bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Outcomes and Complications Following Scapulothoracic Arthrodesis in Patients with Facioscapulohumeral Dystrophy
Authors: Eren İlker , Erşen Ali , Birsel Olgar , Atalar Ata Can , Oflazer Piraye , Demirhan Mehmet
Published: October 2019

Background:

Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant myopathy characterized by facial and shoulder girdle muscle weakness with scapular winging. Scapulothoracic arthrodesis is a successful treatment approach for patients with <90° of shoulder elevation. The purpose of the present study was to assess functional outcomes and complications following scapulothoracic arthrodesis in patients with FSHD.

Methods:

We retrospectively reviewed the records of 40 patients (64 shoulders) in whom scapulothoracic arthrodesis was performed. To achieve fusion, multiple multifilament cables were used together with autologous bone and allograft bone. Preoperative and postoperative shoulder elevation and abduction; Disabilities of the Arm, Shoulder and Hand (Quick version, qDASH) scores; and pulmonary function were compared. Recorded complications were classified as pulmonary or scapular.

Results:

The mean age of the patients at the time of the operation was 25.4 years (range, 15 to 60 years), and the mean duration of follow-up was 71.2 months (range, 12 to 185 months). When the preoperative values were compared with those at the latest follow-up, significant improvement was noted in terms of elevation (from a mean [and standard deviation] of 60.6° ± 17.2° to 123.7° ± 26.7°; p < 0.001), abduction (from 52.7° ± 15.8° to 98.8° ± 20.3°; p < 0.001), and qDASH scores (from 34.7 ± 11.4 to 13.3 ± 13.1; p < 0.001). The overall complication rate was 26.6%. There were 7 pulmonary complications (4 pneumothoraxes, 2 pleural effusions, and 1 major atelectasis), and 5 chest tube placements were required. Ten complications (including 3 rib fractures, 1 brachial plexus palsy, 2 cases of implant irritation, 2 nonunions, 1 delayed union, and 1 scapular fracture) were related to the scapular fixation, and 7 revision procedures were required. Scapulothoracic fusion was achieved in all patients but 1, who had a scapular fracture. Pulmonary function tests were performed for 19 patients, and no difference was observed between preoperative and postoperative results.

Conclusions:

Scapulothoracic arthrodesis with use of multifilament cables is a successful surgical technique with high fusion rates and low morbidity. Pulmonary complications are common but resolve with careful attention.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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

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

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.
HAMİDULLAH MUHAMMED TARIM’IN “TÜRKİSTAN TARİHİ-TÜRKİSTAN 1931-1937 İNKILÂP TARİHİ” ADLI ESERİNDE MEHMET EMİN BUĞRA
Authors: TUNCER Tekin
Published: October 2019

1931 yılında Kumul’da başlayan, akabinde 12 Kasım 1933 tarihinde Kaşgar’da bir hükümet teşekkülü ile neticelenen olaylarda Kaşgar-Hoten çatışması şeklinde yer alan bilgiler bir de olayların içerisinde bulunan kişilerin gözüyle burada yeniden değerlendirilmeye çalışılmıştır. Bu anlamda en azından kaynak olarak ifade edebilecek bir eserdeki bilgilerle olaylar yeniden değerlendirilmeye ve farklı bir bakış açısı kazandırılmaya çalışılmıştır. Bu bakımdan Hamidullah Tarım’ın eserinde Mehmet Emin Buğra ile alakalı bilgiler bu makale ile değerlendirilmeye çalışılmıştır. Makale konusu farklı kaynaklarla mukayese edilerek bilgilerin objektifliği de ortaya konulmaya çalışılmıştır.Hamidullah Tarım, eserini savaş yıllarında ve daha sonra Mekke ve Medine’de not aldığı altı not defterini bir araya getirip tamamlamıştır. Eseri orijinal kılan, bizzat olayların içerisinde bulunan bir şahsın notlarını ihtiva etmesi yanında, bilhassa Kaşgar’da kurulan hükümet yetkilileriyle birlikte hareket eden müellifin, Hoten’de kurulan hükümete bakış açısını göstermesi bakımından da önemlidir.
KUTADGU BİLİG’DE DİL İLE TASAVVUFTA SAMT ‘SUSMA’ MESELESİ
Authors: AYDIN Mehmet
Published: October 2019

İslamî Türk edebiyatının en eski ve önemli metinlerinden biri olarak kabul edilen. KB Türk edebiyatındaki ilk mesnevi ve manzum siyasetnâme örneğidir. KB metninde “dil” konusu ve meselesi -ekler dışında- yedinci bölümdeki otuz beyitte ve on dokuzuncu bölümde doksan beyitte ele alınmıştır Til “dil” göstergesi KB’de 459 defa kullanılmıştır. Dolayısıyla til “dil” sözü, KB metninde en sık kullanılan isim cinsinden kelimeler arasında yer almaktadır. KB metninin yaklaşık olarak 68.000 kelimeden oluştuğu kaydedilmektedir. Buna göre metindeki 2861 madde başı kelimeden biri olan til “dil” kelimesi metinde % 0, 675 oranında kullanılmıştır. Metinde yedinci bölüm dışında da birçok bağlamda til “dil” kelimesinin kullanıldığı görülür. Metnin indeksinde til kelimesine “dil, söz, sözlük” anlamları verilmiştir. Til kelimesinin metindeki sıklığı, “dil kullanımı”nın Yusuf Has Hacip tarafından sadece bir konu değil, önemli bir mesele olarak ele alındığının göstergesidir. Tasavvufun üç ana ilkesi “az konuş, az uyu, az ye” şeklindedir. “Söz gümüşse sükût altındır” atasözü de aynı tasavvufi anlayışı yansıtır. KB’de de esas olan “önce dinlemek ve anlamak, sonra az ve gerektiğinde konuşmak”tır. (KB’de de esas olan “az ve yerinde, gerektiğinde, önce dinlemek ve anlamak sonra konuşmak”tır. Kuşeyrî Risalesi’nde samt “susma, sükût” sûfîlerin makam ve hâlleri arasında sayılır. Kuşeyrî ile Hücvirî bütün öbür mutasavvıflar gibi dinlemeyi, susmayı, sükûtu konuşmadan ve sözden üstün bulur. Hücvirî de Keşfu’l-Mahcub’da Resulüllah’ın -“Ümmetim hakkında korktuğum şeylerden en fazla endişe ettiğim husus dildir”-hadisine dikkati çekerek dil meselesini “samt” çerçevesinde ele almıştır. Agop Dilaçar, KB’i Eflatun’un Devlet’i, Thomas Moore’un Ütopyası vb. Batı dünyasından metinlerle karşılaştırıp ilişkilendirmeye çalışmıştır. Bir metni metin yapan yedi metinlik özellikten biri metinlerarasılıktır. Dolayısıyla Agop Dilaçar’ın yaklaşımının isabeti tartışılamaz. Ancak KB’i aynı iklimde ve aynı dönemde yazılan başka metinlerle karşılaştırmak daha isabetli bir yaklaşım olsa gerektir. Kuşeyrî’nin Risalesi Arapça, Hücvirî’nin Keşfü’l-Mahcûb’u Farsça, Yusuf Has Hâcib’in KB’i gibi XI. yüzyıl içinde Türkçe üretilmiş metinlerdir. Bu metinlerin ikisi de KB’den önce yazılmıştır. Belki Yusuf Has Hâcib doğrudan doğruya Kuşeyrî, Hücvirî ve eserleriyle temas etmiş değildir. Ancak bu eserlerle KB arasında yine de Eflatun’un Devlet’i ile Thomas Moore’un Ütopya’sından daha derin bağlar vardır. Bu çalışmada KB’de dil meselesinin ele alınış biçimi, metinlerarasılık bağlamında Kuşeyrî Risalesi ve Keşfü’l-Mahcûb’la karşılaştırılacak ve ortaklıklar tespit edilmeye çalışılacaktır.
NÂ’İLÎ’NİN GAZELLERİNDE “SİYAH” METAFORUNUN İZİNDE
Authors: UÇAN EKE Nagehan
Published: October 2019

Kaynağını ışıktan alan renkler, tabiattaki unsurları renklendirmenin yanı sıra toplumsal ve kültürel alanda metaforlaşırlar. Bu bağlamda her toplum; kültürel, toplumsal, psikolojik, dinî, siyasî, ekonomik vb. değerlerine göre çağrışım yönünden renklere çok çeşitli manalar yükler. Üst bir dille yaratılan edebî eserlerde ise renkler, belirli bir atmosfer oluşturmada, karakterlerin fiziksel ve ruhsal tasvirleri ile yazarın duygu ve ruh hâlini ifade etmede mühim bir rol oynar. Klasik Türk şiirinin estetik anlayışı doğrultusunda Divan şairleri de, renklerin tasvirî ve metaforik özelliklerinden faydalanarak şiirlerine derinlik kazandırırlar. Bu renklerden “siyah”, dünya mitolojilerinde ve pek çok kültürde boşluk, büyü, ıstırap, karanlık, keder, korku, kötülük, ölüm, üzüntü, tahribat, yas vb. çağrışımları ile olumsuz bir metafor olarak tanımlanır. Esasen tabiattaki bütün renkleri soğurup yutarak oluştuğundan, bilimsel olarak “siyah” renk bile sayılmamaktadır. Belki de ışığın ve aydınlığın örtülmesiyle meydana gelmiş olması, ona atfedilen bütün bu olumsuz manaların en temel sebebidir.Klasik Türk edebiyatının 17. yüzyıldaki en önemli temsilcilerinden ve Sebk-i Hindî’nin kurucularından olan Nâ’ilî-i Kadîm de gerek yaratılışının bir dışavurumu olarak gerekse de bağlı bulunduğu üslûbun “ıstırap” temasının metaforu olarak “siyah”ı; kara bahtını, gamını, kederini, mutsuzluklarını ve ümitsizliklerini ifade etmede kullanmıştır. Çalışmada Nâ’ilî’nin Divan’ında yer alan gazeller, kavramsal metafor teorisi ışığında “siyah metaforu” bağlamında incelenecektir.
IR-spectroscopy of polysaccharide flaxseed (Linum usitatissimum L.) products
Authors: Minevich Irina , Osipova Lidiia , Nechiporenko Alla , Melnikova Mariya , Tsyganova Tatyana
Published: October 2019

Flax seeds are an excellent source of polyunsaturated fatty acids and high-grade protein. They are also rich in non-starch polysaccharides that are concentrated in their mucus cells. Flaxseed polysaccharides are soluble dietary fibres, which makes them an indispensable functional food ingredient. They can also serve as an additive, thus improving the structure of food, e.g. as a stabilizer, structure former, water and fat retention agent, etc. According to various researches, the functional and technological properties of polysaccharide flaxseed products are largely determined by the ratio of polysaccharide fractions and protein content, which depend on the production process. This research featured the effect of the method of obtaining flaxseed polysaccharide products on the protein content. The study employed chemical analysis and attenuated total internal reflection infrared spectroscopy (ATR-IR). The protein polysaccharide products under analysis were obtained by water extraction from two varieties of whole flax seed (Russia), under various conditions of treatment, cleaning, and fractionation. The conditions included pH, temperature, and process time. During water extraction of whole flax seeds, polypeptide-containing polysaccharide complexes were removed from the seed coats. The number, composition, and binding force between the peptide fragments and the polysaccharide matrix depended on the technological parameters of the process. The polysaccharide products were tested for total protein content. The results were consistent with the band intensity in the range of 1700–1500 cm–1, where protein carbonyl groups are usually manifested.
Coconut meal: Nutraceutical importance and food industry application
Authors: Kaur Karandeep , Chhikara Navnidhi , Sharma Poorva , Garg M.K. , Panghal Anil
Published: October 2019

In tropical regions coconut is the tree of great significance: it provides millions of people with food, employment, and business opportunities. The fruit is referred to as ‘miracle fruit’ due to its inherent rich profile of macro- and micro-nutrients for human nutrition and health. Different products, such as coconut water, milk, raw kernels, oil and desiccated coconut are commercially processed. Coconut flour is a byproduct of coconut milk and oil industry which is made from coconut meal leftover after processing. Being a rich source of dietary fibre and protein, it has found numerous applications in different functional foods. Coconut flour can be successfully incorporated into various food products, such as bakery, extruded products, snacks, and sweets. It has antidiabetic and anticancer effects, prevents cardiovascular diseases, and improves immune function. Coconut flour is also gluten-free and its nutritional composition is quite comparable to that of wheat flour. Gluten-free food products enriched with coconut flour are a healthy and viable option for the people with celiac disease. In this paper, we summarised the present use of coconut flour. There is an apparent need to convert the food processing byproducts into functional ingredients in order to implement their environment-friendly and efficient utilisation.
Relación entre eventos extremos de precipitación con inundaciones. Estudio de caso: Tulancingo, Hidalgo
Authors: Herrera Eduardo , Magaña Víctor , Morett Sigrid
Published: October 2019

Se analizó la dinámica de las inundaciones más importantes ocurridas en Tulancingo, Hidalgo, centrándose en la caracterización de la amenaza de eventos de precipitación extrema. El estudio de la climatología de la precipitación permitió determinar patrones temporales y espaciales, así como las fechas de los eventos extremos. Con base a una investigación hemerográfica se relacionaron los casos de eventos extremos con desastres (inundaciones) registrados. Los patrones espaciales asociados a los desastres registrados permiten establecer estrategias de prevención basadas en el pronóstico de precipitación.
The concept of multiple variables
Authors: Obradovich Dragan
Published: October 2019

The article is devoted to the consideration of the multiple variables concept. The author emphasizes that mathematics is one of the most important disciplines for human functioning and mathematical principles are permeated through all spheres of life and activity, making the importance of understanding these principles even greater. For proper conclusion and solution of life's problems, mathematics is more than necessary. The author comes to the conclusion that by learning mathematics, it is actually possible to train your reasoning and logic so that you can respond properly to key life problems.
Calendar festivals as a mirror of culture in foreign language classes
Authors: Sokolova Galina Aleksandrovna
Published: October 2019

The article deals with some ways of forming socio-cultural competence on the example of learning the history of foreign holidays, Christmas and St. Nicholas Day, which are spread in Germany.
Key performance indicators of production activity efficiency in the implementation of lean production methods in mechanical-engineering enterprises
Authors: Streltsova Darya Alekseevna
Published: October 2019

The article is devoted to the consideration of methods of lean production in relation to mechanical-engineering enterprises; the main key indicators of efficiency, productivity and key performance indicators (KPI), their similarities and differences. The key performance indicators, the most preferred in the analysis and management of production at mechanical-engineering enterprises, are defined in the article.
Revisiting the actuarial expectation of the net-premium for franchise insurance certificate
Authors: Tanyukhin Aleksey Vladimirovich
Published: October 2019

This article is related to obtaining methods for calculating the net-premium for franchise insurance certificate without taking into consideration life insurance. The theoretical foundations of such actuarial expectations are revealed, methods for calculating the mathematical expectation of a random value of insurer's loss from an event insured according to the franchise insurance certificate for gamma and logarithmically normal distributions of a random value of losses are presented, methods for statistical estimation of the mathematical expectation of a random value of the insurer's loss from an event insured in the presence of franchise insurance certificate are described in the article. The author comes to the conclusion that the obtained statistical estimation methods allow us to calculate net-premiums based on historical data without involving any known probabilistic distribution of a random value of loss from analytically specified event insured.
«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.
Symptom Distribution Regularity of Insomnia: Network and Spectral Clustering Analysis (Preprint)
Authors: Hu Fang , Li Liuhuan , Huang Xiaoyu , Yan Xingyu , Huang Panpan
Published: October 2019

BACKGROUND

Recent research in machine-learning techniques has led to signiﬁcant progress in various research ﬁelds. In particular, knowledge discovery using this method has become a hot topic in traditional Chinese medicine. As the key clinical manifestations of patients, symptoms play a signiﬁcant role in clinical diagnosis and treatment, which evidently have their underlying traditional Chinese medicine mechanisms.

OBJECTIVE

We aimed to explore the core symptoms and potential regularity of symptoms for diagnosing insomnia to reveal the key symptoms, hidden relationships underlying the symptoms, and their corresponding syndromes.

METHODS

An insomnia dataset with 807 samples was extracted from real-world electronic medical records. After cleaning and selecting the theme data referring to the syndromes and symptoms, the symptom network analysis model was constructed using complex network theory. We used four evaluation metrics of node centrality to discover the core symptom nodes from multiple aspects. To explore the hidden relationships among symptoms, we trained each symptom node in the network to obtain the symptom embedding representation using the Skip-Gram model and node embedding theory. After acquiring the symptom vocabulary in a digital vector format, we calculated the similarities between any two symptom embeddings, and clustered these symptom embeddings into five communities using the spectral clustering algorithm.

RESULTS

The top five core symptoms of insomnia diagnosis, including difficulty falling asleep, easy to wake up at night, dysphoria and irascibility, forgetful, and spiritlessness and weakness, were identified using evaluation metrics of node centrality. The symptom embeddings with hidden relationships were constructed, which can be considered as the basic dataset for future insomnia research. The symptom network was divided into five communities, and these symptoms were accurately categorized into their corresponding syndromes.

CONCLUSIONS

These results highlight that network and clustering analyses can objectively and effectively find the key symptoms and relationships among symptoms. Identification of the symptom distribution and symptom clusters of insomnia further provide valuable guidance for clinical diagnosis and treatment.
Impact of Built Environments on Body Weight (the Moving to Health Study): Protocol for a Retrospective Longitudinal Observational Study (Preprint)
Authors: Mooney Stephen J , Bobb Jennifer F , Hurvitz Philip M , Anau Jane , Theis Mary Kay , Drewnowski Adam , Aggarwal Anju , Gupta Shilpi , Rosenberg Dori E , Cook Andrea J , Shi Xiao , Lozano Paula , Moudon Anne Vernez , Arterburn David
Published: October 2019

BACKGROUND

Studies assessing the impact of built environments on body weight are often limited by modest power to detect residential effects that are small for individuals but may nonetheless comprise large attributable risks.

OBJECTIVE

We used data extracted from electronic health records to construct a large retrospective cohort of patients. This cohort will be used to explore both the impact of moving between environments and the long-term impact of changing neighborhood environments.

METHODS

We identified members with at least 12 months of Kaiser Permanente Washington (KPWA) membership and at least one weight measurement in their records during a period between January 2005 and April 2017 in which they lived in King County, Washington. Information on member demographics, address history, diagnoses, and clinical visits data (including weight) was extracted. This paper describes the characteristics of the adult (aged 18-89 years) cohort constructed from these data.

RESULTS

We identified 229,755 adults representing nearly 1.2 million person-years of follow-up. The mean age at baseline was 45 years, and 58.0% (133,326/229,755) were female. Nearly one-fourth of people (55,150/229,755) moved within King County at least once during the follow-up, representing 84,698 total moves. Members tended to move to new neighborhoods matching their origin neighborhoods on residential density and property values.

CONCLUSIONS

Data were available in the KPWA database to construct a very large cohort based in King County, Washington. Future analyses will directly examine associations between neighborhood conditions and longitudinal changes in body weight and diabetes as well as other health conditions.

INTERNATIONAL REGISTERED REPORT

DERR1-10.2196/16787
Effectiveness and Cost-Effectiveness of a Self-Guided Internet Intervention for Social Anxiety Symptoms in a General Population Sample: Randomized Controlled Trial (Preprint)
Authors: Powell John , Williams Veronika , Atherton Helen , Bennett Kylie , Yang Yaling , Davoudianfar Mina , Hellsing Annika , Martin Angela , Mollison Jill , Shanyinde Milensu , Yu Ly-Mee , Griffiths Kathleen M
Published: October 2019

BACKGROUND

Many people are accessing digital self-help for mental health problems, often with little evidence of effectiveness. Social anxiety is one of the most common sources of mental distress in the population, and many people with symptoms do not seek help for what represents a significant public health problem.

OBJECTIVE

This study aimed to evaluate the effectiveness of a self-guided cognitive behavioral internet intervention for people with social anxiety symptoms in the general population.

METHODS

We conducted a two-group randomized controlled trial in England between May 11, 2016, and June 27, 2018. Adults with social anxiety symptoms who were not receiving treatment for social anxiety were recruited using online advertisements. All participants had unrestricted access to usual care and were randomized in a 1:1 ratio to either a Web-based unguided self-help intervention based on cognitive behavioral principles or a waiting list control group. All outcomes were collected through self-report online questionnaires. The primary outcome was the change in 17-item Social Phobia Inventory (SPIN-17) score from baseline to 6 weeks using a linear mixed-effect model that used data from all time points (6 weeks, 3 months, 6 months, and 12 months).

RESULTS

A total of 2122 participants were randomized, and 6 were excluded from analyses because they were ineligible. Of the 2116 eligible randomized participants (mean age 37 years; 80.24%, 1698/2116 women), 70.13% (1484/2116) had follow-up data available for analysis, and 56.95% (1205/2116) had data on the primary outcome, although attrition was higher in the intervention arm. At 6 weeks, the mean (95% CI) adjusted difference in change in SPIN-17 score in the intervention group compared with control was −1.94 (−3.13 to −0.75; P=.001), a standardized mean difference effect size of 0.2. The improvement was maintained at 12 months. Given the high dropout rate, sensitivity analyses explored missing data assumptions, with results that were consistent with those of the primary analysis. The economic evaluation demonstrated cost-effectiveness with a small health status benefit and a reduction in health service utilization.

CONCLUSIONS

For people with social anxiety symptoms who are not receiving other forms of help, this study suggests that the use of an online self-help tool based on cognitive behavioral principles can provide a small improvement in social anxiety symptoms compared with no intervention, although dropout rates were high.

CLINICALTRIAL

ClinicalTrials.gov NCT02451878; https://clinicaltrials.gov/ct2/show/NCT02451878
Multi-objective Optimization of Succinic Acid Production from Empty Fruit Bunch
Authors: Hafyan R.H. , Prasetyo W.D. , Bhullar L , Putra Z.A. , Bilad M.R. , Wirzal M.D.H , Nordin N.A.H.M.
Published: October 2019

Empty Fruit Bunch (EFB) produced in plantation mill activities in Malaysia creates a major disposal problem. On the other hand, sustainability issues have driven industries to overcome the depletion of fossil fuels and reduction of greenhouse gases emissions. Therefore, as a renewable source, EFB can be an attractive option to address the above problems by converting it into fuels and chemicals. Succinic acid, one of 12 chemical building blocks identified by DOE to be used in synthesis of high-value materials, can be produced from biochemical conversion of the EFB. The present study evaluates succinic acid production process using EFB as the raw material from the perspective of three pillars of sustainability, namely economic, environment, and safety. Flowsheet modeling and techno-economic analysis methods are applied, followed by a multi-objective optimization using genetic algorithm method that simultaneously accounts for maximization of Net Present Value (NPV) and minimization of both Global Warming Potential (GWP) and Toxicity Damage Index (TDI). The pareto frontier reveals a trade-off among all objectives that the maximum NPV is 1,619 MMSD at the maximum EFB of 71,900 kg/hour. Meanwhile, the minimum GWP (12.4 kg CO2-eq/kg succinic acid) and TDI (4.5) are acquired at the minimum EFB of 50,000 kg/hour.
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).
PENGARUH AERASI LARUTAN FeDTA DAN PAKAN TAMBAHAN TEPUNG Spirulina maxima TERHADAP JUMLAH KISTA YANG DIHASILKAN OLEH Artemia salina BETINA OVIPAR
Authors: Noor M.
Published: October 2019

Different media condition, with salinity above the hatching threshold of cysts (100 ppt) and feeding with water flow as the main menu and Spirulina maxima flour as an additional feed encouraged the adult female Artemia salina to be oviparous and produce different amount of cysts depending on the treatments. The average amount of cysts produced by oviparous female Artemia salina during 77 day rearing was 22,719-78,616 cysts each female Artemia salina produced 18-13 cysts. Statistical analysis showed that all treatments did not reduce any significant effects on the production of cysts (p>0.05)
Keadilan Inter-generasi, Malapetaka Lingkungan, dan Pemuda di Era Antroposen
Authors: Astuti Rini
Published: October 2019

-
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.