bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weight gain with add‐on second‐generation antipsychotics in bipolar disorder: a naturalistic study
Authors: Najar H. , Joas E. , Kardell M. , Pålsson E. , Landén M. 
Published: April 2017

ObjectiveOur aim was to investigate the prevalence and magnitude of weight gain in‐patients with bipolar disorder when treated with a second‐generation antipsychotic as an add‐on treatment to a mood stabilizer in routine clinical practice.MethodsData were derived from the quality register for bipolar disorder in Sweden (BipoläR). Patients with bipolar disorder who started add‐on treatment with a SGA (n = 575) were compared at next yearly follow‐up with age and sex matched patients who were only treated with a mood stabilizer (n = 566). The primary outcome measure was change in body weight and body mass index (BMI). We also assessed the prevalence of clinically significant weight gain defined as ≥7% gain in body weight.ResultsThe group that received add‐on treatment with antipsychotics neither gained more weight nor were at higher risk for a clinically significant weight gain than the reference group. Instead, factors associated with clinically significant weight gain were female sex, young age, low‐baseline BMI, and occurrence of manic/hypomanic episodes.ConclusionWe found no evidence of an overall increased risk of weight gain for patients with bipolar disorder after receiving add‐on SGA to a mood stabilizer in a routine clinical setting.
Comorbidity of chronic spontaneous urticaria and autoimmune thyroid diseases: A systematic review
Authors: Kolkhir P. , Metz M. , Altrichter S. , Maurer M. 
Published: April 2017

AbstractPatients with chronic spontaneous urticaria (CSU) are widely held to often have other autoimmune disorders, including autoimmune thyroid disease. Here, we systematically evaluated the literature on the prevalence of thyroid autoimmunity in CSU and vice versa. There is a strong link between CSU and elevated levels of IgG antithyroid autoantibodies (AAbs), with most of a large number of studies reporting rates of ≥10%. Levels of IgG against thyroid peroxidase (TPO) are more often elevated in CSU than those of other IgG antithyroid AAbs (strong evidence). Levels of IgG antithyroid AAbs are more often elevated in adult patients with CSU than in children (strong evidence). Patients with CSU exhibit significantly higher levels of IgG antithyroid AAbs (strong evidence) and IgE‐anti‐TPO (weak evidence) than controls. Elevated IgG antithyroid AAbs in CSU are linked to the use of glucocorticoids (weak evidence) but not to disease duration or severity/activity, gender, age, or ASST response (inconsistent evidence). Thyroid dysfunction rates are increased in patients with CSU (strong evidence). Hypothyroidism and Hashimoto's thyroiditis are more common than hyperthyroidism and Graves’ disease (strong evidence). Thyroid dysfunction is more common in adult patients with CSU than in children (strong evidence) and in female than in male patients with CSU (weak evidence). Urticaria including CSU is more prevalent in patients with thyroid autoimmunity than in controls (weak evidence). CSU can improve in response to treatment with levothyroxine or other thyroid drugs (strong evidence). Pathogenic mechanisms in CSU patients with thyroid autoimmunity may include IgE against autoantigens, immune complexes, and complement.
Transcriptome analysis of severely active chronic spontaneous urticaria shows an overall immunological skin involvement
Authors: Giménez‐Arnau A. , Curto‐Barredo L. , Nonell L. , Puigdecanet E. , Yelamos J. , Gimeno R. , Rüberg S. , Santamaria‐Babi L. , Pujol R.M. 
Published: April 2017

AbstractBackgroundThe knowledge about chronic spontaneous urticaria (CSU) phenotypes is based on its clinical characteristics, associated comorbidities, course of the disease, and its response to the available effective drugs. Genotype expression and its further correlation with CSU phenotypes are still unknown. We describe the cutaneous transcriptome of patients suffering a severely active CSU refractory to antihistamine treatment.MethodsThrough the bioinformatic analysis of the whole Human Genome with Oligo Microarrays and quantitative real‐time polymerase chain reaction (qPCR), relevant genes expressed in nonlesional (NLS‐CSU) and lesional skin (LS‐CSU) and peripheral blood were identified in 20 patients suffering from severely active CSU and 10 healthy controls (HCs).ResultsFrom 39 genes differentially expressed in NLS‐CSU when compared with HCs, 31 (79.48%) were confirmed by qPCR corresponding to genes involved in epidermal homeostasis and dermal repair. From the analysis comparing LS‐CSU with NLS‐CSU, a selection of 142 genes was studied with qPCR, and 103 (72.53%) were confirmed. Differentially expressed genes in the phenomenon of wheal development are involved in a variety of biological functions as, epidermal differentiation, intracellular signal function, transcriptional factors cell cycle differentiation, inflammation, or coagulation. Differentially expressed genes that uniformly increase or decrease along the skin worsening until the wheal appearance is shown.ConclusionThe skin of CSU patients with a severely active disease shows an overall immunological skin involvement showing a peculiar gene profile.
Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes
Authors: Ntontsi P. , Loukides S. , Bakakos P. , Kostikas K. , Papatheodorou G. , Papathanassiou E. , Hillas G. , Koulouris N. , Papiris S. , Papaioannou A. I. 
Published: April 2017

AbstractBackgroundAccording to induced sputum cell count, four different asthma phenotypes have been recognized (eosinophilic, neutrophilic, mixed and paucigranulocytic). The aim of this study was to detect functional and inflammatory characteristics of patients with paucigranulocytic asthma.MethodsA total of 240 asthmatic patients were categorized into the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of fraction of exhaled nitric oxide (FeNO). The levels ofIL‐8,IL‐13 and eosinophilic cationic protein (ECP) were also measured in sputum supernatant. Treatment, asthma control and the presence of severe refractory asthma (SRA) were also recorded.ResultsPatients were categorized into the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and paucigranulocytic (47.9%). Although asthma control test did not differ between groups (P=.288), patients with paucigranulocytic asthma had better lung function (FEV1% pred) [median (IQR): 71.5 (59.0‐88.75) vs 69.0 (59.0‐77.6) vs 68.0 (60.0‐85.5) vs 80.5 (69.7‐95.0),P=.009] for eosinophilic, mixed, neutrophilic and paucigranulocytic asthma, respectively,P=.009).SRAoccurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7%, respectively) and less frequently in the neutrophilic and paucigranulocytic phenotype (25% and 21.7%, respectively,P=.01). FeNO,ECPandIL‐8 were all low in the paucigranulocytic, whereas as expected FeNO andECPwere higher in eosinophilic and mixed asthma, whileIL‐8 was higher in patients with neutrophilic and mixed asthma (P<.001 for all comparisons). Interestingly, 14.8% of patients with paucigranulocytic asthma had poor asthma control.ConclusionPaucigranulocytic asthma most likely represents a “benign” asthma phenotype, related to a good response to treatment, rather than a “true” phenotype of asthma. However, paucigranulocytic patients that remain not well controlled despite optimal treatment represent an asthmatic population that requires further study for potential novel targeted interventions.
Analysis of Multiple Diverse Phenotypes via Semiparametric Canonical Correlation Analysis
Authors: Agniel Denis , Cai Tianxi 
Published: April 2017

Summary
Studying multiple outcomes simultaneously allows researchers to begin to identify underlying factors that affect all of a set of diseases (i.e., shared etiology) and what may give rise to differences in disorders between patients (i.e., disease subtypes). In this work, our goal is to build risk scores that are predictive of multiple phenotypes simultaneously and identify subpopulations at high risk of multiple phenotypes. Such analyses could yield insight into etiology or point to treatment and prevention strategies. The standard canonical correlation analysis (CCA) can be used to relate multiple continuous outcomes to multiple predictors. However, in order to capture the full complexity of a disorder, phenotypes may include a diverse range of data types, including binary, continuous, ordinal, and censored variables. When phenotypes are diverse in this way, standard CCA is not possible and no methods currently exist to model them jointly. In the presence of such complications, we propose a semi-parametric CCA method to develop risk scores that are predictive of multiple phenotypes. To guard against potential model mis-specification, we also propose a nonparametric calibration method to identify subgroups that are at high risk of multiple disorders. A resampling procedure is also developed to account for the variability in these estimates. Our method opens the door to synthesizing a wide array of data sources for the purposes of joint prediction.
Nano‐curcumin safely prevents streptozotocin‐induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus
Authors: Ganugula Raghu , Arora Meenakshi , Jaisamut Patcharawalai , Wiwattanapatapee Ruedeekorn , Jørgensen Heather G , Venkatpurwar Vinod P , Zhou Beiyan , Rodrigues Hoffmann Aline , Basu Rita , Guo Shaodong , Majeti Naga Venkata Ravi Kumar 
Published: April 2017

Background and PurposeApproaches to prevent selective and progressive loss of insulin‐producing beta cells in Type 1 diabetes mellitus (T1DM) will help to manage this prevalent and devastating disease. Curcumin (CUR), a natural anti‐inflammatory substance, suppresses diabetes‐associated inflammation and cell death. However, very high doses need to be used because of poor oral bioavailability, making it difficult to translate the anti‐inflammatory actions to clinical situations.Experimental ApproachWe have prepared biodegradable nanosystems encapsulating curcumin (nCUR), resulting in at least nine‐fold improvement in oral bioavailability. Here, we tested the ability of nCUR to prevent streptozotocin (STZ)‐induced inflammation and apoptosis in pancreatic islets and beta cells, in rats.Key ResultsNon‐fasted rats pretreated with 10 or 50 mg·kg−1 nCUR 6 h prior to STZ challenge had up to 37% reduction in the glucose levels, while plain CUR (50 mg·kg−1) results in 12% reduction. This treatment with nCUR was accompanied by decreased islet or beta cell death, as shown by TUNEL assay and H&E staining. Both CUR and nCUR significantly decreased levels of inflammatory cytokines in pancreatic tissue homogenates that correlated well with minimal histiocytic infiltration. Pre‐treatment with nCUR, but not CUR, decreased 8‐oxo‐2′‐deoxyguanosine, a sensitive biomarker of ROS‐induced DNA damage, in pancreas. In normal rodents, daily dosing for 28 days, with nCUR (25‐100 mg·kg−1) did not cause any deleterious health issues by the carrier.Conclusions and ImplicationsTogether, these data indicate a potentially translatable dose of nCUR that is safe and efficacious in improving beta cell function, which could prevent T1DM.
Dietary salt blunts vasodilation by stimulating epithelial sodium channels in endothelial cells from salt‐sensitive Dahl rats
Authors: Wang Zi‐Rui , Liu Hui‐Bin , Sun Ying‐Ying , Hu Qing‐Qing , Li Yu‐Xia , Zheng Wei‐Wan , Yu Chang‐Jiang , Li Xin‐Yuan , Wu Ming‐Ming , Song Bin‐Lin , Mu Jian‐Jun , Yuan Zu‐Yi , Zhang Zhi‐Ren , Ma He‐Ping 
Published: April 2017

Background and PurposeOur recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague–Dawley rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasorelaxation in Dahl salt‐sensitive (SS) rats.Experimental ApproachWe used the cell‐attached patch‐clamp technique to record ENaC activity in split‐open mesenteric arteries. Western blot and immunofluorescence staining were used to evaluate the levels of aldosterone, ENaC, eNOS and NO. Blood pressure was measured with the tail‐cuff method and the artery relaxation was measured with the wire myograph assay.Key ResultsHigh‐salt (HS) diet significantly increased plasma aldosterone and ENaC activity in the endothelial cells of Dahl SS rats. The endothelium‐dependent artery relaxation was blunted by HS challenge in these rats. Amiloride, a potent blocker of ENaC, increased both phosphorylated eNOS and NO and therefore prevented the HS‐induced loss of vasorelaxation. As, in SS rats, endogenous aldosterone was already elevated by HS challenge, exogenous aldosterone did not further elevate ENaC activity in the rats fed with HS. Eplerenone, a mineralocorticoid receptor antagonist, attenuated the effects of HS on both ENaC activity and artery relaxation.Conclusions and ImplicationsThese data suggest that HS diet blunts artery relaxation and causes hypertension via a pathway associated with aldosterone‐dependent activation of ENaC in endothelial cells. This pathway provides one of the mechanisms by which HS causes hypertension in Dahl SS rats.Linked ArticlesThis article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc
Targeting inflammation to reduce cardiovascular disease risk: a realistic clinical prospect?
Authors: Welsh Paul , Grassia Gianluca , Botha Shani , Sattar Naveed , Maffia Pasquale 
Published: April 2017

Data from basic science experiments is overwhelmingly supportive of the causal role of immune‐inflammatory response(s) at the core of atherosclerosis, and therefore, the theoretical potential to manipulate the inflammatory response to prevent cardiovascular events. However, extrapolation to humans requires care and we still lack definitive evidence to show that interfering in immune‐inflammatory processes may safely lessen clinical atherosclerosis. In this review, we discuss key therapeutic targets in the treatment of vascular inflammation, placing basic research in a wider clinical perspective, as well as identifying outstanding questions.Linked ArticlesThis article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetocandhttp://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc
Rotavirus capsid VP6 tubular and spherical nanostructures act as local adjuvants when co-delivered with norovirus VLPs
Authors: Malm M , Heinimäki S , Vesikari T , Blazevic V 
Published: April 2017

Summary
A subunit protein vaccine candidate based on norovirus (NoV) virus-like particles (VLPs) and rotavirus (RV) VP6 protein against acute childhood gastroenteritis has been proposed recently. RV VP6 forms different oligomeric nanostructures, including tubes and spheres when expressed in vitro, which are highly immunogenic in different animal models. We have shown recently that recombinant VP6 nanotubes have an adjuvant effect on immunogenicity of NoV VLPs in mice. In this study, we investigated if the adjuvant effect is dependent upon a VP6 dose or different VP6 structural assemblies. In addition, local and systemic adjuvant effects as well as requirements for antigen co-delivery and co-localization were studied. The magnitude and functionality of NoV GII.4-specific antibodies and T cell responses were tested in mice immunized with GII.4 VLPs alone or different combinations of VLPs and VP6. A VP6 dose-dependent adjuvant effect on GII.4-specific antibody responses was observed. The adjuvant effect was found to be strictly dependent upon co-administration of NoV GII.4 VLPs and VP6 at the same anatomic site and at the same time. However, the adjuvant effect was not dependent on the types of oligomers used, as both nanotubes and nanospheres exerted adjuvant effect on GII.4-specific antibody generation and, for the first time, T cell immunity. These findings elucidate the mechanisms of VP6 adjuvant effect in vivo and support its use as an adjuvant in a combination NoV and RV vaccine.
The influence of the emergence profile on the amount of undetected cement excess after delivery of cement‐retained implant reconstructions
Authors: Sancho‐Puchades M. , Crameri D. , Özcan M. , Sailer I. , Jung R. E. , Hämmerle C. H. F. , Thoma D. S. 
Published: April 2017

AbstractObjectiveTo test whether or not one of two emergence profile designs (concave or convex) is superior to the other in terms of remaining cement following cementation of reconstructions on individualized abutments and careful cement removal.Materials and methodsA central incisor with a single implant‐supported reconstruction was selected as a model. Six types of abutments (n = 10) with two different emergence profile designs (concave (CC) and convex (CV)) and three crown–abutment margin depths (epimucosal, 1.5 mm submucosal, 3 mm submucosal) were fabricated through a CAD/CAM procedure. Lithium disilicate reinforced ceramic crowns were cemented with chemically polymerized resin cement. A blinded investigator attempted to remove all cement excess. Thereafter, the entire reconstruction was unscrewed and analyzed for the overall amount and the depth of cement excess. Kruskal–Wallis and Mann–Whitney tests were used to investigate differences between groups. When more than two groups were compared between each other, a Bonferroni correction of the P value was performed.ResultsConcave abutments presented significantly more cement remnants than CV abutments when the entire abutment area of the epimucosal margin groups was evaluated (CC0 mm: mean 2.31 mm2 (SD 0.99) vs. CV0 mm: mean 1.57 mm2 (SD 0.55); P = 0.043). A statistically significant increase in remnants was detected when the crown–abutment margin was located more submucosally for every abutment studied (0 mm vs. 1.5 mm: P < 0.000, 0 mm vs 3 mm: P < 0.000, 1.5 mm vs. 3 mm: P < 0.000). The buccal quadrant demonstrated the least, whereas the oral and interdental quadrants showed the greatest amount of cement excess.ConclusionsConcave emergence profile abutments and deep crown–abutment margin positions increased the risk of cement excess. Oral and interdental areas are more prone to cement remnants than other surface areas.
Mediterranean diet decreases adolescent waist circumference
Authors: Bacopoulou Flora , Landis Georgios , Rentoumis Anastasios , Tsitsika Artemis , Efthymiou Vasiliki 
Published: April 2017

AbstractBackgroundTo explore the effects of a multicomponent–multilevel school‐based educational intervention on the nutritional habits and abdominal obesity indices of a representative adolescent sample.Materials and methodsA representative sample of 1610 adolescents aged 12–17 years in 23 public high schools of three municipalities in the Attica region in Greece participated in a programme funded by the European Union (August 2013–August 2014). Participants underwent dietary assessment with the use of the Mediterranean Diet Quality Index in children and adolescents (KIDMED), blood pressure (BP) assessment and screening for general and abdominal obesity by measuring body mass index, waist circumference (WC) and waist‐to‐height ratio (WHtR), at baseline and following a 6‐month school‐based intervention. The intervention involved nutritional education, physical activity and body image awareness using a multilevel approach to the adolescent participants, their parents, school teachers and health staff.ResultsAnalysis included 1032 adolescents (mean age ± SD 14·1 ± 1·6 years). Following intervention, mean KIDMED score ± SD increased significantly from 5·6 ± 2·4 to 5·8 ± 2·4 (P = 0·004). Higher percentage of boys (P = 0·028) and younger adolescents (P < 0·001) had optimal KIDMED scores ≥ 8. Significant decreases were observed in overweight and obesity (P = 0·033), mean systolic (P = 0·049) and diastolic (P < 0·001) BP, WC (P < 0·001) and WHtR (P < 0·001). WC decreased as the KIDMED score increased (P = 0·020). Living with both parents (P = 0·036), higher maternal (P = 0·039) and paternal (P = 0·004) education and having a younger father (P = 0·034) were associated with better adherence to Mediterranean diet, post‐intervention.ConclusionsIncreased adherence to MD was associated with decreased WC, indicating a potential of multicomponent–multilevel school‐based interventions to combat adolescent abdominal obesity.
Finding the optimal dose of vitamin K1 to treat vitamin K deficiency and to avoid anaphylactoid reactions
Authors: Mi Yan‐ni , Ping Na‐na , Li Bo , Xiao Xue , Zhu Yan‐bing , Cao Lei , Ren Jian‐kang , Cao Yong‐xiao 
Published: April 2017

AbstractVitamin K1 injection induces severe dose‐related anaphylactoid reactions and overdose for the treatment of vitamin K deficiency. We aimed to find an optimal and small dose of vitamin K1 injection to treat vitamin K deficiency and avoid anaphylactoid reactions in animal. Rats were administered a vitamin K‐deficient diet and gentamicin to establish vitamin K deficiency model. Behaviour tests were performed in beagle dogs to observe anaphylactoid reactions. The results showed an increased protein induced by vitamin K absence or antagonist II (PIVKA‐II) levels, a prolonging of prothrombin time (PT) and activated partial thromboplastin time (APTT) and a decrease in vitamin K‐dependent coagulation factor (F) II, VII, IX and X activities in the model group. In vitamin K1 0.01 mg/kg group, the liver vitamin K1 levels increased fivefold and the liver vitamin K2 levels increased to the normal amount. Coagulation markers PT, APTT, FVII and FIX activities returned to normal. Both in the 0.1 and 1.0 mg/kg vitamin K1 groups, coagulation functions completely returned to normal. Moreover, the amount of liver vitamin K1 was 40 (0.1 mg/kg) or 100 (1.0 mg/kg) times as in normal. Vitamin K2 was about 4 (0.1 mg/kg) or 5 (1.0 mg/kg) times as the normal amount. There was no obvious anaphylactoid symptom in dogs with the dose of 0.03 mg/kg, which is equivalent to the dose of 0.01 mg/kg in rats. These results demonstrated that a small dose of vitamin K1 is effective to improve vitamin K deficiency and to prevent anaphylactoid reactions, simultaneously.