bluuebunny/crossref_metadata_2025_split huggingface dataset:
Process Evaluation of Implementation Fidelity of the Integrated Chronic Disease Management Model in Two Districts, South Africa
Authors: Lebina Limakatso , Alaba Olufunke , Ringane Ashley , Hlongwane Khuthadzo , Pule Pogiso , Oni Tolu , Kawonga Mary 
Published: October 2019

Abstract
Background

The Integrated Chronic Disease Management (ICDM) model has been implemented in South Africa to enhance quality of clinical services in Primary Healthcare (PHC) clinics in a context of a high prevalence of chronic conditions and multi-morbidity. This study aimed to assess the implementation fidelity (adherence to guidelines) of the ICDM model.Methods

A cross-sectional study in 16 PHC clinics in two health districts in South Africa: Dr Kenneth Kaunda (DKK) and West Rand (WR). A fidelity assessment tool with 89 activities and maximum score of 158 was developed from the four interrelated ICDM model components: facility re-organization, clinical supportive management, assisted self-management and strengthening of support systems. Value stream mapping of patient flow was conducted to analyse waiting time and identify operational inefficiencies. ICDM items were scored based on structured observations, facility document reviews and structured questionnaires completed by healthcare workers. Fidelity scores were summarized using medians and proportions and compared by facilities and districts using Chi-Square and Kruskal Wallis test.Results

The monthly patient headcount over a six-month period in these 16 PHC clinics was a median of 2430 (IQR: 1685-2942) individuals over 20 years. The DKK district had more newly diagnosed TB patients per month [median 5.5 (IQR: 4.00-9.33) vs 2.0 (IQR: 1.67-2.92)], and fewer medical officers per clinic [median 1 (IQR: 1-1) vs 3.5 (IQR:2-4.5)] compared to WR district. The median fidelity scores in both districts for facility re-organization, clinical supportive management, assisted self-management and strengthening of support systems were 78% [29/37, IQR: 27-31)]; 77% [30/39 (IQR: 27-34)]; 77% [30/39 (IQR: 28-34)]; and 80% [35/44 (IQR: 30-37)], respectively. The overall median implementation fidelity of the ICDM model was 79% (125/158, IQR: 117-132); WR was 80% (126/158, IQR: 123-132) while DKK was 74% (117/158, IQR: 106-130), p=0.1409. The lowest clinic fidelity score was 66% (104/158), while the highest was 86% (136/158). A patient flow analysis showed long (2-5 hours) waiting times and one stream of care for acute and chronic services.Conclusion

There was some variability of scores on components of the ICDM model by PHC clinics. More research is needed on contextual adaptations of the model.
NMDA Receptor-mediated CaMKII/ERK Activation Contributes to Renal Fibrosis
Authors: Zhou Jingyi , Liu Shuaihui , Guo Luying , Wang Rending , Chen Jianghua , Shen Jia 
Published: October 2019

Abstract
Background: Renal fibrosis (RF) results in renal function impairment and eventually kidney failure. We found that N-methyl-D-aspartate receptor (NMDAR) played an important role during RF. However, its mechanism of action is yet to be deciphered. Methods: RF was induced in vivo by unilateral ureteral obstruction (UUO) using 8-week-old C57BL/6 mice. The expression levels of the NMDAR’s functional subunit, NR1, was downregulated using lentiviral vector-mediated shRNA interference. Histological changes were observed using Masson’s trichrome staining. Expression of NR1, fibrotic markers (α-smooth muscle actin (α-SMA), type I collagen (COL1A4), S100A4 and fibronectin), and EMT markers (snail and E-cadherin) were measured using immunohistochemistry and western blot analysis. RF was induced after TGF-β-treatment in HK-2 cells in vitro. NMDAR antagonist MK-801 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93 were included in this study for pathway determination. Expression of NR1, total and phosphorylation of CaMKII (p-CaMKII), total and p-ERK were measured using western blot and immunofluorescent assays. Results from in vitro studies were confirmed using in vivo studies for NR1, CaMKII and ERK expression levels. In addition, ischemia-reperfusion injury (IRI) mouse model was used to determine whether oral NMDAR inhibitor dextromethorphan (DXM) could inhibit chronic fibrosis. Results: Increased NR1 expression was observed in both UUO-injured kidneys and TGF-β-treated tubular cells. NR1 knockdown and MK801 administration downregulated CaMKII/ERK activation. In vitro administered CaMKII antagonist KN93 reduced ERK phosphorylation and was not affected by NR1 expression levels. DXM protected IRI-injured kidneys from atrophy and fibrosis. Conclusions: NMDAR participates in renal fibrogenesis by activating the CaMKII/ERK pathway. NMDAR could be a potential therapeutic target for renal fibrosis.
«Divided audience» – a new education model as a reform of the education process in Chinese universities
Authors: Yao Wei 
Published: October 2019

The article is devoted to the idea of a «divided audience» which was proposed by a Chinese scientist, Professor Chang Xuexin. The author outlines that at the moment, it is used as a new educational model in Chinese universities and it is considered reform of the educational process. The author comes to the conclusion that this model has changed the traditional Chinese pedagogical thought – the role of students has become dominant in teaching. It is practically confirmed by improvements in the quality of education in Chinese universities and is acute topic of discussion among teachers and scientists in China.
Suicide Gene Therapy Against Malignant Gliomas by the Local Delivery of Genetically Engineered Umbilical Cord Mesenchymal Stem Cells as Cellular Vehicles
Authors: Wei Dan , Hou JiaLi , Zheng Ke , Jin Xin , Xie Qi , Cheng Lamei , Sun Xuan 
Published: October 2019

Background:Glioblastoma (GBM) is a malignant tumor that is difficult to eliminate, and new therapies are thus strongly desired. Mesenchymal stem cells (MSCs) have the ability to locate to injured tissues, inflammation sites and tumors and are thus good candidates for carrying antitumor genes for the treatment of tumors. Treating GBM with MSCs that have been transduced with the herpes simplex virus thymidine kinase (HSV-TK) gene has brought significant advances because MSCs can exert a bystander effect on tumor cells upon treatment with the prodrug ganciclovir (GCV).Objective:In this study, we aimed to determine whether HSV-TK-expressing umbilical cord mesenchymal stem cells (MSCTKs) together with prodrug GCV treatment could exert a bystander killing effect on GBM.Methods and Results:Compared with MSCTK: U87 ratio at 1:10,1:100 and 1:100, GCV concentration at 2.5µM or 250µM, when MSCTKs were cocultured with U87 cells at a ratio of 1:1, 25 µM GCV exerted a more stable killing effect. Higher amounts of MSCTKs cocultured with U87 cells were correlated with a better bystander effect exerted by the MSCTK/GCV system. We built U87-driven subcutaneous tumor models and brain intracranial tumor models to evaluate the efficiency of the MSCTK/GCV system on subcutaneous and intracranial tumors and found that MSCTK/GCV was effective in both models. The ratio of MSCTKs and tumor cells played a critical role in this therapeutic effect, with a higher MSCTK/U87 ratio exerting a better effect.Conclusion:This research suggested that the MSCTK/GCV system exerts a strong bystander effect on GBM tumor cells, and this system may be a promising assistant method for GBM postoperative therapy.
Combined Transcriptomic and Proteomic Analyses of Cerebral Frontal Lobe Tissue Identified RNA Metabolism Dysregulation as One Potential Pathogenic Mechanism in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Authors: Ritz Marie-Françoise , Jenoe Paul , Bonati Leo , Engelter Stefan , Lyrer Philippe , Peters Nils 
Published: October 2019

Background: :
Cerebral small vessel disease (SVD) is an important cause of stroke and
vascular cognitive impairment (VCI), leading to subcortical ischemic vascular dementia. As a hereditary
form of SVD with early onset, cerebral autosomal dominant arteriopathy with subcortical
infarcts and leukoencephalopathy (CADASIL) represents a pure form of SVD and may thus serve
as a model disease for SVD. To date, underlying molecular mechanisms linking vascular pathology
and subsequent neuronal damage in SVD are incompletely understood.

Objective: :
We performed comparative transcriptional profiling microarray and proteomic analyses
on post-mortem frontal lobe specimen from 2 CADASIL patients and 5 non neurologically diseased
controls in order to identify dysregulated pathways potentially involved in the development
of tissue damage in CADASIL.

Method: :
Transcriptional microarray analysis of material extracted from frontal grey and white
matter (WM) identified subsets of up- or down-regulated genes enriched into biological pathways
mostly in WM areas. Proteomic analysis of these regions also highlighted cellular processes identified
by dysregulated proteins.

Result: :
Discrepancies between proteomic and transcriptomic data were observed, but a number of
pathways were commonly associated with genes and corresponding proteins, such as: “ribosome”
identified by upregulated genes and proteins in frontal cortex or “spliceosome” associated with
down-regulated genes and proteins in frontal WM.

Conclusion::
This latter finding suggests that defective expression of spliceosomal components
may alter widespread splicing profile, potentially inducing expression abnormalities that could
contribute to cerebral WM damage in CADASIL.
Novel 3-Substituted-2, 3-Dihydro-2-Thioxoquinazolin-4-(1H)-one derivative as Anticonvulsants: Synthesis, Molecular Docking and Pharmacological Screening
Authors: jain Nimisha , Singour Pradeep Kumar 
Published: October 2019

Background:According to the World Health Organization, 50 million people worldwide are suffering from epilepsy, making it one of the most common neurological diseases globally. 2,3 disubstituted quinazolinone-4-one derivatives endowed with various pharmacological activity, particularly having anticonvulsant action.Objectives:The aim of this study was to synthesize 3-Substituted-2,3-Dihydro-2-thioxoquinazolin- 4-(1H)-one derivative and evaluate for anticonvulsant activity and neurotoxicity in order to find an efficient, compound with lesser side effects.Methods:A novel series of 3-[4-(2-amino-5, 6-dihydro-4(substituted phenyl)-4H-1, 3-oxazin /thiazin-6yl) phenyl]-2, 3-dihyro-2-thioxoquinazolin-4(1H)-one derivatives (4a-4p) were synthesized. The structures of the synthesized compounds were assigned on the basis of spectral data (UV, IR, 1HNMR, 13CNMR and MS) and performed anticonvulsant activity against maximal electroshock test and Subcutaneous Pentylenetetrazole model. Neurotoxicity was assessed using a rotarod apparatus test. The molecular docking study was performed to assess their binding affinities towards Gamma-Aminobutyric Acid type A receptor. A quantitative estimate of drug-likeness was also performed, which calculates the molecular properties and screen the molecules based on drug-likeness rules.Results:Compounds 4b, 4e, 4j and 4m have shown the highest anticonvulsant activity against tonic seizure with decreased mean duration of tonic hind leg extension of 8.31, 7.35, 8.61 and 8.99 s, respectively in maximal electroshock model and increased onset time clonic convulsion duration of 94.45, 96.65, 93.51 and 91.86 s in Subcutaneous Pentylenetetrazole model. Molecular docking study revealed a better binding affinity with Gamma-Aminobutyric Acid type A receptor.Conclusion:The compound 4b and 4e emerged out as the pilot molecule with a better anticonvulsant activity without any neurotoxicity. The obtained results showed that compounds 4b and 4e could be useful as a template for future design, optimization, and investigation to produce more active analogs.
Comparison in the Glucose Response of Flexible Liposomes Loaded with Insulin with the Addition of Different Surfactants in an Experimental Diabetes Model
Authors: Arciniegas Sara Melisa , Saavedra Sergio Andres , Balderas Danaé , del Carmen Caballero Sara , Bernad María Josefa , Sánchez Julio Cesar , Gracia María Isabel , Rico Héctor Ariel , Vargas Dinorah 
Published: October 2019

Background:
Insulin has been included in a variety of dosage forms; nevertheless, liposomes
have shown protection to degradation and better absorption. The addition of surfactant to liposomes
could give the ability to deform and pass through intact membranes, and could increase the
stability and the release of the drug.

Introduction:
Due to the limitations of the current treatment of insulin in diabetic patients, investigation
in alternatives routes has increased. The oral route is the most convenient because of the
similarity with the natural secretion of this hormone. The aim was to evaluate the in-vivo effect of
fourteen formulations of Insulin-loaded flexible liposomes with different surfactants by oral and
subcutaneous routes.

Methods:
Fourteen formulations of insulin were obtained with the addition of different surfactants.
Size distribution, polydispersion index and Z potential were obtained for all formulations. In-vivo
tests were performed in rats induced with experimental diabetes with streptozotocin, and glucose
curves were obtained during 480 minutes.

Results:
All formulations by the subcutaneous route caused an optimal reduction in glucose levels.
However, the addition of Brij L23 produced a better reduction, lasting for 420 minutes. By the oral
route, the reduction of glucose did not reach the normal levels, but the addition of Poloxamer 407
and Brij S10 showed the best reduction in the glucose levels by this route.

Conclusion:
The addition of surfactants to the lipid structure can modify the release of the insulin
by different routes of administration, but this behavior depends on the characteristics of the surfactant,
such as the melting phase transition temperature of the lipid bilayer.
The Role of Biofilm in Central Venous Catheter Related Bloodstream Infections: Evidence-based Nursing and Review of the Literature
Authors: Ielapi Nicola , Nicoletti Emanuela , Lorè Carmela , Guasticchi Giorgio , Avenoso Tiziana , Barbetta Andrea , de Franciscis Stefano , Andreucci Michele , Sapienza Paolo , Serra Raffaele 
Published: October 2019

Background:Biofilm is a fundamental component in the pathogenesis of infections related to the use of the central venous catheter (CVC,) which can represent an important health issue in everyday practice of nursing and medical staff.Objective:The objective of the following review is to analyze the components of biofilm and their role in catheter-related infection determinism in an evidencebased nursing perspective in such a way as to give health professionals useful suggestions in the prevention and management of these complications.Methods:The following databases were consulted for the bibliographic search: Medline, Scopus, Science Direct. Biofilm can be the cause of CVC extraction and can lead to serious haematogenic infectious complications that can increase the morbidity and mortality of affected patients.Results:Updated pathophysiologic knowledge of biofilm formation and appropriate diagnostic methodology are pivotal in understanding and detecting CVC-related infections. Lock therapy appears to be a useful, preventive, and therapeutic aid in the management of CVCrelated infections. New therapies attempting to stop bacterial adhesion on the materials used could represent new frontiers for the prevention of CVC-related infections.Conclusion:The correct evidence-based nursing methods, based on the use of guidelines, provides the opportunity to minimize the risks of infection through the implementation of a series of preventive measures both during the CVC positioning phase and in the subsequent phase, for example, during device management which is performed by medical and nursing staff.
Serous BMP8A has Clinical Significance in the Ultrasonic Diagnosis of Thyroid Cancer and Promotes Thyroid Cancer Cell Progression
Authors: Liu Kun , Gao Min , Qin Dongdong , Wang Hongjun , Lu Qixiu 
Published: October 2019

Objectives:
This study aims to discover a potential cytokine biomarker for early diagnosis
of thyroid cancer.

Methods:
We employed data mining of The Cancer Genome Atlas (TCGA) and experimentally elucidated
its mechanistic contributions. The differential expression genes (DEGs) between thyroid
cancer and health population were analyzed with TCGA online bioinformatic tools. The relative
expression of Bone Morphogenetic Protein 8A (BMP8A) was determined by real-time PCR in ultrasonic
diagnosed thyroid cancer both in vivo and in vitro. The serous BMP8A content was quantified
with an ELISA kit. Protein levels of BMP8A, OCLN, ZEB1, EZH2 and β-Actin were analyzed by
Western blot. Cell viability was measured by the MTT assay, and anchorage-independent growth
was measured by the soft agar colony formation assay. Cell migrative and invasive capacities were
interrogated with transwell chamber assays.

Results:
We identified aberrantly high expression of BMP8A in thyroid cancer, which was associated
with unfavorable prognosis and tumor progression. The serous BMP8A was also significantly
up-regulated in thyroid cancer patients. Ectopic over-expression of BMP8A remarkably stimulated
cell viability and anchorage-independent growth. Meanwhile, the migrative and invasive capacities
were greatly increased in response to BMP8A over-expression. Mechanistically, we characterized the
positive correlation between BMP8A and TCF7L1, and forced expression of TCF7L1 induced
BMP8A expression in TPC-1 cells.

Conclusion:
In summary, we have identified a novel biomarker for early diagnosis in addition to
Ultrasound for thyroid cancer, which is subjected to TCF7L1 regulation.
Nanoemulsion as Oral Drug Delivery - A Review
Authors: Sabjan Khaleel Basha , Munawar Syed Muzammil , Rajendiran Dhandayuthabani , Vinoji Sugantha Kumari , Kasinathan Kaviyarasu 
Published: October 2019

Background: Objective::
The stability and delivery of drugs remain one of the key hurdles
in the present situation. The present study depends on the design of a novel nanoemulsion drugdelivery
system that would encapsulate a drug and to improve drug stability. The charisma of
nanotechnology is majorly due to the smallest particle size at the nanoscale.

Methods:
Nanoemulsions attention is focused on emphasizing formulation aspect, method of preparation
characterization techniques, evaluation parameters and various application of the nanoemulsions,
several techniques to be used for the preparation of nanoemulsions like microfluidization,
high-pressure homogenization, low energy emulsification and solvent evaporation method and their
parameters to be characterized.

Results:
The design of effective formulations for drugs is being applied to enhance the solubility
and bioavailability of water-insoluble drugs. The nanosized droplets have led to considerable attraction
for this formulation, for the delivery of hydrophilic as well as hydrophobic drugs as drug carriers
because of their improved drug solubilization capacity, long shelf life, ease of preparation and
improvement of bioavailability of drugs.

Conclusion:
The application of these nanoformulation preparations, limitations, their advantages
and disadvantages as nanoemulsions will solve the various problems that current therapeutic agents
face and has opened a new scenario to formulate nanoemulsions with various therapeutic agents
with heightened competence along with oral drug delivery to treat diseases in the near future.
PEMASARAN IKAN SEGAR AIR TAWAR DI PROPINSI DAERAH ISTIMEWA YOGYAKARTA
Authors: Sukardi Sukardi 
Published: October 2019

The special region province of Yogyakarta (DIY) has five regencies with different natural resources to support the development of fishery product. Therefore, fishery product especially fish was distributed from surplus regencies to the other regencies which produced less quantity of the product. The objectives of this study were to know the market structure, market channel, price margin and fluctuation. The study was conducted using analytic discriptive method. Data were collected by survey in 5 regencies in DIY province, covered subjects such as wholesaler, retailer, dealer, farmer (producer) and consumer. Results of this study indicated that (1) market structure in wholesaler level was oligopoly, but in the retailer level was free market. The retailers had stronger relationship to wholesaler specially for keeping continuity of fish supply, (2) fish market channel and price margin depending on fish species and location of markets, (3) prices fluctuation was determined by supply and demand mechanism. The average price margins in wholesalers and retailer ranged from 10 to 15 and 10 to 20%, respectively, (4) marketing of fresh freshwater fishes were still consentrated in the city and its surrounding area. Comparing with the other regencies in DIY, Yogyakarta Regency (Kotamadya Yogyakarta) had the largest demand for freshwaterfish which was dominated by cat fish (lele dumbo).
Utilização da realidade virtual na doença de Alzheimer: uma revisão bibliográfica
Authors: Figueiredo Alice de Leon , Meneghetti Tainá Cazuni , De Gregório Elizama , Bini Ana Carolina Dorigoni 
Published: October 2019

Resumo: A doença de Alzheimer (DA) é neurodegenerativa e progressiva, ocasionando uma série de mudanças na estrutura cerebral e incapacidades funcionais, dificultando a realização das atividades de vida diárias e sociais, presentes e desejadas por toda a sociedade, necessitando de alternativas eficientes no manejo da doença. Nesse sentido a utilização da realidade virtual (RV), vem sendo bastante visada na área da pesquisa, pela possibilidade de vivenciar experiências semelhantes às diárias, capazes de explorar várias emoções, assim como a cognição e aptidão física, tornando a realidade virtual uma estratégia interessante na reabilitação funcional física e cognitiva, útil tanto na avaliação quanto tratamento de diversas patologias. Metodologia: O presente estudo trata-se de uma revisão sistemática da literatura que buscou identificar as diferentes formas de utilização da RV em indivíduos com DA. A busca foi realizada nas seguintes bases de dados eletrônicas: PubMed; PeDro; EBSCO, Lilacs e SciELO. Após os critérios de inclusão e exclusão, foram selecionados quatro artigos científicos. Resultados: A literatura apoia uso da RV como instrumento de tratamento e avaliação de pacientes com DA, tendo resultados satisfatórios e animadores como sendo uma técnica eficaz e que facilita a análise de evolução e de estado desses pacientes. Conclusão: Concluímos que a realidade virtual tem se mostrado promissora no tratamento e avaliação de pacientes com déficits cognitivos associado a Doença de Alzheimer. Porém, novos estudos fazem-se necessário para que possamos eleger os melhores recursos de RV para melhor atender pacientes com DA e suas necessidades específicas.