bluuebunny/crossref_metadata_2025 huggingface dataset:
Health effects of nutrients and environmental pollutants in Baltic herring and salmon: a quantitative benefit-risk assessment
Authors: Tuomisto Jouni T , Asikainen Arja , Meriläinen Päivi , Haapasaari Päivi
Published: October 2019

Background
Dioxin health risks from fish remains a complex policy issue. Especially fatty Baltic fish, such as herring and salmon, contain relatively high concentrations of pollutants although they are otherwise healthy food. We studied the health benefits and risks of Baltic herring and salmon in four countries to identify critical uncertainties and to facilitate evidence-based discussion on the dioxin policy related to these fishes.
Methods
We performed an online survey about consumers' fish consumption and its motivation in Denmark, Estonia, Finland, and Sweden. Dioxin and methylmercury concentrations were estimated based on Finnish data. Exposure-response functions about several health endpoints were evaluated and quantified based on scientific literature. We also quantified infertility risk of men based on a recent European risk assessment about childhood dioxin exposure and its effect on sperm concentration later in life.
Results
Baltic herring and salmon contain e.g. omega-3 fatty acids and vitamin D, and the beneficial impact of these fishes on cardiovascular, mortality, and depression risk clearly outweighs risks of dioxins and methylmercury in people more than 45 years of age and in young men. The critical population subgroup is young women, who may expose their children to pollutants during pregnancy and breast feeding. However, the study suggests that even in this group the health benefits are larger or similar than health risks. Value of information analysis demonstrated that the remaining scientific uncertainties are not large. In contrast, several critical uncertainties are value judgements by nature: whether Baltic fish should be seen as primary or secondary source of nutrients; whether exceeding tolerable intake is an adverse outcome as such; and whether subgroup-specific restrictions are problematic or not.
Conclusions
Potential health risks from dioxins in Baltic fish have decreased to less than a half in ten years. The new risk assessment by European Food Safety Authority clearly increases the fraction of population exceeding the tolerable dioxin intake, but quantitative estimates of net health impacts change only marginally. Increased use of small herring (with less pollutants) is a no-regret option. Further value-based policy discussion rather than research is needed to clarify useful actions related to dioxins in fish.
The Main Infrastructure for Better Dental Implant Management: A Systematic Review on Dental Implant Registries
Authors: Author) Roya Naemi(Former Corresponding , Barikani Hamid Reza , Author) Leila Shahmoradi(New Corresponding
Published: October 2019

Background The importance of dental implant registry system has been well documented. However, no systematic review on the dental implant registry system can be found in the literature. Therefore, the aim of this study is to review the dental implant registry system to determine the goals, data elements, reports, data sources, capabilities and institutions that develop dental implant registry system.Methods A systematic study was conducted in PubMed, Scopus, Web of Science and Embase databases. Also, samples of dental implant registry system were searched in Google and were included into the study. For evaluating the dental implant registry system, all English language studies were examined without time limitation. Non-English studies and papers such as conference abstracts were excluded.Results The primary search identified 16905 articles. After eliminating duplicates, full texts of 53 retrieved articles were reviewed by the researchers and finally, 15 studies were included in this review. In this review, the goals of dental implant registry system were determined to be surveillance, complication management and etc. Also, the data elements of dental implant registry system were include patient information, implant information, etc.Conclusion The results of this study provide dentists and other stakeholders with useful dataset on the development of dental implant registry system. It also provides a framework of the goals, characteristics, data elements and reports, data sources, and capabilities of dental implant registry system. The establishment of dental implant registry system will allow the control of complications of dental implants in the future.Systematic review registration CRD42019126424
Demographic and socioeconomic characteristics of Canadian medical students: A cross-sectional study
Authors: Khan Rishad , Apramian Tavis , Kang Joel Hosung , Gustafson Jeffrey , Sibbald Shannon
Published: October 2019

Background While the importance of medical students’ demographic characteristics in influencing the scope and location of their future practice is recognized, these data are not systematically collected in Canada. This study aimed to characterize and compare the demographics of Canadian medical students with the Canadian population.Methods Through an online survey, delivered in 2018, medical students at fourteen English-speaking Canadian medical schools provided their age, sex, gender identity, ethnicity, educational background, and rurality of the area they grew up in. Respondents also provided information on parental income, occupation, and education as markers of socioeconomic status. Data were compared to the 2016 Canadian Census.Results A total of 1388 students responded to the survey, representing a response rate of 16.6%. Most respondents identified as women (63.1%) and were born after 1989 (82.1%). Respondents were less likely, compared to the Canadian Census population, to identify as black (1.7% vs 6.4%) (P<0.001) or Aboriginal (3.5% vs. 7.4%) (P<0.001), and have grown up in a rural area (6.4% vs. 18.7%) (P<0.001). Respondents had higher socioeconomic status, indicated by parental education (29.0% of respondents’ parents had a master’s or doctoral degree, compared to 6.6% of Canadians aged 45-64), occupation (59.7% of respondents’ parents were high-level managers or professionals, compared to 19.2% of Canadians aged 45-64), and income (62.9% of respondents grew up in households with income >$100,000/year, compared to 32.4% of Canadians). Assessment of non-response bias showed that our sample was representative of all students at English-speaking Canadian medical schools with respect to age, though a higher proportion of respondents were female. Additionally, there were no differences between early and late respondents with respect to ethnicity, rurality, and parental income, occupation, and education.Conclusions Canadian medical students have different socioeconomic characteristics compared to the Canadian population. Collecting and analyzing these characteristics can inform evidence-based admissions policies.
Regional differences in reasons for consultation and general practitioners’ spectrum of services – Results of a cross-sectional observational study
Authors: Schäfer Ingmar , Hansen Heike , Ruppel Thomas , Lühmann Dagmar , Wagner Hans-Otto , Kazek Agata , Scherer Martin
Published: October 2019

Background Among other factors, the patients’ consultation reasons and the GPs’ spectrum of services determine process and outcome of the medical treatment. So far, however, there has been little information on differences in reasons for consultations and performed services between urban and rural areas. Thus, the goal of the study was to investigate these factors in relation to the regional location of the GP practices.Methods We conducted a cross-sectional observational study based on standardised GP interviews in a quota sampling design. All counties and independent cities within a radius of 120km around Hamburg were divided in three regional categories (urban, rural, environs) and stratified proportionally to the population size. Differences in the number of reasons for consultation and services were analysed by multivariate linear regressions in mixed models adjusted for random effects on the levels of the German federal states and administrative districts. Differences in individual consultation reasons and services were identified by logistic regression models via stepwise forward and backward selection.Results Primary care practices in 34 of the 37 selected administrative districts (91.9%) were represented in the dataset. In total, 211 GPs were personally interviewed. On average, GPs saw 1,032 patients per quarter (3-month period) with a slightly higher number of patients in rural areas. They reported 59.1 ± 15.4 different reasons for consultations and 30.3 + 3.9 different services. There was no statistically significant regional variation in the number of different consultation reasons, but there was broader service spectrum by rural GPs (ß=-1.42; 95% confidence interval -2.75/-0.08; p=0.038), which was statistically explained by a higher level of postgraduate training. Additionally, there were differences in the frequency of individual consultation reasons and services between rural and urban areas.Conclusions GPs in rural areas spent less time on communicative, preventive, and consultant medicine than GPs in urban areas. In contrast, GPs in rural areas more often performed services that are usually provided by ambulatory specialist care in urban areas. Depending on the analysed item, primary care in the environs was either similar to “urban areas” or to “rural areas”.
Ubiquitin-specific protease 44 inhibits cell proliferation and migration via inhibition of JNK pathway in clear cell renal cell cancer
Authors: Zhou Jiangqiao , Wang Tianyu , Qiu Tao , Chen Zhongbao , Ma Xiaoxiong , Zhang Long , Zou Jilin
Published: October 2019

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies. USP44 has been reported to be involved in various cancers. This study aimed to investigate the function role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from TCGA data portal and GSO database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. The function of USP44 in cell proliferation and migration was assessed by cellular and molecular analysis. Results: USP44 was lowly expressed in the ccRCC cancer tissues compared to the normal tissue. Further, USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival . USP44 overexpression significantly inhibited tumor cell proliferation and migration of 786-O cell as well as Caki-1 cell. In addition, USP44 overexpression also prohibited cell proliferation by up-regulating P21, down-regulating Cyclin D1 expression, and inhibited cell migration by up-regulating MMP2 and MMP9 expression. In contrast, USP44 knockdown enhances ccRCC cell proliferation and migration. Furthermore, the USP44 function in inhibiting ccRCC cell proliferation and migration is associated with the phosphorylation level of JNK. Conclusion: In summary, this study showed that USP44 may be a marker in predicting the ccRCC progression and USP44 inhibits ccRCC cell proliferation and migration dependent on the JNK pathway.
Comparative genomic analysis of the secondary flagellar (flag-2) system in the order Enterobacterales
Authors: De Maayer Pieter , Pillay Talia , Coutinho Teresa A
Published: October 2019

Background The order Enterobacterales encompasses a broad range of metabolically and ecologically versatile bacterial taxa, most of which are motile by means of peritrichous flagella. Flagellar biosynthesis has been linked to a primary flagella locus, flag -1, encompassing ~ 50 genes. A discrete locus, flag -2, encoding a distinct flagellar system, has been observed in a limited number of enterobacterial taxa, but its function remains largely uncharacterized.Results and Discussion Comparative genomic analyses showed that orthologous flag -2 loci are present in 592/4,028 taxa belonging to 5/8 and 31/76 families and genera, respectively, in the order Enterobacterales. Furthermore, the presence of the outermost flag- 2 genes only in many taxa suggest that this locus was far more prevalent and has subsequently been lost through gene deletion events. The flag -2 loci range in size from ~3.4 to 81.1 kilobases and code for between five and 102 distinct proteins. The discrepancy in size and protein number can be attributed to the presence of cargo gene islands within the loci. Evolutionary analyses revealed a complex evolutionary history for the flag -2 loci, representing ancestral elements in some taxa, while showing evidence of recent horizontal acquisition in other enterobacteria.Conclusions The flag -2 flagellar system is a relatively common, but highly variable feature among members of the Enterobacterales. Given the energetic burden of flagellar biosynthesis and functioning, the prevalence of a second flagellar system suggests it plays important biological roles in the enterobacteria and we postulate on its potential role as locomotory organ or as secretion system.
Healthcare Access and Adverse Family Impact among U.S. Children ages 0-5 years by Prematurity Status
Authors: Lindly Olivia J. , Crossman Morgan K. , Shui Amy M. , Kuo Dennis Z. , Earl Kristen M. , Kleven Amber R. , Perrin James M. , Kuhlthau Karen A.
Published: October 2019

Background: Many children and their families are affected by premature birth. Yet, little is known about their healthcare access and adverse family impact in early childhood. This study aimed to (1) examine differences in healthcare access and adverse family impact among young children by prematurity status and (2) determine associations of healthcare access with adverse family impact among young children born prematurely. Methods: This was a secondary analysis of cross-sectional 2016 and 2017 National Survey of Children’s Health data. The sample included 19,482 U.S. children ages 0-5 years including 242 very low birthweight (VLBW) and 2,205 low birthweight and/or preterm (LBW/PTB) children. Prematurity status was defined by VLBW (i.e., <1,500 grams at birth) and LBW/PTB (i.e., 1,500-2,499 grams at birth and/or born at <37 weeks with or without low birthweight). Healthcare access measures were adequate health insurance, medical home, and developmental screening receipt. Adverse family impact measures were ≥$1,000 annual out-of-pocket medical costs, having a parent cut-back or stop work, parental aggravation, maternal health not excellent, and paternal health not excellent. The relative risk of each healthcare access and adverse family impact measure was computed by prematurity status. Propensity weighted models were fit to estimate the average treatment effect of each healthcare access measure on each adverse family impact measure among children born prematurely (i.e., VLBW or LBW/PTB). Results: Bivariate analysis results showed that VLBW and/or LBW/PTB children generally fared worse than other children in terms of medical home, having a parent cut-back or stop working, parental aggravation, and paternal health. Multivariable analysis results only showed, however, that VLBW children had a significantly higher risk than other children of having a parent cut-back or stop work. Adequate health insurance and medical home were each associated with reduced adjusted relative risk of ≥$1,000 in out-of-pocket costs, having a parent cut-back or stop work, and parental aggravation among children born prematurely. Conclusions: This study’s findings demonstrate better healthcare access is associated with reduced adverse family impact among U.S. children ages 0-5 years born prematurely. Population health initiatives should target children born prematurely and their families.
The association between length of stay in the emergency department and short term mortality
Authors: Wessman Torgny , Ärnlöv Johan , Carlsson Axel , Ekelund Ulf , Melander Olle , Ruge Thoralph
Published: October 2019

Background: Prolonged length of stay at the emergency department (ED-LOS) has been associated with increased mortality and hospital stay. The aim of this study was to investigate the association between ED-LOS and 7- and 30-days mortality in patients triaged according to Rapid Emergency Triage and Treatment System – Adult (RETTS-A), the most common used triage tool in Sweden. Methods: All adult patients (> 18 years) visiting the ED at the Karolinska University Hospital, Sweden, from 1/1/2010 to 1/1/2015 (n=639 385) were included. Logistic regression analysis was used to determine association between prolonged ED-LOS and 7 and 30-days mortality rates. All patients were triaged according to the RETTS-A and subsequently separated into five quintiles of ED-LOS. Results : In patients triaged with the highest medical urgency, longer ED-LOS was associated with a lower risk for 7-days mortality, for triage priority 1: OR 0.94 (CI 95% 0.92-0.96) compared to OR 1.03 (CI 95% 0.99-1.07) for triage priority 4, and for 30-days mortality: OR 0.97 (CI 95% 0.96-0.99) OR for triage priority 1 compared to 1.03 (CI 95% 1.01-1.05) for triage priority 4. In contrast, the opposite pattern appeared evident in the 3 other triage groups, where a longer ED-LOS was generally associated with an increased mortality risk. Pro-longed ED-LOS in patients admitted to in-hospital care was associated with lower 30- and 7-days mortality independently of triage priority whereas the opposite was observed for patients not admitted to in-hospital care. Conclusion: Prolonged ED-LOS was associated with increased short term mortality in patients with lower clinical urgency and in patients not admitted to in-hospital care.
Food handling practice and associated factors among food handlers working in food establishments in Woldia town, Northeast Ethiopia
Authors: Reta Melese Abate , Lemma Mekonnin Tesfa , Gemeda Ashete Adere , Lemlem Getasew Assefa
Published: October 2019

Objective: The aim of this study was to assess food handling practice and associated factors among food handlers working in public food and drink establishments in Woldia town, Northeast Ethiopia.Results: Of the total 288 participated food handlers, 91.7% were females, and 82.3% were single, while 69.8% were literate. Ninety-four (32.6%) of them were under 15-20 years age and the median age was 23.3year. The proportion of good food handling practice was 134 (46.5%)[95% CI (confidence interval): 41.00, 52.40]. Advanced age [AOR (adjusted odds ratio):12.01; 95%CI 1.96-73.52], education (AOR=2.29; 95% CI=1.05-4.61), service year (AOR=2.43; 95% CI=2.08-3.17), received training (AOR=1.79; 95%CI=1.68-4.71), and inspection by regulatory personnel (AOR=2.24; 95%CI=1.05-3.09) were positively associated with food handler's food handling practices. This study showed that the food handling practice was poor. Age, education, service year, training received, and sanitary inspection visit by regulatory personnel were factors significantly associated with food handler's food handling practices. Food handling and safety training to food handlers, establishment owners, and regular sanitary inspection visits of public food service establishments by regulatory authority is compulsory.
Bulk locality and asymptotic causal diamonds
Authors: Krishnan Chethan
Published: October 2019

In AdS/CFT, the non-uniqueness of the reconstructed bulk from
boundary subregions has motivated the notion of code subspaces. We
present some closely related structures that arise in flat space. A
useful organizing idea is that of an asymptotic causal diamond (ACD): a
causal diamond attached to the conformal boundary of Minkowski space.
The space of ACDs is defined by pairs of points, one each on the future
and past null boundaries, I^{\pm}I±.
We observe that for flat space with an IR cut-off, this space (a)
encodes a preferred class of boundary subregions, (b) is a plausible way
to capture holographic data for local bulk reconstruction, (c) has a
natural interpretation as the kinematic space for holography, (d) leads
to a holographic entanglement entropy in flat space that matches
previous definitions and satisfies strong sub-additivity, and, (e) has a
bulk union/intersection structure isomorphic to the one that motivated
the introduction of quantum error correction in AdS/CFT. By sliding the
cut-off, we also note one substantive way in which flat space holography
differs from that in AdS. Even though our discussion is centered around
flat space (and AdS), we note that there are notions of ACDs in other
spacetimes as well. They could provide a covariant way to abstractly
characterize tensor sub-factors of Hilbert spaces of holographic
theories.
Forward osmosis: dyeing draw solutions for water reclamation from feed water resources
Authors: Jingxi Estella Z. , De Jager Debbie , Augustine Robyn , Petrinic Irena , Helix-Nielsen Claus , Sheldon Marshall S.
Published: October 2019

Reactive Black 5 and Basic Blue 41 GRL dyeing solutions (dye-to-salt mixture in a 1:10 dye-to-salt mass ratio) were investigated as draw solutions (DS) in a forward osmosis (FO) system with a biomimetic membrane. Synthetic seawater (SSW) and textile wastewater (TWW1 and TWW2) were evaluated as feed solutions (FS) for water reclamation. Reactive Black 5 and Basic Blue 41 GRL were diluted from 0.02 M to concentrations of 0.002 and 0.004 M, respectively. With Reactive Black 5 as DS and SSW as FS, an initial flux of 20.24 L/m2 h and water recovery of 75% was achieved. Using TWW1 and TWW2, initial water fluxes of 19.51 and 13.43 L/m2 h were achieved, respectively, with a 30% water recovery. Using Basic Blue 41 GRL, initial water fluxes of 18.72, 15.13 and 13.42 L/m2 h were achieved with SSW, TWW1, and TWW2 as FS with water recoveries of 50%, 20% and 20%, respectively. The average reverse solute fluxes for Reactive Black 5 and Basic Blue 41 GRL were 0.06 to 0.34 g/m2 h, respectively. Diluted dyeing solutions were produced, with simultaneous water reclamation from SSW and TWW resulting in similar or higher water fluxes and lower reverse solute fluxes compared with other commercially available membranes.
Phytochemicals and Potential Therapeutic Targets on Toxoplasma gondii Parasite
Authors: Abdullahi Sharif Alhassan , Unyah Ngah Zasmy , Nordin Noshariza , Basir Rusliza , Nasir Wana Mohammed , Alapid Ashraf Ahmad , Hassan Yahaya , Mustapha Tijjani , Majid Roslaini Abd
Published: October 2019

Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.
Thiosemicarbazones as Potent Anticancer Agents and their Modes of Action
Authors: Shakya Bhushan , Yadav Paras Nath
Published: October 2019

:

Thiosemicarbazones (TSCs) are a class of Schiff bases usually obtained by the condensation of thiosemicarbazide with a suitable aldehyde or ketone. TSCs have been the focus of chemists and biologists due to their wide range of pharmacological effects. One of the promising areas in which these excellent metal chelators are being developed is their use against cancer. TSCs have a wide clinical antitumor spectrum with efficacy in various tumor types such as leukemia, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. To obtain better activity, different series of TSCs have been developed by modifying the heteroaromatic system in their molecules. These compounds possessed significant antineoplastic activity when the carbonyl attachment of the side chain was located at a position α to the ring nitrogen atom, whereas attachment of the side chain β or γ to the heterocyclic N atom resulted in inactive antitumor agents. In addition, replacement of the heterocyclic ring N with C also resulted in a biologically inactive compound suggesting that a conjugated N,N,S-tridentate donor set is essential for the biological activities of thiosemicarbazones. Several possible mechanisms have been implemented for the anticancer activity of thiosemicarbazones.
Drug Delivery and Targeting to the Brain Through Nasal Route: Mechanisms, Applications and Challenges
Authors: Kashyap Kanchan , Shukla Rahul
Published: October 2019

:

Blood-brain barrier (BBB) provides restrictions for the transportation of various therapeutic
agents to the brain. Efforts to directly target the brain by olfactory as well as trigeminal nerve pathway,
bypassing BBB, have grown significantly in recent times. The intranasal route of transportation of the
drug encompasses ability for the delivery of drug directly to the brain, improves site-specificity in the
brain and avoids systemic side effects. In the current era, novel drug delivery systems are useful tools
for targeting the brain without providing any harmful effects in nasal mucosa as well as the central
nervous system. The complex structure of nasal cavity, mucociliary clearance, degradation by the enzymes
present in nasal cavity and pathological conditions like rhinitis, common cold, etc. are the major
disputes for nasal drug delivery. The use of nanotechnological approaches like solid lipid nanoparticles,
polymeric nanoparticles, nanoemulsions, liposomes and polymeric micelles provides the ability to overcome
these barriers. There are several emerging nasal drug delivery technologies produced by various
pharmaceutical companies to conquer these hurdles. This review tries to address the recent developments
in the area of direct drug delivery to the brain through the nasal route.
Association of Common Variants in the IL-33/ST2 Axis with Ischemic Stroke
Authors: Li Shuo , Wang Zhijie , Liu Xinjing , Li Yuanzhe , Shi Changhe , Wu Jun , Sun Shilei , Li Yusheng , Li Shaohua , Xu Yuming , Song Bo
Published: October 2019

Background:

Recent studies have reported that the levels of serum interleukin-33 (IL-
33) and its receptor, suppression of tumorigenicity 2 (ST2), are potential biomarkers for susceptibility
of cardiovascular diseases. However, the genetic association of the IL-33/ST2 axis with cardiovascular
diseases remains controversial.

Objective:

We aimed to investigate the association between common variants in the IL-33/ST2 axis
and ischemic stroke in the Han Chinese population.

Methods:

We consecutively enrolled 1166 patients with ischemic stroke and 1079 age- and gender-
matched controls. Eight single nucleotide polymorphisms (SNPs) within IL-33/ST2 axis were
genotyped using the improved Multiple Ligase Detection Reaction platform. We analyzed the association
between the tested SNPs and ischemic stroke at both the genotype and haplotype levels.

Results:

Binary logistic regression analysis indicated that rs10435816 (additive model: odds ratio
[OR]=0.72, 95% confidence interval [CI], 0.54-0.95; recessive model: OR=0.72, 95%CI, 0.56-
0.94) was associated with a decreased risk of ischemic stroke after adjustment of confounding factors.
Subgroup analysis indicated that rs10435816 (additive model: OR=0.61, 95%CI, 0.41-0.89;
recessive model: OR=0.56, 95%CI, 0.40-0.80), rs7025417 (additive model: OR=0.57, 95%CI,
0.39-0.83), rs11792633 (additive model: OR=0.66, 95%CI, 0.46-0.95; recessive model: OR=0.67,
95%CI, 0.49-0.93), and rs7044343 (additive model: OR=0.69, 95%CI, 0.48-0.97; recessive model:
OR=0.67, 95%CI, 0.49-0.91) were associated with a decreased risk of large-artery atherosclerosis
stroke after adjustment of confounding factors.

Conclusion:

Our findings suggested an association between common variants in the IL-33/ST2
axis and a decreased risk of ischemic stroke in the Han Chinese population.
Synthesis and Biological Evaluation of Novel Chromone+Donepezil Hybrids for Alzheimer’s Disease Therapy
Authors: Malek Rim , Refouvelet Bernard , Benchekroun Mohamed , Iriepa Isabel , Moraleda Ignacio , Andrys Rudolf , Musilek Kamil , Marco-Contelles José , Ismaili Lhassane
Published: October 2019

Background:

Many factors are involved in Alzheimer’s Disease (AD) such as amyloid
plaques, neurofibrillary tangles, cholinergic deficit and oxidative stress. To counter the complexity of the
disease the new approach for drug development is to create a single molecule able to act simultaneously
on different targets.

Objective:

We conceived eight drug likeliness compounds targeting the inhibition of cholinesterases and
the scavenging of radicals.

Methods:

We synthesised the new molecules by the Passerini multicomponent reaction and evaluated
their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) as well
as their antioxidant activities by the Oxygen Radical Absorbance Capacity (ORAC) assay. The lipinski’s
rule for drug likeness and in silico ADME prediction was also performed.

Results:

Compounds 4f [IC50 (EeAChE) = 0.30 μM; IC50 (eqBuChE) = 0.09 μM; ORAC = 0.64 TE]
and 4h [IC50 (EeAChE) = 1 μM; IC50 (eqBuChE) = 0.03 μM; ORAC = 0.50 TE] were identified as hits
for further development.

Conclusion:

The Passerini reaction allowed us the facile synthesis of ditarget molecules of interest for
the treatment of AD.
Developing Insulin and BDNF Mimetics for Diabetes Therapy
Authors: Chan Chi Bun , Ahuja Palak , Ye Keqiang
Published: October 2019

Diabetes is a global public health concern nowadays. The majority of diabetes mellitus (DM) patients belong to type 2 diabetes mellitus (T2DM), which is highly associated with obesity. The general principle of current therapeutic strategies for patients with T2DM mainly focuses on restoring cellular insulin response by potentiating the insulin-induced signaling pathway. In late-stage T2DM, impaired insulin production requires the patients to receive insulin replacement therapy for maintaining their glucose homeostasis. T2DM patients also demonstrate a drop of brain-derived neurotrophic factor (BDNF) in their circulation, which suggests that replenishing BDNF or enhancing its downstream signaling pathway may be beneficial. Because of their protein nature, recombinant insulin or BDNF possess several limitations that hinder their clinical application in T2DM treatment. Thus, developing orally active “insulin pill” or “BDNF pill” is essential to provide a more convenient and effective therapy. This article reviews the current development of non-peptidyl chemicals that mimic insulin or BDNF and their potential as anti-diabetic agents.
Epigenetic Effects Mediated by Antiepileptic Drugs and their Potential Application
Authors: Kong Fan-Cheng , Ma Chun-Lai , Zhong Ming-Kang
Published: October 2019

An epigenetic effect mainly refers to a heritable modulation in gene expression in the
short term but does not involve alterations in the DNA itself. Epigenetic molecular mechanisms
include DNA methylation, histone modification, and untranslated RNA regulation. Antiepileptic
drugs have drawn attention to biological and translational medicine because their impact on epigenetic
mechanisms will lead to the identification of novel biomarkers and possible therapeutic strategies
for the prevention and treatment of various diseases ranging from neuropsychological disorders
to cancers and other chronic conditions. However, these transcriptional and posttranscriptional alterations
can also result in adverse reactions and toxicity in vitro and in vivo. Hence, in this review,
we focus on recent findings showing epigenetic processes mediated by antiepileptic drugs to elucidate
their application in medical experiments and shed light on epigenetic research for medicinal
purposes.
Understanding the Binding Mechanism of Antagonist (AZD3293) Against BACE-1: Molecular Insights into Alzheimer’s Drug Discovery
Authors: Sosibo Sphelele , Amoako Daniel Gyamfi , Somboro Anou Moise , Sun Darren Delai , Ngila Jane Catherine , Kumalo Hezekiel
Published: October 2019

Background:

β-site amyloid precursor protein cleaving enzyme (BACE 1) is the ratelimiting enzyme in the formation of neurotoxic β-amyloid (Aβ) residues (Aβ1-40 or Aβ1-42) considered as key players in the onset of Alzheimer’s Disease (AD). Consequently, BACE 1 is one of the principal targets of anti-AD therapy with many small molecule BACE 1 inhibitors (BACE 1Is) in clinical trials. AZD3293 (Lanabecestat) is a BACE 1I that concluded in phase 2/3 clinical trials. Due to the limited knowledge about the interaction of this drug with the BACE 1 enzyme, in the present study, we performed comprehensive Molecular Dynamics (MD) analysis to understand the binding mechanism of AZD3293 to BACE 1.

Methods:

A production run of 120 ns is carried out and results are analysed using Root Mean Square Deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) to explain the stability of enzyme ligand complex. Further, the distance (d1) between the flap tip (Thr72) and the hinge residue of the flexible loop (Thr328), in relation to θ1 (Thr72–Asp228- Thr328), and to the dihedral angle δ (Thr72-Asp35-Asp228-Thr328) were measured.

Results:

The presence of the ligand within the active site restricted conformational changes as shown by decreased values of RMSF and average RMSD of atomic positions when compared to the values of the apoenzyme. Further analysis via the flap dynamics approach revealed that the AZD3293 decreases the flexibility of binding residues and made them rigid by altering the conformational changes.

Conclusion:

The prospective binding modes of AZD3293 from this study may extend the knowledge of the BACE 1-drug interaction and pave the way to design analogues with similar inhibitory properties needed to slow the progression of Alzheimer’s disease.
Biologics in Children with Allergic Diseases
Authors: Licari Amelia , Manti Sara , Marseglia Alessia , De Filippo Maria , De Sando Elisabetta , Foiadelli Thomas , Marseglia Gian Luigi
Published: October 2019

The prevalence of allergic diseases has been remarkably increased in the last decades.
The global health burden of these conditions is substantial, since patients may experience disability,
anxiety and emotional distress, social restrictions, and reduced quality of life and productivity, in
particular, in the most severe cases. Recent advances in understanding the pathophysiology of allergic
disorders have allowed identifying novel therapeutic strategies for the treatment of severe
and uncontrolled allergic diseases. Although most studies have been performed in allergic asthma,
biological drugs targeting other allergic diseases such as chronic spontaneous urticaria, atopic dermatitis,
and food allergy are showing promising results. In this review, the most recent evidence on
biologic therapies for allergic diseases, focusing on the pediatric age has been presented.
Training and Evaluation of Community Health Workers (CHWs): Towards Improving Maternal and Newborn Survival in an Urban Setting in KwaZulu-Natal, South Africa
Authors: Ndaba Thoko , Taylor Myra , Mabaso Musawenkosi
Published: October 2019

Background:

In South Africa, Community Health Workers (CHWs) are a key component of community outreach teams as part of Primary Health Care (PHC) re-engineering. Although the value of CHW programs has been increasingly recognized, published evaluations of CHWs’ training programs are rare. This study documents the training and evaluation of CHWs on maternal and neonatal care towards improved maternal-newborn survival in an impoverished urban setting in KwaZulu-Natal, South Africa.

Methods:

Using a descriptive study design, CHWs were trained to do home visits, assess and support the mother to settle in well at home post-discharge, check on babies’ warmth, cord care, breastfeeding, basic hygiene, size of the baby if underweight and advise on Kangaroo mother care. They were also trained to check if the mothers were given the Road to Health card and to inquire about the immunization and subsequent follow-up visits to the PHC, and encourage mothers to adhere to their follow up dates at PHC clinics. Pre-and post-test scores, shadow visits, and spot checks were used to evaluate their performance.

Results:

Generally, CHWs (n=47) from all three PHC clinics performed well. Overall, the highest post-test score among the PHC CHWs was 72% and the lowest was 50%. On average during shadow visits 67% CHWs were rated as good, 2% were rated as poor, and most CHWs received the highest score at 92% during spot checks.

Conclusion:

CHWs demonstrated social commitment and purpose in the short term observed. The evaluation of the training of CHWs revealed that most demonstrated the necessary skills for referrals to prevent complications, caring for newborns and their mothers at home immediately after discharge from health care centers. CHW upskilling training on maternal-newborn services should be prioritized in the most affected areas.
Microwave Assisted Synthesis, Characterization and Antimicrobial Screening of Thiazolidin-4-one Substituted Pyrazole Derivatives
Authors: Beniwal Meenu , Jain Neelam
Published: October 2019

Background:

This paper describes the synthesis of novel thiazolidin-4-one substituted
pyrazole derivatives from the condensation reaction of hydrazide with acetophenone derivatives.
Herein we describe the synthesis of fourteen compounds by microwave irradiation method. The synthesized
compounds are in excellent yield by utilizing microwave irradiation heating.

Objective:

Compounds using different aromatic or heteroaromatic compounds should be synthesized
and screened for their antibacterial activity to explore the possibility of pyrazole substituted thiazolidin-
4-ones as a novel series of antimicrobials.

Method:

Synthesis of thiazolidin-4-one substituted pyrazole derivatives was carried out under microwave
radiation.

Result:

These compounds were identified on the basis of melting point range, Rf values, IR, 1HNMR
and mass spectral analysis. These compounds were evaluated for their in vitro antimicrobial
activity and their Minimum Inhibitory Concentration (MIC) was determined. Among them Comp. 4b
and Comp. 4k possess appreciable antimicrobial and antifungal activities.

Conclusion:

A novel series of Thiazolidin-4-one substituted pyrazole were synthesized under microwave
irradiation method and identified on the basis of melting point range, Rf values, IR, 1HNMR,
mass spectral data and elemental analysis. The compounds were subjected to in vitro antimicrobial
screening and their Minimum Inhibitory Concentrations (MIC) were determined. Among all
the tested compounds, two compounds 4b and 4k exhibited moderate to significant activity against
all the tested strains of bacteria and fungus were found to have appreciable antimicrobial activities.
The results of antibacterial activity showed that compounds containing electron withdrawing groups
were found to be more active than the compounds containing electron releasing groups.
Framework for Evaluating Appropriateness of Clinical Decision Support Systems Alert in Supporting Clinical Workflow (Preprint)
Authors: Yusof Maryati , Olakotan Olufisayo , Puteh Sharifa Ezat
Published: October 2019

BACKGROUND

Clinical decision support systems (CDSS) generate excessive alerts that lead to alert fatigue and override. Alert overrides have resulted in patient death and medical errors. CDSS with its alert function can also disrupt clinical workflow. Therefore, inefficient clinical processes that contribute to the misfit between CDSS alert and workflows must be evaluated. Evaluation findings can serve as input to the process redesign. Redesigning clinical processes can enhance CDSS alert appropriateness and subsequently improve patient safety.

OBJECTIVE

The paper presents a proposed framework for evaluating CDSS appropriateness in supporting clinical workflow. The paper also discusses the preliminary results of the framework validation.

METHODS

A subjectivist, qualitative case study evaluation was conducted at a 620-bed public teaching hospital using semi-structured interview, observation, and document analysis methods to investigate the features and functions of alert appropriateness and workflow related issues. The current state map for medication prescription process was also modelled to identify problems pertinent to alert appropriateness.

RESULTS

The main findings showed that CDSS is not well designed to fit into clinical workflow due to several influencing factors including technology (system design and implementation), human (information analysis and acquisition), organization (clinical tasks, organizational policies & procedures) and process (process analysis, redesign, implementation, monitoring and improvement) impeding the use of CDSS with its alert function.

CONCLUSIONS

CDSS alerts should be integrated into clinical workflows due to their potentials in enhancing patient safety. Process improvement methods such as Lean can be used to enhance the appropriateness of CDSS alerts by identifying inefficient clinical processes that impede the fit of CDSS alerts with clinical workflow. The validated framework can be used to address alert and workflow related problems in any healthcare setting.
Photocatalytic Hydrogen Production over Ni/La-NaTaO3 Nanoparticles from NaCl-water Solution in the Presence of Glucose as Electron Donor
Authors: Husin Husni , Pontas Komala , Yunardi Yunardi , Salamun Adi , Alam Pocut Nurul , Hasfita Fikri
Published: October 2019

Nanoparticles La-NaTaO3 photocatalyst has been synthesized via a sol-gel route. A Ninanoparticle (NPs) as a cocatalyst is loaded on La-NaTaO3 by a simple impregnation method.The products are characterized by X-ray diffraction (XRD), scanning electron microscope(SEM), a high-resolution transmission electron microscope (HRTEM) and X-ray photoelectronspectroscopy (XPS). X-ray diffraction of the La-NaTaO3 samples shows perovskite-typecrystalline orthorhombic structure. Small particulate solids of La-NaTaO3 (30-250 nm) areobserved by SEM measurement. The nickel particles are detected from HRTEM images isaround 4-8 nm. The hydrogen evolution over La-NaTaO3 with NaCl is much higher than thatwithout NaCl. The photoactivity of La-NaTaO3 is enhanced when Ni is loaded on the surfaceof La-NaTaO3. The optimum loading amount of nickel is found to be 0.3 wt.% for La-NaTaO3,and it is more effective for H2 production from NaCl-water solution in the presence glucose.It is revealed that the loaded Ni can interact with each other and cooperate on improving thephotocatalytic activity. In the case of glucose as an electron donor, the activity ofphotocatalytic hydrogen generation over Ni/La-NaTaO3 increases dramatically. NaCl andglucose can promote markedly the photocatalytic hydrogen evolution. The Ni/La-NaTaO3nanoparticles system appears to be a promising candidate, which is very important to practicalapplications, including the production of H2 from NaCl-water solution in the presence ofglucose.
A Morphological Study of Poly (Vinylidene Fluoride) Pvdf Membranes: In Perspective of Membrane Pervaporation Process
Authors: Rashid Adil Hatem , Hatem M. D. Irfan , Ahmad Muhammad Syarhabil , Othman Mohd. Hafiz Dzarfan
Published: October 2019

Membrane separation plays an important role in chemical industry (Prabhat et al. 2011). Pervaporation is one of the most promising membrane separation processes which is used in a wide range of applications such as separation of organic mixtures and dehydration of solvents. This study investigated the effect of polymer concentration on the morphology of pervaporation membrane, where polyvinylidene fluoride (PVDF) was chosen as the base polymeric material while phase inversion method was employed as a technique to prepare an asymmetric PVDF membrane. The polymer concentration in dope solution was varied from 16 to 20wt% and the prepared membranes were characterized in terms of its structure, porosity, contact angle, and pore size. Five PVDF membrane samples were prepared (without any post-treatment) with polymer concentration of 16, 17, 18, 19, and 20wt% respectively. Depending on permeating component, two main areas of pervaporation processes can be identified: hydrophobic and hydrophilic and consequently two types of membranes could be observed: hydrophobic and hydrophilic membranes. From the results, it was found that the increase in polymer concentration has produced membranes with low pore size and porosity and as a result, high contact angle (low hydrophilicity).The highest contact angle of 83º was found for membrane with highest polymer concentration of 20wt% with the lowest pore size and porosity of (0.4156µm and 65%) respectively. The lowest contact angle of 76º was found for membrane with the lowest polymer concentration of 16wt% with the highest pore size and porosity (0.8671µm and78%) respectively.
Microwave – Assisted Extraction of Chlorogenic Acid from Coffee liberica L
Authors: Borja Josephine Q. , Uy Marylou M , Lim Jose Salvador , Ong Matthew Edson , Ros Alejandro Miguel
Published: October 2019

This study applied microwave-assisted extraction of chlorogenic acid (CGA) from Coffee liberica L. using ethanol as solvent. It sought to determine the effects of temperature, extraction time, solvent-to-solid ratio, and solvent concentration on the CGA yield expressed as gallic acid equivalent per litre (mg GAE L-1). The values of these factors were varied at three levels each and experiments were implemented using the L934 orthogonal array of the Taguchi design of experiment. Results showed that increasing the solvent-to-solid ratio from 2.5 to 7.5 mL g--1decreased the yield significantly. Conversely, increasing the solvent concentration from 0.6 to 0.7 (v v-1) increased the yield, but beyond this, lower yield was obtained. Likewise, yield increased when the extraction time was increased from 5 to 7 minutes but decreased subsequently when extraction was extended to 10 minutes. Temperature did not show significant effect on yield. Among the factors tested the solvent- to-solid ratio has the most significant effect on yield, followed by solvent concentration and extraction time while temperature had no significant effect. In the Taguchi design the highest yield of 304.90±0.58 mg GAE L-1 was obtained at 90°C, extraction time of 7 minutes, solvent-to-solid ratio of 2.5 mL g-1 and solvent concentration of 0.8 (v v-1). Using the same extraction temperature and time and solvent-to-solid ratio but lower solvent concentration, the confirmatory run resulted is significantly higher yield of 854.35±3.35 mg GAE L-1. Chlorogenic acid was identified in the extract at a concentration of 3152 mg L-1. By applying Soxhlet extraction using the same solvent concentration and solvent-to-solid ratio at the same temperature as that of the confirmatory run the yield was significantly lower at 570.42±5.3 mg GAE L-1.