bluuebunny/crossref_metadata_2025 huggingface dataset:
Importance of timely diagnosis of diseases of the larynx during initial examination performed by an otorhinolaryngologist
Authors: Stepanova Yu. E. , Gotovyakhina T. V. , Makhotkina N. N.
Published: November 2018

Diagnosis and treatment of diseases of the larynx in patients with dysphonia are an urgent task of modern otorhinolaryngology. The reason for this is the constant growth of professions with high requirements for voice quality. The modern methods of diagnosis in diseases of the larynx are based on endoscopic diagnostic techniques. The article provides detailed description of the clinical and endoscopic signs of functional and organic diseases of the larynx that are significantly more prevalent in voice professionals: hypotonic and hypo-hypertonic functional dysphonia, soft and hard vocal fold nodules, acute and chronic occupational laryngitis, and vascular pathology of vocal cords. The article presents the main approaches to the treatment of diseases of the larynx, including using the drug Homeovox. The article will be useful to the otorhinolaryngologists of the outpatient network to establish the diagnosis and assign а therapy to the voice and speech professionals.
Multifaced cerumen impaction
Authors: Morozova S. V. , Volkova K. B. , Karpova O. Yu.
Published: November 2018

The problem of cerumen impaction is relevant for patients of both children and adults. Different ways of evacuating excessive accumulations in the auditory canal of cerumen masses — irrigation, dry removal — are not always sufficiently effective. For the prevention and removal of cerumen impaction, the use of modern means, cerumenolitics, which quickly and painlessly contribute to getting rid of this problem, should be recognized as the most reasonable.
Diverse Effects of Different “Protein-Based” Vehicles on the Stability and Bioavailability of Curcumin: Spectroscopic Evaluation of the Antioxidant Activity and Cytotoxicity In Vitro
Authors: Mirzaee Farideh , Hosseinzadeh Leila , Ashrafi-Kooshk Mohammad Reza , Esmaeili Sajjad , Ghobadi Sirous , Farzaei Mohammad Hosein , Zad-Bari Mahmoud Reza , Khodarahmi Reza
Published: November 2018

Background: Curcumin is a natural polyphenolic compound with anti-cancer, antiinflammatory,
and anti-oxidation properties. Low water solubility and rapid hydrolytic degradation
are two challenges limiting use of curcumin.

Objective: In this study, the roles of the native/modified forms of Bovine Serum Albumin (BSA),
β-lactoglobulin (β-lg) and casein, as food-grade biopolymers and also protein chemical modification,
in stabilizing and on biological activity of curcumin were surveyed.

Methods: In this article, we used various spectroscopic as well as cell culture-based techniques
along with calculation of thermodynamic parameters.

Results: Investigation of curcumin stability indicated that curcumin binding to the native BSA and
modified β -lg were stronger than those of the modified BSA and native β -lg, respectively and
hence, the native BSA and modified β-lg could suppress water-mediated and light-mediated curcumin
degradation, significantly. Moreover, in the presence of the native proteins (BSA and casein),
curcumin revealed elevated in vitro anti-cancer activity against MCF-7 (human breast carcinoma
cell line) and SKNMC (human neuroblastoma cell line). As well, curcumin, in the presence of the
unmodified “BSA and β-lg”, was more potent to decrease ROS generation by hydrogen peroxide
(H2O2) whereas it led to an inverse outcome in the presence of native casein. Overall, in the presence
of the protein-bound curcumin, increased anti-cancer activity and decreased ROS generation
by H2O2 in vitro were documented.

Conclusion: It appears that “water exclusion” is major determinant factor for increased stability/
efficacy of the bound curcumin so that some protein-curcumin systems may provide novel tools
to increase both food quality and the bioavailability of curcumin as health promoting agent.
Exploration of Umbelliferone Based Derivatives as Potent MAO Inhibitors: Dry vs. Wet Lab Evaluation
Authors: Dhiman Priyanka , Malik Neelam , Khatkar Anurag
Published: November 2018

Background:

Monoamine oxidase inhibitors are potential drug candidates within therapeutics
of different neuropsychological and neurodegenerative disorders including anxiety, depression and Parkinson’s
disease.

Objective:

We investigated the MAO inhibitory effects of the umbelliferone based derivatives for the
treatment of neurological disorders. The potential antioxidant effects of the derivatives were evaluated
by DPPH and H2O2 scavenging methods.

Method:

A series of different umbelliferone derivatives was designed and synthesized, and the derivatives
were screened for hMAO-A and hMAO-B inhibition. Moreover, the mechanistic insight for enzyme-
compound infractions was achieved by docking simulation. The antioxidant potential was dually
assessed by two spectrophotometric titrations methods.

Results:

Compound 5 with bromo 5-bromo-isatin exhibited a remarkable hMAO-A inhibitory potential
(7.473±0.035 µM and the selectivity index of 0.14) revealing the impact of hybrid coumarin and 5-
bromo-2-oxoindolin-3-yl ring with hydrazine linker on the hMAO-A active site. Compound 13 exhibited
significant hMAO-B inhibition with an IC50 value of 10.32±0.044µM with an exceptional selectivity
index of 8.55. Incorporation of 2-hydroxy-2-phenylacetate moiety on 2-oxo-2H-chromen ring led
the important binding infractions within the hMAO active site.

Conclusion:

Our findings revealed a good correlation between experimental MAO inhibition and docking
score by computational studies. Notably, the compounds with remarkable MAO inhibitory potential
were also observed as potential antioxidants.
Recognizing the Leaky Gut as a Trans-diagnostic Target for Neuroimmune Disorders Using Clinical Chemistry and Molecular Immunology Assays
Authors: Simeonova Denitsa , Ivanovska Mariya , Murdjeva Mariana , Carvalho Andre F. , Maes Michael
Published: November 2018

Background:

Increased intestinal permeability with heightened translocation of Gramnegative
bacteria, also known as “leaky gut”, is associated with the pathophysiology of neuroimmune
disorders, such as Major Depressive Disorder (MDD), Chronic Fatigue Syndrome (CSF) and (deficit)
schizophrenia, as well as with general medical disorders, including irritable bowel syndrome. This review
aims to summarize clinical biochemistry and molecular immunology tests that may aid in the recognition
of leaky gut in clinical practice.

Methods: We searched online libraries, including PubMed/MEDLINE, Google Scholar and Scopus, with
the key words “diagnosis” or “biomarkers” and “leaky gut”, “bacterial translocation”, and “intestinal
permeability” and focused on papers describing tests that may aid in the clinical recognition of leaky gut.

Results: To evaluate tight junction barrier integrity, serum IgG/IgA/IgM responses to occludin and zonulin
and IgA responses to actomyosin should be evaluated. The presence of cytotoxic bacterial products in
serum can be evaluated using IgA/IgM responses to sonicated samples of common Gram-negative gut
commensal bacteria and assays of serum lipopolysaccharides (LPSs) and other bacterial toxins, including
cytolethal distenting toxin, subunit B. Major factors associated with increased gut permeability, including
gut dysbiosis and yeast overgrowth, use of NSAIDs and alcohol, food hypersensitivities (IgE-mediated),
food intolerances (IgG-mediated), small bacterial overgrowth (SIBO), systemic inflammation, psychosocial
stressors, some infections (e.g., HIV) and dietary patterns, should be assessed. Stool samples can be
used to assay gut dysbiosis, gut inflammation and decreased mucosal defenses using assays of fecal
growth of bacteria, yeast and fungi and stool assays of calprotectin, secretory IgA, β-defensin, α-
antitrypsin, lysozyme and lactoferrin. Blood and breath tests should be used to exclude common causes
of increased gut permeability, namely, food hypersensitivities and intolerances, SIBO, lactose intolerance
and fructose malabsorption.

Discussion: Here, we propose strategies to recognize “leaky gut” in a clinical setting using the most adequate
clinical chemistry and molecular immunology assays.
Antiproliferative Properties of Extracts from Stachys sieboldii MIQ
Authors: Na Eun , Lee Jung Woo , Winkler Stefan , Lim Sun Young
Published: November 2018

Background:

The objective of this study was to investigate the antiproliferative effect of
Stachys sieboldii MIQ. extracts on cancer cell lines.

Methods:

Dried S. sieboldii MIQ. was extracted using acetone/methylene chloride (A+M) or methanol
(MeOH), and then fractionated using n-hexane, 85% aq. methanol (MeOH), butanol (BuOH) and distilled
water. The cytotoxic activity of S. sieboldii MIQ. against AGS human gastric, HT-29 human colon
and HT-1080 fibroblast cancer cell lines was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyltetrazolium bromide (MTT) assay.

Results:

The A+M extract showed significantly higher inhibition of cell growth in all three cell lines
compared to the MeOH extract (p < 0.05). All the extracts and fractions from S. sieboldii MIQ. decreased
the growth of AGS cells, and the effect was concentration-dependent. Among the different fractions,
the n-Hexane and 85% aq. MeOH fractions inhibited AGS cell growth by >50% at a concentration
of 0.1 mg/mL (p < 0.05). All fractions inhibited the proliferation of HT-29 cancer cell lines (p <
0.05), showing >50% inhibition at a concentration of 0.25 mg/mL. The A+M extract inhibited the
growth of the HT-1080 cancer cells by 60% at a concentration of 0.25 mg/mL. The n-Hexane and 85%
aq. MeOH fractions showed the highest growth inhibitory effect on the HT-1080 cancer cells (p < 0.05),
similar to that observed in the AGS cancer cells.

Conclusion:

Thus, the n-Hexane and 85% aq. MeOH fractions from S. sieboldii MIQ. likely contain
bioactive compounds such as polyphenols and flavonoids that could prevent cancer proliferation. Further
research is needed to isolate these important compounds from the extracts.
Improved Method for Obtaining of Arctigenin from Arctium Lappa L. and its Antiproliferative Effect on Human Hepatocarcinoma HepG2 Cells
Authors: Teixeira Renan S. , Carvalho Paulo H.D. , Aguiar Jair A.K. , Medeiros Valquíria P. , Da Silva Filho Ademar A. , Nascimento Jorge W.L.
Published: November 2018

Background:

Arctigenin is a lignan found in Arctium lappa L. (Asteraceae) that displays
anti-inflammatory activities. Previous studies showed that the crude extract of A. Lappa has antitumor
activity in human liver carcinoma, lung and stomach cancer cells. The aim of this study was to obtain
arctigenin from A. lappa L., as well as to evaluate its antiproliferative effects in cells of liver carcinoma
(HepG2) and fibroblasts (NIH/3T3).

Methods:

Arctigenin was obtained from the hydrolysis of arctiin, which was isolated from the crude
extract of A. lappa. The effects of arctigenin and arctiin on HepG2 cell viability and cell adhesion were
analyzed by MTT method. Adhesion assay was also carried out to evaluate the antitumor activity.

Results:

Our results showed that the analytical process to obtain arctigenin was fast and easy. In vitro
experiments showed that arctigenin (107-269 μM) decreased HepG2 cells viability and did not cause
cytotoxicity on NIH/3T3 cells. Arctigenin (27-269 μM) demonstrated anti-adhesion in HepG2 cells in a
concentration-dependent manner, when compared with control.

Conclusion:

These results suggest a promising pharmacological activity for arctigenin as an antiproliferative
compound.
Comparison of Mono-dopaminergic and Multi-target Pharmacotherapies in Primary Parkinson Syndrome and Assessment Tools to Evaluate Motor and Non-motor Symptoms
Authors: Werner Felix-Martin , Coveñas Rafael
Published: November 2018

Background:

Primary Parkinson syndrome is mostly treated by dopaminergic drugs, while the progression of the disease is not altered. Some non-dopaminergic are available, which are administered only after the Parkinsonian symptoms get worse.

Objective:

The objective of this review is to give basic results in order to compare a dopaminergic and non-dopaminergic pharmacotherapy in Parkinson’s disease and to control whether the add-on pharmacotherapy with non-dopaminergic drugs can inhibit the progression of the disease.

Methods:

In primary Parkinson syndrome, the altered activity of classical neurotransmitters and neuropeptides in the extrapyramidal system is summarized and up-dated. Anatomical studies on neural networks in the basal ganglia are mentioned. The direct, motor facilitatory pathway (D1 dopaminergic neurons) from the substantia nigra to the thalamus, via the internal globus pallidus, and the indirect, motor inhibitory pathway via D2 dopaminergic neurons have been considered. These established anatomical pathways have been brought in line with the neural interactions derived from neurotransmitter balances or imbalances. Besides, preclinical and clinical studies of effective non-dopaminergic anti-Parkinsonian drugs are reviewed.

Results:

It can be hypothesized that glutamatergic neurons enhance dopamine deficiency in the substantia nigra and putamen through an increased presynaptic inhibition mediated by NMDA receptors. In the putamen, 5-HT2A serotonergic neurons counteract D2 dopaminergic neurons and A2A adenosine neurons antagonize D2 dopaminergic neurons by activating glutamatergic neurons, which presynaptically inhibit via subtype 5 of metabotropic glutamatergic receptors, D2 dopaminergic neurons. In the extrapyramidal system, an up-dated neural network, which harmonizes established anatomical pathways with derived neural interactions, is presented. In Parkinson’s disease, a question should be answered, whether a combination of dopaminergic and non-dopaminergic drugs can promote an increased motor and non-motor functioning.

Conclusion:

A mono-target pharmacotherapy (using only dopaminergic drugs) and a multi-target pharmacotherapy (i.e. by combining dopaminergic and non-dopaminergic drugs) are compared. The alternate administration of dopaminergic and non-dopaminergic anti-Parkinsonian drugs, administered at different times during the day, must be tested in order to inhibit the progression of the disease. Assessment tools can be used to evaluate motor and cognitive functions. Moreover, imaging examination techniques can be also applied to control the course of the disease.
The Computational Prediction Methods for Linear B-cell Epitopes
Authors: Jia Cangzhi , Gong Hongyan , Zhu Yan , Shi Yixia
Published: November 2018

Background:

B-cell epitope prediction is an essential tool for a variety of
immunological studies. For identifying such epitopes, several computational predictors have been
proposed in the past 10 years.

Objective:

In this review, we summarized the representative computational approaches developed
for the identification of linear B-cell epitopes.

Methods: We mainly discuss the datasets, feature extraction methods and classification methods
used in the previous work.

Results:

The performance of the existing methods was not very satisfying, and so more effective
approaches should be proposed by considering the structural information of proteins.

Conclusion:

We consider existing challenges and future perspectives for developing reliable
methods for predicting linear B-cell epitopes.
Extending Arms of Insulin Resistance from Diabetes to Alzheimer’s Disease: Identification of Potential Therapeutic Targets
Authors: Gupta Smriti , Singhal Nitin Kumar , Ganesh Subramaniam , Sandhir Rajat
Published: November 2018

Background & Objective:

Type 3 diabetes (T3D) is chronic insulin resistant state of brain which shares pathology with sporadic Alzheimer’s disease (sAD). Insulin signaling is a highly conserved pathway in the living systems that orchestrate cell growth, repair, maintenance, energy homeostasis and reproduction. Although insulin is primarily studied as a key molecule in diabetes mellitus, its role has recently been implicated in the development of Alzheimer’s disease (AD). Severe complications in brain of diabetic patients and metabolically compromised status is evident in brain of AD patients. Underlying shared pathology of two disorders draws a trajectory from peripheral insulin resistance to insulin unresponsiveness in the central nervous system (CNS). As insulin has a pivotal role in AD, it is not an overreach to address diabetic condition in AD brain as T3D. Insulin signaling is indispensable to nervous system and it is vital for neuronal growth, repair, and maintenance of chemical milieu at synapses. Downstream mediators of insulin signaling pathway work as a regulatory hub for aggregation and clearance of unfolded proteins like Aβ and tau.

Conclusion:

In this review, we discuss the regulatory roles of insulin as a pivotal molecule in brain with the understanding of defective insulin signaling as a key pathological mechanism in sAD. This article also highlights ongoing trials of targeting insulin signaling as a therapeutic manifestation to treat diabetic condition in brain.
Areola Reconstruction: Principles and Techniques
Authors: Simonacci Francesco , Bertozzi Nicolò , Pesce Marianna , Santi Pier Luigi , Raposio Edoardo
Published: November 2018

At the end of breast reconstruction, the creation of a natural-appearing areola is very important for patient satisfaction with the surgical result. The challenging aspects of achieving this include matching the color and texture as well as the size, shape, position, and projection of a normal areola, particularly in unilateral cases. The most common techniques that have been used to create a naturalistic nipple–areola complex have included skin grafting, tattooing, or a combination of both. Surgeons are finding that tattooing, the intradermal electric deposition of pigments, can be used to closely approximate natural areola pigmentation. Using the appropriate technique is essential as it is known that tattoo pigment fades over time and appears somewhat different after intradermal applied. Indeed, physicians’ experience and color selection greatly affect the aesthetic outcome. Skin grafting has long been used in nipple–areola reconstruction, and skin donor sites such as retro- auricular, inner thigh, labia minora and contralateral areola have been employed. The choice of donor site depends on different factors, including the presence of a healthy contralateral areola and the skin tone of the patient. In some cases, tattooing may be used in conjunction with grafting. Regardless of areolar reconstructive technique, medical pigmentation is becoming a preferred method of producing a more realistic-appearing breast, although periodic touch-ups may be required for optimal results.
Non-Criminalisation of Victims of Trafficking in Persons — Principles, Promises, and Perspectives
Authors: Schloenhardt Andreas , Markey-Towler Rebekkah
Published: November 2018

Victim protection is one of the key objectives of international and domestic efforts against trafficking in persons. Existing legal instruments contain a range of mechanisms to protect the rights of victims of trafficking, providing them with material assistance, counselling, and shielding them from coercion, threats, and harm by their traffickers. An additional, more contentious protection mechanism is the principle of noncriminalisation which serves to protect victims from prosecution for offences which they may have committed during the course of their trafficking experience. The rationale of this principle is to recognise that victims often have little choice but to engage in criminal conduct during their trafficking situation and to encourage victims to cooperate with law enforcement in the investigation of their traffickers. This article examines the background and rationale of this principle, analyses existing and proposed expressions of this principle, and develops ideas and recommendations for further debate and developments in this field.
Trapped at Sea. Using the Legal and Regulatory Framework to Prevent and Combat the Trafficking of Seafarers and Fishers.
Authors: Surtees Rebecca
Published: November 2018

The breadth and diversity of trafficking for forced labour has become increasingly recognised over the past several years, including heightened attention to human trafficking within the seafaring and commercial fishing industries. Not only are these sectors where trafficking abuse can and does take place, but there are also aspects of these sectors that may lend themselves particularly to human trafficking abuses due to the nature of this form of trafficking as well as the legal and regulatory framework in place. The article begins by framing what constitutes trafficking at sea, both in the commercial fishing sector and in the merchant fleet and then presents the legal and regulatory framework to combat trafficking at sea – namely, international anti-trafficking law, international maritime law and the international law of the sea. The article then considers the “three P paradigm” of anti-trafficking (that is, prevention, protection and prosecution) and how improved policies, regulation and legislation (and, as importantly, enforcement) in these areas have the potential to contribute to an improved situation for seafarers and fishers—to both prevent and combat trafficking in commercial fishing and the merchant fleet, while also noting differences between the two sectors. The analysis also draws on the perspective and experiences of men trafficked in the seafaring and commercial fishing sectors to firmly situate the discussion in the practical realm and articulate what, in concrete terms, can be done to effectively prevent and combat trafficking of seafarers and fishers.
International Energy Investments: Tracking the Legal Concept
Authors: Varis Ozge
Published: November 2018

International investment flows are rising firmly and rapidly on a daily basis throughout the world. In international investment flow energy plays a valuable role. The common point of international investment law regime and international energy law regime is, they remain many issues still to define and clarify in international investment law and energy law. In these undeveloped legal areas, the clarification of these basic issues has an essential role, as legal systems are established on the basis of clear terminology. While the significance of energy and energy-related issues in international investment law is mentioned above, there are still many blurred lines as to when “energy investments” in particular become relevant. In these situations, the limits of what may be considered an “energy investment” must be clarified. In order to explicitly explain references to “energy investments”, this article will firstly discuss the definition of international investments; secondly, the definition of energy will be analysed and then what is described as “an energy investment” will be thoroughly scrutinised. During these discussions, examples from other sectors’ investment disputes and other legal areas will also be examined and compared to provide more explicit answers as to the limits of the term.
Transparency in International Arbitration: Any (Concrete) Need to Codify the Standard?
Authors: Ruscalla Gabriele
Published: November 2018

In the last decades, transparency has become a fundamental principle in international adjudication. It is usually defined as including concepts such as public access and disclosure of documents or information. Due to the high impact of the activities of international institutions on civil societies and the growing relevance of individuals as subjects of the International Community, it became evident that there was a need to: 1. make the decision-making processes of international organisations more transparent; 2. increase the accountability of the international institutions towards civil societies; 3. give access to the public to international dispute settlement mechanisms. For the purpose of this article, the third aspect, ie access to the public to international dispute settlement mechanisms, will considered. In particular, even though reference will be made to other international dispute settlement systems, the practice of international investment and commercial arbitral tribunals will be dealt with. The article will then study the role of transparency in international arbitration, highlighting three main challenges. First, the author will consider the difficult relation between transparency and confidentiality in arbitral proceedings. As this issue is extremely delicate in international commercial arbitration, this practice will be the focus of this section of the article. Second, transparency as a tool to reach a higher level of consistency in international arbitration will be discussed. This is a highly topical issue in international arbitration, as shown by the United Nations Commission on International Trade Law (UNCITRAL) negotiations that led to the adoption in 2014 of the Rules on Transparency in Treatybased Investor-State Arbitration. As a matter of fact, UNCITRAL looked into the issue of amicus curiae briefs provided by the investor’s home State on issue of treaty interpretation, to secure more consistent and harmonised interpretations of standards in investment arbitration. The author will explore whether consistency through transparency is desirable in international arbitration. Third, the paper will deal with the growing tendency to codify standards in international arbitration. This phenomenon is well illustrated by the current negotiations on investment and trade treaties such as the EU-US Transatlantic Trade and Investment Partnership (TTIP) and the EU-Canada Comprehensive Economic and Trade Agreement (CETA) that provide for specific provisions on transparency relating to investor-to-State disputes. The necessity and effectiveness of this codification will be investigated.
Sovereign Default Disputes in Investment Treaty Arbitration: Jurisdictional Considerations and Policy Implications
Authors: Ostřanský Josef
Published: November 2018

In the aftermath of Argentina’s 2001 economic crisis, creditors not participating in the country sovereign debt restructuring insisted on full payment. The triplet of investment arbitration decisions upheld jurisdiction over the mass claims presented by the holdout creditors.1 Two cases were, however, accompanied by forceful dissents. Subsequently, opinions diverged into two camps on the legal appropriateness and policy desirability of using investment arbitration for solving sovereign default disputes: the first camp supporting the majority’s view, and the second siding with the dissenting arbitrators. This article analyses the two approaches as far as jurisdictional requirements for hearing the sovereign bond disputes are concerned as well as potential policy consequences of the use of investment arbitration for these types of disputes. The article assumes a critical position towards the reasoning of the three awards, mostly due to the misconceived apprehension of the requirement of territoriality. In the policy part, the article argues that even if one assumes that enhancement of the creditor’s rights is desirable (something which is debatable), investment arbitration does not seem to bring advantages towards that goal. First, the argument of better enforcement of arbitral awards seems to be more apparent than real. Second, as Bilateral Investment Treaties base their protection on nationality, this fact creates unjustifiable preference towards certain creditors and increases unpredictability. This uncertainty upsets the original contractual bargain agreed on the issuance of bonds and has negative repercussions in financial markets. The ad hoc nature of investment arbitration only furnishes the uncertainty. Lastly, investment arbitration is a tool for correcting past grievances. Tools for dealing with orderly sovereign defaults should focus on the preventive aspects of sovereign defaults. As a robust multilateral treaty system dealing with sovereign defaults is currently politically unfeasible, a better solution is to reinforce the current system of contractual protections such as collective action clauses or exit consents. Rather than attempting to expand the role of arbitration, resolving sovereign debt issues should be left to actors in financial markets (lenders and borrowers). Financial markets have always proved capable of dealing with sovereign defaults.
Drafting and Interpreting International Investment Agreements from a Sustainable Development Perspective
Authors: Levy Claudia Salgado
Published: November 2018

The proliferation of International Investment Agreements (IIAs) and treaty-based investment arbitration has raised concerns over the extent to which IIAs are actually fair and are able to balance the interests of foreign investors and States. The strong protections afforded by IIAs to investors may restrict the host State’s ability to regulate for the public interest and potentially allow newly adopted public policies to be subject to compensation. Several economic transactions that have qualified as investments for treaty protection have fallen short of contributing to the host State’s sustainable development. They have not added to the generation of employment and growth, the transfer of new technologies and knowledge or the strengthening of infrastructure. Nor have many of these economic transactions contributed to the home country’s development. Moreover, regulatory measures adopted with the aim of fostering sustainable development (ie environmental measures) have been successfully challenged by investors. In some cases tribunals have interpreted these measures as creeping or indirect expropriations, therefore requiring compensation. Both the lack of consideration for the host State’s interests under international investment law and the limitation to the State’s policy space have been perceived as having negative implications for the development of the country, and in particular for the adoption of sustainable policies. Though little empirical evidence exists, it has been suggested that investment arbitration is a threat to the adoption of public policy regulations and may even have a ‘chilling effect’ on them. A possible way forward is the negotiation of a new generation of investment treaties, as well as the renegotiation and revision of the existing ones. These changes are needed in order to balance the interests of States and investors and to incorporate innovative features in light of the necessary policy space that States require in order to foster sustainable development through the application of dynamic social and environmental norms and regulations. Another alternative is the adoption of interpretative approaches, which ultimately foster sustainable development goals. The preferred options are the contextual and dynamic interpretation of the intention of the contracting States, as well as the systemic integration of international rules and norms into investor-State disputes.
Publication of Investment Treaty Awards: The Qualified Potential of Domestic Access to Information Laws
Authors: Balcerzak Filip , Hepburn Jarrod
Published: November 2018

Investment treaties and arbitral rules traditionally impose few legally binding duties on States to release investment treaty awards. Despite this, possibly in light of the growing recognition of a human right of access to public information, recent efforts towards transparency in investment arbitration proceedings have led to significant changes in both legal instruments and State practice. However, many States remain reluctant to commit to transparency obligations, or to comply with transparency obligations where they already exist. This article reviews the utility of one lesserknown tool, domestic freedom of information (FOI) laws, in promoting transparency in the particular context of investment arbitration. The article focuses on the Republic of Poland, a State known to be holding a sizeable number of unpublished investment treaty awards. The Polish experience discussed in this article suggests that, despite the many problems encountered, domestic FOI laws do have the potential, even if qualified, to constitute a factor in the growing trend towards transparency.
Foreign Terrorist Fighters and International Law
Authors: Bílková Veronika
Published: November 2018

The phenomenon of foreign fighting is not new. What is however unprecedented about it today is, in addition to its scale, the fact that it is more and more often conceptualized through the prism of the fight against terrorism. Attention has been turned from the situation at the battlefield to that in the countries of origin. The regulation no longer falls under the laws of armed conflict but under international criminal law or, even, under an emerging international counter-terrorism law. And foreign fighters have become foreign terrorist fighters. These developments may seem relatively insignificant; however, they represent a paradigmatic shift. And this shift comes with a price. The concept of foreign terrorist fighters and the international legal regulation applicable to it, stemming primarily from the UN Security Council Resolutions 2178 (2014) and 2396 (2017), give rise to legal challenges. The paper discusses three such challenges pertaining to the definition of foreign terrorist fighters, the construction of foreign terrorist fighters-related offences and the impact on human rights. The main message that the paper seeks to impart is to caution against an excessive ‘terror-isation’ of international life which, even if motivated by laudable purposes, has problematic consequences, thus constituting of itself a threat to the values that it is supposed to protect.
Autonomous Weapons in Humanitarian Law: Understanding the Technology, Its Compliance with the Principle of Proportionality and the Role of Utilitarianism
Authors: Winter Elliot
Published: November 2018

Autonomous machines are moving rapidly from science fiction to science fact. The defining feature of this technology is that it can operate independently of human control. Consequently, society must consider how ‘decisions’ are to be made by autonomous machines. The matter is particularly acute in circumstances where harm is inevitable no matter what course of action is taken. This dilemma has been identified in the context of autonomous vehicles driving under the regulation of domestic law and, there, governments seem to be moving towards a utilitarian solution to inevitable harm. This leads one to question whether utilitarianism should be transposed into the context of autonomous weapons which might soon operate on the battlefield under the gaze of humanitarian law. The argument here is that it should because humanitarian law includes the core principle of ‘proportionality’, which is fundamentally a utilitarian concept – requiring that any gain derived from an attack outweighs the harm caused. However, while human soldiers are always able to come to a view on proportionality, albeit subjective, there is much doubt over how an autonomous weapon might determine what is proportionate. There is a very large gap between our embryonic understanding of utilitarianism in relation to autonomous vehicles manoeuvring around a city on one hand; and what would be required for armed robots patrolling a battlespace on the other. Bridging this gap is fraught with difficulty but perhaps the best starting point is to take Bentham’s expression of utilitarian mechanics and build upon them. With conscious effort and, ideally, collaboration, states could use the process of applying his classic theory to this very modern problem to raise the standard of protection offered to those caught up in conflict.
Association of Monoclonal Gammopathy with Progression to ESKD among US Veterans
Authors: Burwick Nicholas , Adams Scott V. , Todd-Stenberg Jeffrey A. , Burrows Nilka Rios , Pavkov Meda E. , O’Hare Ann M.
Published: November 2018

Background and objectives

Whether patients with monoclonal protein are at a higher risk for progression of kidney disease is not known. The goal of this study was to measure the association of monoclonal protein with progression to ESKD.

Design, setting, participants, & measurements

This was a retrospective cohort study of 2,156,317 patients who underwent serum creatinine testing between October 1, 2000 and September 30, 2001 at a Department of Veterans Affairs medical center, among whom 21,898 had paraprotein testing within 1 year before or after cohort entry. Progression to ESKD was measured using linked data from the US Renal Data System.

Results

Overall, 1,741,707 cohort members had an eGFR≥60 ml/min per 1.73 m2, 283,988 had an eGFR of 45–59 ml/min per 1.73 m2, 103,123 had an eGFR of 30–44 ml/min per 1.73 m2and 27,499 had an eGFR of 15–29 ml/min per 1.73 m2. The crude incidence of ESKD ranged from 0.7 to 80 per 1000 person-years from the highest to lowest eGFR category. Patients with low versus preserved eGFR were more likely to be tested for monoclonal protein but no more likely to have a positive test result. In adjusted analyses, a positive versus negative test result was associated with a higher risk of ESKD among patients with an eGFR≥60 ml/min per 1.73 m2(hazard ratio, 1.67; 95% confidence interval, 1.22 to 2.29) and those with an eGFR of 15–29 ml/min per 1.73 m2(hazard ratio, 1.38; 95% confidence interval, 1.07 to 1.77), but not among those with an eGFR of 30–59 ml/min per 1.73 m2.Progression to ESKD was attributed to a monoclonal process in 21 out of 76 versus seven out of 174 patients with monoclonal protein and preserved versus severely reduced eGFR at cohort entry.

Conclusions

The detection of monoclonal protein provides little information on ESKD risk for most patients with a low eGFR. Further study is required to better understand factors contributing to a positive association of monoclonal protein with ESKD risk in patients with preserved and severely reduced levels of eGFR.
Home-Based Kidney Care, Patient Activation, and Risk Factors for CKD Progression in Zuni Indians
Authors: Nelson Robert G. , Pankratz V. Shane , Ghahate Donica M. , Bobelu Jeanette , Faber Thomas , Shah Vallabh O.
Published: November 2018

Background and objectives

The burden of CKD is greater in ethnic and racial minorities and persons living in rural communities, where access to care is limited.

Design, setting, participants, & measurements

A 12-month clinical trial was performed in 98 rural adult Zuni Indians with CKD to examine the efficacy of a home-based kidney care program. Participants were randomized by household to receive usual care or home-based care. After initial lifestyle coaching, the intervention group received frequent additional reinforcement by community health representatives about adherence to medicines, diet and exercise, self-monitoring, and coping strategies for living with stress. The primary outcome was change in patient activation score, which assesses a participant’s knowledge, skill, and confidence in managing his/her own health and health care.

Results

Of 125 randomized individuals (63 intervention and 62 usual care), 98 (78%; 50 intervention and 48 usual care) completed the 12-month study. The average patient activation score after 12 months was 8.7 (95% confidence interval, 1.9 to 15.5) points higher in the intervention group than in the usual care group after adjusting for baseline score using linear models with generalized estimating equations. Participants randomized to the intervention had 4.8 (95% confidence interval, 1.4 to 16.7) times the odds of having a final activation level of at least three (“taking action”) than those in the usual care group. Body mass index declined by 1.1 kg/m2 (P=0.01), hemoglobin A1c declined by 0.7% (P=0.01), high-sensitivity C-reactive protein declined by 3.3-fold (P<0.001), and the Short-Form 12 Health Survey mental score increased by five points (P=0.002) in the intervention group relative to usual care.

Conclusions

A home-based intervention improves participants’ activation in their own health and health care, and it may reduce risk factors for CKD in a rural disadvantaged population.
Developing flash media of Quranic-based human reproduction system material
Authors: Kurniawan Arif Didik , Muldayanti Nuri Dewi , Putri Banita Eka
Published: November 2018

The problem of implementing Islamic values in the learning process is one of the concerns in Islamic-based schools, in particular, Rahmatan Lil’alamin Islamic Senior High School in Pontianak. This study aimed to develop learning media based on the Quran verses in the human reproductive system using Macromedia flash software. This research and development used three phases of the 4D model developed by Thiagarajan, namely define, design, and development. The development results were validated by expert appraisal consisted of instructional review (appropriateness, effectiveness, feasibility) and technical review (media and language). Instruments used in this study were interview guide sheet (define phase), validation sheets, student response questionnaires, and post-test for product trial (development phase). Product trials were carried out by testing large groups consisted of 64 students majoring in social science at Rahmatan Lil’alamin Islamic Senior High School. The expert appraisal results showed that media reached “very valid” criteria with the validation scores 83.33 (instructional review), 80.42 (media),  and 85.00 (language). Therefore, the flash media of Quranic-based human reproductive system material is potential to be used as media in teaching Islamic values integrated within the learning process.
FISH MUCUS: A NEGLECTED RESERVOIR FOR ANTIMICROBIAL PEPTIDES
Authors: Hedmon Okella
Published: November 2018

Antimicrobial resistance has posed a great global burden, with the fear that by 2050 it would have killed more people than cancer if nothing much is done about it. Alongside several attempts in place, zoo-therapy is becoming one of important remedies in the modern society, with hope for solution believed to be hidden in nature. In this study, the authors present a review of journal articles and reports obtained through key word search of several literature databases on recent developments in the battle against the antimicrobial resistance using fish derived antimicrobial peptides. The findings indicate despite some limitations of these antimicrobial peptides, their very broad spectrum activity against pathogens keeps them among  promising antibiotics as far as the battle against multidrug resistance is concerned. Much as various methods to study antimicrobial peptides do exist, fish mucus remains less explored. The study recommends aquatic habitat exploration in search for novel bacterial antimicrobial peptides.
FORMULATION DEVELOPMENT OF ACYCLOVIR MICROSPHERE USING NOVEL NATURAL POLYMER
Authors: Singh Priyanka , Lariya Shailendra K
Published: November 2018

Acyclovir [9-(2-hydroxyethoxymethyl) guanine] is an acyclic nucleoside analogue of guanosine that is a potent and selective antiviral agent. It has a relatively short plasma half-life (3 hr). When orally administered, it is slowly and scarcely absorbed from the gastrointestinal tract. The objective of the present work was to formulate and evaluate microspheres of Acyclovir and produced sustained drug delivery. In these 14 batches of acyclovir microspheres was prepared with using natural polymer Kondagogu gum and other ingredients by solvent evaporation technique. The prepared microspheres were evaluated for different parameters i.e % Drug yield, % drug entrapment, shape, surface morphology, particles size, polydispersity index, zeta potential and in-vitro drug release for 48 hrs in phosphate buffer 7.4. The best batch was performed stability studies for 6 months. The research concluded that Acyclovir microspheres could be an alternative for conventional dosage form and other phytochemical in herbs.

Keywords: Acyclovir, Microspheres, Kondagogu gum, Polydispersity index, in-vitro drug release
A STUDY ON ANXIETY AND DEPRESSION AMONG PATIENTS WITH POLYCYSTIC OVARY SYNDROME
Authors: Radhakrishnan Rahul , Verghese Anna
Published: November 2018

Background: Patients with polycystic ovarian syndrome (PCOS) often suffer from psychiatric co-morbidities, such as anxiety and depression. The prevalence of PCOS is increasing In India.

Objective: To Study anxiety and depression among PCOS Patients.

Materials and Methods: It was a cross-sectional observational study, which was conducted in Obstetrics and Gynaecology department of a tertiary care hospital. Patients diagnosed with PCOS were assessed on hospital anxiety depression scale and sociodemographic and clinical information was gathered using semi-structured questionnaire.

Result: The prevalence of anxiety of 36% and depression 16% were observed.

Discussion: PCOS patients were found to have high prevalence of anxiety and depression due to the Symptoms of PCOS.

Keywords: Anxiety, PCOS, psychological problems, Depression
PEDIATRIC NASAL SPRAY SOLUTION: FACTORIAL DESIGN DEVELOPMENT AND EVALUATION
Authors: Bhuva Falgun , Patel LD
Published: November 2018

The work was aimed to develope the meter dose formulation of pediatric xylometazoline nasal spray formulation. The 32 factorial design was utilized for development of the pediatric formulation. The independent factors were sodium cholate (X1) and Polyethyleneglycol 400 concentration (X2). The optimized formulation composition consisted of 0.105 g sodium cholate and 1.35 ml polyethyleneglycol 400. The formulation was evaluated for solution parameters like drug content, pH, viscosity, % diffusion, sterility and spray evaluation parameters like spray content uniformity, pump delivery, spray pattern, and weight loss. The results for spray content uniformity were in the range of 95-102 %, while pH in the range of 6.5 ± 0.3. The ovality of spray was 1.118, while perimeter and area of spray pattern were found to be 57.42 mm and 258.8 mm2 respectively for optimized formulation. The least value for repriming was 97.6 % while the extreme value was 102.2 % indicating one actuation was satisfactory for repriming. The results for droplet size test were obtained in the range of 51.63 to 58.90 µm. The formulation along with its container closure was evaluated for its stability up to 12 months at long term conditions. The formulated batch PFE showed better performance for in-vitro drug release with marketed product thus providing another option for treatment of nasal congestion.