov registration no. NCT00610584) assessed the impact of acupuncture on SAR, showing significant improvements in rhinitis-specific QoL (RQoL) and in rescue medication (RM) use.

Objective

A secondary analysis of SAR patients’ use of antihistamine.

Methods

Patients were randomised into three study groups: acupuncture plus RM, sham acupuncture plus RM, and RM alone. The patients documented their medication use before and during the intervention period (8 weeks). The main outcome was the number of days with antihistamine use. Statistical analyses were conducted using parametric and non-parametric tests. The robustness of the results was tested by sensitivity analyses using non-parametric bootstrapping.

Results

The data from 414 patients were analysed. The acupuncture group used antihistamines significantly less often compared with the other groups (acupuncture vs sham acupuncture: mean difference −4.49 days, p=0.01; acupuncture vs RM: mean difference −9.15 days, p<0.001). Approximately 38% of the acupuncture group did not use any antihistamine in contrast to only 16% in the RM group. The pre-post comparison suggested that the acupuncture patients did not need to increase the days of antihistamine use to alleviate their symptoms, unlike the other groups.

Conclusions

Acupuncture appeared to significantly reduce the number of days of antihistamine use while improving RQoL and SAR symptoms; it can therefore be considered a valuable, additional treatment option for patients with SAR.

Trial Registration Number

NCT00610584; Post-results.
Hospitals at night
Authors: Bonner John
Published: February 2018

Three years into the scheme,
John Bonner
reviews progress