bluuebunny/crossref_metadata_2025 huggingface dataset:
Repurposing Glyburide as Antileishmanial Agent to Fight Against Leishmaniasis
Authors: Rub Abdur , Shaker Kamal , Kashif Mohammad , Arish Mohd , Dukhyil Abdul Aziz Bin , Alshehri Bader Mohammed , Alaidarous Mohammed A. , Banawas Saeed , Amir Khwaja
Published: March 2019

Background:

Leishmaniasis is caused by a protozoan parasite, Leishmania. It is common in more than 98 countries throughout the world. Due to insufficient availability of antileishmanial chemotherapeutics, it is an urgent need to search for new molecules which have better efficacy, low toxicity and are available at low cost.

Objectives:

There is a high rate of diabetic cases throughout the world that is why we planned to test the antileishmanial activity of glyburide, an effective sugar lowering drug used for the treatment of diabetes. In this study, glyburide showed a significant decrease in the parasite growth and survival in vitro in a dose-dependent manner.

Methods:

Anti-leishmanial activity of glyburide was checked by culturing Leishmania donovani promastigotes in the presence of glyburide in a dose and time dependent manner. Docking study against Leishmania donovani-Trypanothione synthetase (LdTrySyn) protein was performed using Autodock Vina tool.

Results:

Growth reversibility assay shows that growth of treated parasite was not reversed when transferred to fresh culture media after 7 days. Moreover, docking studies show efficient interactions of glyburide with key residues in the catalytic site of Leishmania donovani- Trypanothione synthetase (LdTrySyn), a very important leishmanial enzyme involved in parasite’s survival by detoxification of Nitric Oxide (NO) species, generated by the mammalian host as a defense molecule. Thus this study proves that the drug-repurposing is a beneficial strategy for identification of new and potent antileishmanial molecules.

Conclusion:

The results suggest that glyburide binds to LdTrySyn and inhibits its activity which further leads to the altered parasite morphology and inhibition of parasite growth. Glyburide may also be used in combination with other anti-leishmanial drugs to potentiate the response of the chemotherapy. Overall this study provides information about combination therapy as well as a single drug treatment for the infected patients suffering from diabetes. This study also provides raw information for further in vivo disease model studies to confirm the hypothesis.
Insights into the Design of Inhibitors of the Urease Enzyme - A Major Target for the Treatment of Helicobacter pylori Infections
Authors: Fiori-Duarte Ana Thereza , Rodrigues Ricardo Pereira , Kitagawa Rodrigo Rezende , Kawano Daniel Fábio
Published: March 2019

Expressed by a variety of plants, fungi and bacteria, the urease enzyme is directly associated with the virulence factor of many bacteria, including Helicobacter pylori, a gram-negative bacterium related to several gastrointestinal diseases and responsible for one of the most frequent bacterial infections throughout the world. The Helicobacter pylori Urease (HPU) is a nickel-dependent metalloenzyme expressed in response to the environmental stress caused by the acidic pH of the stomach. The enzyme promotes the increase of gastric pH through acid neutralization by the products of urea hydrolysis, then critically contributing to the colonization and pathogenesis of the microorganism. At the same time, standard treatments for Helicobacter pylori infections have limitations such as the increasing bacterial resistance to the antibiotics used in the clinical practice. As a strategy for the development of novel treatments, urease inhibitors have proved to be promising, with a wide range of chemical compounds, including natural, synthetic and semisynthetic products to be researched and potentially developed as new drugs. In this context, this review highlights the advances in the field of HPU inhibition, presenting and discussing the basis for the research of new molecules aiming at the identification of more efficient therapeutic entities.
Atherosclerosis and Nanomedicine Potential: Current Advances and Future Opportunities
Authors: Jiang Fan , Zhu Yunqi , Gong Changyang , Wei Xin
Published: March 2019

Atherosclerosis is the leading inducement of cardiovascular diseases, which ranks the first cause of global deaths. It is an arterial disease associated with dyslipidemia and changes in the composition of the vascular wall. Besides invasive surgical strategy, the current conservative clinical treatment for atherosclerosis falls into two categories, lipid regulating-based therapy and antiinflammatory therapy. However, the existing strategies based on conventional drug delivery systems have shown limited efficacy against disease development and plenty of side effects. Nanomedicine has great potential in the development of targeted therapy, controlled drug delivery and release, the design of novel specific drugs and diagnostic modalities, and biocompatible scaffolds with multifunctional characteristics, which has led to an evolution in the diagnosis and treatment of atherosclerosis. This paper will focus on the latest nanomedicine strategies for atherosclerosis diagnosis and treatment as well as discussing the potential therapeutic targets during atherosclerosis progress, which could form the basis of development of novel nanoplatform against atherosclerosis.
The Application of Microfluidic Techniques on Tissue Engineering in Orthopaedics
Authors: Wang Lingtian , Jiang Dajun , Wang Qiyang , Wang Qing , Hu Haoran , Jia Weitao
Published: March 2019

Background:

Tissue engineering (TE) is a promising solution for orthopaedic diseases such as bone or
cartilage defects and bone metastasis. Cell culture in vitro and scaffold fabrication are two main parts of TE, but
these two methods both have their own limitations. The static cell culture medium is unable to achieve multiple
cell incubation or offer an optimal microenvironment for cells, while regularly arranged structures are unavailable
in traditional cell-laden scaffolds, which results in low biocompatibility. To solve these problems, microfluidic
techniques are combined with TE. By providing 3-D networks and interstitial fluid flows, microfluidic platforms
manage to maintain phenotype and viability of osteocytic or chondrocytic cells, and the precise manipulation of
liquid, gel and air flows in microfluidic devices leads to the highly organized construction of scaffolds.

Methods:

In this review, we focus on the recent advances of microfluidic techniques applied in the field of tissue
engineering, especially in orthropaedics. An extensive literature search was done using PubMed. The introduction
describes the properties of microfluidics and how it exploits the advantages to the full in the aspects of TE. Then
we discuss the application of microfluidics on the cultivation of osteocytic cells and chondrocytes, and other
extended researches carried out on this platform. The following section focuses on the fabrication of highly organized
scaffolds and other biomaterials produced by microfluidic devices. Finally, the incubation and studying of
bone metastasis models in microfluidic platforms are discussed.

Conclusion:

The combination of microfluidics and tissue engineering shows great potentials in the osteocytic cell
culture and scaffold fabrication. Though there are several problems that still require further exploration, the future
of microfluidics in TE is promising.
PI3K/Akt-Nrf2 and Anti-Inflammation Effect of Macrolides in Chronic Obstructive Pulmonary Disease
Authors: Sun Xuejiao , Chen Lin , He Zhiyi
Published: March 2019

Background:

Chronic Obstructive Pulmonary Disease (COPD) is a systematic inflammatory disease, and
smoking is an important risk factor for COPD. Macrolide can reduce COPD inflammation. However, the
inflammatory mechanism of COPD remains unclear and the anti-inflammatory mechanism of Macrolide is complex
and not exactly known.

Methods:

We read and analysed thirty-eight articles, including original articles and reviews.

Results:

The expression of Nrf2 was lower in COPD patients and might have a protective role against apoptosis
caused by CSE-induced oxidative stress. Nrf2 may play an important role in COPD inflammation. Nrf2 is a key
factor in downstream of PI3K/Akt and is involved in the regulation of oxidative stress and inflammatory response.
Therefore, PI3K/Akt pathway may play an important role in the activation of Nrf2 and COPD inflammation. Macrolide
reduces lung and systemic inflammation of COPD by regulating PI3K/Akt pathway.

Conclusion:

This review indicates that PI3K/Ak-Nrf2 may play an important role in COPD inflammation and
macrolides may reduce lung and systemic inflammation of COPD by regulating PI3K/Akt-Nrf2 pathway. However,
many crucial and essential questions remain to be answered. Further understanding of the mechanisms of macrolide
efficacy and PI3K/Akt-Nrf2-mediated inflammatory responses may provide a new clue for exploring COPD treatment
in the future.
Some Possibilities to Study New Prophylactics against Nerve Agents
Authors: Bajgar J. , Kassa J. , Kucera T. , Musilek K. , Jun D. , Kuca K.
Published: March 2019

Nerve agents belong to the most dangerous chemical warfare agents and can be/were misused by terrorists. Effective prophylaxis and treatment is necessary to diminish their effect. General principles of prophylaxis are summarized (protection against acetylcholinesterase inhibition, detoxification, treatment “in advance” and use of different drugs). They are based on the knowledge of mechanism of action of nerve agents. Among different examinations, it is necessary to test prophylactic effectivity in vivo and compare the results with protection in vitro. Chemical and biological approaches to the development of new prophylactics would be applied simultaneously during this research. Though the number of possible prophylactics is relatively high, the only four drugs were introduced into military medical practice. At present, pyridostigmine seems to be common prophylactic antidote; prophylactics panpal (tablets with pyridostigmine, trihexyphenidyl and benactyzine), transant (transdermal patch containing HI-6) are other means introduced into different armies as prophylactics. Scavenger commercionally available is Protexia®. Future development will be focused on scavengers, and on other drugs either reversible cholinesterase inhibitors (e.g., huperzine A, gallantamine, physostigmine, acridine derivatives) or other compounds.
Association of ATG7 Polymorphisms and Clear Cell Renal Cell Carcinoma Risk
Authors: Wang Zhenlong , Tao Lei , Xue Yuquan , Xue Li , Wang Ziming , Chong Tie
Published: March 2019

Background:

Kidney cancer is one of the most common cancers
worldwide. Recent studies have suggested that single nucleotide polymorphisms
(SNPs) in autophagy-related gene are associated with the risk of kidney cancer.

Objective:

This study was undertaken to investigate the association of autophagyrelated
gene 7 (ATG7) polymorphisms with the risk of clear cell renal cell carcinoma
(ccRCC) in the Chinese Han population.

Methods:

A significant association was observed between allele A of rs6442260 and
ccRCC risk (OR = 0.76, 95% CI: 0.58-0.99, p = 0.039). Genetic model analysis
revealed that rs2606736 (OR = 0.57, 95% CI: 0.34-0.95, p = 0.031) and rs6442260
(OR = 0.44, 95% CI: 0.22-0.90, p = 0.021) were associated with decreased risk of
ccRCC under recessive model. Age stratification analysis showed that rs2606736 (OR =
0.67, 95% CI: 0.46-0.98, p = 0.036) and rs6442260 (OR = 0.26, 95% CI: 0.07-0.89, p =
0.014) were significantly decreased risk of ccRCC under the log-additive model in age > 55 years
old and ≤ 55 years old, respectively.

Results:

A significant association was observed between allele A of rs6442260 and
ccRCC risk (OR = 0.76, 95% CI: 0.58-0.99, p = 0.039). Genetic model analysis
revealed that rs2606736 (OR = 0.57, 95% CI: 0.34-0.95, p = 0.031) and rs6442260
(OR = 0.44, 95% CI: 0.22-0.90, p = 0.021) were associated with decreased risk of
ccRCC under recessive model. Age stratification analysis showed that rs2606736 (OR =
0.67, 95% CI: 0.46-0.98, p = 0.036) and rs6442260 (OR = 0.26, 95% CI: 0.07-0.89, p =
0.014) were significantly decreased risk of ccRCC under the log-additive model in age > 55 years
old and ≤ 55 years old, respectively.

Conclusions:

This study indicated that ATG7 polymorphisms (rs2606736 and
rs6442260) have a protective role for ccRCC risk. Further large sample size and
functional assays are needed to confirm our findings and reveal the role of ATG7
polymorphisms in ccRCC carcinogenesis.
Risk Factors for Aphasia in Cerebral Small Vessel Diseases
Authors: Xin Jiawei , Huang Xuanyu , Pan Xiaodong , Lin Lin , Sun Mingyao , Liu Chen , Ye Qinyong
Published: March 2019

Background:

Lacunes and white matter hyperintensities (WMH) are two common findings seen on neuroimaging in patients with cerebral small vessel disease (cSVD). Clinically we observed that some patients with cSVD have aphasia through the language assessment scale. Our study aimed to explore the underlying risk factors for aphasia in cSVD patients.

Methods:

This study retrospectively analyzed 38 patients, with and without aphasia, aged 50 or over, Chinese Han population, diagnosed as cSVD with lacunes and/or WMH. We collected demographic characteristics and vascular risk factors. The severity of WMH was assessed by the age related white matter changes (ARWMC) rating scale.

Results:

Risk factors associated with aphasia were: lower education (p = 0.029), higher total cholesterol (TC) levels (p = 0.023), and higher low-density lipoprotein cholesterol (LDL-C) levels (p = 0.027). After controlling for age and sex, levels of TC (odds ratios, 1.96; 95% confidence interval, 1.06-3.62; p = 0.032) remained associated with aphasia independently.

Conclusion:

High level of TC was significantly associated with a higher risk of aphasia in clinically silent cSVD patients. Early interventions including lipid-lowering treatment, cranial magnetic resonance imaging (MRI) and ARWMC rating scale should be performed. Further studies are needed to explore proper methods of prevention and treatment for aphasia in clinically silent cSVD patients, in addition to understanding the pathophysiological mechanism.
An Overview of HDAC Inhibitors and their Synthetic Routes
Authors: Peng Xiaopeng , Liao Guochao , Sun Pinghua , Yu Zhiqiang , Chen Jianjun
Published: March 2019

Epigenetics play a key role in the origin, development and metastasis of cancer. Epigenetic processes include DNA methylation, histone acetylation, histone methylation, and histone phosphorylation, among which, histone acetylation is the most common one that plays important roles in the regulation of normal cellular processes, and is controlled by histone deacetylases (HDACs) and histone acetyltransferases (HATs). HDACs are involved in the regulation of many key cellular processes, such as DNA damage repair, cell cycle control, autophagy, metabolism, senescence and chaperone function, and can lead to oncogene activation. As a result, HDACs are considered to be an excellent target for anti-cancer therapeutics like histone deacetylase inhibitors (HDACi) which have attracted much attention in the last decade. A wide-ranging knowledge of the role of HDACs in tumorigenesis, and of the action of HDACi, has been achieved. The primary purpose of this paper is to summarize recent HDAC inhibitors and the synthetic routes as well as to discuss the direction for the future development of new HDAC inhibitors.
Acid Ceramidase: A Novel Therapeutic Target in Cancer
Authors: Vijayan Yadu , Lankadasari Manendra Babu , Harikumar Kuzhuvelil B.
Published: March 2019

Sphingolipids are important constituents of the eukaryotic cell membrane which govern
various signaling pathways related to different aspects of cell survival. Ceramide and Sphingosine are
interconvertible sphingolipid metabolites, out of which Ceramide is pro-apoptotic and sphingosine is
anti-apoptotic in nature. The conversion of ceramide to sphingosine is mediated by Acid Ceramidase
(ASAH1) thus maintaining a rheostat between a tumor suppressor and a tumor promoter. This rheostat
is completely altered in many tumors leading to uncontrolled proliferation. This intriguing property of
ASAH1 can be used by cancer cells to their advantage, by increasing the expression of the tumor promoter,
sphingosine inside cells, thus creating a favorable environment for cancer growth. The different
possibilities through which this enzyme serves its role in formation, progression and resistance of different
types of cancers will lead to the possibility of making Acid Ceramidase a promising drug target.
This review discusses the current understanding of the role of acid ceramidase in cancer progression,
metastasis and resistance, strategies to develop novel natural and synthetic inhibitors of ASAH1 and
their usefulness in cancer therapy.
Harnessing Metal Homeostasis Offers Novel and Promising Targets Against Candida albicans
Authors: Hameed Saif , Hans Sandeep , Singh Shweta , Fatima Zeeshan
Published: March 2019

Fungal infections, particularly of Candida species, which are the commensal organisms of human, are one of the major debilitating diseases in immunocompromised patients. The limited number of antifungal drugs available to treat Candida infections, with the concomitant increasing incidence of multidrug-resistant (MDR) strains, further worsens the therapeutic options. Thus, there is an urgent need for the better understanding of MDR mechanisms, and their reversal, by employing new strategies to increase the efficacy and safety profiles of currently used therapies against the most prevalent human fungal pathogen, Candida albicans. Micronutrient availability during C. albicans infection is regarded as a critical factor that influences the progression and magnitude of the disease. Intracellular pathogens colonize a variety of anatomical locations that are likely to be scarce in micronutrients, as a defense strategy adopted by the host, known as nutritional immunity. Indispensable critical micronutrients are required both by the host and by C. albicans, especially as a cofactor in important metabolic functions. Since these micronutrients are not freely available, C. albicans need to exploit host reservoirs to adapt within the host for survival. The ability of pathogenic organisms, including C. albicans, to sense and adapt to limited micronutrients in the hostile environment is essential for survival and confers the basis of its success as a pathogen. This review describes that micronutrients availability to C. albicans is a key attribute that may be exploited when one considers designing strategies aimed at disrupting MDR in this pathogenic fungi. Here, we discuss recent advances that have been made in our understanding of fungal micronutrient acquisition and explore the probable pathways that may be utilized as targets.
Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment
Authors: Wilson Anthony L. , Gandhi Jason , Suh Yiji , Joshi Gunjan , Smith Noel L. , Khan Sardar Ali
Published: March 2019

Background:

Advances in treatment and increased awareness have improved the prognosis
for many patients with hypertension (HTN). Resistant hypertension (RH) refers to a subset of
hypertensive individuals who fail to achieve a desired blood pressure (BP) despite concurrent use of
3 different classes antihypertensive agents, one being a diuretic, and proper lifestyle changes. The
prevalence and prognosis of RH are unclear owing to its heterogeneous etiologies, risk factors, and
secondary comorbidities. Previous research has provided evidence that increased renal sympathetic
nerve activity (RSNA) within the renal artery contributes to RH development. Renal denervation
(RDN) is a procedure that attempts to ameliorate the effects of heightened RSNA via ablation renal
sympathetic fibers. BP reductions associated with RDN may be attributed to decreased norepinephrine
spillover, restoration of natriuresis, increasing renal blood flow, and lowering plasma renin
activity. Early clinical trials perpetuated positive results, and enthusiasm grew exponentially. However,
recent clinical trials have called into question RDN's efficacy. Numerous limitations must be
addressed to discern the true effectiveness of RDN as a therapeutic option for RH.

Objective:

We aimed to review the current understanding of RH, the anatomy of renal arteries,
physiology of RH on renal arteries, anatomical pathways of the sympathetic involved in RH, RDN
as a treatment option, and all relevant clinical trials treating RH with RDN.

Methods:

We piloted a MEDLINE® database search of literature extending from 1980 to 2017, with
emphasis on the previous five years, combining keywords such as "resistant hypertension" and
"renal denervation."

Conclusion:

A plethora of information is available regarding heightened RSNA leading to RH.
RDN as a possible treatment option has shown a range of results. Reconciling RDN's true efficacy
requires future trials to increased sites of nerve ablation, standardized protocol, increased anatomical
understanding per individual basis, stricter guidelines regarding study design, increased operator
experience, and integrating the use of a multielectrode catheter.
Positive and Negative Effects of Antipsychotic Medication: An International Online Survey of 832 Recipients
Authors: Read John , Williams James
Published: March 2019

Background:

Antipsychotic medication is currently the treatment of choice for psychosis, but
few studies directly survey the first-hand experience of recipients.

Objective:

To ascertain the experiences and opinions of an international sample of users of antipsychotic
drugs, regarding positive and negative effects.

Methods:

An online direct-to-consumer questionnaire was completed by 832 users of antipsychotics, from
30 countries – predominantly USA, UK and Australia. This is the largest such sample to date.

Results:

Over half (56%) thought, the drugs reduced the problems they were prescribed for, but 27%
thought they made them worse. Slightly less people found the drugs generally ‘helpful’ (41%) than found
them ‘unhelpful’ (43%). While 35% reported that their ‘quality of life’ was ‘improved’, 54% reported that
it was made ‘worse’. The average number of adverse effects reported was 11, with an average of five at the
‘severe’ level. Fourteen effects were reported by 57% or more participants, most commonly: ‘Drowsiness,
feeling tired, sedation’ (92%), ‘Loss of motivation’ (86%), ‘Slowed thoughts’ (86%), and ‘Emotional
numbing’ (85%). Suicidality was reported to be a side effect by 58%. Older people reported particularly
poor outcomes and high levels of adverse effects. Duration of treatment was unrelated to positive outcomes
but significantly related to negative outcomes. Most respondents (70%) had tried to stop taking the drugs.
The most common reasons people wanted to stop were the side effects (64%) and worries about long-term
physical health (52%). Most (70%) did not recall being told anything at all about side effects.

Conclusion:

Clinical implications are discussed, with a particular focus on the principles of informed consent,
and involving patients in decision making about their own lives.
Glacial Acetic Acid Catalyzed Synthesis, Physicochemical and Biological Evaluation of Benzodiazepines as Potent CNS Agents
Authors: Kumar Vipin , Verma Shweta , Kumar Sushil
Published: March 2019

Background:

Approach for green chemistry for chemical synthesis is found to be very efficient as it makes the reaction more easily, less tedious, maximize desired products and minimize by-products.

Materials & Methods:

Utilizing this approach 1, 5-benzodiazepines and its derivatives have been synthesized and evaluated for skeletal muscle and antianxiety activity. 1, 5-benzodiazepine derivatives have attracted great attention due to its diversity of pharmacological activities and its application in heterocyclic synthesis and medicines. The target compounds were synthesized by first reacting o-phenylenediamine with acetophenone to yield 1, 5-benzodiazepines. In the next step the NH of 1, 5-benzodiazepines were chloroacetylated and then the chloro group was substituted with different anilines. The structures were confirmed on the basis of their TLC, IR, 1H NMR and CHN elemental studies. The physicochemical parameters were determined for BBB penetration through online software.

Results:

The Log P values of the compounds tested showed that compounds have the potential to be CNS active. The compounds were evaluated for the skeletal muscle relaxant activity and antianxiety activity. It was investigated that 1, 5-benzodiazepines derivatives possess significant differences between control group and treated group.

Conclusion:

Among these derivatives, the compound bearing chloro group possesses the highest skeletal muscle relaxant and antianxiety activity.
Ultramicronized Palmitoylethanolamide (um-PEA) as Add-on Treatment in Fibromyalgia Syndrome (FMS): Retrospective Observational Study on 407 Patients
Authors: Schweiger Vittorio , Martini Alvise , Bellamoli Paola , Donadello Katia , Schievano Carlo , Balzo Giovanna D. , Sarzi-Puttini Piercarlo , Parolini Massimo , Polati Enrico
Published: March 2019

Background:

Fibromyalgia syndrome is a chronic multifaceted disease characterized by
widespread pain, muscle stiffness, fatigue, unrefreshing sleep and cognitive disorders. To date, no
medication has been shown to significantly improve pain, associated symptoms and Quality of Life in
fibromyalgic patients.

Methods:

In this retrospective observational study, we analyzed data regarding 407 patients with
diagnosis of fibromyalgia syndrome who between 2013 and 2016 have been prescribed orally
ultramicronized palmitoylethanolamide tablets (Normast® Epitech Group SpA, Saccolongo, Italy) regardless
of the concomitant pharmacological therapy (add-on treatment).

Results:

Regarding efficacy, in the 359 analyzed patients, the change over time in Visual Analogue
Scale pain score was statistically significant, ranging from 75.84 (±15.15) to 52.49 (±16.73)
(p<0.001). Regarding quality of life, the change over time in Fibromyalgia Impact Questionnaire score
was statistically significant, ranging from 68.4 (±14.1) to 49.1 (±19.6) (p<0.001). In the treated population,
only 36 patients (13,7%) reported Adverse Events predominantly of gastrointestinal type
(diarrhea, dyspepsia, bloating, constipation, vomiting). Globally, 151 patients (57,63%) left the treatment
due to inefficacy.

Conclusion:

The results of ultramicronized palmitoylethanolamide treatment in this retrospective
analysis represent an important step for the development of a new and well-tolerated therapy for
fibromyalgia syndrome, mostly suitable for these patients who need long-term treatments. Further
methodologically stronger studies will be necessary to validate our observation.
Liraglutide Exerts Potential Anti-inflammatory Effect in Type 1 Diabetes by Inhibiting IFN-γ Production via Suppressing JAK-STAT Pathway
Authors: Zhao Yunjuan , Xie Yunliang , Li Wangen
Published: March 2019

Background:

Type 1 diabetes is a T cell-mediated autoimmune disease. Interferon γ plays a
critical role in the pathogenesis of type 1 diabetes. Signal transducer and activator of transcription
transduces type I interferon cytokines in T cells, leading to Th1 cell differentiation and production of
interferon γ. Recent studies suggest that liraglutide reduces the plasma concentration of C-reative protein
in patients with type 1 diabetes and protects β cell function in the non-obese diabetic mouse.

Objective:

The study aimed to explore the effect of glucagon-like peptide-1 analogue on interferon γ
production and the underlying signaling pathway in vitro.

Methods:

Jurkat E6-1 cells were intervened with different concentrations of glucose and liraglutide
during different time periods. Protein was extracted from Jurkat E6-1 cells. The target proteins (total
and activated Janus kinase 2, signal transducers and activators of transcription 4 and interferon γ) were
detected by Western blot.

Results:

Glucose stimulates interferon γ expression and activates Janus kinase 2/signal transducers and
activators of transcription 4 signaling pathway in Jurkat E6-1 cells in a concentration and timedependent
manner. Under high glucose condition, liraglutide inhibits interferon γ expression and Janus
kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells in a
concentration and time-dependent manner. The Janus kinase responsible for liraglutide-inhibited signal
transducers and activators of transcription 4 phosphorylation is Janus kinase 2, which is also required
for the interferon γ induction. Finally, we demonstrated that under high glucose condition, liraglutide
inhibits interferon γ expression via Janus kinase 2/signal transducers and activators of transcription 4
signaling pathway in Jurkat E6-1 cells.

Conclusion:

Liraglutide inhibits Jurkat E6-1 cells to produce interferon γ via the Janus kinase/signal
transducers and activators of transcription signaling pathway under high glucose condition, which implies
its potential in the immunoregulatory effect of type 1 diabetes.
Effect of vagbhattokta tambula sevana as per ayurveda on mukha roga
Authors: Rathore Neha , Paul Smita , Jain Ashutosh Kumar
Published: March 2019

The diseases of oral cavity termed as Mukharoga in Ayurveda which involve various pathological conditions such as; Danta Gata Roga and Austha Gata Roga etc. Ayurveda described that Mukharogas may occur at different site of oral cavity and Acharya Charaka has mentioned 64 Mukha rogas in Swayathu Chikitsa Adhyaya depended on Doshik predominance. Vatika Mukha Roga, Paittik Mukha Roga, Kaphaja Mukha Roga and Sannipatika Mukha Roga are some disease of oral cavity emphasized in Ayurveda classic. Vagbhattokta Tambula Sevana is an Upkrama of Dinacharya practices since long in India and it alter pathological manifestation of Mukha rogas. Considering this fact present article described effect of Vagbhattokta Tambula Sevana as an Upkrama of Dinacharya.
Stakeholders’ User Experience of Using Mobile Apps Facilitating Connected Healthcare after Enterostomy: Qualitative Study (Preprint)
Authors: Shi Zhen-Xian , Lee Ying-Li , Chang Polun , Hou Zi-Mei , Liu Jing , Tu Ming-Hsiang , Wen Tzu-Ning , Cui Yan-Yan , Liu Yongrong , Liu Yongrong
Published: March 2019

BACKGROUND

Post-discharge care involving telephone follow-up by an enterostomal therapy (ET) nurse is a common form of connected healthcare (cHealth) for post-operative patients with enterostomy. Although telephone follow-up may compensate for the inconvenience of a home visit or a return visit, the present telehomecare cannot completely meet the various needs of patients with enterostomy. Mobile health (mHealth) with apps had shown some promising results in disease management, the success factors for its practical promotion to patients with enterostomy are not elear. The explorations of user experiences are necessary for enhancing the design of cHealth systems.

OBJECTIVE

The study was aimed to explore the patients’, primary caregivers’, families’, and ET nurses’ health behavior intentions, user experiences, and other recommendations after using the system in telehomecare.

METHODS

A cHealth system was designed for patients with enterostomy. Two ET nurses, 10 patients (or primary caregivers), and 10 families were recruited for the study. After training, participants were asked to use their mobile applications daily. After 3 patient follow-ups (at the time of enrollment and 1 week and 2 weeks after enrolling), a semi-structured interview was conducted for each participant. Researchers transcribed the interview contents to texts, performed coding with NVivo 11 Pro for Windows (QSR International, Melbourne, Australia) qualitative data analysis Software, and the content through content analysis.

RESULTS

From the set of stakeholders, 5 patients,5 primary caregivers,10 families and 2 ET nurses were selected. They were all between 21 and 67 years. The results indicated that the stakeholders have 2 primary health behavior intentions: sudden threats and distress and social support and ambient intimacy. There were 3 primary user experiences: intuitive at a glance, self-empowerment and participation and the conflict between utility and value. They also provided some other recommendations for enhancing the design of cHealth systems.

CONCLUSIONS

This study investigated the health behavior intentions and user experiences of the stakeholders of patients with enterostomy who used mobile apps and a cHealth system for telehomecare and proposed system improvement recommendations. Understanding user experiences and expectations is crucial for system developers to identify the defects in the design of mobile apps and cHealth systems for facilitating the app of cHealth for patients with enterostomy. It is recommended that researchers refer to the recommendations of the users in this study to improve cHealth system designs and to explore the costs and benefits of systems that implement cHealth models for patients after enterostomy.
Development of a digital content-free speech analysis for the measurement of mental health and follow-up of mental disorders (Preprint)
Authors: Tonn Peter , Degani Yoav , Hersko Shani , Klein Amit , Seule Lea , Schulze Nina
Published: March 2019

UNSTRUCTURED

Background
Worldwide, the prevalence of mental disorders is very high and the guideline-oriented care of patients depends greatly on an early diagnosis as well as a regular and valid evaluation of the course, to be able to intervene quickly in case of imminent recurrence or deterioration in therapeutic terms. Experienced physicians and psychotherapists are neccessary for diagnostics and treatment but not available in sufficient numbers everywhere, especially in rural areas or in less well-developed countries.
The human language is capable of revealing the psychic situation of the speaker by altering the non-contentual aspects (speech melody, intonations, speech rate, etc.). The time and experience to learn the speechpatterns of a patient in healthy and ill moments is often unavailable, leaving the opportunities inherent in capturing linguistic, non-contentual information unused.
In order to improve the care of patients with mental disorders just under these aspects, we have developed a concept for assessing the most important mental parameters through a non-contentual analysis of the active speech. Using speech analysis for assessment and tracking of mental health patients, opens also the invaluable possibilities of remote, automatic and ongoing evaluation, when used with patients‘ smartphones, as part of the strong digital and mobile health trends.

Methods/Design
In this paper, we describe a two-arm, randomized controlled trial. The participants are all recruited in one outpatient neuropsychiatric treatment center. Inclusion criteria are e.g. a psychiatric diagnosis made by a specialist, no terminal or life-threatening illness, fluent use of the German language, exclusion criteria are e.g. psychosis, dementia, speech or language disorders, addiction history or suicide attempt currently or in the last 12 months.
The measuring instruments are the "VoiceSense" voice analysis tool, which enables the analysis of 200 specific speech parameters and assessment of the findings through the use of psychometric questionnaires.

Discussion
The importance of content-free speech patterns should not be overestimated. This is particularly evident in the interpretation of the psychological findings. Applying a software analysis tool can increase the accuracy of finding assignments and improve patient care.

Trial Registration
This study is registered at „clinicaltrials.gov“, Number was NCT03700008, registration date 09 October 2018, http://www.clinicaltrials.gov.
Human-Centered Design for Women’s Health Screening Tool Redevelopment: Participant Experiences (Preprint)
Authors: Ostrach Bayla
Published: March 2019

BACKGROUND

Human-Centered Design (HCD) is a formative innovation or design process that emphasizes stakeholder input. A growing body of literature examines the formative science of patient and community engagement in health research yet little qualitative research to date examines how community members recruited to collaborate on designing health practice variations and delivery of care perceive and experience such a process.

OBJECTIVE

Examine perceptions of an HCD process as an engagement tool to inform delivery of care and practice innovation in women’s health screening.

METHODS

Data sources/study setting. Primary qualitative data collected at a medical education center/network of clinics, and in the surrounding community.
Study Design. Qualitative study used opportunistic and purposive sampling recruiting participants from an earlier HCD process undertaken to redesign screening tools. Participants were purposively and sampled from among eligible participants who participated in the Human-Centered Design process to develop women’s health screening tools and who were community members and/or clinicians/clinical staff. There was no randomization, intervention, and no diagnostic or therapeutic procedures.
Data collection/extraction methods. All eligible participants who agreed to participate were interviewed using a semi-structured, open-ended guide. Interviews were audio-recorded, transcribed, hand-coded, and analyzed using modified Grounded Theory.

RESULTS

Principal findings. Community members and clinicians reported divergent views of the HCD process; both groups valued the opportunity to participate. Some found the process easy to engage; others found it confusing or even embarrassing.

CONCLUSIONS

Conclusions. Community members and clinicians valued being part of determining the best process for healthcare delivery and practice innovation or variation; concerns remained about access to and full participation in the process. Though a promising option and valuable process, the HCD process was not equally comfortable or accessible for all. Community engagement beyond the clinical team to developing practice variation is important but must be undertaken thoughtfully.

CLINICALTRIAL

n/a
2D Mapping and boundary detection using 2D LIDAR sensor for prototyping Autonomous PETIS (Programable Vehicle with Integrated Sensor)
Authors: Sidharta Hanugra Aulia , Sidharta Sidharta , Sari Wina Permana
Published: March 2019

PETIS (Programable Vehicle with Integrated Sensor) is a research project with goal make a robot that move independently with specific purpose. Due complexity of PETIS, research divide into several important sequence. In this research author focus on sense of sight for PETIS, LIDAR chosen due flexible and comprehensive. There is many LIDAR sensor in marketplace, LDS-01 as one of commercial LIDAR sensor available on market, produced by ROBOTIS as one of low-cost LIDAR sensor. Compare with another sensor that cost more than $1000, LDS-01 just cost lower than $500. On this research study focus with LDS-01 sensor reading, include hardware, software connection, and data handling. Based on this research LDS-01 as LIDAR sensor can read obstacle with minimum 29,9 cm and maximal 290,7 cm. Comparing with datasheet LDS-01 should work from 12 cm through 350 cm.
Recursos de citación de estudiantes universitarios: contraste entre textos académicos y posts en la red social Facebook
Authors: Ciro Lirian Astrid
Published: March 2019

Actualmente, se observa una disociación entre la actividad vernácula que desarrolla el estudiante en su vida social y la actividad del aula; teniendo en cuenta que en dicha vida social el ámbito virtual cobra cada vez más una mayor relevancia, se propone el análisis de posts en la red social Facebook y de textos académicos de estudiantes de la Licenciatura en Lenguas Extranjeras de la Universidad del Valle. Específicamente, nos centramos en los mecanismos que emplean para introducir una cita textual directa, en el caso del texto académico; y un enlace, imagen o video, cuando no sea de su autoría, en el caso de la red social. El objetivo principal es establecer un contraste entre los recursos de citación en el ámbito académico y en el virtual. Este estudio cualitativo es de corte descriptivo, lo que permite brindar un panorama general acerca del manejo de la citación de estos estudiantes y su influencia en la construcción de los saberes disciplinares. El análisis de los datos evidencia carencias en el manejo académico de las tecnologías de la información y la comunicación (TIC), pues de forma general se observa que los estudiantes se apropian del contenido digital como si fuera habla coloquial, sin prestar atención a su autoría, fiabilidad o procedencia, e ignoran aspectos básicos de su reutilización en contextos académicos, como la citación o las convenciones académicas establecidas. Finalmente, se considera pertinente describir los recursos de las nuevas escrituras digitales, para realizar una caracterización completa y proponer acciones didácticas para abordar la escritura académica y su relación con internet.
Implementación del modelo TRIGRS con análisis de confiabilidad para la evaluación de la amenaza a movimientos en masa superficiales detonados por lluvia
Authors: García-Aristizábal Edwin Fabián , Aristizabal Giraldo Edier Vicente , Marín Sánchez Roberto José , Guzman Martinez Juan Carlos
Published: March 2019

Los deslizamientos detonados por la infiltración de las lluvias son comunes en las regiones tropicales. La falla de taludes representa una de las causas más comunes de pérdidas humanas y económicas en todo el mundo. El presente trabajo presenta una metodología para la evaluación de la amenaza a deslizamientos superficiales detonados por lluvia. La metodología implementada utiliza el modelo de base física - TRIGRS (Transient Rainfall Infiltration and Gridbased Slope-Stability), así como un análisis de confiabilidad a través del método probabilístico FOSM (First Order Second Moment), permitiendo incorporar la incertidumbre sobre los parámetros de resistencia del suelo (cohesión y fricción) y el espesor de la superficie de falla. Estos parámetros presentan gran variabilidad asociada a las condiciones geológicas y geomorfológicas de cada zona en particular. Adicionalmente, la metodología utilizada permite un análisis adecuado del efecto del proceso de infiltración de la lluvia en la inestabilidad de los suelos, ya que considera tanto las características de la lluvia (intensidad-duración), como la permeabilidad y los parámetros de resistencia del suelo. El contraste de los resultados obtenidos utilizando FOSM en relación con los resultados determinísticos, resalta la importancia de considerar la incertidumbre dentro del análisis de estabilidad. El procedimiento presentado y los resultados obtenidos pretenden mostrar una herramienta útil para la ordenación y planificación del territorio que permita una mirada progresiva y sostenible en el desarrollo socio-económico de las zonas susceptibles a deslizamientos detonados por lluvia.
Insights of innovation and competitiveness in meat supply chains
Authors: Fernandes Alice Munz , de Souza Teixeira Odilene , Rios Heitor Vieira , Canozzi Maria Eugênia Andrighetto , Schultz Glauco , Barcellos Júlio Otávio Jardim
Published: March 2019

The world demand for food in parallel with environmental concerns is a paradigm for the competitiveness of agro-industrial production chains. The present study intended to propose insights on the contribution of innovation and competitiveness in meat production chains. A systematic review of the literature was carried out, considering manuscripts published in the Scopus, Web of Science and Science Direct databases. Based on the search and exclusion criteria, the analyzed portfolio consisted of 18 works related to the main animal production chains (i.e. pork, chicken, beef, and sheep). The results obtained include three theoretical constructs, under which the studies of competitiveness and innovation in meat production chains were based, namely: (1) institutional environment; (2) business capacity; and (3) consumer behavior. These are composed of a posteriori variables, which have influences in the innovation and competitiveness of such systems, meeting the postulate by the literature.
Strategic resources and smallholder performance at the bottom of the pyramid
Authors: Olthaar Matthias , Dolfsma Wilfred , Lutz Clemens , Noseleit Florian
Published: March 2019

In a competitive business environment at the Bottom of the Pyramid smallholders supplying global value chains may be thought to be at the whims of downstream large-scale players and local market forces, leaving no room for strategic entrepreneurial behavior. In such a context we test the relationship between the use of strategic resources and firm performance. We adopt the Resource Based Theory and show that seemingly homogenous smallholders deploy resources differently and, consequently, some do outperform others. We argue that the ‘resource-based theory’ results in a more fine-grained understanding of smallholder performance than approaches generally applied in agricultural economics. We develop a mixed-method approach that allows one to pinpoint relevant, industry-specific resources, and allows for empirical identification of the relative contribution of each resource to competitive advantage. The results show that proper use of quality labor, storage facilities, time of selling, and availability of animals are key capabilities.
Partial characterization of bean and maize root peroxidases and their ability to crosslink potato protein
Authors: Glusac Jovana , Isaschar-Ovdat Sivan , Fishman Ayelet , Kukavica Biljana
Published: March 2019

Two fractions of Class III peroxidases (POX; EC 1.11.1.7), soluble and ionically bound to the cell wall, were partially purified from bean and maize roots and characterized. According to the measured Km, both the soluble and ionically bound to the cell wall fractions of POX had high affinity for H2O2 and the high specificity for caffeic acid. Approximate molecular weights of POX in their tertiary (native) structure were determined by modified sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE). Proteomic analysis resolved the identity and pI of different enzyme bands. The ability of maize and bean soluble peroxidase to crosslink native potato proteins was evaluated. The results obtained by SDSPAGE showed that both POX enzymes were capable of crosslinking potato protein, in particular patatin, a globular protein, with and without the presence of H2O2. To investigate the possible role of phenolic compounds in facilitating crosslinking, commercial horseradish peroxidase (HRP) with/without the addition of caffeic acid was used to crosslink potato protein. Information provided here could be useful for the purification of POX from maize and bean roots and for examination of protein-protein interactions.
PCAOB Form AP: Leveraging Information about Audit Personnel
Authors: Downey Denise H. , Rousseau Linette M. , Zehms Karla M.
Published: March 2019

The PCAOB's Form AP (audit personnel) includes the identity of the engagement partner, an indication of whether the audit report is dual-dated, and an indication of whether and to what extent other auditors participate in the engagement (in addition to the primary auditor). We review the nature of this information and prior literature relevant to audit partner identification, dual-dating, and involvement of other auditors as part of distributed audits, along with posing research questions and providing relevant instructional resources. Practitioners can use this information to garner insights from academic research on these important topics as they relate to their own audits. Academics can use this information to leverage the PCAOB's Form AP database in their research. Academics can also use the brief teaching resources to introduce the PCAOB's resources in this regard to students.