bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical course and mortality by etiology of liver cirrhosis in Sweden: a population based, long‐term follow‐up study of 1317 patients
Authors: Nilsson Emma , Anderson Harald , Sargenti Konstantina , Lindgren Stefan , Prytz Hanne
Published: April 2019

Background

Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by ascites, bleeding from esophageal varices or hepatic encephalopathy.

Aim

To compare the clinical course, patterns of survival and causes of death by etiology during long‐term follow‐up in a large population‐based cohort of patients with incident cirrhosis.

Methods

We used population‐based medical registries for a cohort study of patients with liver cirrhosis diagnosed January 2001 to December 2010, in the Scania region of Sweden. Medical records were reviewed. Patients were classified according to etiology and clinical parameters were registered. Patients were followed until December 2017.

Results

The cohort comprised 1317 patients, 631 were decompensated at diagnosis and 387 decompensated during follow‐up. The cumulative 10‐year incidence of decompensation, with death and transplantation as competing risks, was 89% in alcoholic cirrhosis, 58% in hepatitis C and 75% in cryptogenic cirrhosis. The lowest 10‐year transplantation‐free survival rates were found in cryptogenic cirrhosis (11%), alcohol‐related cirrhosis (18%) and alcohol combined with hepatitis C (12%). Autoimmune hepatitis cirrhosis showed the best 10‐year survival (53%) and hepatitis C, non‐alcoholic steatohepatitis, primary biliary cholangitis, and primary sclerosing cholangitis and other causes averaged 30%. Decompensation at diagnosis was an important predictor for death in all etiologies apart from alcoholic cirrhosis. 991 patients died and 91 were transplanted.

Conclusion

Our results show that the clinical course and survival in cirrhosis differ considerably by both etiology and state at diagnosis.
Who were the first urban settlers of Oslo? A discussion of early medieval urbanization based on isotopic analyses of human remains
Authors: Naumann E. , Glørstad A. Z. T. , Breiby M. P. , Mills R. D. , Fullagar P. D.
Published: April 2019

This paper investigates the process of early urbanization in Oslo, Norway, during the initial period of early 11th–late 12th Century using a bioarchaeological approach. Through the use of isotope analyses performed on teeth and bone from 20 humans buried in Oslo during the first phases of urban settlement, individual dietary change and mobility are reconstructed. Oslo is traditionally perceived as one of many urban settlements initiated by royal power, and this paper contributes to this discussion by investigating the origin of the first settlers, and also how the early urban process affected their way of living. Results suggest that most individuals in the study were of local origin, and had a constant diet throughout life from childhood to its last phase. The absence of individual dietary change sharply contrasts the dynamic dietary patterns observed in people from the Viking age. Dietary variation between individuals does suggest, however, social differences among the early urban population of Oslo.
Blockade of myeloid differentiation 2 attenuates diabetic nephropathy by reducing activation of the renin‐angiotensin system in mouse kidneys
Authors: Wang Yi , Fang Qilu , Jin Yiyi , Liu Zhoudi , Zou Chunpeng , Yu Weihui , Li Weixin , Shan Xiaoou , Chen Ruijie , Khan Zia , Liang Guang
Published: April 2019

Background and Purpose

Both innate immunity and the renin‐angiotensin system (RAS) play important roles in the pathogenesis of diabetic nephropathy (DN). Myeloid differentiation factor 2 (MD2) is a co‐receptor of toll‐like receptor 4 (TLR4) in innate immunity. While TLR4 is involved in the development of DN, the role of MD2 in DN has not been characterized. It also remains unclear whether the MD2/TLR4 signalling pathway is associated with RAS activation in diabetes.

Experimental Approach

MD2 was blocked using siRNA or the low MW inhibitor, L6H9, in renal proximal tubular cells (NRK‐52E cells) exposed to high concentrations of glucose (HG). In vivo, C57BL/6 and MD2−/− mice were injected with streptozotocin to induce Type 1 diabetes and nephropathy.

Key Results

Inhibition of MD2 by genetic knockdown or the inhibitor L6H9 suppressed HG‐induced expression of ACE and angiotensin receptors and production of angiotensin II in NRK‐52E cells, along with decreased fibrosis markers (TGF‐β and collagen IV). Inhibition of the MD2/TLR4‐MAPKs pathway did not affect HG‐induced renin overproduction. In vivo, using the streptozotocin‐induced diabetic mice, MD2 was overexpressed in diabetic kidney. MD2 gene knockout or L6H9 attenuated renal fibrosis and dysfunction by suppressing local RAS activation and inflammation.

Conclusions and Implications

Hyperglycaemia activated the MD2/TLR4‐MAPKs signalling cascade to induce renal RAS activation, leading to renal fibrosis and dysfunction. Pharmacological inhibition of MD2 may be considered as a therapeutic approach to mitigate DN and the low MW inhibitor L6H9 could be a candidate for such therapy.
Long‐term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma
Authors: Yamazaki Naoya , Kiyohara Yoshio , Uhara Hisashi , Uehara Jiro , Fujisawa Yasuhiro , Takenouchi Tatsuya , Otsuka Masaki , Uchi Hiroshi , Ihn Hironobu , Hatsumichi Masahiro , Minami Hironobu
Published: April 2019

The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long‐term follow up of a single‐arm, open‐label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post–hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression‐free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment‐related adverse events (TRAE), including select immune‐related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3‐year OS rate was 43.5%, and the 3‐year PFS rate was 17.2%. A long‐term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long‐term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type.
Children Born of Sexual and Gender‐Based Violence in Conflict: The International Criminal Court, Ecological Environments and Human Development
Authors: Dowds Eithne
Published: April 2019

Children born of sexual and gender‐based violence in conflict have slowly gained international attention, even featuring in international criminal justice processes, such as those at the International Criminal Court (ICC). These children suffer unique harms due to the circumstances surrounding their birth, with a burgeoning literature documenting the long‐term and multigenerational impact on their development. This article contributes to this existing literature by applying Bronfenbrenner's ecological model of human development toICCresponses to these children, yielding a more nuanced understanding of theICCas part of the ecological environment in which child development occurs.
Human Security Perspectives on Refugee Children in Germany
Authors: Rosenow‐Williams Kerstin , Zimmermann Inga , Bergedieck Alina
Published: April 2019

This research identifies challenges and solutions for the situation of accompanied children in German refugee accommodations along the seven human security dimensions (economy, environment, food, health, personal, community and political rights). It analyses existing binding and non‐binding standards for the protection of refugee children at federal, state and municipal level, and their development since 2014. In particular, the United Nations Children's Fund's role for the development of voluntary protection standards is discussed as a role model to enhance the awareness for the protection of refugee children in Germany.
Storytelling, Science, and Religion: Promoting Reflection and Conversation about Societal Issues
Authors: Ostman Rae , Zirulnik Michael L. , McCullough Cosgrove Jenny
Published: April 2019

The Science & Religion project explored the relationship of science and religion through creative nonfiction stories and public programs. The overarching goal of this work was to investigate whether and how museums can encourage reflection and conversation around big, important, and difficult questions. In this paper, we contextualize the project in the movement to address societal issues in museums, describe some of the design and delivery strategies we used to create public programs that were inclusive of diverse points of view, report the programs’ impact on participants, and offer lessons learned for museum practitioners interested in similar programmatic approaches or topics. We also reflect on our own attitudes and preconceptions as museum educators, considering why we felt this was a controversial topic and why we were surprised to discover that audiences were so receptive to it.
‘Forget me not’: Urine cytology in a male with hematuria
Authors: Gupta Ojas , Gupta Parikshaa , Rajwanshi Arvind
Published: April 2019

Tuberculosis (TB) of the urinary tract is a common disease in developing countries of the world. Establishing a clinical diagnosis is challenging owing to the variable clinical presentations of the disease and often a high index of suspicion is required. Identification of epithelioid cell granulomas, Langhans’ type of multinucleated giant cells, variable inflammation and demonstration of acid fast bacilli on Ziehl‐Neelson (ZN) stain are essential for establishing a cytologic diagnosis. We present a case of urinary tract TB, which could be diagnosed based on cytomorphologic examination of urine smears and ZN stain.
Weight loss induced by deep transcranial magnetic stimulation in obesity: A randomized, double‐blind, sham‐controlled study
Authors: Ferrulli Anna , Macrì Concetta , Terruzzi Ileana , Massarini Stefano , Ambrogi Federico , Adamo Michela , Milani Valentina , Luzi Livio
Published: April 2019

Aim

To test the hypothesis that deep transcranial magnetic stimulation (dTMS) reduces food craving and causes weight loss via neuromodulation.

Materials and methods

This pilot study was designed as a randomized, double‐blind, sham‐controlled study. A total of 33 obese people (nine men, 24 women, mean age 48.1 ± 10.6 years, body mass index [BMI] 36.9 ± 4.7 kg/m2) were randomized and completed the study: 13 participants underwent a 5‐week treatment with high‐frequency (HF) dTMS (18 Hz; HF group), 10 were treated with low‐frequency (LF) dTMS (1 Hz; LF group), and 10 were sham‐treated (sham group). Food craving, and metabolic and neuro‐endocrine variables were evaluated at baseline, after the 5‐week treatment, and at follow‐up visits (1 month, 6 months, 1 year after the end of treatment).

Results

The mixed‐model analysis for repeated measures showed a significant interaction of time and groups for body weight (P = 0.001) and BMI (P = 0.001), with a significant body weight (−7.83 ± 2.28 kg; P = 0.0009) and BMI (−2.83 ± 0.83, P = 0.0009) decrease in the HF versus the sham group. A decreasing trend in food craving in the HF versus the LF and sham groups (P = 0.073) was observed. A significant improvement of metabolic and physical activity variables was found (P < 0.05) in the HF group.

Conclusions

We demonstrated the safety and efficacy of dTMS, in addition to physical exercise and a hypocaloric diet, in reducing body weight for up to 1 year in obese people. We hypothesize that a possible mechanism of HF dTMS treatment is modulation of the dopaminergic pathway and stimulation of physical activity.
Predicting and reducing “hospital‐acquired infections” using a knowledge‐based e‐surveillance system
Authors: Noaman Amin Y. , Ragab Abdul Hamid M. , Al‐Abdullah Nabeela , Jamjoom Arwa , Nadeem Farrukh , Ali Anser G.
Published: April 2019

The use of automated computer methods when detecting hospital‐acquired infections (HAIs) enhances the validity of the surveillance in an effective manner. This is because manual infection control systems used by hospitals are time consuming and are often restricted to intensive care units. This paper proposes a new knowledge‐based electronic surveillance system to predict and reduce HAIs. The system can gather patient‐associated data from hospital databanks to automatically predict patient injury based on the standard central line‐associated bloodstream infection algorithm for HAI detection rules. The application of the proposed electronic system reduces the number of central lines associated with infection of the bloodstream and reduces the length of stay for patient treatment and thus reduces costs. The proposed system has several advantages: (a) It is a web‐based system that collects actual data from patients from several IT sources, which will help collect patient data safely and quickly, thereby predicting HAIs effectively. (b) It has an integrated simulator to generate patient records, providing the ability to train medical personnel and nurses to enhance their skills. (c) It is a multimedia‐based system to improve patient health reporting. (d) It assists policymakers in reviewing and approving control plans and policies to reduce and prevent hospital injuries. (e) The investigational results of the system showed an enhancement value equal to 87%.
R180T variant of δ‐ornithine aminotransferase associated with gyrate atrophy: biochemical, computational, X‐ray and NMR studies provide insight into its catalytic features
Authors: Montioli Riccardo , Paiardini Alessandro , Giardina Giorgio , Zanzoni Serena , Cutruzzola Francesca , Cellini Barbara , Borri Voltattorni Carla
Published: April 2019

Among the over 50 gyrate atrophy‐causing mutations of ornithine δ‐aminotransferase (OAT), the R180T involves an active site residue located at the dimer interface, which in the crystal structure of OAT complexed with 5‐fluoromethylornithine engages a salt bridge with the α‐carboxylate of the substrate analogue. Starting from the previous finding that no transaminase activity was detected in CHO‐K1 cells expressing the R180T variant, here we try to shed light at the protein level on the structural and/or functional defects of the R180T variant. To this aim, the variant has been cloned, expressed, purified and characterized by a combination of biochemical and structural studies. Although the R180T variant shares a similar overall conformation with the wild‐type, its crystal structure solved at 1.8 Ǻ reveals slight structural alterations at the active site and at the dimeric interface. These changes are consistent with the spectroscopic and kinetic results, indicating that the variant, as compared with the wild‐type OAT, shows (a) an increased Km value for l‐ornithine (l‐Orn), (b) an altered pyridoxal 5′‐phosphate binding mode and affinity and (c) an increased thermostability. In addition, the R180T mutant exhibits a remarkable loss of catalytic activity and is endowed with the ability to catalyse not only the δ‐transamination but also, albeit to a lesser extent, the α‐transamination of l‐Orn. Overall, these data indicate that the slight structural changes caused by the R180T mutation, preventing a proper collocation of l‐Orn at the active site of OAT, are responsible for the notable reduction of the catalytic efficiency.

Enzymes

Ornithine aminotransferase EC 2.6.1.13.

Databases

6HX7.pdb.
Nonlinear fatigue crack propagation in a baffle module of Wendelstein 7‐X under cyclic bending loads
Authors: Lepore Marcello , Berto Filippo , Maligno Angelo R. , Fellinger Joris
Published: April 2019

Simulation of the fatigue crack propagation in a Wendelstein 7‐X baffle module is performed in this study using both a finite element method‐based software and the UniGrow nonlinear model for small‐scale yielding (SSY) conditions. Some experimental fatigue tests of several cracked baffle modules have been performed through a servo‐hydraulic machine. One of these experimental tests has been considered to simulate fatigue crack propagation in the baffle module. Before starting the experimental test, a first crack partly contained in the welding seam and partly in the steel pipe is found. Subsequently, owing to the applied load, the crack propagated both into the welding seam and into the steel pipe until the plastic zone in the near field attains SSY conditions. Finally, owing to the increase in the extension of the plastic zone, SSY conditions are not more valid, and the breakage of the steel pipe is produced by plastic collapse.
Translation and validation of the Greek version of an ageism scale for dental students (ASDS_Gr)
Authors: Kossioni Anastassia E. , Ioannidou Kyriaki , Kalyva Daphne , Marchini Leonardo , Hartshorn Jennifer , Kaufman Laura , Smith Becky , Barlow Patrick B.
Published: April 2019

Objectives

To describe the validation of a new 27‐item ageism scale for dental students in Greece.

Background

A new ageism scale for dental students has been developed by American and European Gerodontology educators and was preliminary validated in the United States.

Methods

The scale was translated into Greek and administered to 8th‐ and 10th‐semester dental students in Athens. Principal components analysis was used to explore the internal structure of the measure; internal consistency reliability was assessed using Cronbach's α coefficient; corrected item‐total correlations were calculated to decide which low contributing items should be removed from the scale; and discriminant validity was tested investigating variation in relation to demographic and educational factors.

Results

A total of 152 students responded to the questionnaire. The Principal component analysis offered a 15‐item scale distributed into four factors that accounted for 56.4%, of the total variance, produced stronger factor loadings, a comparable amount of overall component variance and logical sets of components. The four factors produced were values/ethics about older people (four items, α = 0.71), patient compliance (four items, α = 0.72), barriers to dental care (four items, α = 0.57) and dentist‐older patient interaction (three items, α = 0.64). Discriminant validity revealed statistically significant differences in factors and items related to semester of studies, gender and family's permanent residence.

Conclusion

The preliminary validation of the Greek version of the ageing scale for dental students revealed a 15‐item questionnaire that demonstrated acceptable validity and reliability and could be further tested in larger samples.
Cluster Headache in Subjects With Substance Use Disorder: A Case Series and a Review of the Literature
Authors: Ponté Camille , Giron Aurélie , Crequy Marie , Lapeyre‐Mestre Maryse , Fabre Nelly , Salles Juliette
Published: April 2019

Objective

To describe a case series of 7 patients presenting cluster headache (CH) criteria and a substance use disorder, reported to a French Addictovigilance center. Then, to assess clinical, pharmacological, and neurobiological linkages between substance use and CH onset.

Background

CH patients are presenting a higher prevalence of comorbidities, among which the use of psychoactive substances, licit or illicit, have been explored by a few authors. Recently, 3 cases of CH in patients seen in the hospital‐based addiction care center have been reported to the Toulouse addictovigilance center.

Methods

Other cases have been identified in the same tertiary hospital after a collaborative investigation done with the departments of neurology and psychiatry and included in the case series. A narrative review was performed to assess the potential of psychoactive substance consumption to induce or facilitate CH.

Results

From 2016 to 2018, 6 males and 1 female aged between 26 and 54 years old, presenting CH criteria and a substance use disorder, were included in our case series. Among substances used, there are: (1) daily use of tobacco and alcohol in 5/7 subjects; (2) daily or almost daily use of cocaine in 5/7 subjects; (3) regular use of cannabis before attacks beginning in 4/7 subjects; and (4) opioids, as a substitutive medication or abused, in 5/7 subjects. The intranasal route administration is reported by all the subjects and precedes the beginning of attacks for 5/7 subjects.

Conclusions

We have found a CH prevalence of 0.9% in our studied population, while it is estimated at 0.1% in the general population. The coexistence of cluster headache and addiction behaviors reflects possible common neurobiological pathways, which would include the hypothalamus. Research could be conducted on the potential of hypothalamic therapeutic targets.
Deteriorated outcome of recent patients with acute liver failure and late‐onset hepatic failure caused by infection with hepatitis A virus: A subanalysis of patients seen between 1998 and 2015 and enrolled in nationwide surveys in Japan
Authors: Nakao Masamitsu , Nakayama Nobuaki , Uchida Yoshihito , Tomiya Tomoaki , Oketani Makoto , Ido Akio , Tsubouchi Hirohito , Takikawa Hajime , Mochida Satoshi
Published: April 2019

Aim

A nationwide survey of acute liver failure (ALF) and late‐onset hepatic failure (LOHF) has revealed that the outcomes of recent patients whose diseases were caused by infection with hepatitis A virus (HAV) have worsened, compared with those of previously reported patients. The factors associated with this deterioration were evaluated.

Methods

A total of 83 patients with HAV infection seen between 1998 and 2015 were enrolled. All the patients had a prothrombin time–international normalized ratio of 1.5 or more and hepatic encephalopathy of grade 2 or more severe. The demographic and clinical features of 45 patients seen prior to 2003 (cohort 1) and 38 patients seen during 2004 and thereafter (cohort 2) were compared.

Results

Three and four patients in cohort 1 and cohort 2, respectively, received liver transplantations; the survival rates among the remaining patients were 56% for cohort 2 and 79% for cohort 1 (P < 0.05). The mean age (±standard deviation) of the patients was higher in cohort 2 than in cohort 1 (58 ± 11 vs. 48 ± 13 years; P < 0.01). The percentages of patients with underlying metabolic diseases were 22% in cohort 1 and 61% in cohort 2 (P < 0.01). Diabetic mellitus was more common among deceased patients than among rescued patients (29% vs. 8%; P < 0.05) among patients who did not receive liver transplantations, and a multivariate analysis revealed that patient age and disease type were significantly and independently associated with the outcome.

Conclusion

The outcomes of recent patients with ALF or LOHF caused by HAV infection have recently worsened mainly because of an increase in underlying metabolic diseases as a consequence of aging.
Evaluation of the bond strengths of two novel bioceramic cement using a modified thin‐slice push‐out test model
Authors: Orhan Ekim Onur , Irmak Özgür , Mumcu Emre
Published: April 2019

OrthoMTA (OrthoMTA, BioMTA, Korea) and RetroMTA (OrthoMTA, BioMTA, Korea) have been newly developed bioceramic cements or tricalcium silicate cements (TCSs). The aim of this study was to examine the dislocation resistance of these two novel TCSs from radicular dentin, using a modified thin slice push‐out test design that simulated canal spaces of uniform dimensions. Twenty‐five single‐rooted human canine teeth were used. Longitudinal slabs were obtained from each tooth using a diamond saw. Standardized canal‐like holes were created using size #2 Peeso Reamer along the coronal, middle and apical thirds of longitudinal tooth slabs. The cavities were filled with OrthoMTA or RetroMTA. The slabs were kept at 37°C for 14‐day in 100% humidity before push‐out evaluation (MPa). Failure modes were examined with stereomicroscopy. Data were calculated using unpaired t test (P < 0.05). Location of the TCS‐filled cavities did not affect push‐out strengths. OrthoMTA (9.809 ± 2.176 MPa) had significantly higher push‐out bond strength values than ProRoot MTA (7.103 ± 2.145 MPa) (P < 0.0001). The leaf‐like bodies were seen in the fractured specimens of both TCS groups. Failure modes were predominantly adhesive in both TCS groups. It can be concluded 14‐day push‐out bond strength of OrthoMTA is higher than that of RetroMTA.
Health data linkage research in Australia remains challenging
Authors: Palamuthusingam Dharmenaan , Johnson David W. , Hawley Carmel , Pascoe Elaine , Fahim Magid
Published: April 2019

Data linkage is a valuable technique for uniting information from multiple sources that relates to the same person, place, family or event. Despite its value, establishing such linkages in Australia remains challenging. Existing policies are a missed opportunity for research and innovation and engender a negative attitude among researchers when considering data linkage as a research means. Greater leadership from the Population Health Research Network and cooperation from data custodians and Human Research Ethics Committees are necessary to access optimally Australia’s enormous data potential.
Higher risk of phaeochromocytoma/paraganglioma (Phaeo‐Pgl) in SDHD than SDHB carriers: an Australian cohort study
Authors: Hong Alice , Shanahan Mary , Schenberg Tess , Inder Warrick , MacIsaac Richard , James Paul , Sachithanandan Nirupa
Published: April 2019

Carriers of succinate dehydrogenase (SDHx) mutations are at risk of developing phaeochromocytomas, catecholamine secreting extra‐adrenal paragangliomas and non‐secretory head and neck paragangliomas and require lifelong surveillance. There is no current consensus on the optimal surveillance strategy. This study describes the outcomes of a cohort of 50 SDHx mutation carriers followed at a tertiary Australian hospital using a surveillance protocol involving annual clinical review with plasma/urine metanephrines and biennial magnetic resonance imaging from skull base to pelvis.
Electronic cigarettes in physician practice: a complex debate
Authors: Stone Emily , Marshall Henry
Published: April 2019

E‐cigarettes, or electronic nicotine delivery systems (ENDS), have been suggested as a potential aid for smoking cessation, but many questions about their efficacy and safety remain unanswered. Until very recently, the evidence for ENDS in smoking cessation was largely based on observational studies or randomised controlled trials with methodological flaws and did not provide adequate evidence to support strongly ENDS for smoking cessation. Concerns about the uptake of ENDS by nonsmoking populations (such as adolescents) remain. More recent evidence may indicate the effect of ENDS in smoking cessation, but many questions remain unanswered. In this article, we address recent claims that failure to recommend ENDS for smoking cessation represents unethical practice. We strongly dispute this claim, analysing the many complex issues that clinicians working in smoking cessation should consider.
The influence of mean arterial pressure on the efficacy and safety of dual antiplatelet therapy in minor stroke or transient ischemic attack patients
Authors: Ma Yan , Liu Ying , Xu Jie , Wang Yilong , Du Fenghe , Wang Yongjun
Published: April 2019

Mean arterial pressure (MAP) is the strongest predictor of stroke. The combination of clopidogrel and aspirin within 24 hours after onset has been suggested by the Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) study to be superior to aspirin alone. However, it is not clear whether poststroke blood pressure has an influence on the efficacy and safety of dual antiplatelet treatment. We have performed a post hoc analysis from the CHANCE trial. Patients were stratified into three groups based on MAP levels. Among patients with MAP <102 mm Hg, there was no significant difference in stroke recurrence between the clopidogrel‐aspirin group and the aspirin group (7.7% vs 7.5%; hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.73‐1.45). However, compared to aspirin treatment, the clopidogrel‐aspirin dual treatment was more effective at reducing the risk of stroke in patients with MAP ≥113 mm Hg (6.9% vs 12.3%, HR, 0.55; 95% CI, 0.39‐0.78) or 102‐113 mm Hg (9.5% vs 14.9%, HR, 0.62; 95% CI, 0.48‐0.81). There was a significant interaction between MAP and antiplatelet therapy as it relates to stroke recurrence (P for interaction = 0.037), and a similar result was found for combined vascular events (P for interaction = 0.027). In conclusion, dual antiplatelet therapy may be more effective at reducing combined vascular events in patients with higher MAP after minor stroke or transient ischemic attack.
Treatment of atopic dermatitis with dupilumab: experience from a tertiary referral centre
Authors: Olesen C.M. , Holm J.G. , Nørreslet L.B. , Serup J.V. , Thomsen S.F. , Agner T.
Published: April 2019

Background

Management of moderate‐to‐severe atopic dermatitis (AD) frequently requires treatment with systemic therapies. Dupilumab is the first biological agent approved for treatment of moderate‐to‐severe AD. Although promising results have appeared in clinical trials, real‐life data on efficacy and safety are lacking.

Objectives

To assess effectiveness and safety of treatment with dupilumab in the real‐life clinical setting at a Danish tertiary referral centre.

Methods

All patients with AD treated with dupilumab from October 2017 to October 2018 at Bispebjerg Hospital, Denmark, were included in the study. Patients were evaluated three times: at treatment initiation and at 1 and 3 months after first dupilumab injection. At each visit, disease activity was assessed by severity score (Eczema Area and Severity Index, EASI), patient‐reported outcomes (Dermatology Life Quality Index, DLQI, pruritus and sleep score) and serological markers [immunoglobulin (Ig)E, eosinophil count and lactate dehydrogenase (LDH)].

Results

A total of 43 patients were included in the study. The mean reduction in EASI score from baseline was 19.6 points (72.4%) at 1‐month and 22.6 points (76.7%) at 3‐month follow‐up. EASI, DLQI, pruritus score, sleep score, IgE and LDH were all statistically significantly reduced between baseline and 1‐ and 3‐month follow‐up. Mean reductions in EASI score and LDH at 3‐month follow‐up were significantly correlated (P = 0.003). One patient (2.3%) discontinued treatment due to side‐effects, and seven patients (18.4%) developed conjunctivitis during the study period.

Conclusion

The effectiveness and safety of dupilumab treatment in a real‐life clinical setting are comparable to that of phase 3 clinical trials. LDH is suggested as a potential serological marker predictive of treatment response.
Persistence of cyprinid herpesvirus 2 in asymptomatic goldfish Carassius auratus (L.) that survived an experimental infection
Authors: Wei Chang , Iida Hayato , Chuah QiuYuan , Tanaka Mikio , Kato Goshi , Sano Motohiko
Published: April 2019

Cyprinid herpesvirus 2 (CyHV‐2) is the causative agent of herpesviral haematopoietic necrosis (HVHN) in goldfish, Carassius auratus, and Prussian carp, C. auratus gibelio. In this study, we investigated virus persistence in goldfish experimentally infected with CyHV‐2. Virus DNA presence in organs was monitored in survivors reared at a virus permissive temperature and also in survivors treated with a non‐permissive temperature for 4 days, initiated at three different time points post‐infection in order to obtain fish with different virus loads. We detected virus DNA in all organs tested at 51 days post‐infection (dpi) and in the spleen, trunk kidney and gills of survivors at 81 dpi, although the virus load in fish influenced the subsequent number of organs that tested positive for virus DNA. In addition, some organs dissected from four out of five asymptomatic survivors tested positive by PCR following incubation in vitro in a medium for 5 days. Following inoculation with the homogenate of PCR‐positive kidney incubated in vitro, one of the three inoculated fish died, showing that the detected virus by PCR produced infectious particles. This study suggests that CyHV‐2 can establish a persistent infection in some organs, especially the spleen and trunk kidney, and that asymptomatic surviving fish can be a source of infection.
clpV is a key virulence gene during in vivo Pseudomonas plecoglossicida infection
Authors: Luo Gang , Xu Xiaojin , Zhao Lingmin , Qin Yingxue , Huang Lixing , Su Yongquan , Yan Qingpi
Published: April 2019

Interaction between bacterial pathogen and aquatic animal host is exceedingly complex, which involves large dynamic changes in gene expression during different stages of the disease. However, research on identifying key virulence genes based on the dynamics of gene expression changes of a one‐sided bacterial pathogen in tissue has not been reported so far across different stages of infectious disease. The clpV for the T6SS of Pseudomonas plecoglossicida was identified for a candidate for key virulence gene based on dynamic changes of gene expression. For the Epinephelus coioides infected using clpV‐RNAi strain, no deaths were observed up to 20 dpi. The spleens, kidneys and livers of all the E. coioides that received clpV‐RNAi strain failed to develop visible nodules at 5–8 dpi, with the swelling gradually disappearing. The burdens of clpV‐RNAi strain in the spleen and blood were greatly reduced at most of the time points after injection, and the burdens of clpV‐RNAi strain in the head kidneys and trunk kidneys also had a sharp reduction from 72 to 120 hpi. This paper provides a new insight into the discovery of key virulence genes of pathogens in infected tissue systems.
Using Implementation Science to Promote the Use of the G8 Screening Tool in Geriatric Oncology
Authors: Gulasingam Pauline , Haq Rashida , Mascarenhas Johnson Alekhya , Togo Elikem , Moore Julia , Straus Sharon E. , Wong Camilla L.
Published: April 2019

OBJECTIVES

Evidence supports the integration of geriatric assessment in the care of older adults with cancer. The G8 screening tool is a validated instrument to target a geriatric assessment. Use of the G8 tool in clinical practice, however, is suboptimal. We systematically analyzed the barriers and facilitators to G8 tool use in oncology clinics and selected interventions tailored to the local context to enhance its uptake.

DESIGN

This qualitative study used semistructured interviews and site observations.

SETTING

St. Michael's Hospital, Toronto, Canada.

PARTICIPANTS

Ten participants including G8 tool adopters and stakeholders at St. Michael's Hospital were interviewed.

MEASUREMENTS

An interview guide based on the Theoretical Domains Framework (TDF) was developed to identify beliefs about G8 tool use. Barriers and facilitators to G8 tool use were mapped to the TDF domains and corresponding intervention functions from the Capability, Opportunity, Motivation, and Behavior model. Evidence‐based implementation strategies were selected from two databases.

RESULTS

Key TDF domains influencing G8 tool use behavior were social/professional role, goals, beliefs about consequences, and social influences. The behavior change domains were mapped to four mechanisms of change: persuasion (conduct local consensus discussions), modeling (identify and prepare a champion), education (distribute educational materials), and enablement (use materials to prepare patients to be active participants in understanding the evidence behind the G8 tool and answering questions accurately).

CONCLUSION

This study identified barriers to G8 tool use. Local consensus discussions, identifying and preparing a champion, using educational materials, and preparing patients to be active participants may be implementation strategies to improve G8 tool use. J Am Geriatr Soc 67:898–904, 2019.
Midwifery Care for Transfeminine Individuals
Authors: Ellis Simon Adriane , Dalke Lily
Published: April 2019

This article focuses on the provision of gender‐affirming care and preventive care for transfeminine individuals—those assigned male at birth who identify as female or on the feminine spectrum. To meet the learning needs of health care providers less familiar with gender‐affirming care, this article begins with an overview of gender identity concepts. Initiation and management of feminizing gender‐affirming hormone therapy is then covered in detail, including common gender‐affirming medications and their adverse effects, diagnostic criteria, psychosocial evaluation, initial physical examination and laboratory work, and recommendations for follow‐up visits and laboratory monitoring. Lastly, the article briefly reviews health care of transfeminine individuals before and after surgical gender‐affirming interventions and details best practices for transfeminine preventive care.
Stressing the importance of choice: Validity of a preclinical free‐choice high‐caloric diet paradigm to model behavioural, physiological and molecular adaptations during human diet‐induced obesity and metabolic dysfunction
Authors: Slomp Margo , Belegri Evita , Blancas‐Velazquez Aurea S. , Diepenbroek Charlene , Eggels Leslie , Gumbs Myrtille C.R. , Joshi Anil , Koekkoek Laura L. , Lamuadni Khalid , Ugur Muzeyyen , Unmehopa Unga A. , la Fleur Susanne E. , Mul Joram D.
Published: April 2019

Humans have engineered a dietary environment that has driven the global prevalence of obesity and several other chronic metabolic diseases to pandemic levels. To prevent or treat obesity and associated comorbidities, it is crucial that we understand how our dietary environment, especially in combination with a sedentary lifestyle and/or daily‐life stress, can dysregulate energy balance and promote the development of an obese state. Substantial mechanistic insight into the maladaptive adaptations underlying caloric overconsumption and excessive weight gain has been gained by analysing brains from rodents that were eating prefabricated nutritionally‐complete pellets of high‐fat diet (HFD). Although long‐term consumption of HFDs induces chronic metabolic diseases, including obesity, they do not model several important characteristics of the modern‐day human diet. For example, prefabricated HFDs ignore the (effects of) caloric consumption from a fluid source, do not appear to model the complex interplay in humans between stress and preference for palatable foods, and, importantly, lack any aspect of choice. Therefore, our laboratory uses an obesogenic free‐choice high‐fat high‐sucrose (fc‐HFHS) diet paradigm that provides rodents with the opportunity to choose from several diet components, varying in palatability, fluidity, texture, form and nutritive content. Here, we review recent advances in our understanding how the fc‐HFHS diet disrupts peripheral metabolic processes and produces adaptations in brain circuitries that govern homeostatic and hedonic components of energy balance. Current insight suggests that the fc‐HFHS diet has good construct and face validity to model human diet‐induced chronic metabolic diseases, including obesity, because it combines the effects of food palatability and energy density with the stimulating effects of variety and choice. We also highlight how behavioural, physiological and molecular adaptations might differ from those induced by prefabricated HFDs that lack an element of choice. Finally, the advantages and disadvantages of using the fc‐HFHS diet for preclinical studies are discussed.
Multicentre retrospective study of 97 cases of intraoral lipoma
Authors: Perez‐Sayáns Mario , Blanco‐Carrión Andrés , Oliveira‐Alves Monica G. , Almeida Janete Dias , Anbinder Ana Lia , Lafuente‐Ibáñez de Mendoza Irene , Aguirre‐Urízar José Manuel
Published: April 2019

Background

Lipomas are benign neoplasms derived from adipose tissue that are unfrequently found in the oral cavity. The objective of this study is to identify the main clinicopathological characteristics of this tumour in a case series of oral lipomas (OL) in a population from Spain and Brazil.

Material and Methods

A multicentre retrospective observational study was conducted in collaboration with the Oral Pathology Unit of the São Paulo State University (UNESP), São José dos Campos, in Brazil, and the Oral Medicine and Pathology Units of the University of Santiago de Compostela (USC) and the University of the Basque Country (UPV/EHU) in Spain.

Results

This multicentre series consists of a total of 97 of OL cases, 31 (32%) of which correspond to Spain, and 66 (68%) to Brazil with an overall prevalence of 0.33%. The average age of the patients is 56.44 years old, with a range of 10‐92 (SD = 15.52). Buccal mucosa was the most frequent location (42.3%). Cases from Spain coexisted with other lesions in a significant number of cases, 12.9%, vs Brazil, 1.5% (P = 0.018). According to the progression time, Brazil has an average of 60.35 months (CI: 27.20‐93.51), compared to 5.41 months in Spain (CI: 3.17‐7.65) (P = 0.022). Average size is 12.55 mm (SD = 11.06), ranging from 2 to 75 mm. A positive correlation is also seen between the increase in the lesion size and a greater progression time (CC = 0.367; P = 0.008).

Conclusions

Correct differential diagnosis of the clinical lesion is key, followed by a good histopathological study, to achieve the final diagnosis.
Cullen's and Grey Turner's signs in unconscious children
Authors: Apicella Andrea , Dolcini Anna , D'Amato Luigia , Bencivenga Carmela , Silvestri Susanna
Published: April 2019

See Answer
Cardiorespiratory fitness and long‐term risk of sleep apnea: A national cohort study
Authors: Crump Casey , Sundquist Jan , Winkleby Marilyn A. , Sundquist Kristina
Published: April 2019

Sleep apnea is increasing in prevalence, and is an important cause of cardiometabolic diseases and mortality worldwide. Its only established modifiable risk factor is obesity; however, up to half of all sleep apnea cases may occur in non‐obese persons, and hence there is a pressing need to identify other modifiable risk factors to facilitate more effective prevention. We sought to examine, for the first time, cardiorespiratory fitness in relation to the risk of sleep apnea, independent of obesity. A national cohort study was conducted to examine cardiorespiratory fitness in all 1,547,478 Swedish military conscripts during 1969–1997 (97%–98% of all 18‐year‐old men) in relation to risk of sleep apnea through 2012 (maximum age 62 years). Cardiorespiratory fitness was measured as maximal aerobic workload in Watts, and sleep apnea was identified from nationwide outpatient and inpatient diagnoses. A total of 44,612 (2.9%) men were diagnosed with sleep apnea in 43.7 million person‐years of follow‐up. Adjusting for age, height, weight, socioeconomic factors and family history of sleep apnea, low cardiorespiratory fitness at age 18 years was associated with a significantly increased risk of sleep apnea in adulthood (lowest versus highest cardiorespiratory fitness tertile: incidence rate ratio, 1.44; 95% confidence interval, 1.40–1.49; p < 0.001; continuous cardiorespiratory fitness per 100 Watts: incidence rate ratio, 0.71; 95% confidence interval, 0.70–0.73; p < 0.001). An increased risk was observed even among men with normal body mass index (lowest versus highest cardiorespiratory fitness tertile: incidence rate ratio, 1.30; 95% confidence interval, 1.26–1.35; p < 0.001). These findings identify low cardiorespiratory fitness early in life as a new modifiable risk factor for development of sleep apnea in adulthood.
Association between improvement of clinical signs and decrease of ventricular volume after ventriculoperitoneal shunting in dogs with internal hydrocephalus
Authors: Schmidt Martin J. , Hartmann Antje , Farke Daniela , Failling Klaus , Kolecka Malgorzata
Published: April 2019

Background

One of the remaining questions in treating dogs with internal hydrocephalus is the association between the decrease of ventricular volume and re‐expansion of cerebral parenchyma with clinical improvement.

Hypothesis

A decrease in ventricular volume and re‐expansion of brain tissue occur after ventriculoperitoneal shunting (VPS). Clinical improvement defined by resolution of ≥1 clinical signs is associated with decreased size of cerebral ventricles and that the extent of change in ventricular size is associated with clinical improvement.

Animals

Forty‐five client‐owned dogs with newly diagnosed communicating internal hydrocephalus.

Methods

Ventricular volume, brain volume, and clinical status of dogs that underwent VPS were measured before and 3 months after surgery. Multiple logistic regression analysis was performed to assess the influence of decrease in ventricular size in addition to the covariates “age of the animal” and “duration of clinical signs before surgery” on improvement of clinical signs.

Results

Decreased volume of cerebral ventricles was associated with resolution of ≥1 preoperative clinical sign (P< .003). The covariates “age of the animal” and “duration of clinical signs” were not associated with improvement of clinical signs. The percentage decrease in ventricular size was associated with resolution of ataxia (P= .008) and obtundation (P= .011).

Conclusion and Clinical Importance

The decrease in ventricular volume and increase in brain parenchyma after VPS are associated with improvement in clinical signs.
A novel method to predict dark diversity using unconstrained ordination analysis
Authors: Brown Joel J. , Mennicken Sophie , Massante Jhonny C. , Dijoux Samuel , Telea Alexandra , Benedek Ana M. , Götzenberger Lars , Májeková Maria , Lepš Jan , Šmilauer Petr , Hrček Jan , de Bello Francesco
Published: April 2019

Questions

Species pools are the product of complex ecological and evolutionary mechanisms, operating over a range of spatial scales. Here, we focus on species absent from local sites but with the potential to establish within communities — known as dark diversity. Methods for estimating dark diversity are still being developed and need to be compared, as well as tested for the type, and amount, of reference data needed to calibrate these methods.

Location

South Bohemia (48°58′ N, 14°28′ E) and Železné Hory (49°52′ N, 15°34′ E), Czech Republic.

Method

We compared a widely accepted algorithm to estimate species pools (Beals smoothing index, based on species co‐occurrence) against a novel method based on an unconstrained ordination (UNO). Following previous work, we used spatially nested sampling for target plots, with the dark diversity estimates computed from smaller plots validated against additional species present in larger plots, and a reference dataset (Czech National Phytosociological Database of >30,000 plots as global reference data). We determined which method provides the best estimate of dark diversity with an index termed the “Success Rate Index”.

Results

When using the whole reference dataset (national scale), both UNO and Beals provided comparable predictions of dark diversity that were better than null expectations based on species frequency. However, when predicting from regionally restricted spatial scales, UNO performed significantly better than Beals. UNO also tended to detect less common species better than Beals. The success rate of combining UNO and Beals slightly outperformed the results obtained from the single methods, but only with the largest reference dataset.

Conclusions

The UNO method provides a consistently reliable estimate of dark diversity, particularly when the reference dataset is size‐limited. For future calculations, we urge caution regarding the choice of dark diversity methods with respect to the reference data available, and how different methods handle species of high, and low, occurrence frequency.