bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Microbiota-Gut-Brain Axis by Berberine Resulting in Improved Metabolic Status in High-Fat Diet-Fed Rats
Authors: Sun Honglin , Wang Ningjian , Cang Zhen , Zhu Chaoxia , Zhao Li , Nie Xiaomin , Cheng Jing , Xia Fangzhen , Zhai Hualing , Lu Yingli
Published: November 2016

Objective: To investigate whether or not berberine could improve metabolic status of high-fat-fed rats through modulation of microbiota-gut-brain axis. Methods: Berberine was administered on high-fat-fed Sprague-Dawley rats. Brain-gut hormones were detected, and changes of gut microbiota were analyzed by 16S rRNA gene sequencing. Results: Berberine could reduce weight gain and lipolysis in the high-fat diet-fed group. Moreover, trends of ameliorated insulin resistance and decreased endogenous glucose production were observed. In addition, the microbiota-gut-brain axis was found to be modulated, including structural and diversity changes of microbiota, elevated serum glucagon-like peptide-1 and neuropeptide Y level, decreased orexin A level, up-regulated glucagon-like peptide-1 receptor mRNA level as well as ultra-structural improvement of the hypothalamus. Conclusion: Taken together, our findings suggest that berberine improved metabolic disorders induced by high-fat diet through modulation of the microbiota-gut-brain axis.
Low Incidence of Atrial Fibrillation in Patients with Transient Ischemic Attack
Authors: Pedersen Kenneth Bruun , Chemnitz Alexander , Madsen Charlotte , Sandgaard Niels C.F. , Bak Søren , Brandes Axel
Published: November 2016

Background: Atrial fibrillation (AF) is a major cause of stroke. Therefore, all patients with ischemic stroke or transient ischemic attack (TIA) should be examined with 12-lead electrocardiogram (ECG) and continuous monitoring to detect AF. Current guidelines recommend at least 24 h continuous ECG monitoring, which is primarily based on studies investigating patients with ischemic stroke. The aim of our study was to investigate the diagnostic yield of 12-lead ECG and Holter monitoring in patients with TIA. Methods: We retrospectively investigated all patients diagnosed with TIA at Odense University Hospital, Denmark, from January 1, 2014 to December 31, 2014. TIA was a clinical diagnosis according to the WHO definition. Patients received admission ECG and 72-hour Holter monitoring after discharge. Results: 171 patients without known AF were diagnosed with TIA. Four (2.3%) were diagnosed with AF on admission ECG. Another 2 (1.2%) were diagnosed with AF on Holter monitoring. In total, 6 patients (3.5%) were diagnosed with AF. Patients with AF were significantly older (mean age 79.4 [95% CI 65.1-93.6] years) than patients without AF (mean age 67.6 [95% CI 65.6-69.5] years) but otherwise showed no difference in baseline characteristics. Conclusion: In this retrospective study, patients with TIA had a low incidence of AF detected with ECG and 72-hour Holter monitoring. Prospective studies are needed to confirm these findings.
Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats
Authors: Zhao Qing , Yin Jianyong , Lu Zeyuan , Kong Yiwei , Zhang Guangyuan , Zhao Binghui , Wang Feng
Published: November 2016

Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H2O2-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.
Cadmium Exposure is Associated with the Prevalence of Dyslipidemia
Authors: Zhou Zhou , Lu Yong-hui , Pi Hui-feng , Gao Peng , Li Min , Zhang Lei , Pei Li-ping , Mei Xiang , Liu Lin , Zhao Qi , Qin Qi-Zhong , Chen Yu , Jiang Yue-ming , Zhang Zhao-hui , Yu Zheng-ping
Published: November 2016

Background: Cadmium is a widespread environmental and occupational pollutant that accumulates in human body with a biological half-life exceeding 10 years. Cadmium exposure has been demonstrated to increase rates of cardiovascular diseases. Whether occupational cadmium exposure is associated with the increase in the prevalence of dyslipidemia and hence contributes to the risk of cardiovascular diseases is still equivocal. To test the hypothesis that exposure to cadmium is related to the prevalence of dyslipidemia, we examined the associations between blood cadmium concentration and the prevalence of dyslipidemia in workers occupationally exposed to cadmium in China. Methods: A cross-sectional survey on demographic data, blood cadmium level and lipid profile in cadmium exposed workers from seven cadmium smelting factories in central and southwestern China was conducted. We measured blood cadmium concentration and lipid components of 1489 cadmium exposed workers. The prevalence of dyslipidemia was compared across blood cadmium quartiles. Associations between the blood cadmium concentrations and the prevalence of dyslipidemia were assessed using confounder adjusted linear and logistic regressions. Results: The blood cadmium concentration was 3.61±0.84µg/L ( mean ±SD). The prevalence of dyslipidemia in this occupational population was 66.3%. Mean blood cadmium concentration of workers with dyslipedemia was significantly higher than that of workers without dyslipidemia (p <0.01). The prevalence of dyslipidemia increased dose-dependently with elevations in blood cadmium concentrations (p for trend <0.001). Elevated levels of blood cadmium were associated with BMI, education attainment, income, smoking status and duration of exposure (all p <0.01). Furthermore, the profile of blood lipid was obviously changed in this occupational population. The prevalence of high TC, high TG, Low HDL-C and high LDL-C rose with increases in blood cadmium levels dose-dependently (p for trend <0.001). The odds ratios (95% confidence interval) for dyslipidemia across the increasing blood cadmium quartiles were 1.21(1.16-1.55), 1.56(1.11-1.87), 1.79(1.26-2.25) respectively (referencing to 1.00; p for trend <0.001), after multivariate adjustment for BMI, education attainment, income, lifestyle factors and duration of exposure, the association between blood cadmium concentrations and the prevalence of dyslipidemia remained unchanged (all p for trend <0.001). Conclusion: Elevated blood cadmium concentration is associated with prevalence of dyslipidemia. Cadmium exposure could alter lipid metabolism in humans. It is imperative to control cadmium exposure of occupational population in cadmium related industries and reduce adverse health effects.
Expression Pattern and Regulatory Role of microRNA-23a in Conjugated Linoleic Acids-Induced Apoptosis of Adipocytes
Authors: Qi Renli , Wang Qi , Wang Jing , Huang Jinxiu , Jiang Shan , Xiao Rong , Liu Zuohua , Yang Feiyun
Published: November 2016

Background/Aims: Conjugated linoleic acids (CLAs) are known to induce apoptosis in adipocytes; however, the cellular mechanisms involved remained illdefined. We explored the different apoptotic induction effects of two CLA isomers on adipocytes and then investigated the expression and function of microRNAs (miRNAs) related to the apoptosis. Methods: TUNEL and FCM assays were used to detect CLAs-induced adipocyte apoptosis. Microarrays were used to compare the differential expression of miRNAs. MiR-23a, a miRNA that showed significant changes in expression in the CLA-treated cells, was selected for the subsequent functional studies via over-expression and knock down in in vivo and in vitro experiments. Results: C9, t11-CLA exhibited a stronger induction of apoptosis in the differentiated 3T3-L1 adipocytes than t10, c12-CLA. However, t10, c12-CLA could rapidly activate NF-κB, which may have caused their different apoptotic effects. MiR-23a was markedly down-regulated by the CLAs treatment and miR-23a over-expression attenuated CLA-induced apoptosis. Apoptosis protease-activating factor 1 (APAF1) was identified as a target gene of miR-23a. In an in vivo experiment endogenous miR-23a was down-regulated in mice fed with a mixture of both CLAs. The mice also exhibited less fat deposition and more apoptotic fat cells in adipose tissue. Moreover, endogenous miR-23a was suppressed in mice via intravenous injection with an antagomir which resulted in decreased body weight, increased number of apoptotic fat cells and increased APAF1 expression in adipose tissue. Conclusion: Taken together, our results suggest that miR-23a plays a critical role in CLA-induced apoptosis in adipocytes via controlling APAF1 expression.
Role of Osteoprotegerin (OPG) in Bone Marrow Adipogenesis
Authors: Zhang Lili , Liu Mengmeng , Zhou Xiaokang , Liu Yi , Jing Bo , Wang Xiaogang , Zhang Qi , Sun Yao
Published: November 2016

Background/Aims: Bone marrow adipogenesis is one of the major characteristics of aged bone. Bone marrow mesenchymal stem cells (BMMSCs) prefer to differentiate into adipocytes instead of osteoblasts in the bone marrow cavity in aged hosts. The mechanism of formation and function of adipocytes in aged bone marrow needs further investigation. Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor (TNFR) super family, and it can inhibit the activities of osteoclasts. We found that adipocyte numbers increased in the bone marrow of Opg knockout mice. In this study, we investigated the role of OPG in the differentiation of BMMSCs and bone marrow adipogenesis. Methods: Histological analyses were performed on the bone tissues of Opg knockout (Opg-KO) and wild-type (WT) mice of different ages. BMMSCs obtained from mice were cultured in vitro to evaluate their differentiation abilities. Results: With aging, the expression of Opg in the bone marrow of WT mice markedly decreased, but that of the adipogenic specific transcription factor peroxisome proliferator-activated receptor γ (Ppar-γ) increased. Adipocytes formed in the bone marrow of Opg-KO mice at a relative young age, and the number of adipocytes increased dramatically with age. Compared with the WT control, the osteogenic differentiation of Opg-KO BMMSCs decreased, but the adipogenic differentiation increased. Moreover, exogenous OPG could inhibit the adipogenic differentiation and promote the osteogenic differentiation of Opg-KO BMMSCs in vitro. Conclusions: OPG plays an important role in regulating BMMSC differentiation and bone marrow adipogenesis.
Prolonged Fasting Improves Endothelial Progenitor Cell-Mediated Ischemic Angiogenesis in Mice
Authors: Xin Bao , Liu Chun-Long , Yang Hong , Peng Cheng , Dong Xiao-Hui , Zhang Chuan , Chen Alex F. , Xie He-Hui
Published: November 2016

Background/Aims: Prolonged fasting (PF) was shown to be of great potency to promote optimal health and reduce the risk of many chronic diseases. This study sought to determine the effect of PF on the endothelial progenitor cell (EPC)-mediated angiogenesis in the ischemic brain and cerebral ischemic injury in mice. Methods: Mice were subjected to PF or periodic PF after cerebral ischemia, and histological analysis and behavioral tests were performed. Mouse EPCs were isolated and examined, and the effects of EPC transplantation on cerebral ischemic injury were investigated in mice. Results: It was found that PF significantly increased the EPC functions and angiogenesis in the ischemic brain, and attenuated the cerebral ischemic injury in mice that was previously subjected to cerebral ischemia. Periodic PF might reduce cortical atrophy and improve long-term neurobehavioral outcomes after cerebral ischemia in mice. The eNOS and MnSOD expression and intracellular NO level were increased, and TSP-2 expression and intracellular O2- level were reduced in EPCs from PF-treated mice compared to control. In addition, transplanted EPCs might home into ischemic brain, and the EPCs from PF-treated mice had a stronger ability to promote angiogenesis in ischemic brain and reduce cerebral ischemic injury compared to the EPCs from control mice. The EPC-conditioned media from PF-treated mice exerted a stronger effect on cerebral ischemic injury reduction compared to that from control mice. Conclusion: Prolonged fasting promoted EPC-mediated ischemic angiogenesis and improved long-term stroke outcomes in mice. It is implied that prolonged fasting might potentially be an option to treat ischemic vascular diseases.
Cocaine Withdrawal Reduces Gamma-Aminobutyric Acid-Ergic Transmission and Gephyrin Expression at Medial Prefrontal Cortex in Cocaine-Conditioned Place-Preference Rats, Which Shows Increased Cocaine Seeking
Authors: Yang Wenqiong , He Hongsheng , Pan Yan , Duan Falan , Zhao Dan , Hu Bo , Zhou Qingzhen , Liu Wanhong
Published: November 2016

Aims: Chronic cocaine abuse decreases the inhibitory synaptic transmission via unknown mechanisms, while pharmacologically augmenting gamma-aminobutyric acid-ergic (GABAergic) transmission attenuates cocaine craving. Here, we propose that prolonged cocaine withdrawal downregulates GABAergic transmission and its important regulator gephyrin in medial prefrontal cortex (mPFC), in cocaine-conditioned place-preference (CPP) rats. Methods: CPP test, patch clamp, and Western blot analysis are engaged to test this proposal. Results: Two-week cocaine withdrawal further increased CPP score, as compared to the 24-hour withdrawn group. The amplitude of GABAergic inhibitory postsynaptic currents (IPSCs) was decreased in 2-week-withdrawn mPFC neurons from cocaine-CPP rats, compared to that of saline-CPP rats. Two-week withdrawal did not alter the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) in mPFC in cocaine-CPP rats. Two-week withdrawal increased the ratio of EPSCs/IPSCs (E/I) in the same mPFC neuron in cocaine-CPP rats. In addition, Western blots showed 2-week cocaine-withdrawn down-regulated gephyrin at postsynaptic density (PSD) sites of mPFC. Conclusion: We found decreased GABAergic IPSCs and downregulated gephyrin in PSD at mPFC in 2-week cocaine-withdrawn rats that showed increased CPP, suggesting that an increased E/I ratio and neuron excitability in mPFC may associate with a cocaine-seeking tendency. Strategies aimed at GABAergic synapses in mPFC may therapeutically benefit to cocaine addiction treatment.
Mucoepidermoid Carcinoma of the Breast Found during Treatment of Lymphoma
Authors: Fujino Minoru , Mori Daisuke , Akashi Michiaki , Yamamoto Hidetaka , Aibe Hitoshi , Matake Kunishige , Shirahane Kengo
Published: November 2016

A 71-year-old woman, previously treated for malignant lymphoma, was admitted to our hospital with a tumor in the right breast. The tumor size was 2.0 cm in diameter, and the borderline was unclear. The core needle biopsy material revealed an invasive adenocarcinoma with metaplastic change. Right mastectomy and sentinel lymph node biopsy was performed. Histologically, the tumor was composed of mucus-secreting, epidermoid, and intermediate cells. These findings confirmed the diagnosis as mucoepidermoid carcinoma (MEC) of the breast. MEC is more frequently observed in the salivary glands and occurs rarely in the breast, with an incidence of approximately 0.3% of all breast cancers. Because of the rarity of the disease, the clinicopathological features and clinical outcome have not been fully investigated. The relationship between MEC of the breast and lymphoma are unclear. Here we report a rare case of MEC of the breast.
Surgical Therapy of Cholangiocarcinoma
Authors: Radtke Arnold , Königsrainer Alfred
Published: November 2016

Background: The majority of patients with cholangiocarcinoma present with advanced disease that is often challenging to diagnose and to treat. The optimal preoperative evaluation requires a coordinated multidisciplinary approach. Surgical resection is the mainstay of therapy. Methods: This systematic review delineates surgical treatment strategies for cholangiocarcinoma in general as well as special considerations concerning the particular tumor localization. A literature search (see keywords) was conducted using PubMed and publications between 1990 and 2016 regarding resectable and advanced cholangiocarcinoma were reviewed. Selected studies were utilized based on their significance and innovation. Results: The type and extent of resection performed depends on the location of the cholangiocarcinoma within the liver or biliary tree and the extent of local tumor invasion. The common surgical strategy contains: (i) for intrahepatic tumors: tailored partial hepatectomy combined with extended hilar, suprapancreatic, celiac axis lymphadenectomy, (ii) for hilar tumors: complete resection of the extrahepatic biliary tree combined with extended hepatectomy inclusive of segment I, resection of portal vein bifurcation, and systematic N1/N2 lymphadenectomy, and (iii) for distal tumors: en bloc pancreatoduodenectomy combined with complete resection of the extrahepatic bile duct below the hepatic confluence and systematic N1/N2 lymphadenectomy. Pathologic confirmation is not required prior to resection. Preoperative biliary drainage and remnant liver volume augmentation are necessary in selected patients with intrahepatic or hilar cholangiocarcinoma considered for extensive liver resection. Conclusion: Cure for cholangiocarcinoma requires complete surgical resection with histologically negative margins. R0 resection provides a satisfactory long-term outcome in patients with lymph node-negative stage. Neoadjuvant treatment followed by liver transplantation provides long-term survival in highly selected cases with localized, unresectable, lymph node-negative hilar cholangiocarcinoma.
Beneficial Effects of Education on Emotional Distress, Self-Management, and Coping in Patients with Inflammatory Bowel Disease: A Prospective Randomized Controlled Study
Authors: Berding Anja , Witte Christine , Gottschald Marion , Kaltz Birgit , Weiland Romy , Gerlich Christian , Reusch Andrea , Kruis Wolfgang , Faller Hermann
Published: November 2016

Background: Patients with inflammatory bowel disease (IBD) suffer from various physical as well as psychological impairments, and patient education may help improve their well-being. Therefore, we developed a manualized education program for IBD patients addressing medical and psychological issues. This study aimed to evaluate it in a large controlled trial. Methods: A total of 181 IBD outpatients participated in a prospective, randomized, waitlist-controlled trial; assessments were made before as well as 2 weeks and 3 months after intervention. Analysis of covariance was used to assess intervention effects on disease-related worries and concerns (primary outcome), fear of progression, coping with anxiety, health competencies, health-related quality of life (HRQoL), perceived disease activity, symptoms of depression and anxiety, disease-related knowledge, and coping strategies. Participants' satisfaction with the program was also evaluated. Results: At 2 weeks and 3 months after intervention, we found significant large effects of our education program on skill and technique acquisition, knowledge, and coping with IBD. Moreover, we found significant medium effects on disease-related worries and concerns, fear of progression, coping with anxiety, constructive attitudes and approaches, as well as coping with disease-related negative emotions. The number of coping strategies used was significantly higher at 3 months. We did not find any effects on perceived disease activity, HRQoL, positive and active engagement in life, or symptoms of anxiety and depression. The program was rated very favorably by the attendees. Conclusion: Our education program contributed to improvements in psychological distress, self-management skills, and coping and was appreciated by its attendees.
Rapid Molecular Genetic Diagnosis with Next-Generation Sequencing in 46,XY Disorders of Sex Development Cases: Efficiency and Cost Assessment
Authors: Özen Samim , Onay Hüseyin , Atik Tahir , Solmaz Aslı Ece , Özkınay Ferda , Gökşen Damla , Darcan Şükran
Published: November 2016

Background/Aim: The aim of this study was to use targeted next-generation sequencing (TNGS) including all known genes associated with 46,XY disorders of sex development (DSD) for a fast molecular genetic diagnosis. Methods: Twenty pediatric patients were recruited, and 56 genes related to 46,XY DSD were sequenced using TNGS. The time elapsed between initial appointment and final diagnosis as well as the mean expenditure was determined. Results: A total of 9 (45%) mutations in 4 different genes were identified. Mutations in the HSD17B3 gene were observed in 6 (30%) patients. A heterozygous mutation in WT1 gene and a hemizygous mutation in SRY gene were detected in patients with gonadal dysgenesis. One patient had a homozygous mutation in LHCGR gene. Prior to the molecular diagnosis, the mean number of clinical visits, time elapsed until diagnosis, and expenditure were 27.4 ± 14.6 visits, 5.9 ± 4.1 years per patient, and USD 2,142 ± 1,038, respectively. With TNGS, time elapsed until diagnosis was significantly reduced (3 days), and expenditure per patient was only one third of the conventional approach (USD 761). Conclusions: TNGS is an efficient, rapid, and cost-effective technique for mutation detection in 46,XY DSD.
MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions
Authors: Eken Suzanne M. , Jin Hong , Chernogubova Ekaterina , Li Yuhuang , Simon Nancy , Sun Changyan , Korzunowicz Greg , Busch Albert , Bäcklund Alexandra , Österholm Cecilia , Razuvaev Anton , Renné Thomas , Eckstein Hans Henning , Pelisek Jaroslav , Eriksson Per , González Díez María , Perisic Matic Ljubica , Schellinger Isabel N. , Raaz Uwe , Leeper Nicholas J. , Hansson Göran K. , Paulsson-Berne Gabrielle , Hedin Ulf , Maegdefessel Lars
Published: November 2016

Rationale:

In the search for markers and modulators of vascular disease, microRNAs (miRNAs) have emerged as potent therapeutic targets.

Objective:

To investigate miRNAs of clinical interest in patients with unstable carotid stenosis at risk of stroke.

Methods and Results:

Using patient material from the BiKE (Biobank of Karolinska Endarterectomies), we profiled miRNA expression in patients with stable versus unstable carotid plaque. A polymerase chain reaction–based miRNA array of plasma, sampled at the carotid lesion site, identified 8 deregulated miRNAs (miR-15b, miR-29c, miR-30c/d, miR-150, miR-191, miR-210, and miR-500). miR-210 was the most significantly downregulated miRNA in local plasma material. Laser capture microdissection and in situ hybridization revealed a distinct localization of miR-210 in fibrous caps. We confirmed that miR-210 directly targets the tumor suppressor gene APC (adenomatous polyposis coli), thereby affecting Wnt (Wingless-related integration site) signaling and regulating smooth muscle cell survival, as well as differentiation in advanced atherosclerotic lesions. Substantial changes in arterial miR-210 were detectable in 2 rodent models of vascular remodeling and plaque rupture. Modulating miR-210 in vitro and in vivo improved fibrous cap stability with implications for vascular disease.

Conclusions:

An unstable carotid plaque at risk of stroke is characterized by low expression of miR-210. miR-210 contributes to stabilizing carotid plaques through inhibition of APC, ensuring smooth muscle cell survival. We present local delivery of miR-210 as a therapeutic approach for prevention of atherothrombotic vascular events.
Development of Left Ventricular Hypertrophy in Treated Hypertensive Outpatients
Authors: Izzo Raffaele , Losi Maria-Angela , Stabile Eugenio , Lönnebakken Mai Tone , Canciello Grazia , Esposito Giovanni , Barbato Emanuele , De Luca Nicola , Trimarco Bruno , de Simone Giovanni
Published: November 2016

There is little information on left ventricular (LV) hypertrophy (LVH) development during antihypertensive treatment. We evaluate incident LVH in a treated hypertensive cohort, the Campania Salute Network registry. We analyzed prospectively 4290 hypertensives (aged 50.3±11.1 years, 40% women) with at least 1-year follow-up, without LVH at baseline. Incident LVH was defined as the first detection of echocardiographic LV mass index ≥47 in women or ≥50 g/m
2.7
in men. During a median 48-month follow-up, 915 patients (21.3%) developed LVH. They were older, more frequently women, and obese (
P
<0.0001), with initial higher fasting glucose, diastolic and systolic blood pressure, LV mass index, lower heart rate and glomerular filtration rate, longer hypertension history and follow-up, and higher average systolic blood pressure during follow-up (all
P
<0.05), despite a more frequent treatment with Ca
++
-channel blockers and diuretics (both
P
<0.02). At multivariable Cox regression, incident LVH was independently associated with older age, female sex, obesity, higher average systolic blood pressure during follow-up, and initial greater LV mass index (all
P
<0.02). By categorizing patients according to obesity and sex, obesity independently increased the risk for incident LVH in both sexes (obese versus nonobese men: hazard ratio, 1.34; confidence interval, 1.05–1.72;
P
=0.019; and obese versus nonobese women: hazard ratio, 1.34; confidence interval, 1.08–1.66;
P
=0.007). Despite more aggressive antihypertensive therapy, 21% of hypertensive patients develop clear-cut LVH. After adjusting for confounders, risk of incident LVH is particular relevant among women and is further increased by the presence of obesity.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02211365.
Caveolin-1 Deletion Prevents Hypertensive Vascular Remodeling Induced by Angiotensin II
Authors: Forrester Steven J. , Elliott Katherine J. , Kawai Tatsuo , Obama Takashi , Boyer Michael J. , Preston Kyle J. , Yan Zhen , Eguchi Satoru , Rizzo Victor
Published: November 2016

It has been proposed that membrane microdomains, caveolae, in vascular cells are critical for signal transduction and downstream functions induced by angiotensin II (AngII). We have tested our hypothesis that caveolin-1 (Cav1), a major structural protein of vascular caveolae, plays a critical role in the development of vascular remodeling by AngII via regulation of epidermal growth factor receptor and vascular endothelial adhesion molecule-1. Cav1
−/−
and control Cav
+/+
mice were infused with AngII for 2 weeks to induce vascular remodeling and hypertension. On AngII infusion, histological assessments demonstrated medial hypertrophy and perivascular fibrosis of aorta and coronary and renal arteries in Cav1
+/+
mice compared with sham-operated Cav1
+/+
mice. AngII-infused Cav1
+/+
mice also showed a phenotype of cardiac hypertrophy with increased heart weight to body weight ratio compared with control Cav1
+/+
mice. In contrast, Cav1
−/−
mice infused with AngII showed attenuation of vascular remodeling but not cardiac hypertrophy. Similar levels of AngII-induced hypertension were found in both Cav1
+/+
and Cav1
−/−
mice as assessed by telemetry. In Cav1
+/+
mice, AngII enhanced tyrosine-phosphorylated epidermal growth factor receptor staining in the aorta, which was attenuated in Cav1
−/−
mice infused with AngII. Enhanced Cav1 and vascular endothelial adhesion molecule-1 expression was also observed in aorta from AngII-infused Cav1
+/+
mice but not in Cav1
−/−
aorta. Experiments with vascular cells further provided a potential mechanism for our in vivo findings. These data suggest that Cav1, and presumably caveolae, in vascular smooth muscle and the endothelium plays a critical role in vascular remodeling and inflammation independent of blood pressure or cardiac hypertrophy regulation.
Organum Vasculosum of the Lamina Terminalis Detects NaCl to Elevate Sympathetic Nerve Activity and Blood Pressure
Authors: Kinsman Brian J. , Simmonds Sarah S. , Browning Kirsteen N. , Stocker Sean D.
Published: November 2016

High-salt diet elevates NaCl concentrations in the cerebrospinal fluid to increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. The organum vasculosum of the lamina terminalis (OVLT) resides along the rostral wall of the third ventricle, lacks a complete blood–brain barrier, and plays a pivotal role in body fluid homeostasis. Therefore, the present study used a multifaceted approach to examine whether OVLT neurons of Sprague–Dawley rats are intrinsically sensitive to changes in extracellular NaCl concentrations and mediate the sympathoexcitatory responses to central NaCl loading. Using in vitro whole-cell recordings, step-wise increases in extracellular NaCl concentrations (2.5–10 mmol/L) produced concentration-dependent excitation of OVLT neurons. Additionally, these excitatory responses were intrinsic to OVLT neurons because hypertonic NaCl evoked inward currents, despite pharmacological synaptic blockade. In vivo single-unit recordings demonstrate that the majority of OVLT neurons (72%, 13/19) display concentration-dependent increases in neuronal discharge to intracarotid (50 μL/15 s) or intracerebroventricular infusion (5 μL/10 minutes) of hypertonic NaCl. Microinjection of hypertonic NaCl (30 nL/60 s) into the OVLT, but not adjacent areas, increased lumbar SNA, adrenal SNA, and arterial blood pressure in a concentration-dependent manner. Renal SNA decreased and splanchnic SNA remained unaffected. Finally, local inhibition of OVLT neurons with the GABA
A
receptor agonist muscimol (24 nL/10 s) significantly attenuated the sympathoexcitatory and pressor responses to intracerebroventricular infusion of 0.5 mol/L or 1.0 mol/L NaCl. Collectively, these findings indicate that OVLT neurons detect changes in extracellular NaCl concentrations to selectively alter SNA and raise arterial blood pressure.
Systematic Characterization and Prediction of Human Hypertension Genes
Authors: Li Yan-Hui , Zhang Gai-Gai , Wang Nanping
Published: November 2016

Hypertension is a major cardiovascular risk factor and accounts for a large part of cardiovascular mortality. In this work, we analyzed the properties of hypertension genes and found that when compared with genes not yet known to be involved in hypertension regulation, known hypertension genes display distinguishing features: (1) hypertension genes tend to be located at network center; (2) hypertension genes tend to interact with each other; and (3) hypertension genes tend to enrich in certain biological processes and show certain phenotypes. Based on these features, we developed a machine-learning algorithm to predict new hypertension genes. One hundred and seventy-seven candidates were predicted with a posterior probability >0.9. Evidence supporting 17 of the predictions has been found.
Dopamine Alters the Fidelity of Working Memory Representations according to Attentional Demands
Authors: Fallon Sean James , Zokaei Nahid , Norbury Agnes , Manohar Sanjay G. , Husain Masud
Published: November 2016

Capacity limitations in working memory (WM) necessitate the need to effectively control its contents. Here, we examined the effect of cabergoline, a dopamine D2 receptor agonist, on WM using a continuous report paradigm that allowed us to assess the fidelity with which items are stored. We assessed recall performance under three different gating conditions: remembering only one item, being cued to remember one target among distractors, and having to remember all items. Cabergoline had differential effects on recall performance according to whether distractors had to be ignored and whether mnemonic resources could be deployed exclusively to the target. Compared with placebo, cabergoline improved mnemonic performance when there were no distractors but significantly reduced performance when distractors were presented in a precue condition. No significant difference in performance was observed under cabergoline when all items had to be remembered. By applying a stochastic model of response selection, we established that the causes of drug-induced changes in performance were due to changes in the precision with which items were stored in WM. However, there was no change in the extent to which distractors were mistaken for targets. Thus, D2 agonism causes changes in the fidelity of mnemonic representations without altering interference between memoranda.
Domain-general Stroop Performance and Hemispheric Asymmetries: A Resting-state EEG Study
Authors: Ambrosini Ettore , Vallesi Antonino
Published: November 2016

The ability to suppress irrelevant information while executing a task, also known as interference resistance ability, is a function of pFC that is critical for successful goal-directed human behavior. In the study of interference resistance and, more generally, executive functions, two key questions are still open: Does pFC contribute to cognitive control abilities through lateralized but domain-general mechanisms or through hemispheric specialization of domain-specific processes? And what are the underlying causes of interindividual differences in executive control performance? To shed light on these issues, here we employed an interindividual difference approach to investigate whether participants' hemispheric asymmetry in resting-state electrophysiological brain dynamics may reflect their variability in domain-general interference resistance. We recorded participants' resting-state electroencephalographic activity and performed spectral power analyses on the estimated cortical source activity. To measure participants' lateralized brain dynamics at rest, we computed the right–left hemispheric asymmetry score for the β/α power ratio. To measure their domain-general interference resistance ability, verbal and spatial Stroop tasks were used. Robust correlations followed by intersection analyses showed that participants with stronger resting-state-related left-lateralized activity in different pFC regions, namely the mid-posterior superior frontal gyrus, middle and posterior middle frontal gyrus, and inferior frontal junction, were more able to inhibit irrelevant information in both domains. The present results confirm and extend previous findings showing that neurophysiological difference factors may explain interindividual differences in executive functioning. They also provide support for the hypothesis of a left pFC hemispheric specialization for domain-independent phasic cognitive control processes mediating Stroop performance.
High-intensity Interval Exercise Promotes Motor Cortex Disinhibition and Early Motor Skill Consolidation
Authors: Stavrinos Ellen L. , Coxon James P.
Published: November 2016

Gamma-aminobutyric acid (GABA) inhibition shapes motor cortex output, gates synaptic plasticity in the form of long-term potentiation, and plays an important role in motor learning. Remarkably, recent studies have shown that acute cardiovascular exercise can improve motor memory, but the cortical mechanisms are not completely understood. We investigated whether an acute bout of lower-limb high-intensity interval (HIT) exercise could promote motor memory formation in humans through changes in cortical inhibition within the hand region of the primary motor cortex. We used TMS to assess the input–output relationship, along with inhibition involving GABAA and GABAB receptors. Measures were obtained before and after a 20-min session of HIT cycling (exercise group) or rest (control group). We then had the same participants learn a new visuomotor skill and perform a retention test 5 hr later in the absence of sleep. No differences were found in corticomotor excitability or GABAB inhibition; however, synaptic GABAA inhibition was significantly reduced for the exercise group but not the control group. HIT exercise was found to enhance motor skill consolidation. These findings link modification of GABA to improved motor memory consolidation after HIT exercise and suggest that the beneficial effects of exercise on consolidation might not be dependent on sleep.
Cognitive Training in the Elderly: Bottlenecks and New Avenues
Authors: Zokaei Nahid , MacKellar Christopher , Čepukaitytė Giedrė , Patai Eva Zita , Nobre Anna Christina
Published: November 2016

Development of measures to preserve cognitive function or even reverse cognitive decline in the ever-growing elderly population is the focus of many research and commercial efforts. One such measure gaining in popularity is the development of computer-based interventions that “exercise” cognitive functions. Computer-based cognitive training has the potential to be specific and flexible, accommodates feedback, and is highly accessible. As in most budding fields, there are still considerable inconsistencies across methodologies and results, as well as a lack of consensus on a comprehensive assessment protocol. We propose that the success of training-based therapeutics will rely on targeting specific cognitive functions, informed by comprehensive and sensitive batteries that can provide a “fingerprint” of an individual's abilities. Instead of expecting a panacea from training regimens, focused and personalized training interventions that accommodate individual differences should be developed to redress specific patterns of deficits in cognitive rehabilitation, both in healthy aging and in disease.
SOAP Opera: Self as Object and Agent in Prioritizing Attention
Authors: Truong Grace , Todd Rebecca M.
Published: November 2016

A growing body of evidence has demonstrated that multiple sources of salience tune attentional sets toward aspects of the environment, including affectively and motivationally significant categories of stimuli such as angry faces and reward-associated target locations. Recent evidence further indicates that objects that have gained personal significance through ownership can elicit similar attentional prioritization. Here we discuss current research on sources of attentional prioritization that shape our awareness of the visual world from moment to moment and the underlying neural systems and contextualize what is known about attentional prioritization of our possessions within that research. We review behavioral and neuroimaging research on the influence of self-relevance and ownership on cognition and discuss challenges to this literature stemming from different modes of conceptualizing and operationalizing the self. We argue that ownership taps into both “self-as-object,” which characterizes the self as an object with a constellation of traits and attributes, and “self-as-subject,” which characterizes the self as an agentic perceiver and knower. Despite an abundance of research probing neural and behavioral indices of self-as-object and its effects on attention, there exists a paucity of research on the influence of self-relevance of attention when self is operationalized from the perspective of a first-person subject. To begin to address this gap, we propose the Self as Ownership in Attentional Prioritization (SOAP) framework to explain how ownership increases salience through attention to external representations of self-identity (i.e., self as object) and attention to contextually mediated permission to act (i.e., self as subject).
Geographies of Revival and Erasure: Neo-Ottoman Sites of Memory in Istanbul, Thessaloniki, and Budapest
Authors: Walton Jeremy F.
Published: November 2016

In this article, I draw on Pierre Nora’s concept of “sites of memory” to explore the material textures and political effects of neo-Ottomanism in three locations: Miniatürk, a theme park in Istanbul that features scale replicas of many prominent Ottoman structures; Thessaloniki’s New Mosque, a former place of worship for the syncretic religious community of the dönme; and the Tomb of Gül Baba, a 16th-century Sufi dervish and saint, in Budapest. My exposition moves in two directions. On the one hand, I emphasize how sites of memory frequently serve to bolster dominant, politicized discourses of neo-Ottomanism. On the other hand, I trace how sites of renascent Ottoman memory – especially those outside of Turkey – undermine and contradict the premises of neo-Ottomanism in unanticipated ways. Over the course of my article, I develop the concept of “disciplined historicity” as a method for approaching sites of memory that integrates both historical knowledge and appreciation for the material and aesthetic qualities of the spaces in question.
Early Accusations of Well Poisoning against Jews: Medieval Reality or Historiographical Fiction?
Authors: Barzilay Tzafrir
Published: November 2016

This article reexamines the idea prevalent in existing historiography that Jews were accused of well poisoning before 1321. It argues that the historians who studied the origins of such accusations were misled by sources written in the early modern period to think that Jews were charged with well poisoning as early as the eleventh century. However, a careful analysis of the sources reveals that there is little reliable evidence that such cases happened before the fourteenth century, much less on a large scale. Thus, the conclusions of the article call for a new chronology of well-poisoning charges made against Jews, starting closer to the fourteenth century.
Captives or Slaves and Masters in Eivissa (Ibiza), 1235–1600
Authors: Abárzuza Antoni Ferrer
Published: November 2016

This article concerns captivity or slavery on the island of Eivissa (Ibiza) from the time of its conquest by Christians until the end of the sixteenth century. Captives were used to cultivate and harvest vineyards and to labor on public building works in accordance to the strict calendar for agricultural and salt production. The sources have been examined for quantitative data and for the identity of their masters. They contain valuable information on the characteristics of these captives (sex, origins) and on their mode of arrival to the island. Slave masters have also been evaluated in search of common features, such as economic position, political offices held, and properties owned. These data have been used to test Claude Meillassoux’s (1986) definition of slavery. Simultaneously, Charles Verlinden’s work has also been analyzed, with special regard to the motivation behind his turning of what the medieval sources referred to as “captives” into “slaves.”
Holiness and Worldliness
Authors: Andemicael Awet
Published: November 2016

What was truly distinctive about the black Gospel music style of the Sanctified Church was its extensive use of musical instruments previously associated with “the world.” Yet, this fact presents a theological conundrum. The very churches that were so enthusiastically “embracing” the Gospel style were, at the same time, ardently emphasizing strict moral living and the repudiation of all things carnal. In this article, I suggest lines of theological reasoning that may have informed early black Holiness and pentecostal Christians in their widespread liturgical use of the Gospel style. Drawing on primary source material from COGIC founding Bishop Charles Mason, I expand Lawrence Levine’s model of the relationship between early black Sanctified churches and the secular black musical world and argue that a more nuanced conception of the Christ-world relation than is generally assumed may have undergirded Sanctified development of early Gospel music.
Discourses of Power and State Formation: The State of Emergency from Protectorate to Post-uprising Tunisia
Authors: Mullin Corinna , Rouabah Brahim
Published: November 2016

Extending the timeframe of analysis beyond the post-uprising period, Corinna Mullin and Brahim Rouabah retrace the way in which the state of emergency has functioned as a discourse of power and a modality of governance throughout the colonial and postcolonial eras. Specifically, the article focuses on how the state of emergency contributes to the reinforcement of dominant narratives about national identity, and the foreclosure of more radical alternative political, social and economic projects outside of the colonial-modern norm.
Art, Power and Knowledge: Claiming Public Space in Tunisia
Authors: Tripp Charles
Published: November 2016

Charles Tripp argues that through artistic interventions – graffiti, visual street art, performances, demonstrations, banners, slogans – citizens have appropriated the public sphere. Despite the monitoring of political dissent through persuasion or coercion, an activist public has created highly visible public spaces, assisted and encouraged by citizen artists. They have generated debates and have helped to give substance to competing visions of the republic.
The Role of International ngos in the Development of Democracy in Rural China
Authors: Yin Dongshui , Guo Xiaoguang
Published: November 2016

The involvement of international non-governmental organizations (ingos) in the efforts to develop democracy is a global phenomenon in the context of globalization. ingos have played a part in the development of democracy in rural China. Given domestic reformers’ technical need for village elections, the important role of village elections, and the vision of ingos for boosting democracy, ingos have sought cooperation with the government and reached where village elections are held with their resources to provide financial, technical, intellectual and other support for pushing forward elections and the reform. To some extent, these ingos have contributed to the development of democracy in rural China. However, the large-scale fast movement of people in China has resulted in a large number of “vacant” villages. Against such a backdrop, ingos have shown less interest in village elections and shifted some of their attention to other areas. In the process of developing democracy, China should adopt an open and rational attitude towards the ingos, take advantage of their strengths, and avoid considering them either angels or demons.