bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene-Gene Interplay and Gene-Diet Interactions Involving the MTNR1B rs10830963 Variant with Body Weight Loss
Authors: Goni Leticia , Cuervo Marta , Milagro Fermin I. , Martínez J. Alfredo
Published: May 2015

Background/Aims: Investigation of the genetic makeup may facilitate the implementation of more personalized nutritional interventions. The aims were to examine whether the rs10830963 MTNR1B polymorphism affects weight loss in response to a hypocaloric diet and to find potential gene-gene interplays and gene-diet interactions. Methods: 167 subjects enrolled in a personalized nutritional intervention for weight loss (3-6 weeks) were examined for anthropometric measurements, dietary habits and physical activity at baseline and at the first follow-up visit. Three polymorphisms, which have previously been associated with body weight regulation, rs10830963 (MTNR1B), rs9939609 (FTO) and rs17782313 (MC4R), were analyzed using the Luminex® 100/200™ System. Results: After adjusting for covariates, females with the rs10830963 CG/GG genotype showed lower weight loss than those with the CC genotype. In the total population, carriers of variant alleles of both FTO and MC4R showed a significant association with MTNR1B and weight loss outcome. Moreover, among women, higher total protein and animal protein intakes were associated with a lower weight loss in G allele carriers of the MTNR1B variant. Conclusions: Our data evidenced that rs10830963 MTNR1B polymorphism could be associated with individual differences in weight loss induced by a hypocaloric diet. This association was influenced by FTO and MC4R loci and modified by baseline protein intake.
Chronic Pain in Multiple Sclerosis Patients: Utility of Sensory Quantitative Testing in Patients with Fibromyalgia Comorbidity
Authors: Pompa Alessandra , Clemenzi Allessandro , Troisi Elio , Pace Luca , Casillo Paolo , Catani Sheila , Grasso Maria Grazia
Published: May 2015

Background: Lower thermal and discomfort thresholds may predispose multiple sclerosis (MS) patients to chronic pain, but a possible effect of fibromyalgia (FM) comorbidity has never been investigated. Aims were to investigate the thermal and discomfort thresholds in the evaluation of pain intensity between MS patients with FM (PFM+) and MS patients with pain not associated to FM (PFM−). Methods: One hundred thirty three MS patients were investigated for chronic pain. FM was assessed according to the 1990 ACR diagnostic criteria. An algometer was used to measure the thresholds in the patients and 60 matched healthy subjects. Results: Chronic pain was present in 88 (66.2%) patients; 12 (13.6%) had neuropathic pain, 22 (17.3%) were PFM+ and 65 (48.9%) PFM−. PFM+ were predominantly female (p = 0.03) and had a greater EDSS (p = 0.01) than NoP; no other significant differences emerged than PFM−. The thresholds were lower in MS patients than controls (p < 0.01), mainly in the PFM+. FM severity influenced the thermal threshold (p < 0.001), while the female gender influenced the discomfort threshold (p < 0.001). Conclusion: Thermal and discomfort thresholds were lower in patients than controls and were the lowest in PFM+. Their more severely impaired thermal threshold supports a neurophysiological basis of such association.
Urine Metabolomics by 1H-NMR Spectroscopy Indicates Associations between Serum 3,5-T2 Concentrations and Intermediary Metabolism in Euthyroid Humans
Authors: Pietzner Maik , Homuth Georg , Budde Kathrin , Lehmphul Ina , Völker Uwe , Völzke Henry , Nauck Matthias , Köhrle Josef , Friedrich Nele
Published: May 2015

Context: 3,5-Diiodo-L-thyronine (3,5-T2) is a thyroid hormone metabolite which exhibited versatile effects in rodent models, including the prevention of insulin resistance or hepatic steatosis typically forced by a high-fat diet. With respect to euthyroid humans, we recently observed a putative link between serum 3,5-T2 and glucose but not lipid metabolism. Objective: The aim of the present study was to widely screen the urine metabolome for associations with serum 3,5-T2 concentrations in healthy individuals. Study Design and Methods: Urine metabolites of 715 euthyroid participants of the population-based Study of Health in Pomerania (SHIP-TREND) were analyzed by 1H-NMR spectroscopy. Multinomial logistic and multivariate linear regression models were used to detect associations between urine metabolites and serum 3,5-T2 concentrations. Results: Serum 3,5-T2 concentrations were positively associated with urinary levels of trigonelline, pyroglutamate, acetone and hippurate. In detail, the odds for intermediate or suppressed serum 3,5-T2 concentrations doubled owing to a 1-standard deviation (SD) decrease in urine trigonelline levels, or increased by 29-50% in relation to a 1-SD decrease in urine pyroglutamate, acetone and hippurate levels. Conclusion: Our findings in humans confirmed the metabolic effects of circulating 3,5-T2 on glucose and lipid metabolism, oxidative stress and enhanced drug metabolism as postulated before based on interventional pharmacological studies in rodents. Of note, 3,5-T2 exhibited a unique urinary metabolic profile distinct from previously published results for the classical thyroid hormones.
Visual Attention and Saccadic Oculomotor Control in Parkinson's Disease
Authors: Buhmann Carsten , Kraft Stefanie , Hinkelmann Kim , Krause Sven , Gerloff Christian , Zangemeister Wolfgang H.
Published: May 2015

Background: In patients with Parkinson's disease (PD) we aimed at differentiating the relation between selective visual attention, deficits of programming and dynamics of saccadic eye movements while searching for a target and hand-reaction time as well as hand-movement time. Visual attention is crucial for concentrating selectively on one aspect of the visual field while ignoring other aspects. Eye movements are anatomically and functionally related to mechanisms of visual attention. Saccadic dysfunction might confound selective visual attention in PD. Methods: We studied visual selective attention in 22 medicated PD patients (clinical ON status, mild to moderate disease severity) and 22 age matched controls. We looked for possible interferences through oculomotor deficits. Two tasks were compared: free viewing of photographs and time optimal visual search of a hidden target. Visual search times (VST), task related dynamics of saccades, and hand-reaction and hand-movement times were analyzed. Results: In the free viewing task mild to moderately affected PD patients did not differ statistically from healthy subjects with respect to saccade dynamics. However, patients differed significantly from healthy subjects in the time optimal visual search task with 25% lower rates of successful searches. Hand movement reaction time did not differ in both groups, whereas hand movement execution time was significantly prolonged in PD patients. Conclusion: Saccadic oculomotor control and hand movement reaction times were intact, whereas in our less severely affected treated PD patients, visual selective attention was not. The highly reduced successful search rate might be related to disturbed programming and delayed execution of saccades during time optimal visual search due to decreased execution of serial-order sequential generation of saccades.
Cortical Morphology in Patients with Orthostatic Intolerance
Authors: Shin Kyong Jin , Kim Tae Hyung , Han Yong Hee , Mun Chi Woong , Kim Sung Eun , Ha Sam Yeol , Park Jin Se , Park Kang Min
Published: May 2015

Background: We evaluated the cortical morphology in patients with orthostatic intolerance. Methods: Thirty patients with orthostatic intolerance, as well as age- and sex-matched normal controls, were enrolled in this study. We divided the patients into orthostatic hypotension (n = 22) and postural tachycardia syndrome (n = 8) groups based on their response to a head-up tilt table test. We analyzed whole-brain T1-weighted MRI images using FreeSurfer 5.1. The measures of cortical morphology were compared between the groups. Results: The cortical thickness in the right hemisphere, including the medial orbitofrontal, peri-calcarine, post-central, inferior temporal, and lateral occipital cortex, and in the peri-calcarine cortex of the left hemisphere was thinned in patients with orthostatic hypotension compared to normal controls. The other measures of cortical morphology, including the surface area, volume, and curvatures, did not differ between patients with orthostatic hypotension and normal controls. However, none of the measures of cortical morphology differed between patients with postural tachycardia syndrome and normal controls. Conclusions: We demonstrated that the cortical morphology significantly changed in patients with orthostatic hypotension but not in patients with postural tachycardia syndrome compared to normal controls. These findings support the hypothesis that orthostatic intolerance is a heterogeneous syndrome.
Passive Immunization against Congenital Cytomegalovirus Infection: Current State of Knowledge
Authors: Jückstock Julia , Rothenburger Markus , Friese Klaus , Traunmüller Friederike
Published: May 2015

Primary infection with the human cytomegalovirus (CMV) occurs in 1-4% of pregnancies. The rates of maternal-fetal CMV transmissions are around 25, 36, 41, and 66%, for infections occurring in the peri-conceptional weeks, first, second, and third trimester of pregnancy, respectively. On the other hand, the severity of fetal organ damage and dysfunction diminishes with increasing gestational age. Congenitally CMV-infected newborns may have neurosensory impairments like mental retardation, cerebral palsy, epilepsy, progressive hearing loss or visual defects, or even may have a fatal outcome. In in-vitro experiments, CMV specific neutralizing IgG antibodies - which are abundant in CMV specific hyperimmune globulin (HIG) products - inhibited the entry of the virus into target cells and hampered viral cell-to-cell spread. This article provides a brief overview on the epidemiology and diagnostic tools in congenital CMV infection. It also concisely summarizes the currently available study results on the safety and effectiveness of HIG treatment. Accordingly, in clinical studies HIG administration to expectant mothers following primary CMV infection (prophylactic use) was shown to lower the risk of maternal-fetal transmission of CMV compared to untreated controls. HIG was also able to ameliorate the disease sequelae in evidently infected fetuses (therapeutic use), as demonstrated by the regression or even resolution of sonographic pathologies including placental inflammation.
Tapering from Methadone or Buprenorphine during Pregnancy: Maternal and Neonatal Outcomes in Norway 1996-2009
Authors: Welle-Strand Gabrielle K. , Skurtveit Svetlana , Tanum Lars , Waal Helge , Bakstad Brittelise , Bjarkø Lisa , Ravndal Edle
Published: May 2015

Background: The tapering of methadone or buprenorphine during pregnancy is an understudied and controversial issue. The aim of this study was to determine to what extent women tapered their opioid medication dose during pregnancy and what the neonatal outcomes were for those who tapered compared to the women who did not. Methods: The study was a mixed prospective/retrospective national cohort study of 123 Norwegian women in opioid maintenance treatment (OMT) during pregnancy and their neonates. A standardized questionnaire was administered to the women and medical information that could be used for verification was collected from hospitals and municipalities. Results: Two of the women came off the OMT-medication during pregnancy and another 15% tapered their OMT-medication dose more than 50%. The birth weights of methadone-exposed neonates of the women who tapered more than 50% were significantly higher than for the methadone-exposed neonates of the women tapering between 11 and 50%. No other significant differences were found. Conclusion: Pregnant women in OMT who taper their OMT-medication dose should be monitored closely. We need studies that document the maternal well-being and fetal safety of maternal tapering of the OMT-medication during pregnancy.
Role of Red Meat and Resistant Starch in Promutagenic Adduct Formation, MGMT Repair, Thymic Lymphoma and Intestinal Tumourigenesis in Msh2-Deficient Mice
Authors: Winter Jean M. , Hu Ying , Young Graeme P. , Kohonen-Corish Maija R.J. , Le Leu Richard K.
Published: May 2015

Red meat may increase promutagenic lesions in the colon. Resistant starch (RS) can reduce these lesions and chemically induced colon tumours in rodents. Msh2 is a mismatch repair (MMR) protein, recognising unrepaired promutagenic adducts for removal. We determined if red meat and/or RS modulated DNA adducts or oncogenesis in Msh2-deficient mice. A total of 100 Msh2-/- and 60 wild-type mice consumed 1 of 4 diets for 6 months: control, RS, red meat and red meat + RS. Survival time, aberrant crypt foci (ACF), colon and small intestinal tumours, lymphoma, colonic O6-methyl-2-deoxyguanosine (O6MeG) adducts, methylguanine methyltransferase (MGMT) and cell proliferation were examined. In Msh2-/- mice, red meat enhanced survival compared to control (p < 0.01) and lowered total tumour burden compared to RS (p < 0.167). Msh2-/- mice had more ACF than wild-type mice (p < 0.014), but no colon tumours developed. Msh2-/- increased cell proliferation (p < 0.001), lowered DNA O6MeG adducts (p < 0.143) and enhanced MGMT protein levels (p < 0.001) compared to wild-type mice, with RS supplementation also protecting against DNA adducts (p < 0.01). No link between red meat-induced promutagenic adducts and risk for colorectal cancer was observed after 6 months' feeding. Colonic epithelial changes after red meat and RS consumption with MMR deficiency will differ from normal epithelial cells.
Comparison of the Brain Volume in Essential Tremor and Parkinson's Disease Tremor Using an Automated Segmentation Method
Authors: Choi Seong-Min , Kim Byeong C. , Chang Jane , Choi Kang-Ho , Nam Tai-Seung , Kim Joon-Tae , Lee Seung-Han , Park Man-Seok , Yoon Woong , de Leon Mony J.
Published: May 2015

Background: Essential tremor (ET) and Parkinson's disease (PD) are common neurological disorders in elderly people, and some features of ET and PD may overlap. Quantitative analysis of brain atrophy may be useful in differentiating neurodegenerative disorders. The aim of this study was to identify the volumetric differences of subcortical structures in patients with ET and PD tremor using an automated segmentation method. Methods: Volumetric MRIs were obtained in 45 patients with ET, 45 patients with PD tremor, and 45 age- and sex-matched control subjects. The volume of the different brain structures was measured by the automated segmentation method (FreeSurfer). Results: Volumetric data obtained with automated segmentation of cerebral regions showed a significant atrophy of the cerebellum in patients with ET. Cerebellar atrophy of ET patients was more significant in the white matter than in the grey matter, and it was noted only in patients with ET having a head tremor. No volumetric differences were found between the PD group and the control group. Conclusion: Our study suggests that volumetric differences in subcortical structures using whole brain segmentation method may help to differentiate ET from PD tremor.
Retrospective Analysis of Vancomycin Nephrotoxicity in Elderly Chinese Patients
Authors: Liu Yan , Yin You , Liu Xin-Zhu , Yao Hui-Juan , Li Li-Xia , Chen Ji-Hui , Chen Ting , Lu Xiao-Tong , Bu Shu-Hong , Zhang Jian
Published: May 2015

This study explored nephrotoxicity in elderly Chinese patients after exposure to vancomycin and other nephrotoxic risk factors. This was a single-center retrospective study. The patient population included those who were ≥60 years of age, had normal baseline serum creatinine values, and received vancomycin for ≥48 h between January 1, 2013 and August 30, 2014. Nephrotoxicity occurred in 29% of 124 patients. A baseline creatinine clearance ≥63.5 ml/min was more common in the nephrotoxic group. Patients with high (≥15 mg/l) rather than low (<15 mg/l) average vancomycin troughs had elevated nephrotoxicity (47.2 vs. 27.3%, p = 0.0001). Of the comorbid conditions evaluated, there were more patients with shock (p = 0.001), hypertension (p = 0.020) and congestive heart failure (p = 0.04) in the nephrotoxic group. Drugs frequently given at the same time with vancomycin, such as angiotensin receptor blockers and furosemide, were also associated with increased nephrotoxic risk. In conclusion, nephrotoxicity was frequently observed in patients with concurrent vancomycin trough concentrations ≥15 μg/ml and hypertension, shock, congestive heart failure. In addition, drugs concurrently used with vancomycin may also increase its nephrotoxicity. Therefore, renal function and vancomycin serum troughs should be closely monitored, especially in patients with other renal injury risk factors.
Stem Cells in Wound Healing: The Future of Regenerative Medicine? A Mini-Review
Authors: Duscher Dominik , Barrera Janos , Wong Victor W. , Maan Zeshaan N. , Whittam Alexander J. , Januszyk Michael , Gurtner Geoffrey C.
Published: May 2015

The increased risk of disease and decreased capacity to respond to tissue insult in the setting of aging results from complex changes in homeostatic mechanisms, including the regulation of oxidative stress and cellular heterogeneity. In aged skin, the healing capacity is markedly diminished resulting in a high risk for chronic wounds. Stem cell-based therapies have the potential to enhance cutaneous regeneration, largely through trophic and paracrine activity. Candidate cell populations for therapeutic application include adult mesenchymal stem cells, embryonic stem cells and induced pluripotent stem cells. Autologous cell-based approaches are ideal to minimize immune rejection but may be limited by the declining cellular function associated with aging. One strategy to overcome age-related impairments in various stem cell populations is to identify and enrich with functionally superior stem cell subsets via single cell transcriptomics. Another approach is to optimize cell delivery to the harsh environment of aged wounds via scaffold-based cell applications to enhance engraftment and paracrine activity of therapeutic stem cells. In this review, we shed light on challenges and recent advances surrounding stem cell therapies for wound healing and discuss limitations for their clinical adoption.
Anaphylaxis to Intravenous Ranitidine in a Child
Authors: Mori Francesca , Barni Simona , Pecorari Lisa , Sarti Lucrezia , Pucci Neri , Novembre Elio
Published: May 2015

Although reversible H2 receptor antagonists are usually well tolerated, there are few reports on anaphylactic reactions triggered by ranitidine. Here we report the first case of anaphylaxis to ranitidine in a child. This was an IgE-mediated event occurring in a patient who had never used ranitidine before.
A Pilot Study Evaluating Fine-Needle Aspiration Cytology of Clear-Cell Renal Cell Carcinoma: Comparison of Ancillary Immunocytochemistry and Cytomorphological Characteristics of SurePath™ Liquid-Based Preparations with Conventional Smears
Authors: Lee Chung Hun , Chung Soo Young , Moon Kyung Chul , Park In Ae , Chung Yul Ri , Ryu Han Suk
Published: May 2015

Objective: Fine-needle aspiration cytology (FNAC) based on a liquid-based preparation is a safe and valuable diagnostic tool. However, due to unfamiliarity with this method and the considerably altered morphology that is associated with it, diagnosing renal cell carcinoma (RCC) from this type of preparation remains a challenge for cytopathologists. The aim of this study was to evaluate the cytomorphological characteristics of SurePath™ (SP)-based preparations compared with conventional smear (CS), and also the role of SP-based FNAC in the diagnosis of clear-cell RCC (CRCC), the most common primary renal malignancy. Study Design: Ex vivo FNAC of both tumors and normal renal parenchyma was prepared from 73 cases. Comparative cytomorphological analysis between liquid-based cytology (LBC) and CS as well as Fuhrman nuclear grading (FNG) was carried out. Immunocytochemistry was performed from normal and CRCC cytology specimens. Results: Normal renal cytology (NRC) showed no significant morphological differences between LBC and CS. For CRCC, LBC showed small, fragmented cell clusters, a 3-dimensional configuration, distinct cytoplasmic vacuoles, and irregular nuclear contours when compared with CS. FNG was overgraded with LBC compared to with CS. AMACR was the most valuable immunocytochemical marker for distinguishing CRCC from NRC. Conclusion: Once cytopathologists become familiar with the altered cytomorphological features of CRCC, FNAC, along with immunocytochemistry, may prove helpful for diagnosis.
Brain-Derived Neurotrophic Factor and Delayed Verbal Recall in Crack/Cocaine Dependents
Authors: Viola Thiago Wendt , Tractenberg Saulo Gantes , Kluwe-Schiavon Bruno , Levandowski Mateus Luz , Sanvicente-Vieira Breno , Wearick-Silva Luis Eduardo , de Azeredo Lucas Araújo , Teixeira, Jr. Antônio Lucio , Grassi-Oliveira Rodrigo
Published: May 2015

Background/Aims: Considering the role of brain-derived neurotrophic factor (BDNF) in memory processes and its peripheral response during the detoxification of cocaine, the aim of this study was to investigate whether plasma BDNF levels could be related to memory performance in women with crack/cocaine dependence. Methods: Twenty-five abstinent female crack/cocaine users (CCD) and 25 unmedicated healthy women (HW), carefully matched for age and years of formal education, were assessed regarding memory performance. Logical Memory was used to assess the immediate verbal recall (IVR), delayed verbal recall (DVR) and memory retention. Plasma BDNF levels were measured by Elisa immunoassay. Beck Depression Inventory was used to assess the severity of depressive symptoms, and the Cocaine Selective Severity Assessment the severity of cocaine abstinence symptoms. Results: The CCD group had lower DVR scores and higher plasma BDNF levels when compared to HW group. In addition, a linear regression model showed that BDNF levels predicted DVR scores within CCD group independently of depressive symptoms (R = 0.51; R2 = 0.26; t(22) = 4.025, p = 0.03). Conclusion: Despite higher plasma BDNF levels, crack users exhibited memory impairments when compared to healthy women. Specifically, peripheral BDNF levels predicted better cognitive performance only within individuals who already had cognitive impairment.
Evolutionary Conservation of 3-Iodothyronamine as an Agonist at the Trace Amine-Associated Receptor 1
Authors: Cöster Maxi , Biebermann Heike , Schöneberg Torsten , Stäubert Claudia
Published: May 2015

Objectives: The trace amine-associated receptor 1 (Taar1) is a Gs protein-coupled receptor activated by trace amines, such as β-phenylethylamine (β-PEA) and 3-iodothyronamine (T1AM). T1AM is an endogenous biogenic amine and thyroid hormone derivative that exerts several biological functions. However, the physiological relevance of T1AM acting via Taar1 is still under discussion. Therefore, we studied the structural and functional evolution of Taar1 in vertebrates to provide evidence for a conserved Taar1-mediated T1AM function. Study Design: We searched public sequence databases to retrieve Taar1 sequence information from vertebrates. We cloned and functionally characterized Taar1 from selected vertebrate species using cAMP assays to determine the evolutionary conservation of T1AM action at Taar1. Results: We found intact open reading frames of Taar1 in more than 100 vertebrate species, including mammals, sauropsids and amphibians. Evolutionary conservation analyses of Taar1 protein sequences revealed a high variation in amino acid residues proposed to be involved in agonist binding, especially in rodent Taar1 orthologs. Functional characterization showed that T1AM, β-PEA and p-tyramine (p-Tyr) act as agonists at all tested orthologs, but EC50 values of T1AM at rat Taar1 differed significantly when compared to all other tested vertebrate Taar1. Conclusions: The high structural conservation of Taar1 throughout vertebrate evolution highlights the physiological relevance of Taar1, but species-specific differences in T1AM potency at Taar1 orthologs suggest a specialization of rat Taar1 for T1AM recognition. In contrast, β-PEA and p-Tyr potencies were rather conserved throughout all tested Taar1 orthologs. We provide evidence that the observed differences in potency are related to differences in constraint during Taar1 evolution.
Neurohypophyseal Neuregulin 1 Is Derived from the Hypothalamus as a Potential Prolactin Modulator
Authors: Zhao Wei-jiang , Jiang Qiong , Mei Jin-ping
Published: May 2015

Although neuregulin 1 (Nrg1) has been identified in the rat hypothalamus, the localisation of Nrg1 in the hypothalamus-hypophyseal structure and its functions remain unclear and require further elucidation. In this study, we identified the existence of Nrg1β types I-III in the rat hypothalamus. We demonstrated that Nrg1 was partially localised in somatostatin-positive cells in the periventricular nucleus. It was also co-localised with arginine vasopressin in the supraoptic nucleus, median eminence and pituitary stalk. Nrg1 was also extensively distributed in the posterior pituitary (PP), including the projected neuronal fibres that surround the vascular structure and Herring bodies. Western blotting confirmed that these signals were primarily produced by soluble Nrg1 derived from a 45-kDa Nrg1 precursor mainly identified in the hypothalamus. Similar to Nrg1α, Nrg1β increased the prolactin (PRL) expression in rat pituitary RC-4B/C cells, which can be inhibited by an Akt inhibitor. In addition, Nrg1β had no apparent effect on growth hormone expression at the mRNA or protein levels. Collectively, we conclude that hypothalamic Nrg1 may be transported to the PP as the β form. We further hypothesise that Nrg1β may function via the regulation of PRL expression through a paracrine mechanism.
Long-Term Outcomes of Surgical Management of Pancreatic Neuroendocrine Tumors with Synchronous Liver Metastases
Authors: Partelli Stefano , Inama Marco , Rinke Anja , Begum Nehara , Valente Roberto , Fendrich Volker , Tamburrino Domenico , Keck Tobias , Caplin Martyn E. , Bartsch Detlef , Thirlwell Christina , Fusai Giuseppe , Falconi Massimo
Published: May 2015

Background: The value of surgical resection in the management of pancreatic neuroendocrine tumors (PNET) with liver metastases (LM) is still debated. The aim of this study was to evaluate the outcomes of surgery of PNET with LM. Methods: Patients with PNET with synchronous LM between 2000 and 2011 from 4 high-volume institutions were included. The patients were divided into 3 groups: curative resection, palliative resection, and no resection. Results: Overall, 166 patients were included. Eighteen patients (11%) underwent curative resection, 73 patients (43%) underwent palliative resection, and 75 patients (46%) underwent conservative treatment. The median overall survival (OS) from the time of diagnosis was 73 months. Patients who underwent curative resection had a significantly better median OS from the initial diagnosis compared with those who underwent palliative resection and those who were conservatively treated (97 vs. 89 vs. 36 months, p = 0.0001). The median OS from the time of diagnosis in those patients who underwent radical or palliative resection was 97 months, with a 5-year survival rate of 76%. On multivariate analysis, factors associated with OS from the time of diagnosis were the presence of bilobar metastases, tumor grading, and curative resection in a first model. On a second model, curative or palliative surgery was an independent predictor of OS. Among 91 patients who underwent surgery, the presence of pancreatic neuroendocrine carcinoma G3 was the only factor independently associated with a poorer survival after surgery (median OS: 35 vs. 97 months, p < 0.0001). Conclusions: Patients with LM from PNET benefit from surgical resection, although surgery should be reserved to well- or moderately differentiated forms.
Association between statin use and plasma D-dimer levels
Authors: Mikhailidis Dimitri , Undas Anetta , Lip Gregory , Muntner Paul , Bittner Vera , Ray Kausik , Watts Gerald , Hovingh G. Kees , Rysz Jacek , Kastelein John , Sahebkar Amirhossein , Serban Corina , Banach Maciej ,   Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
Published: May 2015

D-dimers, specific breakdown fragments of cross-linked fibrin, are generally used as circulating markers of activated coagulation. Statins influence haemostatic factors, but their effect on plasma D-dimer levels is controversial. Therefore, the aim of this meta-analysis was to evaluate the association between statin therapy and plasma D-dimer levels. We searched PubMed, Web of Science, Cochrane Library, Scopus and EMBASE (up to September 25, 2014) to identify randomised controlled trials (RCTs) investigating the impact of statin therapy on plasma D-dimer levels. Two independent reviewers extracted data on study characteristics, methods and outcomes. Meta-analysis of data from nine RCTs with 1,165 participants showed a significant effect of statin therapy in reducing plasma D-dimer levels (standardised mean difference [SMD]: –0.988 µg/ml, 95 % confidence interval [CI]: –1.590 – –0.385, p=0.001). The effect size was robust in sensitivity analysis and omission of no single study significantly changed the overall estimated effect size. In the subgroup analysis, the effect of statins on plasma D-dimer levels was significant only in the subsets of studies with treatment duration ≥ 12 weeks (SMD: –0.761 µg/ml, 95 %CI: –1.163– –0.360; p< 0.001), and for lipophilic statins (atorvastatin and simvastatin) (SMD: –1.364 µg/ml, 95 % CI: –2.202– –0.526; p=0.001). Hydrophilic statins (pravastatin and rosuvastatin) did not significantly reduce plasma D-dimer levels (SMD: –0.237 µg/ml, 95 %CI: –1.140–0.665, p=0.606). This meta-analysis of RCTs suggests a decrease of plasma D-dimer levels after three months of statin therapy, and especially after treatment with lipophilic statins. Well-designed trials are required to validate these results.

Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.
Classic thrombophilic gene variants
Authors: Franchini Massimo , Mannucci Pier Mannuccio
Published: May 2015

Thrombophilia is defined as a condition predisposing to the development of venous thromboembolism (VTE) on the basis of a hypercoagu-lable state. Over the past decades, great advances in the pathogenesis of VTE have been made and nowadays it is well established that a thrombophilic state may be associated with acquired and/or inherited factors. The rare loss-of-function mutations of the genes encoding natural anticoagulant proteins (i. e. protein C, protein S and antithrombin) and the more common gain-of-function polymorphisms factor V Leiden and prothrombin G20210A are the main genetic determinants of thrombophilia. In addition, non-O blood group has been consistently demonstrated to be the most frequent inherited marker of an increased risk of VTE. The mechanism role of these inherited thrombophilia markers will be discussed in this narrative review.
Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: De Ferrari Gaetano M. , Dusi Veronica , Spazzolini Carla , Bos J. Martijn , Abrams Dominic J. , Berul Charles I. , Crotti Lia , Davis Andrew M. , Eldar Michael , Kharlap Maria , Khoury Asaad , Krahn Andrew D. , Leenhardt Antoine , Moir Christopher R. , Odero Attilio , Olde Nordkamp Louise , Paul Thomas , Rosés i Noguer Ferran , Shkolnikova Maria , Till Jan , Wilde Arthur A.M. , Ackerman Michael J. , Schwartz Peter J.
Published: May 2015

Background—

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder causing life-threatening arrhythmias whenever sympathetic activity increases. β-Βlockers are the mainstay of therapy; when they fail, implantable cardioverter-defibrillators (ICDs) are used but often cause multiple shocks. Preliminary results with flecainide appear encouraging. We proposed left cardiac sympathetic denervation (LCSD) as useful additional therapy, but evidence remains anecdotal.

Methods and Results—

We report 63 patients with CPVT who underwent LCSD as secondary (n=54) or primary (n=9) prevention. The median post-LCSD follow-up was 37 months. The 9 asymptomatic patients remained free of major cardiac events. Of the 54 patients with prior major cardiac events either on (n=38) or off (n=16) optimal medical therapy, 13 (24%) had at least 1 recurrence: 0 patients had an aborted cardiac arrest, 2 patients had syncope only, 10 patients had ≥1 appropriate ICD discharges, and 1 patient died suddenly. The 1- and 2-year cumulative event-free survival rates were 87% and 81%. The percentage of patients with major cardiac events despite optimal medical therapy (n=38) was reduced from 100% to 32% (
P
<0.001) after LCSD, and among 29 patients with a presurgical ICD, the rate of shocks dropped by 93% from 3.6 to 0.6 shocks per person per year (
P
<0.001). Patients with an incomplete LCSD (n=7) were more likely to experience major cardiac events after LCSD (71% versus 17%;
P
<0.01) than those with a complete LCSD.

Conclusions—

LCSD is an effective antifibrillatory intervention for patients with CPVT. Whenever syncope occurs despite optimal medical therapy, LCSD could be considered the next step rather than an ICD and could complement ICDs in patients with recurrent shocks.
Geographic Variations in Cardiovascular Health in the United States: Contributions of State‐ and Individual‐Level Factors
Authors: Gebreab Samson Y. , Davis Sharon K. , Symanzik Jürgen , Mensah George A. , Gibbons Gary H. , Diez‐Roux Ana V.
Published: May 2015

Background

Improving cardiovascular health (CVH) of all Americans by 2020 is a strategic goal of the American Heart Association. Understanding the sources of variation and identifying contextual factors associated with poorCVHmay suggest important avenues for prevention.

Methods and Results

Cross‐sectional data from the Behavioral Risk Factor Surveillance System for the year 2011 were linked to state‐level coronary heart disease and stroke mortality data from the National Vital Statistics System and to state‐level measures of median household income, income inequality, taxes on soda drinks and cigarettes, and food and physical activity environments from various administrative sources. PoorCVHwas defined according to the American Heart Association definition using 7 self‐reportedCVHmetrics (current smoking, physical inactivity, obesity, poor diet, hypertension, diabetes, and high cholesterol). Linked micromap plots and multilevel logistic models were used to examine state variation in poorCVHand to investigate the contributions of individual‐ and state‐level factors to this variation. We found significant state‐level variation in the prevalence of poorCVH(median odds ratio 1.32,P<0.001). Higher rates of poorCVHand cardiovascular disease mortality were clustered in the southern states. Minority and low socioeconomic groups were strongly associated with poorCVHand explained 51% of the state‐level variation in poorCVH; state‐level factors explained an additional 28%. State‐level median household income (odds ratio 0.89; 95%CI0.84–0.94), taxes on soda drinks (odds ratio 0.94; 95% CI 0.89–0.99), farmers markets (odds ratio 0.91; 95% CI 0.85–0.98), and convenience stores (odds ratio 1.09; 95% CI 1.01–1.17) were predictive of poorCVHeven after accounting for individual‐level factors.

Conclusions

There is significant state‐level variation in poorCVHthat is partly explained by individual‐ and state‐level factors. Additional longitudinal research is warranted to examine the influence of state‐level policies and food and physical activity environments on poorCVH.
The Crucial Role of Internal Variability in Modulating the Decadal Variation of the East Asian Summer Monsoon–ENSO Relationship during the Twentieth Century
Authors: Song Fengfei , Zhou Tianjun
Published: May 2015

This study investigates the role of internal variability in modulating the East Asian summer monsoon (EASM)–ENSO relationship using Twentieth-Century Reanalysis (20CR) data and simulations from phase 5 of CMIP (CMIP5). Analysis of 20CR data reveals an unstable EASM–ENSO relationship during the twentieth century. During the high-correlation periods of 1892–1912 and 1979–99, an evident western Pacific anticyclone (WPAC) and dipole sea level pressure (SLP) pattern are present in the decaying El Niño summer, accompanied by Indian Ocean warming and a tropospheric temperature Matsuno–Gill pattern. However, these are weaker or absent during low-correlation periods (1914–34 and 1958–78). After removing the external forcings based on historical simulations from 15 CMIP5 models, all the above features remain almost unchanged, suggesting the crucial role of internal variability. In a 501-yr preindustrial control (piControl) simulation without external forcing variation from CCSM4, the EASM–ENSO relationship also shows significant decadal variation, with a magnitude comparable to the 20CR data. The analysis demonstrates that the EASM–ENSO relationship’s variation is modulated by the interdecadal Pacific oscillation (IPO). Compared to negative IPO phases, the warmer East China Sea in positive IPO phases weakens the western North Pacific subtropical high (WNPSH), inducing more precipitation. Thus, the Kelvin wave–induced interannual divergence suppresses more mean-state precipitation and leads to a stronger WPAC. Hence, the IPO modulates the EASM–ENSO relationship through the WNPSH, which is evident in both 20CR and the piControl simulation.
Historical Changes in the Beaufort–Chukchi–Bering Seas Surface Winds and Waves, 1971–2013
Authors: Wang Xiaolan L. , Feng Yang , Swail Val R. , Cox Andrew
Published: May 2015

This study characterizes historical changes in surface wind speed and ocean surface waves in the Beaufort–Chukchi–Bering Seas using Environment Canada’s Beaufort Wind and Wave Reanalysis for the period 1970–2013. The results show that both the significant wave height () and mean wave period () have increased significantly over the Bering Sea in July and August and over the Canadian Beaufort Sea westward to the northern Bering Sea in September, and that the 1992–2013 trends in September mean agree well with satellite-based trend estimates for 1993–2010. Most outstandingly, the regional mean has increased at a rate of 3%–4% yr−1 of the corresponding 1970–99 climatology; it has more than tripled since 1970. Also, the regional mean has increased at a rate of 0.3% to 0.8% yr−1. The trends of lengthening wave period and increasing wave height imply a trend of increasing wave energy flux, providing a mechanism to break up sea ice and accelerate ice retreat. The results also show that changes in the local wind speeds alone cannot explain the significant changes in waves. The wind speeds show significant increases over the Bering Sea to the north of Alaska in July and over the central part of the domain in August and September, with decreases in the region off the Canadian coasts in August. In the region west of the Canadian coast, the climatological mean wind direction has rotated clockwise in July and August, with the climatological anticyclonic center being displaced northeastward in August.
Central nervous system medication use in older adults with intellectual disability: Results from the successful ageing in intellectual disability study
Authors: Chitty Kate M , Evans Elizabeth , Torr Jennifer J , Iacono Teresa , Brodaty Henry , Sachdev Perminder , Trollor Julian N
Published: May 2015

Objective:

Information on the rates and predictors of polypharmacy of central nervous system medication in older people with intellectual disability is limited, despite the increased life expectancy of this group. This study examined central nervous system medication use in an older sample of people with intellectual disability.

Methods:

Data regarding demographics, psychiatric diagnoses and current medications were collected as part of a larger survey completed by carers of people with intellectual disability over the age of 40 years. Recruitment occurred predominantly via disability services across different urban and rural locations in New South Wales and Victoria. Medications were coded according to the Monthly Index of Medical Specialties central nervous system medication categories, including sedatives/hypnotics, anti-anxiety agents, antipsychotics, antidepressants, central nervous system stimulants, movement disorder medications and anticonvulsants. The Developmental Behaviour Checklist for Adults was used to assess behaviour.

Results:

Data were available for 114 people with intellectual disability. In all, 62.3% of the sample was prescribed a central nervous system medication, with 47.4% taking more than one. Of those who were medicated, 46.5% had a neurological diagnosis (a seizure disorder or Parkinson’s disease) and 45.1% had a psychiatric diagnosis (an affective or psychotic disorder). Linear regression revealed that polypharmacy was predicted by the presence of neurological and psychiatric diagnosis, higher Developmental Behaviour Checklist for Adults scores and male gender.

Conclusion:

This study is the first to focus on central nervous system medication in an older sample with intellectual disability. The findings are in line with the wider literature in younger people, showing a high degree of prescription and polypharmacy. Within the sample, there seems to be adequate rationale for central nervous system medication prescription. Although these data do not indicate non-adherence to guidelines for prescribing in intellectual disability, the high rate of polypharmacy and its relationship to Developmental Behaviour Checklist for Adults scores reiterate the importance of continued medication review in older people with intellectual disability.
The conceptualization of country attractiveness: a review of research
Authors: Lee Kwang-Hoon
Published: May 2015

Despite the growth of literature on country attractiveness covering a wide range of research areas, minimal effort has been expended on its conceptualization in public administration. This article seeks to add to previous scholarly works by clarifying the concept and operationalizing its multi-dimensions to explain the effects of the attractiveness of nations based on theoretical grounding. More specifically, by examining prior studies in international business, tourism and migration research, the article attempts to reorganize the constituent elements of the concept into a multi-dimensional framework from a sustainable development perspective. This can be broken down conceptually into three spheres: economic, social and environmental attractiveness. The theoretical background for each dimensional effect is taken from signaling and soft power theories. The article presents a synthesis of the concept intended to cover all aspects of the empirical findings.

Points for practitioners

As globalization results in more and more competition, it is imperative that every country employ marketing and promotion strategies/policies to raise global public awareness of its image to stakeholders including companies, customers, citizens, tourists and highly-skilled migrants. Therefore, public administration researchers and policy makers must take into account the concept of country attractiveness, the core element of a country’s soft power, as it can play a key role in enhancing the success of the strategies and policies of countries in the various fields of international competition.
Rethinking Social Welfare Fraud from a Complex Adaptive Systems Perspective
Authors: Kim Yushim , Maroulis Spiro
Published: May 2015

Despite efforts to control fraud in public assistance programs, the perception and realities of the problem persist. Serious barriers related to data collection and research methods impede the understanding of how and why fraud occurs, thereby limiting options for improving program integrity. This article argues that based on a complex adaptive systems (CAS) perspective, social welfare fraud can be understood as a collective outcome emerging from repeated interactions among stakeholders during the routinized business processes of public assistance programs. While dealing with fraud, great attention must be paid to how it occurs and persists, not just how serious the problem is or who commits these crimes.
Bosniak classification system: a prospective comparison of CT, contrast-enhanced US, and MR for categorizing complex renal cystic masses
Authors: Graumann Ole , Osther Susanne Sloth , Karstoft Jens , Hørlyck Arne , Osther Palle Jörn Sloth
Published: May 2015

Background

The Bosniak classification was originally based on computed tomographic (CT) findings. Magnetic resonance (MR) and contrast-enhanced ultrasonography (CEUS) imaging may demonstrate findings that are not depicted at CT, and there may not always be a clear correlation between the findings at MR and CEUS imaging and those at CT.

Purpose

To compare diagnostic accuracy of MR, CEUS, and CT when categorizing complex renal cystic masses according to the Bosniak classification.

Material and Methods

From February 2011 to June 2012, 46 complex renal cysts were prospectively evaluated by three readers. Each mass was categorized according to the Bosniak classification and CT was chosen as gold standard. Kappa was calculated for diagnostic accuracy and data was compared with pathological results.

Results

CT images found 27 BII, six BIIF, seven BIII, and six BIV. Forty-three cysts could be characterized by CEUS, 79% were in agreement with CT (κ = 0.86). Five BII lesions were upgraded to BIIF and four lesions were categorized lower with CEUS. Forty-one lesions were examined with MR; 78% were in agreement with CT (κ = 0.91). Three BII lesions were upgraded to BIIF and six lesions were categorized one category lower. Pathologic correlation in six lesions revealed four malignant and two benign lesions.

Conclusion

CEUS and MR both up- and downgraded renal cysts compared to CT, and until these non-radiation modalities have been refined and adjusted, CT should remain the gold standard of the Bosniak classification.
Fibroblast Growth Factor 23
Authors: Hardcastle M. R. , Dittmer K. E.
Published: May 2015

Traditionally, control of phosphorus in the body has been considered secondary to the tighter control of calcium by parathyroid hormone and vitamin D. However, over the past decade, substantial advances have been made in understanding the control of phosphorus by the so-called phosphatonin system, the lynchpin of which is fibroblast growth factor 23 (FGF23). FGF23 binds to the klotho/FGFR1c receptor complex in renal tubular epithelial cells, leading to upregulation of Na/Pi cotransporters and subsequent excretion of phosphorus from the body. In addition, FGF23 inhibits parathyroid hormone and the renal 1α-hydroxylase enzyme, while it stimulates 24-hydroxylase, leading to decreased 1,25-dihydroxyvitamin D3. FGF23 is intimately involved in the pathogenesis of a number of diseases, particularly the hereditary hypophosphatemic rickets group and chronic kidney disease, and is a target for the development of new treatments in human medicine. Little work has been done on FGF23 or the other phosphatonins in veterinary medicine, but increases in FGF23 are seen with chronic kidney disease in cats, and increased FGF23 expression has been found in soft tissue sarcomas in dogs.