bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Review of Acupuncture for the Treatment of Alcohol Withdrawal Syndrome
Authors: Liu Xiaoxu , Qin Zongshi , Zhu Xiaoming , Yao Qin , Liu Zhishun
Published: July 2018

Background

Acupuncture has been used as a potential therapy for alcohol withdrawal syndrome (AWS), but evidence for its effects on this condition is limited.

Objective

To assess the effects and safety of acupuncture for AWS.

Data sources

Central Register of Controlled Trials (CENTRAL), PubMed, Embase, the Cochrane Library, PsycINFO, Chinese Biomedicine Literature (CBM), China National Knowledge Infrastructure (CNKI) and Wan-Fang Database were searched from their inception to August 2016.

Study eligibility criteria

Randomised controlled trials (RCTs) of drug plus acupuncture or acupuncture alone for the treatment of AWS were included.

Data collection and analysis

Continuous data were expressed as mean difference (MD) with 95% confidence intervals (95% CI). Dichotomous data were expressed as risk ratio (RR) with 95% CI.

Results

Eleven RCTs with 875 participants were included. In the acute phase, two trials reported no difference between drug plus acupuncture and drug plus sham acupuncture in the reduction of craving for alcohol; however, two positive trials reported that drug plus acupuncture was superior to drug alone in the alleviation of psychological symptoms. In the protracted phase, one trial reported acupuncture was superior to sham acupuncture in reducing the craving for alcohol, one trial reported no difference between acupuncture and drug (disulfiram), and one trial reported acupuncture was superior to sham acupuncture for the alleviation of psychological symptoms. Adverse effects were tolerable and not severe.

Conclusion

There was nosignificant difference between acupuncture (plus drug) and sham acupuncture (plus drug) with respect to the primary outcome measure of craving for alcohol among participants with AWS, and no difference in completion rates (pooled results). There was limited evidence from individual trials that acupuncture may reduce alcohol craving in the protracted phase and help alleviate psychological symptoms; however, given concerns about the quantity and quality of included studies, further large-scale and well-conducted RCTs are needed.

Protocol registration

PROSPERO CRD42016039862.
Antidepressant medication and ocular factors in association with the need for anti-VEGF retreatment in neovascular age-related macular degeneration
Authors: Mantel Irmela , Zola Marta , Mir Olivier , Gaillard Raphael , Behar-Cohen Francine
Published: July 2018

Background/Aims

Vascular endothelial growth factor (VEGF) is a key player in the pathogenesis of neovascular age-related macular degeneration (nAMD) and is also involved in the final common pathway of antidepressant medication. This study investigated the relationship between the need for anti-VEGF retreatment in patients with nAMD and antidepressant medication, and the potential impact of ocular structural factors.

Methods

Data from two identical prospective 2-year treatment protocols using ranibizumab or aflibercept in a variable-dosing regimen (‘Observe-and-Plan’) were analysed. Retreatment requirement was compared with antidepressant medication intake (primary outcome) and a variety of ocular factors from baseline and from month 3 response (secondary outcomes), using univariate and multivariate analyses.

Results

Of the 206 included patients (227 eyes), 19 were on antidepressant medication. Their nAMD eyes significantly more often had pigment epithelium detachment (PED, p=0.04). Multivariate analysis revealed a significant association between anti-VEGF retreatment requirement and antidepressant medication use (p=0.027), as well as thicker central retinal thickness at month 3 (p<0.0001) and month 3 PED height (p=0.001).

Conclusion

This study provides evidence that treatment with antidepressant medication increases the anti-VEGF retreatment requirement in patients with nAMD, possibly through the interplay of antidepressant medication, depression status and VEGF levels.
Lower extremity osteoarthritis: optimising musculoskeletal health is a growing global concern: a narrative review
Authors: Leech Richard D , Eyles Jillian , Batt Mark E , Hunter David J
Published: July 2018

The burden of non-communicable diseases, such as osteoarthritis (OA), continues to increase for individuals and society. Regrettably, in many instances, healthcare professionals fail to manage OA optimally. There is growing disparity between the strength of evidence supporting interventions for OA and the frequency of their use in practice. Physical activity and exercise, weight management and education are key management components supported by evidence yet lack appropriate implementation. Furthermore, a recognition that treatment earlier in the disease process may halt progression or reverse structural changes has not been translated into clinical practice. We have largely failed to put pathways and procedures in place that promote a proactive approach to facilitate better outcomes in OA. This paper aims to highlight areas of evidence-based practical management that could improve patient outcomes if used more effectively.
Is sex ratio at birth an appropriate measure of prenatal sex selection? Findings of a theoretical model and its application to India
Authors: Dubuc Sylvie , Sivia Devinderjit Singh
Published: July 2018

Son preference and prenatal sex selection against females have resulted in significant sex ratio at birth (SRB) imbalances well documented in several Asian countries, including India and China. The SRB bias is generally used as indicator for the extent and trends of prenatal sex selection against females. Decreasing fertility levels are expected to increase sex selection and thus SRB bias, since desiring fewer children increases the risk for families to remain sonless (fertility squeeze effect). We developed and employ mathematical models linking family size, birth order and childbearing strategies with population SRB bias. We show that SRB bias can increase despite fewer sex selection interventions occurring, inconsistent with the expectation of the fertility squeeze effect. We show that a disproportionality effect of fertility reduction amplifies SRB bias, in addition to the fertility squeeze effect, making SRB bias an inaccurate indicator for changes in sex selection practices within a population. We propose to use sex selection propensity (proportion of couples intervening) to measure behavioural change and evaluate policies targeting sex selection practices. We apply our findings to India, showing for instance that sex selection propensity in Punjab and Delhi was lower than in Rajasthan or Uttar Pradesh, despite significantly higher SRB bias in the former. While we observe a continuous overall increase in the SRB over the 2005–2010 period in India, our results indicate that prenatal sex selection propensity started declining during that period.
Do ‘physicians in the lead’ support a holistic healthcare delivery approach? A qualitative analysis of stakeholders’ perspectives
Authors: Malik Romana Fattimah , Hilders Carina G J M , Scheele Fedde
Published: July 2018

Objectives

Value-based healthcare implies that healthcare issues are addressed most effectively with the ‘physicians in the lead' (PIL) strategy. This study explores whether PIL also supports a holistic care approach that patients are increasingly demanding.

Design

A qualitative research design was used.

Setting

This study was conducted in a general hospital in the Netherlands with an integrated PIL strategy.

Participants

Semistructured interviews were conducted with 14 hospital stakeholders: 13 stakeholders of an Obstetrics and Gynaecology department (the hospital’s Patient Council (n=1), nurses (n=2), midwives (n=2), physicians (n=2), residents (n=2), the non-medical business managers of the Obstetrics and Gynaecology department (n=2) the Board of Directors (n=2)) and a member of the Dutch National Healthcare Institute’s Innovative Healthcare Professions programme.

Results

According to diverse stakeholders, PIL does not support a holistic healthcare delivery approach, primarily because of the strong biomedical focus of the physicians. Although physicians can be educated to place more emphasis on the holistic outcome, holistic care delivery requires greater integration and teamwork in the care chain. As different healthcare professions are complementary to each other, a new strategy of a ‘team in the lead' was suggested to meet the holistic healthcare demands. Besides this new strategy, there is a need for an extramural care management coordination centre where patients are able to receive support in managing their own care. This centre should also facilitate services similar to the core function of a church or community centre. These services should help patients to deal with different holistic dimensions that are important for their well-being.

Conclusions

The PIL strategy appears to be insufficient for holistic healthcare delivery. A ‘team in the lead’ approach should be considered to meet the holistic healthcare demands. Further research should focus on observing PIL in different cultures and exploring the effectiveness of the strategy ‘team in the lead’.
Diagnostic Value of the Late-Night Salivary Cortisol in the Diagnosis of Clinical and Subclinical Cushing's Syndrome: Results of a Single-Center 7-Year Experience
Authors: Yilmaz Nusret , Tazegul Gokhan , Bozoglan Humeyra , Sari Ramazan , Ozdem Sebahat , Altunbas Hasan Ali , Balci Mustafa Kemal
Published: July 2018

Late-night salivary cortisol (LNSaC) is an easy-to-use test reflecting the free cortisol level in the serum and does not require hospitalization. Controlled studies reported that LNSaC has a high sensitivity and specificity, but have not set a clearly defined cut-off value to be used in the diagnosis of Cushing's syndrome. In this study, we aimed to evaluate the diagnostic performance of LNSaC in patients with clinical Cushing's syndrome (CCS) and subclinical Cushing's syndrome (SCS). The data of 543 patients, whose LNSaC levels were assessed using electrochemiluminescence immunoassay method, were retrospectively evaluated. The study included a total of 324 patients: 58 patients with CCS, 53 patients with SCS, and 213 patients without Cushing's syndrome (NoCS). The cause of the Cushing's syndrome was hypophyseal in 26 patients (45%), adrenal in 24 patients (41%), and ectopic in 8 patients (14%) in the CCS group. Median LNSaC levels were 0.724 (0.107–33) μg/dL in CCS group, 0.398 (0.16–1.02) μg/dL in SCS group, and 0.18 (0.043–0.481) μg/dL in NoCS group (p=0.001). Accordingly, LNSaC had 89.6% sensitivity and 81.6% specificity at a cut-off value of 0.288 μg/dL in the diagnosis of CCS; and had 80.7% sensitivity and 85.1% specificity at a cut-off value of 0.273 μg/dL in the diagnosis of SCS. In the present study, a lower sensitivity and specificity than previously reported was found for LNSaC in the diagnosis of CCS. Moreover, the diagnostic performance of LNSaC in patients with SCS was close to its diagnostic performance in patients with CCS. Each center should determine its own cut-off value based on the method adopted for LNSaC measurement, and apply that cut-off value in the diagnosis of Cushing's syndrome.
4 Use of topical haemostatic dressings in an extended field care model of external haemorrhage
Authors: Barratt J , Welch M , Wright C
Published: July 2018

Introduction

The use of Celox gauze has been established in military practice as an adjunct in the treatment of external haemorrhage. The future character of conflict means that casualties may take longer to reach definitive care. The aim of this study was to test whether Celox Rapid, a topical haemostatic dressing, would maintain haemostasis during extended use in a junctional haemorrhage model.

Methods

An anaesthetised swine underwent simultaneous bilateral femoral arteriotomies; after 30 s of free bleeding Celox Rapid gauze was applied to the wound and pressure was maintained for 1 min. Following inspection for re-bleeding the Celox gauze was covered with standard field dressings and checked for re-bleeding every hour until the 6 hours had elapsed or the animal deceased.

Results

There was no evidence of re-bleeding at any point up to and including 6 hours. The animal was declared deceased shortly afterwards. Celox Rapid gauze maintained haemostasis in extended use in this limited single animal model. Post mortem examination revealed a stable clot at the site of the arteriotomy with no evidence of re-bleeding.

Conclusion

Celox Rapid was effective at achieving initial homeostasis and preventing re-bleeding in this limited study using a single anaesthetised swine. Its potential for use in situations where evacuation and definitive care may be delayed should be explored.
5 The fluro project: a review of the approach and understanding of fluid resuscitation in a military tertiary centre from the perspective of care providers in the emergency setting
Authors: Lowe J , Stevenson L , Wilding D , McLaughlin D , West M
Published: July 2018

Introduction

The term fluid resuscitation (FR) is defined as the use of fluids to restore a state of normovolaemia, or to correct a hypovolaemic state. To establish normovolaeamia via FR, the term ‘fluid bolus’ is used to describe a prescribed fluid volume. As such, the authors looked to investigate the understanding of this term and to review approaches to fluid resuscitation by those healthcare workers closely associate with critically unwell patients.

Methods

A questionnaire was distributed to all clinical staff across Emergency Medicine (EM), Anaesthesia and Theatres (AT), Intensive Care Medicine (ICM) and Acute Medicine (AM). The questionnaire recorded role, area of responsibility, training grade, type, volume and administration time, time to reassessment and parameters to be assessed in relation to a clinical vignette. The results were then compared directly to the NICE Clinical Audit Standards (NCAS) for FR.

Results

153 responses were received from across all working environments. Overall, 52% of respondents gave volumes aligned with NCAS (500 ml). 99% of respondents suggested crystalloid use with 88% giving an appropriate time for administration of less than 15 min. 55% of respondents suggested appropriate review times (0–5 min). 99% of respondents agreed heart rate and blood pressure should be reassessed, but other parameters for monitoring were poorly recognised.

Between specialties, EM suggested larger volumes while ICM were more likely to continuously review the patient during a bolus. AM were the only group to administer fluids over 60 min. EM and ICM were more likely to review lactate as a marker for effect. Higher specialist trainees were more likely to give a larger volume when compared to other grades.

Discussion

The overall perception of a fluid bolus varies between specialties and training grades. Most responses were aligned to NCAS with notable outliers. This suggests a discrepancy in the understanding of the term fluid bolus. This may also cause issues in fluid administration with multiple patients. It is therefore suggested that further work be undertaken on clarifying the term ‘fluid bolus’, aiming to minimise uncertainty and increase understanding to prevent adverse effects.
Who uses rollies? Trends in product offerings, price and use of roll-your-own tobacco in Australia
Authors: Bayly Megan , Scollo Michelle M , Wakefield Melanie A
Published: July 2018

Objective

We examined the roll-your-own (RYO) tobacco product market in Australia from 2001 to 2016. Trends in use of RYO tobacco among Australian adults were examined for 2004–2016.

Methods

Changes in brand availability, pouch sizes and lowest priced products were noted from trade magazines. Prevalence of smoking of RYO and factory-made (FM) cigarettes among those 18 years and older was obtained from five consecutive waves of a large (n>21 000) nationally representative triennial survey from 2004 to 2016. Trends in cigarette use were examined using logistic regression.

Results

Changes in the Australian RYO market from 2001 to 2016 included a doubling in the number of brands, progressively smaller pouch sizes with smaller increases in price than in traditional RYO and comparable FM products. While use of FM cigarettes declined between 2004 and 2016, the proportion of adults exclusively using RYO tobacco linearly increased with each survey wave (OR 1.03, 95% CI 1.02 to 1.05, p<0.001), from 1.2% in 2004 to 1.7% in 2016. Exclusive RYO use among current smokers increased more among females than males, and young adults compared with those aged 30 years or older, but did not differ by socioeconomic status.

Conclusions

In contrast to substantial declines in FM cigarette use, exclusive use of RYO cigarettes increased in Australians since 2004, particularly among females and young adults. This has corresponded to a period of substantial changes to the RYO market, including progressively smaller and relatively more affordable products. Policy action to reduce price-related marketing and correct consumer misinformation about RYO tobacco are urgently required.
Response of Royal Gala apples to multiple applications of chemical thinners and the dynamics of fruitlet drop
Authors: Cline John A. , Bakker Catherine J. , Gunter Amanda
Published: July 2018

Apple trees bear an abundance of flowers that produce a surplus of fruit that the tree is unable to support. A self-regulatory mechanism enhances the abscission of immature fruitlets, leading to a reduced fruit load, but this is often insufficient to achieve fruit of marketable size. Supplementary fruit thinning is usually required to optimize economic fruit load and annual bearing. This 2 yr study investigated the response of Royal Gala apple trees to primary single and combination sprays of 6-benzyladenine (6-BA) and carbaryl during fruit set, followed by secondary sprays of either treatment 7 d later. The objective was to determine the effect of a second application of chemical thinner on fruitlet abscission, which compounds are most efficacious, and to characterize the pattern of fruitlet drop. The combinations of chemical thinners varied in their effectiveness at reducing crop density. About 12–14 d were required from the time of the first application of chemical thinner to observed fruitlet beneath trees. A single application of both thinners applied at 8 mm advanced fruit drop by 7 d in most instances. The tank-mix of 6-BA and carbaryl applied at 8–10 mm followed by a secondary spray of carbaryl at 15 mm was the most efficacious thinning combination. Secondary sprays of 6-BA at 15 mm were ineffective at inducing additional fruit drop. Combination sprays of 6-BA and carbaryl were more effective than repeat sprays of the same product. This study enhances our understanding of the dynamics of fruitlet abscission and the benefits of multiple applications of post-bloom chemical thinners.
ECONOMIC CONSEQUENCES OF POPULATION AGING IN JAPAN: EFFECTS THROUGH CHANGES IN DEMAND STRUCTURE
Authors: KATAGIRI MITSURU
Published: July 2018

In this paper, I investigate the effects of changes in demand structure caused by population aging on the Japanese economy using a multi-sector new Keynesian model with job creation/destruction analysis. I consider upward revisions in forecast for the speed of Japanese population aging as unexpected shocks to its demand structure. I find that the shocks caused around 0.3% point deflationary pressure on year-to-year inflation, 0.3% to 0.4% point increase in unemployment rates, and 1.8% point decrease in real GDP from the early 1990s to the 2000s in Japan. I also find that the repetition of such upward revisions made those effects look more persistent.
Some recent directions in finite semifields
Authors: Wene Gregory P.
Published: July 2018

A brief history of finite semifields upto 1965 is followed by a more detailed examination of recent discoveries with particular emphasis on constructions, fractional dimensions and cyclic semifields. Other results are also developed.
Singular knots and involutive quandles
Authors: Churchill Indu R. U. , Elhamdadi Mohamed , Hajij Mustafa , Nelson Sam
Published: July 2018

This is an Erratum for our paper “Singular Knots and Involutive Quandles” in [1]. It replaces Sec. 5 in the published version of the paper.
IN SILICO GENOME-SCALE RECONSTRUCTION AND ANALYSIS OF THE SHEWANELLA LOIHICA PV-4 METABOLIC NETWORK
Authors: XU ZIXIANG , GUO JING , YUE YUNXIA , MENG JING , SUN XIAO
Published: July 2018

Microbial Fuel Cells (MFCs) are devices that generate electricity directly from organic compounds with microbes (electricigens) serving as anodic catalysts. As a novel environment-friendly energy source, MFCs have extensive practical value. Since the biological features and metabolic mechanism of electricigens have a great effect on the electricity production of MFCs, it is a big deal to screen strains with high electricity productivity for improving the power output of MFC. Reconstructions and simulations of metabolic networks are of significant help in studying the metabolism of microorganisms so as to guide gene engineering and metabolic engineering to improve their power-generating efficiency. Herein, we reconstructed a genome-scale constraint-based metabolic network model of Shewanella loihica PV-4, an important electricigen, based on its genomic functional annotations, reaction databases and published metabolic network models of seven microorganisms. The resulting network model iGX790 consists of 902 reactions (including 71 exchange reactions), 798 metabolites and 790 genes, covering the main pathways such as carbon metabolism, energy metabolism, amino acid metabolism, nucleic acid metabolism and lipid metabolism. Using the model, we simulated the growth rate, the maximal synthetic rate of ATP, the flux variability analysis of metabolic network, gene deletion and so on to examine the metabolism of S. loihica PV-4.
A class of vector-valued subspace weak Gabor duals of type II
Authors: Zhao Jing , Li Yun-Zhang
Published: July 2018

The theory of vector-valued frames (also called superframes) has important applications in signal multiplexing, and has interested many mathematicians in recent years. In this paper, we introduce the notion of weak Gabor duals of type II under the setting of subspaces [Formula: see text], where [Formula: see text] is a periodic subset of [Formula: see text]. Using the Zak transform matrix method, we characterize weak Gabor duals of type II and their uniqueness. An example is also presented to illustrate the generality of our results.
The bactericidal effect of continuous wave laser with strongly absorbing coating at the fiber tip
Authors: Elagin Vadim , Smirnov Anton , Yusupov Vladimir , Kirillov Alexey , Ignatova Nadezhda , Streltsova Olga , Grebenkin Evgeniy , Kamensky Vladislav
Published: July 2018

The bactericidal effect of laser radiation with a quartz fiber-based transmission system with a strong absorption coating converter against bacteria associated with urological stones has been studied. Gram-negative rod Escherichia coli and the Gram-positive coccus Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium were used in this study. Each bacterial species was treated by continuous-wave near infrared laser coupled with bare fiber tip or strongly absorption coating fiber tip. After treatment, the temperature of bacterial suspension was measured. In addition, the temperature distribution was analyzed. It has been shown that using laser with a strongly absorption coating fiber tip results in significant bactericidal effect. The decrease of the amount of E. coli and S. epidermidis was 100% after treatment with an output power of 6[Formula: see text]W of radiation at a wavelength of 0.97[Formula: see text][Formula: see text]m for 40[Formula: see text]s. Number of S. aureus and Ent. faecium colony-forming unit was reduced to 70% after same exposure. The peak temperature of bacterial suspension was [Formula: see text]C after treatment by laser with a strongly absorption coating fiber tip. Laser with a strongly absorption coating fiber tip provides large-scale hydrodynamic flows directed away from the fiber tip. The laser with a strongly absorption coating fiber tip has bactericidal effect. The main role is associated with the effect of high temperature, which, in the form of flow in a liquid medium, affects bacteria.
Improving Zr0.5Hf0.5O2-based charge-trapped performance by graphene oxide quantum dots
Authors: Wang Hong , Ding Bangfu , Tian Xiaoyan , Zhao Rui , Zhang Yuanyuan , Lu Chao , Ren Deliang , Yan Xiaobing
Published: July 2018

In this work, graphene oxide quantum dots (GOQDs) are introduced as an electron-trapped layer in Pd/Zr[Formula: see text]Hf[Formula: see text]O2 (ZHO)/SiO2/Si memory device. This structure possessed longer than 104 s retention capability, a low operation voltage around [Formula: see text][Formula: see text]V and 2.61[Formula: see text]V storage windows. GOQDs contained carbon–carbon and carbon–oxygen single/double bonds based on the analysis of C-1[Formula: see text] and O-1[Formula: see text] X-ray photoelectron spectra. It is proposed that the GOQDs’ wide bandgap with many oxygen-containing functional groups favors charge capture to a greater extent. This new type of charge-trapping memory can be a promising candidate for wide application to storing information with non-volatility in the big data era.
Modeling and computation by artificial neural network of fracture toughness of low alloy steel to study the effect of alloy composition
Authors: Paul Subir , Bhattacharjee Shibasish
Published: July 2018

The unpredictable structure failures of carbon steel and low alloy steel leading to accidents may be caused by the propagation of a flaw or crack already present in the structure. Fracture toughness which describes the ability of a material containing a crack to resist fracture is one of the most important material properties for design applications of metallic structures. Since this material property is influenced by several parameters, namely material chemistry, heat treatment, morphology of structure, it requires millions of experiments to be conducted to understand and predict it. So, mathematical modeling is one of the solutions to find the effect of these parameters and design future alloys. Stress–intensity factor [Formula: see text] is a quantitative parameter of fracture toughness determining a maximum value of stress which may be applied to a specimen containing a crack (notch) of a certain length. An artificial neural network (ANN) model was developed using over 100 sets of data to study the effect of alloying elements on fracture toughness, [Formula: see text] for the low alloy steel. 20% of data was used for training, 60% to develop predictive model and rest of the 20% for validation. The model can predict the fracture toughness of unknown new data close to 80% accuracy which is good enough for statistical modeling. The details of program code with ANN modeling steps have been explained. Prediction of fracture toughness by the model with variation of alloy composition as well as yield stress gives interesting and important information which may help in designing alloy which will resist crack propagation in a structure and hence enhance the life of structure to fail.
Acute iodine deficiency induces a transient VEGF-dependent microvascular response in mammary glands involving HIF-1, ROS, and mTOR
Authors: Vanderstraeten Jessica , Derradji Hanane , Sonveaux Pierre , Colin Ides M. , Many Marie-Christine , Gérard Anne-Catherine
Published: July 2018

Iodine deficiency (ID), which affects almost two billion people worldwide, is associated with breast pathologies such as fibrosis in human and induces breast atypia in animal models. Because ID induces vascular activation in the thyroid, another iodide-uptaking organ, and as breast is also sensitive to ID, we aimed to characterize ID-induced effects on the breast microvasculature in vivo and in two different breast cell lines in vitro. Virgin and lactating NMRI mice received an iodide-deficient diet and a Na+/I− symporter inhibitor for 1 to 20 days. Some virgin mice were treated with vascular endothelial growth factor A (VEGF) or VEGF receptor inhibitors. In vitro, ID was induced in MCF7 and MCF12A cells by replacing the iodide-containing medium by an iodide-deficient medium. In vivo, VEGF expression was increased following ID in mammary tissues. Consequently, ID induced a transient increase in mammary gland blood flow, measured after anesthesia, in virgin and lactating mice, which was repressed by VEGF or VEGF receptor inhibitors. In MCF7 cells, ID induced a transient increase in reactive oxygen species, followed by an increase in hypoxia-inducible factor-1α (HIF-1α) protein and VEGF mRNA expression. Antioxidant N-acetylcysteine and mammalian target of rapamycin (mTOR) inhibitor blocked ID-induced HIF-1α protein increase and VEGF transcription. However, mTOR activity was not inhibited by N-acetylcysteine. Similar responses were observed in MCF12A cells. These data indicate that ID activates the canonical VEGF pathway and mTOR in breast tissues, which provides new insights to better understand the correlation between ID, vascular activation, and breast pathologies.
The human ion channel TRPM2 modulates neuroblastoma cell survival and mitochondrial function through Pyk2, CREB, and MCU activation
Authors: Hirschler-Laszkiewicz Iwona , Chen Shu-jen , Bao Lei , Wang JuFang , Zhang Xue-Qian , Shanmughapriya Santhanam , Keefer Kerry , Madesh Muniswamy , Cheung Joseph Y. , Miller Barbara A.
Published: July 2018

Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential function in cell survival and is highly expressed in many cancers. Inhibition of TRPM2 in neuroblastoma by depletion with CRISPR technology or expression of dominant negative TRPM2-S has been shown to significantly reduce cell viability. Here, the role of proline-rich tyrosine kinase 2 (Pyk2) in TRPM2 modulation of neuroblastoma viability was explored. In TRPM2-depleted cells, phosphorylation and expression of Pyk2 and cAMP-responsive element-binding protein (CREB), a downstream target, were significantly reduced after application of the chemotherapeutic agent doxorubicin. Overexpression of wild-type Pyk2 rescued cell viability. Reduction of Pyk2 expression with shRNA decreased cell viability and CREB phosphorylation and expression, demonstrating Pyk2 modulates CREB activation. TRPM2 depletion impaired phosphorylation of Src, an activator of Pyk2, and this may be a mechanism to reduce Pyk2 phosphorylation. TRPM2 inhibition was previously demonstrated to decrease mitochondrial function. Here, CREB, Pyk2, and phosphorylated Src were reduced in mitochondria of TRPM2-depleted cells, consistent with their role in modulating expression and activation of mitochondrial proteins. Phosphorylated Src and phosphorylated and total CREB were reduced in TRPM2-depleted nuclei. Expression and function of mitochondrial calcium uniporter (MCU), a target of phosphorylated Pyk2 and CREB, were significantly reduced. Wild-type TRPM2 but not Ca2+-impermeable mutant E960D reconstituted phosphorylation and expression of Pyk2 and CREB in TRPM2-depleted cells exposed to doxorubicin. Results demonstrate that TRPM2 expression protects the viability of neuroblastoma through Src, Pyk2, CREB, and MCU activation, which play key roles in maintaining mitochondrial function and cellular bioenergetics.
Molecular mechanisms of somatostatin-mediated intestinal epithelial barrier function restoration by upregulating claudin-4 in mice with DSS-induced colitis
Authors: Cai Lin , Li Xiao , Geng Chong , Lei Xuelian , Wang Chunhui
Published: July 2018

Intestinal barrier dysfunction plays a crucial role in the pathogenesis of ulcerative colitis (UC). Previous studies have shown somatostatin (SST) can protect intestinal barrier structure possibly through upregulating tight junction (TJ) protein expression, but the mechanisms of this upregulation remain undefined. This study aimed to investigate the molecular mechanisms of interaction of SST with its downstream regulatory elements in DSS-induced colitis mice. In DSS-induced colitis mice, exogenous SST supplement (octreotide) effectively ameliorated disease progression, restored colonic barrier structure and function, and stimulated claudin-4 expression. Similar effects were also observed for SST on Caco-2 cells intervened by TNF-α. SST receptor 5 (SSTR5) agonist L-817,818 upregulated the claudin-4 expression whereas the SSTR2 agonist seglitide could not reverse TNF-α-induced reduction of claudin-4. SST treatment significantly decreased the phosphorylation levels of ERK1/2 and p38 induced by TNF-α. PD-98059 (ERK1/2 pathway inhibitor) but not SB-202190 (p38 pathway inhibitor) could reverse TNF-α-induced suppression of claudin-4 expression. Both inhibitors could improve the TJ barrier function damaged by TNF-α. Our studies suggest that the protective effect of SST on intestinal barrier achieved by upregulating claudin-4 expression through activation of SSTR5 and suppression of the ERK1/2 pathways. These findings will benefit the development of novel treatment regimens for UC.
Diabetes-associated alterations in the cecal microbiome and metabolome are independent of diet or environment in the UC Davis Type 2 Diabetes Mellitus Rat model
Authors: Piccolo Brian D. , Graham James L. , Stanhope Kimber L. , Nookaew Intawat , Mercer Kelly E. , Chintapalli Sree V. , Wankhade Umesh D. , Shankar Kartik , Havel Peter J. , Adams Sean H.
Published: July 2018

The composition of the gut microbiome is altered in obesity and type 2 diabetes; however, it is not known whether these alterations are mediated by dietary factors or related to declines in metabolic health. To address this, cecal contents were collected from age-matched, chow-fed male University of California, Davis Type 2 Diabetes Mellitus (UCD-T2DM) rats before the onset of diabetes (prediabetic PD; n = 15), 2 wk recently diabetic (RD; n = 10), 3 mo (D3M; n = 11), and 6 mo (D6M; n = 8) postonset of diabetes. Bacterial species and functional gene counts were assessed by shotgun metagenomic sequencing of bacterial DNA in cecal contents, while metabolites were identified by gas chromatography-quadrupole time-off-flight-mass spectrometry. Metagenomic analysis showed a shift from Firmicutes species in early stages of diabetes (PD + RD) toward an enrichment of Bacteroidetes species in later stages of diabetes (D3M + D6M). In total, 45 bacterial species discriminated early and late stages of diabetes with 25 of these belonging to either Bacteroides or Prevotella genera. Furthermore, 61 bacterial gene clusters discriminated early and later stages of diabetes with elevations of enzymes related to stress response (e.g., glutathione and glutaredoxin) and amino acid, carbohydrate, and bacterial cell wall metabolism. Twenty-five cecal metabolites discriminated early vs. late stages of diabetes, with the largest differences observed in abundances of dehydroabietic acid and phosphate. Alterations in the gut microbiota and cecal metabolome track diabetes progression in UCD-T2DM rats when controlling for diet, age, and housing environment. Results suggest that diabetes-specific host signals impact the ecology and end product metabolites of the gut microbiome when diet is held constant.
New insights into arterial stiffening: does sex matter?
Authors: Ogola Benard O. , Zimmerman Margaret A. , Clark Gabrielle L. , Abshire Caleb M. , Gentry Kaylee M. , Miller Kristin S. , Lindsey Sarah H.
Published: July 2018

This review discusses sexual dimorphism in arterial stiffening, disease pathology interactions, and the influence of sex on mechanisms and pathways. Arterial stiffness predicts cardiovascular mortality independent of blood pressure. Patients with increased arterial stiffness have a 48% higher risk for developing cardiovascular disease. Like other cardiovascular pathologies, arterial stiffness is sexually dimorphic. Young women have lower stiffness than aged-matched men, but this sex difference reverses during normal aging. Estrogen therapy does not attenuate progressive stiffening in postmenopausal women, indicating that currently prescribed drugs do not confer protection. Although remodeling of large arteries is a protective adaptation to higher wall stress, arterial stiffening increases afterload to the left ventricle and transmits higher pulsatile pressure to smaller arteries and target organs. Moreover, an increase in aortic stiffness may precede or exacerbate hypertension, particularly during aging. Additional studies are needed to elucidate the mechanisms by which females are protected from arterial stiffness to provide insight into its mechanisms and, ultimately, therapeutic targets for treating this pathology.
Soluble (pro)renin receptor as a potential therapy for diabetes insipidus
Authors: Yang Kevin T. , Yang Tianxin , Symons J. David
Published: July 2018

The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs) on the basolateral membrane of principal cells of the collecting duct (CD) to regulate fluid permeability. The VP-evoked endocrine pathway is essential in determining urine concentrating capability. For example, a defect in any component of the VP signaling pathway can result in polyuria, polydipsia, and hypotonic urine, collectively termed diabetes insipidus (DI). A lack of VP production precipitates central diabetes insipidus (CDI), which can be managed effectively by VP supplementation. A majority of cases of nephrogenic diabetes insipidus (NDI) result from V2R mutations that impair receptor sensitivity. No specific therapy is currently available for management of NDI. Evidence is evolving that (pro)renin receptor (PRR), a newly identified member of the renin-angiotensin system, is capable of regulating VP production and action. As such, PRR should be considered strongly as a therapeutic target for treating CDI and NDI. The current review will summarize recent advances in understanding the physiology of renal and central PRR as it relates to the two types of DI.
Using transcranial magnetic stimulation to investigate the neural mechanisms of inhibitory control
Authors: Puri Rohan , Nikitenko Tess , Kemp Sarah
Published: July 2018

Many everyday actions require inhibitory control. The success of these actions depends on the availability of prior information regarding stopping demands. Using transcranial magnetic stimulation (TMS), Cirillo and colleagues (Cirillo J, Cowie MJ, MacDonald HJ, Byblow WD. J Neurophysiol 119: 877–886, 2018) provide novel neurophysiological evidence for distinct roles of intracortical inhibitory mechanisms underlying inhibitory control. Other, nonexclusive mechanisms such as disfacilitation of excitatory pathways and interhemispheric inhibition may also contribute to inhibitory control. Accordingly, diverse TMS protocols are a valuable assessment tool to investigate these mechanisms.
Relationship between vestibular sensitivity and multisensory temporal integration
Authors: Shayman Corey S. , Seo Jae-Hyun , Oh Yonghee , Lewis Richard F. , Peterka Robert J. , Hullar Timothy E.
Published: July 2018

A single event can generate asynchronous sensory cues due to variable encoding, transmission, and processing delays. To be interpreted as being associated in time, these cues must occur within a limited time window, referred to as a “temporal binding window” (TBW). We investigated the hypothesis that vestibular deficits could disrupt temporal visual-vestibular integration by determining the relationships between vestibular threshold and TBW in participants with normal vestibular function and with vestibular hypofunction. Vestibular perceptual thresholds to yaw rotation were characterized and compared with the TBWs obtained from participants who judged whether a suprathreshold rotation occurred before or after a brief visual stimulus. Vestibular thresholds ranged from 0.7 to 16.5 deg/s and TBWs ranged from 13.8 to 395 ms. Among all participants, TBW and vestibular thresholds were well correlated ( R2 = 0.674, P < 0.001), with vestibular-deficient patients having higher thresholds and wider TBWs. Participants reported that the rotation onset needed to lead the light flash by an average of 80 ms for the visual and vestibular cues to be perceived as occurring simultaneously. The wide TBWs in vestibular-deficient participants compared with normal functioning participants indicate that peripheral sensory loss can lead to abnormal multisensory integration. A reduced ability to temporally combine sensory cues appropriately may provide a novel explanation for some symptoms reported by patients with vestibular deficits. Even among normal functioning participants, a high correlation between TBW and vestibular thresholds was observed, suggesting that these perceptual measurements are sensitive to small differences in vestibular function.

NEW & NOTEWORTHY While spatial visual-vestibular integration has been well characterized, the temporal integration of these cues is not well understood. The relationship between sensitivity to whole body rotation and duration of the temporal window of visual-vestibular integration was examined using psychophysical techniques. These parameters were highly correlated for those with normal vestibular function and for patients with vestibular hypofunction. Reduced temporal integration performance in patients with vestibular hypofunction may explain some symptoms associated with vestibular loss.
Giant Solitary Cyst at the Site of Knee Osteoarthritis: Treatment with a Synthetic Resorbable Bone Graft Substitute and Primary Total Knee Arthroplasty
Authors: Thiery Andreas , Tapos Octavian , Anagnostakos Konstantinos
Published: July 2018

A 48-year-old male patient presented in our department with knee osteoarthritis and a giant cystic lesion of the lateral femoral condyle. Bone biopsy of the lesion was performed. Histopathological examination confirmed the presence of a solitary bone cyst. The patient was treated by curettage of the cyst, filling with a synthetic resorbable bone graft substitute (Cerament™), and primary, cruciate-retaining total knee arthroplasty. 4 months after surgery, complete osseointegration of the bone graft substitute was evident on X-rays. The use of modern bone graft substitutes might be a novel alternative to other established techniques in the management of large bone lesions, even at the site of primary total knee replacement.
Dirac Equation in the Presence of Hartmann and Ring-Shaped Oscillator Potentials
Authors: Bakhshi Zahra
Published: July 2018

The importance of the energy spectrum of bound states and their restrictions in quantum mechanics due to the different methods have been used for calculating and determining the limit of them. Comparison of Schrödinger-like equation obtained by Dirac equation with the nonrelativistic solvable models is the most efficient method. By this technique, the exact relativistic solutions of Dirac equation for Hartmann and Ring-Shaped Oscillator Potentials are accessible, when the scalar potential is equal to the vector potential. Using solvable nonrelativistic quantum mechanics systems as a basic model and considering the physical conditions provide the changes in the restrictions of relativistic parameters based on the nonrelativistic definitions of parameters.
Wireless Stimulus-on-Device Design for Novel P300 Hybrid Brain-Computer Interface Applications
Authors: Kuo Chung-Hsien , Chen Hung-Hsuan , Chou Hung-Chyun , Chen Ping-Nan , Kuo Yu-Cheng
Published: July 2018

Improving the independent living ability of people who have suffered spinal cord injuries (SCIs) is essential for their quality of life. Brain-computer interfaces (BCIs) provide promising solutions for people with high-level SCIs. This paper proposes a novel and practical P300-based hybrid stimulus-on-device (SoD) BCI architecture for wireless networking applications. Instead of a stimulus-on-panel architecture (SoP), the proposed SoD architecture provides an intuitive control scheme. However, because P300 recognitions rely on the synchronization between stimuli and response potentials, the variation of latency between target stimuli and elicited P300 is a concern when applying a P300-based BCI to wireless applications. In addition, the subject-dependent variation of elicited P300 affects the performance of the BCI. Thus, an adaptive model that determines an appropriate interval for P300 feature extraction was proposed in this paper. Hence, this paper employed the artificial bee colony- (ABC-) based interval type-2 fuzzy logic system (IT2FLS) to deal with the variation of latency between target stimuli and elicited P300 so that the proposed P300-based SoD approach would be feasible. Furthermore, the target and nontarget stimuli were identified in terms of a support vector machine (SVM) classifier. Experimental results showed that, from five subjects, the performance of classification and information transfer rate were improved after calibrations (86.00% and 24.2 bits/ min before calibrations; 90.25% and 27.9 bits/ min after calibrations).
Spatial and Temporal Variations of Water Quality of Mateur Aquifer (Northeastern Tunisia): Suitability for Irrigation and Drinking Purposes
Authors: Tlili-Zrelli Besma , Gueddari Moncef , Bouhlila Rachida
Published: July 2018

The present study aims to assess the spatial and temporal variations of the hydrochemical characteristics of Mateur aquifer groundwaters, a crucial water resource in the northeast of Tunisia. The aquifer was subject to water quality deterioration due to salinization and nitrate contamination, and a new assessment of water quality was needed. For this purpose, 40 groundwater samples were collected during wet and dry seasons and analyzed for salinity, pH, T, O2, major cations and anions, and nutrient elements using standard methods and Water Quality Index (WQI). The results showed that most of the groundwater parameters were not within the permissible limits set by the World Health Organization in both seasons. The geochemical data were interpreted using WQI for drinking water. The spatial distribution maps of Water Quality Index showed that the highest quality was found, during both seasons, in the northwest and the southeast part of the aquifer, corresponding to the recharge zone, whereas the poor and very poor water quality was found in the outflow part of the aquifer. According to sodium adsorption ratio (SAR) and Na% values, most of the groundwater samples were not suitable for irrigation purposes and characterizing the eastern part of the aquifer and the outflow part of the aquifer, around the Ichkeul marshes.
Clinical Arterial Peripheral Vascular Pathology Does Not Impact Short- or Long-Term Survival after Transcatheter Aortic Valve Replacement
Authors: Klinkhammer Brent
Published: July 2018

Introduction. The dramatic changes in vascular hemodynamics after transcatheter aortic valve replacement (TAVR) are well noted. However, little postprocedural data exists on the outcomes in patients with clinical arterial peripheral vascular pathology [abdominal aortic aneurysm (AAA), carotid artery stenosis (CAS), and peripheral artery disease (PAD)] undergoing TAVR for severe aortic stenosis. Setting. A single center healthcare system. Methodology. A retrospective chart review case-control study of 342 consecutive patients who underwent a TAVR for severe aortic stenosis at Sanford Health in Fargo; ND was performed to determine if preprocedural comorbid AAA, CAS, or PAD was associated with worse outcomes after TAVR. Results. Patients with preprocedural comorbid AAA, CAS, or PAD had no significant difference overall survival at 1 month (94% versus 95% p =.812), 6 months (88% versus 89% p = .847), 1 year (74% versus 83%, p =.130), or 2 years (58% versus 63%, p =.611) after TAVR. Patients with clinical arterial peripheral vascular pathology also had no significant difference in preprocedural outcomes. Conclusion. This study gives evidence to suggest that patients with a comorbid clinical peripheral arterial pathology at the time of TAVR do not have a statistically significant increase in mortality out to 2 years after TAVR and no increase in procedural complications. These results affirm the safety and feasibility of TAVR in patients with AAA, CAS, and/or PAD.