bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved glucose homeostasis in male obese Zucker rats coincides with enhanced baroreflexes and activation of the nucleus tractus solitarius
Authors: Chaudhary Parul , Schreihofer Ann M.
Published: September 2018

Young adult male obese Zucker rats (OZR) develop insulin resistance and hypertension with impaired baroreflex-mediated bradycardia and activation of nucleus tractus solitarius (NTS). Because type 1 diabetic rats also develop impaired baroreflex-mediated NTS activation, we hypothesized that improving glycemic control in OZR would enhance compromised baroreflexes and NTS activation. Fasting blood glucose measured by telemetry was comparable in OZR and lean Zucker rats (LZR) at 12–17 wk. However, with access to food, OZR were chronically hyperglycemic throughout this age range. By 15–17 wk of age, tail samples yielded higher glucose values than those measured by telemetry in OZR but not LZR, consistent with reports of exaggerated stress responses in OZR. Injection of glucose (1g/kg ip) produced larger rises in glucose and areas under the curve in OZR than LZR. Treatment with metformin (300 mg·kg−1·day−1) or pioglitazone (5 mg·kg−1·day−1) in drinking water for 2–3 wk normalized fed glucose levels in OZR with no effect in LZR. After metformin treatment, area under the curve for blood glucose after glucose injection was reduced in OZR and comparable to LZR. Hyperinsulinemia was slightly reduced by each treatment in OZR, but insulin was still greatly elevated compared with LZR. Neither treatment reduced hypertension in OZR, but both treatments significantly improved the blunted phenylephrine-induced bradycardia and NTS c-Fos expression in OZR with no effect in LZR. These data suggest that restoring glycemic control in OZR enhances baroreflex control of heart rate by improving the response of the NTS to raising arterial pressure, even in the presence of hyperinsulinemia and hypertension.
Heat stress decreases metabolic flexibility in skeletal muscle of growing pigs
Authors: Zhao Lidan , McMillan Ryan P. , Xie Guohao , Giridhar Samantha G. L. W. , Baumgard Lance H. , El-Kadi Samer , Selsby Joshua , Ross Jason , Gabler Nicholas , Hulver Matthew W. , Rhoads Robert P.
Published: September 2018

Heat-stressed pigs experience metabolic alterations, including altered insulin profiles, reduced lipid mobilization, and compromised intestinal integrity. This is bioenergetically distinct from thermal neutral pigs on a similar nutritional plane. To delineate differences in substrate preferences between direct and indirect (via reduced feed intake) heat stress effects, skeletal muscle fuel metabolism was assessed. Pigs (35.3 ± 0.8 kg) were randomly assigned to three treatments: thermal neutral fed ad libitum (TN; 21°C, n = 8), heat stress fed ad libitum (HS; 35°C, n = 8), and TN, pair-fed/HS intake (PF; n = 8) for 7 days. Body temperature (TB) and feed intake (FI) were recorded daily. Longissimus dorsi muscle was biopsied for metabolic assays on days −2, 3, and 7 relative to initiation of environmental treatments. Heat stress increased TBand decreased FI ( P < 0.05). Heat stress inhibited incomplete fatty acid oxidation and glucose oxidation ( P < 0.05). Metabolic flexibility decreased in HS pigs compared with TN and PF controls ( P < 0.05). Both phosphofructokinase and pyruvate dehydrogenase (PDH) activities increased in PF ( P < 0.05); however, TN and HS did not differ. Heat stress inhibited citrate synthase and β-hydroxyacyl-CoA dehydrogenase (β-HAD) activities ( P < 0.05). Heat stress did not alter PDH phosphorylation or carnitine palmitoyltransferase 1 abundance but reduced acetyl-CoA carboxylase 1 (ACC1) protein abundance ( P < 0.05). In conclusion, HS decreased skeletal muscle fatty acid oxidation and metabolic flexibility, likely involving β-HAD and ACC regulation.
Microneurography as a tool to study the function of individual C-fiber afferents in humans: responses from nociceptors, thermoreceptors, and mechanoreceptors
Authors: Ackerley Rochelle , Watkins Roger Holmes
Published: September 2018

The technique of microneurography—recording neural traffic from nerves in awake humans—has provided us with unrivaled insights into afferent and efferent processes in the peripheral nervous system for over 50 years. We review the use of microneurography to study single C-fiber afferents and provide an overview of the knowledge gained, with views to future investigations. C-fibers have slowly conducting, thin-diameter, unmyelinated axons and make up the majority of the fibers in peripheral nerves (~80%). With the use of microneurography in humans, C-fiber afferents have been differentiated into discrete subclasses that encode specific qualities of stimuli on the skin, and their functional roles have been investigated. Afferent somatosensory information provided by C-fibers underpins various positive and negative affective sensations from the periphery, including mechanical, thermal, and chemical pain (C-nociceptors), temperature (C-thermoreceptors), and positive affective aspects of touch (C-tactile afferents). Insights from microneurographic investigations have revealed the complexity of the C-fiber system, methods for delineating fundamental C-fiber populations in a translational manner, how C-fiber firing can be used to identify nerve deficits in pathological states, and how the responses from C-fibers may be modified to change sensory percepts, including decreasing pain. Understanding these processes may lead to future medical interventions to diagnose and treat C-fiber dysfunction.

NEW & NOTEWORTHY The technique of microneurography allows us to directly investigate the functional roles of single C-fiber afferents in awake human beings. Here we outline and discuss the current field of C-fiber research on this heterogeneous population of afferents in healthy subjects, in pathological states, and from a translational perspective. We cover C-fibers encoding touch, temperature, and pain and provide perspectives on the future of C-fiber microneurography investigations in humans.
Extrasynaptic α5GABAA receptors on proprioceptive afferents produce a tonic depolarization that modulates sodium channel function in the rat spinal cord
Authors: Lucas-Osma Ana M. , Li Yaqing , Lin Shihao , Black Sophie , Singla Rahul , Fouad Karim , Fenrich Keith K. , Bennett David J.
Published: September 2018

Activation of GABAA receptors on sensory axons produces a primary afferent depolarization (PAD) that modulates sensory transmission in the spinal cord. While axoaxonic synaptic contacts of GABAergic interneurons onto afferent terminals have been extensively studied, less is known about the function of extrasynaptic GABA receptors on afferents. Thus, we examined extrasynaptic α5GABAA receptors on low-threshold proprioceptive (group Ia) and cutaneous afferents. Afferents were impaled with intracellular electrodes and filled with neurobiotin in the sacrocaudal spinal cord of rats. Confocal microscopy was used to reconstruct the afferents and locate immunolabelled α5GABAA receptors. In all afferents α5GABAA receptors were found throughout the extensive central axon arbors. They were most densely located at branch points near sodium channel nodes, including in the dorsal horn. Unexpectedly, proprioceptive afferent terminals on motoneurons had a relative lack of α5GABAA receptors. When recording intracellularly from these afferents, blocking α5GABAA receptors (with L655708, gabazine, or bicuculline) hyperpolarized the afferents, as did blocking neuronal activity with tetrodotoxin, indicating a tonic GABA tone and tonic PAD. This tonic PAD was increased by repeatedly stimulating the dorsal root at low rates and remained elevated for many seconds after the stimulation. It is puzzling that tonic PAD arises from α5GABAA receptors located far from the afferent terminal where they can have relatively little effect on terminal presynaptic inhibition. However, consistent with the nodal location of α5GABAA receptors, we find tonic PAD helps produce sodium spikes that propagate antidromically out the dorsal roots, and we suggest that it may well be involved in assisting spike transmission in general.

NEW & NOTEWORTHY GABAergic neurons are well known to form synaptic contacts on proprioceptive afferent terminals innervating motoneurons and to cause presynaptic inhibition. However, the particular GABA receptors involved are unknown. Here, we examined the distribution of extrasynaptic α5GABAA receptors on proprioceptive Ia afferents. Unexpectedly, these receptors were found preferentially near nodal sodium channels throughout the afferent and were largely absent from afferent terminals. These receptors produced a tonic afferent depolarization that modulated sodium spikes, consistent with their location.
Epithelial Cells Attenuate Toll-Like Receptor-Mediated Inflammatory Responses in Monocyte-Derived Macrophage-Like Cells to Mycobacterium tuberculosis by Modulating the PI3K/Akt/mTOR Signaling Pathway
Authors: Yang Yi , Sun Yingfei , Xu Jinrui , Bao Kangda , Luo Meihui , Liu Xiaoming , Wang Yujiong
Published: September 2018

Both alveolar macrophages (AMs) and alveolar epithelial cells (AECs) are main targets of Mycobacterium tuberculosis (M. tuberculosis (Mtb)). Intercellular communications between mucosal AECs and AMs have important implications in cellular responses to exogenous insults. However, molecular mechanisms underpinning interactions responding to Mtb remain largely unknown. In this study, impacts of AECs on Toll-like receptor- (TLR-) mediated inflammatory responses of AMs to Mtb virulent strain H37Rv were interrogated using an air-liquid interface (ALI) coculture model of epithelial A549 cells and U937 monocyte-derived macrophage-like cells. Results showed that Mtb-activated TLR-mediated inflammatory responses in U937 cells were significantly alleviated when A549 cells were coinfected with H37Rv, in comparison with the infection of U937 cells alone. Mechanistically, PI3K/Akt/mTOR signaling was involved in the epithelial cell-modulated Mtb-activated TLR signaling. The epithelial cell-attenuated TLR signaling in U937s could be reversed by PI3K inhibitor LY294002 and mTOR inhibitor rapamycin, but not glycogen synthase kinase 3β inhibitor LiCl, suggesting that the epithelially modulated-TLR signaling in macrophages was in part caused by inhibiting the TLR-triggered PI3K/Akt/mTOR signaling pathway. Together, this study demonstrates that mucosal AEC-derived signals play an important role in modulating inflammatory responses of AMs to Mtb, which thus also offers an insight into cellular communications between AECs and AMs to Mtb infections.
Effects of Selenium Supplementation on Graves’ Disease: A Systematic Review and Meta‐Analysis
Authors: Zheng Huijuan , Wei Junping , Wang Liansheng , Wang Qiuhong , Zhao Jing , Chen Shuya , Wei Fan
Published: September 2018

Low selenium status is associated with increased risk of Graves’ disease (GD). While several trials have discussed the efficacy of selenium supplementation for thyroid function, in GD patients, the effectiveness of selenium intake as adjuvant therapy remains unclear. In this systematic review and meta‐analysis, we aimed to determine the efficacy of selenium supplementation on thyroid function in GD patients. Two reviewers searched PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and four Chinese databases for studies published up to October 31, 2017. RCTs comparing the effect of selenium supplementation on thyroid hyperfunction in GD patients on antithyroid medication to placebo were included. Serum free thyroxine (FT4), free triiodothyronine (FT3), thyrotrophic hormone receptor antibody (TRAb), and thyroid‐stimulating hormone (TSH) levels were assessed. Ten trials involving 796 patients were included. Random‐effects meta‐analyses in weighted mean difference (WMD) were performed for 3, 6, and 9 months of supplementation and compared to placebo administration. Selenium supplementation significantly decreased FT4 (WMD=‐0.86 [confidence interval (CI)‐1.20 to ‐0.53]; p=0.756; I2=0.0%) and FT3 (WMD=‐0.34 [CI‐0.66 to ‐0.02]; p=0.719; I2=0.0%) levels at 3 months, compared to placebo administration; these findings were consistent at 6 but not 9 months. TSH levels were more elevated in the group of patients taking selenium than in the control group at 3 and 6, but not 9 months. TRAb levels decreased at 6 but not 9 months. At 6 months, patients on selenium supplementation were more likely than controls to show improved thyroid function; however, the effect disappeared at 9 months. Whether these effects correlate with clinically relevant measures remains to be demonstrated.
The Role of Acetyl Cysteine in Cocaethylene (Non-Acetaminophen) Acute Liver Failure
Authors: Hassen Getaw Worku , Dhaliwal Amaninder , Jenninigs Catherine Ann , Kalantari Hossein
Published: September 2018

Background.Acute liver failure can result from acetaminophen overdose, viral infection, toxins, and other disease conditions. Liver transplant is available in limited fashion and the criteria are strict as to who should get an available liver. N- Acetyl Cysteine (NAC) has been used in non-acetaminophen induced liver failure with success. Here we report a case of acute liver failure from cocaethylene that was reversed with NAC along with other medical therapy.Case Presentation.A 50-year-old female patient presented to the Emergency Department (ED) with a two-day history of coffee ground vomiting and hematemesis. She reported occasional substance abuse and heavy alcoholism. She reported shortness of breath and chest pain from the recurrent forceful vomiting. The rest of the review of systems was unremarkable except a fall from intoxication. Physical examination revealed anicteric conjunctiva and nontender abdomen and her vital signs were within normal limits. Initial blood work revealed acute liver and renal failure. The patient was started with general medical management and liver transplant service rejected the case due to active substance abuse. She underwent brief hemodialysis and was started on NAC. Over the course of her hospital stay her liver function and kidney function improved significantly and patient was discharged to home.Conclusion.In cases where liver transplant is not an option for various reasons including active substance abuse, a trial of N-Acetyl Cysteine may be beneficial and should be considered in the Emergency Department.
Numerical Analysis of Laterally Loaded Piles Affected by Bedrock Depth
Authors: Choi Younggyun , Kim Janghwan , Youn Heejung
Published: September 2018

This study investigates the lateral behavior of pile foundations socketed into bedrocks using 3D finite difference analysis. The lateral load‐displacement curve, pile deflection, and bending moment distribution were obtained for different bedrock depths between 3 and 20 m. It was discovered that bedrocks that have a depth of 7 m (7D) or less influence the lateral behavior of the pile. The p‐y curves were collected at depths of 2.0–4.5 m, and the effect of the bedrock on the curves was evaluated. It was observed that the p‐y curves were significantly affected by the material properties of the bedrock if the rock is located in close proximity (within 3D), but the effect is diminished if the p‐y curves were 3.5 m (3.5D) or farther from the bedrock.
Di-2-ethylhexylphthalate May Be a Natural Product, Rather than a Pollutant
Authors: Ortiz Aurelio , Sansinenea Estibaliz
Published: September 2018

Di-2-ethylhexylphtalate is an ester of phthalic acid that has been used as plasticizer in many materials. Due to the extended use, it has been persistently found in different environments being classified as a pollutant with some risks for human health. However, in the last years, it has been found that this compound is produced by plants or microorganisms like bacteria or fungi. This finding opened a serious debate about the origin of this compound and questioned if it is a real pollutant or a natural metabolite with some biological activities that could help us in several ways. This review tries to give some data of the different points of view about this question.
DC/TMD Examiner Protocol: Longitudinal Evaluation on Interexaminer Reliability
Authors: Skeie Marit Slåttelid , Frid Paula , Mustafa Manal , Aßmus Jörg , Rosén Annika
Published: September 2018

Objectives. The objectives of this study were to assess the interexaminer agreement between one “reference” (gold standard) and each of two examiners, using the DC/TMD examination method, Axis I and to evaluate whether a recalibration changed reliability values. Methods. Participants (4 healthy and 12 TMD patients) in 2013 underwent a clinical examination according to DC/TMDs, Axis I. In 2014, additionally 16 participants (4 healthy and 12 TMD patients) were recruited. Two trainee examiners (one more experienced) and one “reference examiner” (gold standard) at both sessions assessed the participants. Calibration preparation (2013): The clinical protocol was sent to the trainee examiners with a request that its verbal commands should be learned by heart. An eight-hour-course was provided on the day preceding the examination session day. Recalibration preparation (2014): The same examiners in advance to this year’s examination session were also asked to recapture the protocol’s instructions (verbal commands to be learned by heart) and go through the information from the 2013 course and encouraged to contact by e-mail in case of unclear subjects. At a meeting prior to the examination session, they were also given the opportunities to ask questions. The interexaminer agreements in 2013 and 2014 between the “reference” and each examiner were analysed using Bland–Altman plots, intraclass correlation coefficient, Cohen’s kappa, and consistency values. Results. For the majority of the gathered data, no clear change of agreement between 2013 and 2014 could be observed, and only one muscle zone in 2014 could show any clear difference in agreement between the examiners. Conclusions. No clear and consistent difference in the level of agreement between the two examiners could be observed, although one was more experienced than the other. Likewise, for most components of the DC/TMD tool, recalibration of examiners did not change the reliability findings.
Cosine Matching Imaging Method for Rotating Scanning Synthesis Aperture Imaging Radiometer
Authors: Chen Jianfei , Zhu Xiaowei , Zhang Sheng , Li Yuanjiang
Published: September 2018

Millimeter-wave synthesis aperture imaging radiometer (SAIR) can realize high-resolution observations without requiring the real large aperture antenna. Among the SAIRs, the Rotating Scanning SAIR (RS-SAIR) with linear sparse array is a popular system with low redundancy and high reliability. However, due to the lack of matched imaging methods, its imaging precision is usually low. For improving its imaging precision, a novel Cosine Matching Imaging (CMI) method is proposed in this paper. In CMI method, according to the characteristic of rotating projection imaging, the angle-orientation image is constituted by the 1D projection images measured by RS-SAIR in a series of angles firstly. Then, according to the trajectory of the target in angle-orientation image, the pixel values of the brightness temperature image are extracted by cosine matching method from the angle-orientation image one by one. The simulation results demonstrate that the proposed CMI imaging method has higher reconstruction accuracy for the RS-SAIR.
Data-Driven and Low-Sparsity False Data Injection Attacks in Smart Grid
Authors: Tian Jiwei , Wang Buhong , Li Xia
Published: September 2018

Recent researches on data-driven and low-sparsity data injection attacks have been presented, respectively. To combine the two main goals (data-driven and low-sparsity) of research, this paper presents a data-driven and low-sparsity false data injection attack strategy. The proposed attacking strategy (EID: Eliminate-Infer-Determine) is divided into three stages. In the first step, the intercepted data is preprocessed by sparse optimization techniques to eliminate the outliers. The recovered data is then exploited to learn about the system matrix based on the parallel factorization algorithm in the second step. In the third step, the approximated system matrix is applied for the design of sparse attack vector based on the convex optimization. The simulation results show that the EID attack strategy achieves a better performance than the improved ICA-based attack strategy in constructing perfect sparse attack vectors. What is more, data-driven implementation of the proposed strategy is also presented which ensures attack performance even without the prior information of the system.
Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes
Authors: Wang Kexin , Li Hongyan , Wang Hongxing , Wang Jun-hui , Song Feng , Sun Yu
Published: September 2018

Neurons suffer detrimental effects from β-amyloid toxicity in Alzheimer’s disease. The exercise hormone, irisin, is found to induce a neuroprotective gene program and facilitates the beneficial effects on cognitive function. But no effort is made to test its direct protective effects on neurons against the Aβ-induced cell toxicity so far. In the present study, we investigated whether irisin could protect neurons against Aβ- (25–35) induced cell damage and explored the possible underlying mechanisms. Primary cell cultures of astrocytes and neurons were established. Conditioned medium from astrocyte was collected for the treatment and biochemistry assay study. To explore the protein expression changes, Western blot and ELISA assays were used in these in vitro cell culture models. Exposure of hippocampal neurons to 10 μM Aβ (25–35) caused significant reduction on cell viability, and the toxic effect was not significantly reduced by the coadministration of irisin. However, pretreated astrocyte-conditioned medium with irisin for 12 hours notably protected the neurons from the toxicity of Aβ. Also, we found that irisin could attenuate the release of IL-6 and IL-1β from cultured astrocytes and decrease the expression level of COX-2 and phosphorylation of AKT. Last, we found that irisin could reduce NFκB activation in astrocyte exposed to Aβ by preventing the phosphorylation and the loss of IκBα. Our finding may provide novel evidence for the future application of irisin in the treatment of Alzheimer’s disease and the memory dysfunction in diabetes mellitus.
Long-Term Consequences of Nonclosure of Mesenteric Defects after Traditional Right Colectomy
Authors: Tsai Kai-Lung , Lai Wei-Hung , Lee Ko-Chao , Lin Shung-Eing , Chang Chia-Lo , Lu Chien-Chang , Hu Wan-Hsiang , Chuah Seng-Kee , Chen Hong-Hwa
Published: September 2018

Background. There are still discrepancies among general/colorectal surgeons regarding closure of mesenteric defect in scientific literature. This study aimed to assess the long-term consequences of nonclosure of the mesenteric defect after open right colectomy.Methods. A 7-year retrospectively collected and continuous database revealed 212 consecutive patients who had undergone traditional right colectomy without closing the mesenteric defects at Kaohsiung Chung-Gung Memorial Hospital; all patients were operated by a single surgeon. Among these patients, 17 were excluded (those who died within 30 days after surgery or those who received an end ileostomy). The mean age of the 195 patients (58% men and 42% women) was 61.6 ± 12.6 years, and the follow-up period was 4.1 ± 2.8 years (interquartile range 0.09 ~ 10.4).Results. Forty-four patients (22.5%) encountered intestinal obstruction. Nine (20.4%) required surgical intervention. The cause of intestinal obstruction was adhesion (n=1), ventral hernia (n=1), and cancer recurrence (n=7). Conservative treatment was successful in 35 patients. The intestinal obstruction group (n = 44) were similar to the no-intestinal obstruction group (n = 151) in terms of the following parameters: age, sex, previous abdominal surgery, indication for colectomy, and procedure related complications. Carcinomatosis was found to increase the incidence of intestinal obstruction. No patient developed intestinal obstruction because of the nonclosure of mesenteric defects after right colectomy.Conclusion. This study suggested that routine procedure of closing the mesenteric defect after open right colectomy might not be beneficial. Additional studies with extended long-term follow-up periods are needed to confirm the benefits of the nonclosure.
Radiotherapy Activates and Protease Inhibitors Inactivate Matrix Metalloproteinases in the Dentinoenamel Junction of Permanent Teeth
Authors: Queiroz Alexandra Mussolino , Bonilla Claudia María Carpio , Palma-Dibb Regina Guenka , Oliveira Harley Francisco , Nelson-Filho Paulo , Silva Léa Assed Bezerra , Lucisano Marília Pacífico , Paula-Silva Francisco Wanderley Garcia
Published: September 2018

The objectives of this study were to investigate changes in the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9 in permanent teeth with or without exposure to radiotherapy, and the role of proteinase inhibitors in their inactivation. In situ zymography and immunofluorescence assays were performed to evaluate the activity and expression of two key gelatinases (MMP-2 and MMP-9) in sections of permanent molars, assigned to irradiated and nonirradiated subgroups. Dental fragments were exposed to radiation at a dose of 2 Gy fractions for 5 consecutive days until a cumulative dose of 60 Gy was reached. To evaluate the effect of protease inhibitors on MMPs, teeth were immersed in 0.5 mL of 0.12% chlorhexidine digluconate (CHX), 0.05% sodium fluoride (NaF), 400 μM polyphenol epigallocatechin-3-gallate (EGCG), or distilled water (control) for 1 h. Fluorescence in the dentinoenamel junction (DEJ) was evaluated in 3 areas of the tooth: cervical, cuspal, and pit. These regions were photographed using a fluorescence microscope at 1.25× and 5× magnifications. Results were analyzed using the D’Agostino-Person normality test, and the Kruskal-Wallis, Dunn, and Wilcoxon tests for intergroup and paired comparisons (α = 0.05). The fluorescence intensity/mm2 in the DEJ at the three regions studied was higher in the irradiated teeth (p < 0.05) than in the nonirradiated teeth, revealing regions of expression of MMP-2 and MMP-9 by immunofluorescence. Postradiotherapy treatment with different solutions (CHX, NaF, and EGCG) led to lower fluorescence intensity/mm2 in irradiated teeth than in the control group (distilled water; p < 0.05), as a result of MMP inactivation. In conclusion, irradiation increased gelatinase activity in all regions of the DEJ. Treatment with 0.12% CHX, 0.05% NaF, and 400 μM polyphenol EGCG postradiotherapy inactivated enzyme activity.
The Future: Experimental Therapies for Renal Disease in Diabetes
Authors: Fouli Georgia E. , Gnudi Luigi
Published: September 2018

Diabetic nephropathy is the commonest cause of end-stage renal disease and affects between 30 and 45% of patients with diabetes mellitus. There is no cure for diabetic nephropathy and the current management of this condition includes glycaemic control, blockade of the renin-angiotensin aldosterone system and lifestyle changes. However, many patients eventually progress to end-stage renal disease. The exact pathogenesis of diabetic nephropathy is still being researched, and recent advances have led to the development of several novel potential therapeutic targets. There are a number of different experimental therapies that are currently being assessed. Generally, these can be separated into drugs targeting vasculature/haemodynamic effects, drugs targeting inflammation and drugs targeting oxidative stress. Drugs targeting the vasculature include Tie-2 activators, ­sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists. Anti-inflammatory therapies include inflammatory cytokines inhibitors, pentoxifylline, as well as anti-transforming growth factor α/­epiregulin therapies. Finally, anti-oxidative stress therapies include nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors and allopurinol. Many new trials are providing promising results and it is likely that some of these therapies will be available for clinical use within the next decade. This article will seek to outline the main advancements in each of these experimental therapies for diabetic nephropathy. Results: Abnormal vascular remodelling, inflammation and oxidative stress seem to be the 3 main sources from which future new drugs for diabetic kidney disease will originate.
Quantitative Measurements of Motor Function in Alzheimer’s Disease, Frontotemporal Dementia, and Dementia with Lewy Bodies: A Proof-of-Concept Study
Authors: Jeppesen Kragh Frederikke , Bruun Marie , Budtz-Jørgensen Esben , Hjermind Lena Elisabeth , Schubert Robin , Reilmann Ralf , Nielsen Jørgen Erik , Hasselbalch Steen Gregers
Published: September 2018

Background: This study examines the efficacy of using quantitative measurements of motor dysfunction, compared to clinical ratings, in Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Methods: In this cross-sectional study, 49 patients with a diagnosis of AD (n = 17), FTD (n = 19), or DLB (n = 13) were included and underwent cognitive testing, clinical motor evaluation, and quantitative motor tests: pronation/supination hand tapping, grasping and lifting, and finger and foot tapping. Results: Our results revealed significantly higher Q-Motor values in pronation/supination and in grip lift force assessment in AD, FTD, and DLB compared to healthy controls (HC). Q-Motor values detected significant differences between AD and HC, while clinical ratings did not. Conclusion: Our results suggest that quantitative measurements provide more objective and sensitive measurements of motor dysfunction in dementia.
Elevation of the Chemokine Pair CXCL10/CXCR3 Initiates Sequential Glial Activation and Crosstalk During the Development of Bimodal Inflammatory Pain after Spinal Cord Ischemia Reperfusion
Authors: Yu Qian , Tian Da-Li , Tian Ye , Zhao Xi-Tong , Yang Xue-Ying
Published: September 2018

Background/Aims: Spinal microglia and astrocytes are the main responders to the inflammatory cascade and process pain through various neural interactions. CXCL10 is a late-phase protein that accelerates arteriogenesis during reperfusion through CXCR3. However, the early-phase expression (within 72 h postoperatively) of CXCL10 and CXCR3 during the development of ischemia-reperfusion (IR)-induced inflammatory pain remains unclear. We investigated whether this chemokine pair participates in glial interactions during early-phase IR injury. Methods: A rat model was induced by an 8-min occlusion of the aortic arch. Temporal assessments of mechanical and thermal allodynia and the protein levels of CXCL10 and CXCR3 were determined through measurements of paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) and Western blotting assays. The co-localization of various cells with glial cells was detected by double immunofluorescence. The effects of CXCL10/CXCR3 on glial interactions were explored by intrathecal treatment with specific inhibitors (AMD487, minocycline and fluorocitrate) and recombinant CXCL10, and subsequent release of cytokines was assessed by ELISAs. Results: The IR injury initiated bimodal allodynia within 72 h of reperfusion, as illustrated by two W-shape trends in the PWTs and PWLs with two minima at 12 and 48 h post-IR. Allodynia was highly correlated with overexpression of CXCL10 and CXCR3, which were expressed in microglia at the early stage and in both microglia and astrocytes at the late stage, as shown by increased CXCL10 and CXCR3 immunoreactivities and double-labeled cells. AMD487 and minocycline injections exerted comparable inhibitory effects on CXCR3 and Iba-1 and on GFAP immunoreactivity at 12 and 48 h post-IR, and these inhibitory effects were only observed at 48 h following fluorocitrate injection. The levels of TNF-α and IL-6 showed variations in concert with the changes in Iba-1 and GFAP immunoreactivities. Recombinant CXCL10 injection reversed the abovementioned effects. Conclusion: The results showed that CXCL10/CXCR3 are involved in bimodal inflammatory pain during early-phase IR injury. The sequential activation of and crosstalk between microglia and astrocytes mediated through CXCR3 upregulation suggested that treatments targeting specific cell types are important in post-IR allodynia.
The first record of The Blue Admiral Kaniska canace Linnaeus, 1763 (Nymphalidae: Lepidoptera) from Bangladesh
Authors: Neogi Amit Kumer , Islam Md Jayedul , Shalauddin Md , Mondal Anik Chandra , Hossain Safayat
Published: September 2018

Moulvibazar district has been recognized as one of the biodiversity rich pockets close to the boundary side of Assam of India and situated in the North-eastern part of Bangladesh. Adompur reserve forest is one of the biodiversity hotspot  in the North-eastern. The current article confirm, the presence of  Kaniska canace Linnaeus, 1763, (Nymphalidae: Lepidoptera) which was not previously recorded in Bangladesh. This species was first recorded on 17 March 2017 at 15.30 (GMT+6) local time in the coordination of  N 24°18'9.46"; E 91°55'4.23" at Kauyargola   forest   beat, Adampur reserve forest in Moulvibazar District.
Alarming population status of the Grizzled Giant Squirrel Ratufa macroura (Mammalia: Rodentia: Sciuridae) in Chinnar Wildlife Sanctuary, the Western Ghats, India
Authors: Thomas Kiran , Nameer Paingamadathil Ommer
Published: September 2018

This study was carried out to assess the population of Ratufa macroura in Chinnar Wildlife Sanctuary located in the Kerala part of the southern Western Ghats.  The population density of Ratufa macroura was estimated to be 15.26 squirrels/km2.  The total count method, however, gave the population range between 11 to 14 squirrels.  The current population estimation is about 78–85 % lesser than the previous population estimation of the Ratufa macroura carried out in 1993 and 2007 respectively, which is quite alarming.  The following conservation recommendations are suggested for the long-term conservation of R. macroura, which include habitat restoration to maintain the canopy contiguity and regulation of the pilgrimage and the tourism activities in and around the R. macroura habitat.  Urgent steps should also be taken to undertake studies on the genetics of R. macroura.  It is also suggested that systematic and scientific monitoring of the population of R. macroura be undertaken on a regular basis.
Checklist of the avifauna of Sagareshwar Wildlife Sanctuary, Maharashtra, India
Authors: Apte Sharad Datt , Tuljapurkar Vijay Bhagwan , Jathar Girish Avinash
Published: September 2018

Sagareshwar Wildlife Sanctuary in southern Maharashtra is one of the smallest sanctuaries in the state encompassing 10.87km2.  Our studies documenting avifauna of this wildlife sanctuary revealed the presence of 138 bird species including 71 residents, 21 local migrants, nine breeding migrants, 24 winter visitors and 13 species whose status could not be determined.  The sanctuary harbours three Indian endemics, 23 South Asian endemics, and one Near Threatened bird species.
Notes on Jasminum andamanicum N.P. Balakr. & N.G. Nair (Oleaceae) from Andaman & Nicobar Islands, India
Authors: Murugan P. , Karthigeyan K.
Published: September 2018

Jasminum andamanicum is endemic to the Andaman group of Islands. It is assessed as Endangered as per the IUCN red list criteria using primary and secondary information on trends in EOO, AOO and numbers of collection. Taxonomy of the species, distribution, herbarium image, and causes of rarity are discussed.
Impact of Aortic Valve Stenosis on Coronary Hemodynamics and the Instantaneous Effect of Transcatheter Aortic Valve Implantation
Authors: Wiegerinck Esther M.A. , van de Hoef Tim P. , Rolandi M. Cristina , Yong ZeYie , van Kesteren Floortje , Koch Karel T. , Vis Marije M. , de Mol Bas A.J.M. , Piek Jan J. , Baan Jan
Published: September 2018

Background—

Aortic valve stenosis (AS) induces compensatory alterations in left ventricular hemodynamics, leading to physiological and pathological alterations in coronary hemodynamics. Relief of AS by transcatheter aortic valve implantation (TAVI) decreases ventricular afterload and is expected to improve microvascular function immediately. We evaluated the effect of AS on coronary hemodynamics and the immediate effect of TAVI.

Methods and Results—

Intracoronary pressure and flow velocity were simultaneously assessed at rest and at maximal hyperemia in an unobstructed coronary artery in 27 patients with AS before and immediately after TAVI and in 28 patients without AS. Baseline flow velocity was higher and baseline microvascular resistance was lower in patients with AS as compared with controls, which remained unaltered post-TAVI. In patients with AS, hyperemic flow velocity was significantly lower as compared with controls (44.5±14.5 versus 54.3±18.6 cm/s;
P
=0.04). Hyperemic microvascular resistance (expressed in mm Hg·cm·s
−1
) was 2.10±0.69 in patients with AS as compared with 1.80±0.60 in controls (
P
=0.096). Coronary flow velocity reserve in patients with AS was lower, 1.9±0.5 versus 2.7±0.7 in controls (
P
<0.001). Improvement in coronary hemodynamics after TAVI was most pronounced in patients without post-TAVI aortic regurgitation. In these patients (n=20), hyperemic flow velocity increased significantly from 46.24±15.47 pre-TAVI to 56.56±17.44 cm/s post-TAVI (
P
=0.003). Hyperemic microvascular resistance decreased from 2.03±0.71 to 1.66±0.45 (
P
=0.050). Coronary flow velocity reserve increased significantly from 1.9±0.4 to 2.2±0.6 (
P
=0.009).

Conclusions—

The vasodilatory reserve capacity of the coronary circulation is reduced in AS. TAVI induces an immediate decrease in hyperemic microvascular resistance and a concomitant increase in hyperemic flow velocity, resulting in immediate improvement in coronary vasodilatory reserve.
Stent Fracture After Sirolimus-Eluting Stent Implantation
Authors: Ohya Masanobu , Kadota Kazushige , Tada Takeshi , Habara Seiji , Shimada Takenobu , Amano Hidewo , Izawa Yu , Hyodo Yusuke , Miyake Koshi , Otsuru Suguru , Hasegawa Daiji , Tanaka Hiroyuki , Maruo Takeshi , Katoh Harumi , Fuku Yasushi , Goto Tsuyoshi , Mitsudo Kazuaki
Published: September 2018

Background—

Stent fracture (SF) after sirolimus-eluting stent implantation is reported to be associated with target lesion revascularization (TLR) and stent thrombosis. We aimed to assess the clinical impact of SF at 8 years.

Methods and Results—

Between 2002 and 2005, 972 patients (1795 lesions) underwent sirolimus-eluting stent implantation and follow-up angiography within 1 year after index procedure. SF, defined as the complete separation of stent segments or stent struts at follow-up angiography, was observed in 105 lesions (5.8%). The study sample comprised 954 patients (1630 lesions), excluding 147 lesions undergoing TLR and 18 patients (18 lesions) who died or in whom stent thrombosis developed within 1 year after sirolimus-eluting stent implantation. The median follow-up duration was 9.1 years (the first and third quarters, 8.7 and 9.4 years). The primary end point was defined as any TLR. The 8-year cumulative rates of adverse events were estimated by Kaplan–Meier methods with
P
values from log-rank tests. Between patients with and without SF, there were no significant differences in the cumulative rates of all-cause death (23.5% versus 27.6%,
P
=0.35) and cardiac death (4.7% versus 9.1%,
P
=0.14), whereas patients with SF had significantly higher cumulative rates in myocardial infarction (10.1% versus 3.3%,
P
=0.001), very late stent thrombosis (6.8% versus 0.7%,
P
<0.001), any TLR (38.1% versus 10.8%,
P
<0.001), and clinically driven TLR (26.2% versus 6.6%,
P
<0.001).

Conclusions—

SF after sirolimus-eluting stent implantation was consistently associated with higher rates of adverse cardiac events during the 8-year follow-up.
Sildenafil in the Treatment of Raynaud’s Phenomenon Resistant to Vasodilatory Therapy
Authors: Fries Roland , Shariat Kaveh , von Wilmowsky Hubertus , Böhm Michael
Published: September 2018

Background—

Vasodilatory therapy of Raynaud’s phenomenon represents a difficult clinical problem because treatment often remains inefficient and may be not tolerated because of side effects.

Methods and Results—

To investigate the effects of sildenafil on symptoms and capillary perfusion in patients with Raynaud’s phenomenon, we performed a double-blinded, placebo-controlled, fixed-dose, crossover study in 16 patients with symptomatic secondary Raynaud’s phenomenon resistant to vasodilatory therapy. Patients were treated with 50 mg sildenafil or placebo twice daily for 4 weeks. Symptoms were assessed by diary cards including a 10-point Raynaud’s Condition Score. Capillary flow velocity was measured in digital nailfold capillaries by means of a laser Doppler anemometer. While taking sildenafil, the mean frequency of Raynaud attacks was significantly lower (35±14 versus 52±18,
P
=0.0064), the cumulative attack duration was significantly shorter (581±133 versus 1046±245 minutes,
P
=0.0038), and the mean Raynaud’s Condition Score was significantly lower (2.2±0.4 versus 3.0±0.5,
P
=0.0386). Capillary blood flow velocity increased in each individual patient, and the mean capillary flow velocity of all patients more than quadrupled after treatment with sildenafil (0.53±0.09 versus 0.13±0.02 mm/s,
P
=0.0004). Two patients reported side effects leading to discontinuation of the study drug.

Conclusions—

Sildenafil is an effective and well-tolerated treatment in patients with Raynaud’s phenomenon.
TLR2 and MyD88 Contribute to
Lactobacillus casei
Extract–Induced Focal Coronary Arteritis in a Mouse Model of Kawasaki Disease
Authors: Rosenkranz Margalit E. , Schulte Danica J. , Agle Lucila M.A. , Wong Michelle H. , Zhang Wenxuan , Ivashkiv Lionel , Doherty Terence M. , Fishbein Michael C. , Lehman Thomas J.A. , Michelsen Kathrin S. , Arditi Moshe
Published: September 2018

Background—

Kawasaki disease is the most common cause of acquired cardiac disease and acute vasculitis in children, targets the coronary arteries, and can occasionally be fatal. The pathogenesis and the molecular mechanisms remain unknown. After injection of
Lactobacillus casei
cell-wall extract (LCCWE), mice develop a focal coronary arteritis that histopathologically resembles Kawasaki disease, but the mechanism remains unclear. Here, we tested the hypothesis that signaling by Toll-like receptors (TLRs) through their key downstream adaptor molecule myeloid differentiation factor 88 (MyD88) is required for the cellular activation and coronary arteritis produced by LCCWE.

Methods and Results—

Bone marrow–derived macrophages from TLR2- or MyD88-deficient mice were unresponsive to LCCWE-induced stimulation. In contrast, macrophages obtained from TLR4-deficient mice produced the same amount of interleukin-6 as macrophages from wild-type mice after stimulation with LCCWE. Intraperitoneal injection of LCCWE produced severe focal coronary arteritis in TLR4
−/−
and C57BL/6 control mice but not in TLR2
−/−
or MyD88
−/−
mice. Collectively, these results indicate that LCCWE is a potent inducer of nuclear factor-κB via TLR2 but not TLR4 and that this activation proceeds via the MyD88-dependent signaling pathway. In vivo studies suggest that TLR2
−/−
mice are protected from LCCWE-induced coronary arteritis and that this protection is mediated through the adaptor molecule MyD88.

Conclusions—

Our results provide important insights into the molecular signaling in this mouse model of coronary arteritis. We show here that LCCWE-induced coronary arteritis is dependent on intact TLR2 and MyD88 signaling.
Activation of NLRP3 Inflammasome Promotes Foam Cell Formation in Vascular Smooth Muscle Cells and Atherogenesis Via HMGB1
Authors: Wang Rui , Wu Weibin , Li Wen , Huang Shuichuan , Li Zilun , Liu Ruiming , Shan Zhen , Zhang Chunxiang , Li Wen , Wang Shenming
Published: September 2018

Background

This study aimed at investigating whether
NLRP
3 (the Nod like receptor family, pyrin domain‐containing 3 protein) inflammasome activation induced
HMGB
1 (high mobility group box‐1 protein) secretion and foam cell formation in human vascular smooth muscle cells (
VSMC
s) and atherosclerosis in ApoE
−/−
mice.

Methods and Results

VSMC
s or ApoE
−/−
mice were treated with lipopolysaccharides (
LPS
) and/or
ATP
or
LPS
and high‐fat diet to induce
NLRP
3 inflammasome activation.
HMGB
1 distribution and foam cell formation in
VSMC
s were characterized. Liver X receptor α and
ATP
‐binding cassette transporter expression were determined. The impact of
NLRP
3 or receptor for advanced glycation end product silencing,
ZYVAD
‐
FMK
(caspase‐1 inhibitor), glycyrrhizin (
HMGB
1 inhibitor) or receptor for advanced glycation end product antagonist peptide on
HMGB
1 secretion, foam cell formation, liver X receptor α and
ATP
‐binding cassette transporter expression was examined. Expression level of
HMGB
1 in human atherosclerosis obliterans arterial tissues was characterized. Our results found that
NLRP
3 inflammasome activation promoted foam cell formation and
HMGB
1 secretion in
VSMC
s. Extracellular
HMGB
1 was a key signal molecule in inflammasome activation‐mediated foam cell formation. Furthermore, inflammasome activation‐induced
HMGB
1 activity and foam cell formation were achieved by receptor for advanced glycation end product/liver X receptor α /
ATP
‐binding cassette transporter glycyrrhizin. Experiments in vivo found glycyrrhizin significantly attenuated the
LPS
/high‐fat diet‐induced atherosclerosis and serum
HMGB
1 levels in mice. Finally, levels of
HMGB
1 and
NLRP
3 were increased in tunica media adjacent to intima of atherosclerosis obliteran arteries.

Conclusions

Our results revealed that HMGB1 is a key downstream signal molecule of
NLRP
3 inflammasome activation and plays an important role in
VSMC
s foam cell formation and atherogenesis by downregulating liver X receptor α and
ATP
‐binding cassette transporter expression through receptor for advanced glycation end product.
Prognostic Value of Biventricular Strain in Risk Stratifying in Patients With Acute Heart Failure
Authors: Park Jae‐Hyeong , Park Jin Joo , Park Jun‐Bean , Cho Goo‐Yeong
Published: September 2018

Background

Few studies have shown that right ventricular (
RV
) function is independently related to adverse events regardless of left ventricular (
LV
) function in heart failure. We evaluated the prognostic value of global longitudinal strain (
GLS
) of both ventricles in patients with acute heart failure.

Methods and Results

We measured biventricular strains in 1824 randomly selected patients (973 men, aged 70±14 years) from a strain registry. A total of 799 patients (43.8%) died during the median follow‐up duration of 31.7 months. In univariate analysis,
LVGLS
and
RVGLS
were significantly associated with all‐cause mortality. We classified them into 4 strain groups according to
LVGLS
(≥9%) and
RVGLS
(≥12%). On Cox proportional hazards analysis, group 4 (<9%
LVGLS
and <12%
RVGLS
) had the worst prognosis, with a hazard ratio (
HR
) of 1.755 (95% confidence interval [
CI
], 1.473–2.091;
P
<0.001) compared with that of group 1 (≥9%
LVGLS
and ≥12%
RVGLS
). After multivariate analysis, both
LVGLS
(per 1% decrease;
HR
: 1.057; 95%
CI
, 1.029–1.086;
P
<0.001) and
RVGLS
(per 1% decrease;
HR
: 1.022; 95%
CI
, 1.004–1.040;
P
=0.014) were also significant. The
HR
of
RVGLS
<12% was higher in patients without pulmonary hypertension (assessed by maximal tricuspid regurgitation ≤2.8 m/s) after the adjustment of
LVGLS
(
HR
: 1.40 [95%
CI
, 1.11–1.77] versus 1.07 [95%
CI
, 0.88–1.30] with pulmonary hypertension; interaction,
P
=0.043).

Conclusions

In the patients with acute heart failure,
RVGLS
was significantly associated with all‐cause mortality regardless of
LVGLS
, and those with decreased biventricular
GLS
showed the worst prognosis. The predictive power of
RVGLS
was more prominent in the absence of pulmonary hypertension.
The Genealogy and Theology of Isaiah 11:1
Authors: Sumner Stephen T.
Published: September 2018

Isaiah 11:1 traces the genealogy of ideal king back to Jesse and not a Davidic king in order to portray him as a new, or second, David. This depiction was motivated by the religious decline of the Davidides, and it allowed for a sense of disjuncture, or distance, from the Davidic line in order to claim royal legitimacy on theological grounds.