bluuebunny/crossref_metadata_2025 huggingface dataset:
La mortalidad por VIH en las jurisdicciones sanitarias de México de 1990 a 2015
Authors: Bravo-García Enrique , Magis-Rodríguez Carlos , Palacios-Martínez Manuel , Guarneros-Soto Noé , Uribe-Zúñiga Patricia
Published: August 2019

Objetivo. Analizar la distribución y tendencias de la mor­talidad por VIH en las jurisdicciones sanitarias (JS) de México. Material y métodos. Se calcularon las tasas estandariza­das de mortalidad utilizando las cifras oficiales de defunciones (Instituto Nacional de Estadística y Geografía) y estimaciones de población (Consejo Nacional de Población). Se analizó la magnitud, distribución y tendencias de la mortalidad por VIH a nivel nacional, por entidad federativa y JS utilizando el modelo de regresión JoinPoint. Resultados. De 2008 a 2015, la mortalidad por VIH disminuyó más de 20%. En las 25 JS con mayor mortalidad por VIH reside 11% de la población nacional, pero concentra 28.6% de las muertes, con el doble o triple de la mortalidad nacional. Conclusiones. Se identifi­caron las 25 JS en donde deben focalizarse las acciones para reducir la mortalidad por VIH. Por primera vez se analizó un problema de salud en todas las JS mexicanas.
GhYGL1d, a pentatricopeptide repeat protein, is required for chloroplast development in cotton
Authors: He Peng , Wu Shuyin , Jiang Yanli , Zhang Lihua , Tang Meiju , Xiao Guanghui , Yu Jianing
Published: August 2019

Background: The pentatricopeptide repeat (PPR) gene family, which contains multiple 35-amino acid repeats, constitutes one of the largest gene families in plants. PPR proteins function in organelles to target specific transcripts and are involved in plant development and growth. However, the function of PPR proteins in cotton is still unknown.
Results: In this study, we characterized a PPR gene YELLOW-GREEN LEAF (GhYGL1d) that is required for cotton plastid development. The GhYGL1d gene has a DYW domain in C-terminal and is highly express in leaves, localized to the chloroplast fractions. GhYGL1d share high amino acid-sequence homology with AtECB2. In atecb2 mutant, overexpression of GhYGL1d rescued the seedling lethal phenotype and restored the editing of accD and ndhF transcripts. Silencing of GhYGL1d led to the reduction of chlorophyll and phenotypically yellow-green leaves in cotton. Compared with wild type, GhYGL1d-silenced cotton showed significant deformations of thylakoid structures. Furthermore, the transcription levels of plastid-encoded polymerase (PEP) and nuclear-encoded polymerase (NEP) dependent genes were decreased in GhYGL1d-silenced cotton.
Conclusions: Our data indicate that GhYGL1d not only contributes to the editing of accD and ndhF genes, but also affects the expression of NEP- and PEP-dependent genes to regulate the development of thylakoids, and therefore regulates leaf variegation in cotton.
Recombinant cold shock domain containing protein is a potential antigen to detect specific antibody during early and late infections of Haemonchus contortus in goat
Authors: Naqvi Muhammad Ali-ul-Husnain , Aimulajiang KaLiBiXiaTi , Memon Muhammad Ali , Hasan Muhammad Waqqas , Naqvi Sana Zahra , Lakho Shakeel Ahmed , Chu Wen , Xu Lixin , Song Xiaokai , Li XiangRui , Yan RuoFeng
Published: August 2019

Background: Haemonchus contortus (H. contortus) is the most abundant nematode causing haemonchosis with major economic losses to the small ruminant industry farming worldwide. Effective prognosis and treatment depend upon the early diagnosis of H. contortus infection. To date, no widely-approved methods are available to identify prepatent H. contortus infection. The aim of this study was to evaluate the diagnostic potential of recombinant cold shock H. contortus protein (rHc-CS) during early and late infections of H .contortus in goat. Results: Purified rHc-CS exhibited a clear band, with a molecular weight about 38 kDa. No eggs of H. contortus were detected in feces collected at 14 days post infection. However, Specific anti rHc-CS antibodies were detectable in sera of all infected goats during early stage (2nd week of infection) and late stage (3rd to 14th week of infection) using immunoblotting assay. Furthermore, no cross reactivity was observed against most commonly found pathogens (Trichinella spiralis, Fasciola hepatica, and Toxoplasma gondii) and uninfected goats. The format variables for rHc-CS indirect-ELISA were optimized. The optimum antigen coating concentration was found 0.28μg/well at 37℃ 1h and overnight at 4°C. Optimum dilution ratio of serum and rabbit anti-goat IgG was recorded 1:100 and 1:4000 respectively. The best blocking buffer was 5% bovine serum albumin (BSA) and the best time for blocking, serum incubation and TMB reaction was recorded as 60, 120 and 10 minutes respectively. The cut-off value for positive and negative interpretation was determined as 0.352 (OD450). The diagnostic specificity and sensitivity of the rHc-CS, both were recorded 100%. Conclusion: These results demonstrated that rHc-CS is a potential immunodiagnostic antigen to detect specific antibodies at early and late H. contortus infections in goat.
Developing an experimental necrotic enteritis model in turkeys - the impact of Clostridium perfringens, Eimeria meleagrimitis and host age on frequency of severe intestinal lesions
Authors: Hardy Simon P. , Benestad Sylvie L. , Hamnes Inger Sofie , Moldal Torfinn , David Bruce , Barta John R. , Reperant Jean-Michel , Kaldhusdal Magne
Published: August 2019

Background: Little information exists concerning the pathogenesis, immunity, microbiota or experimental reproduction of turkey necrotic enteritis. Necrotic enteritis in turkeys and chickens differ with regard to important aspects. The objective of this study was to contribute to the development of in vivo experimental models of necrotic enteritis in turkeys.
Results: A four tier (0-3) scoring system with clearly defined degrees of severity of macroscopic intestinal lesions was developed, based on 2312 photographic images of opened intestines from 810 B.U.T. 10 or B.U.T. Premium turkeys examined in nine experiments. Loss of macroscopically recognizable villi in the anterior small intestine was established as the defining lesion qualifying for a score 3 (severe intestinal lesions). The developed scoring system was used to identify important factors in promoting high frequencies of turkeys with severe lesions: a combined Eimeria meleagrimitis and Clostridium perfringens challenge, challenge at five rather than three weeks of age, the use of an Eimeria meleagrimitis dose level of at least 5 000 oocysts per bird and finally, examination of the intestines of 5-week-old turkeys at 125 to 145 hours after Eimeria meleagrimitis inoculation. Numbers of oocysts excreted were not influenced by Clostridium perfringens inoculation or turkey age. Three different outcome variables (median lesion score, frequency of severe lesions and frequency of mucosal pseudomembranes/ulcers/depressions) were compared regarding ability to differentiate statistically between effects of dissimilar combinations of Clostridium perfringens inoculation and turkey age at challenge. Frequency of severe lesions was the superior outcome variable in this comparison.
Conclusions: This study represents a first and major step forward in the development of in vivo experimental models of necrotic enteritis in turkeys.
Urinary stone composition analysis of 3684 patients in the eastern Shandong region of China
Authors: Zhang Xuebao , Ma Jiajia , Wang Ning , Lin Chunhua
Published: August 2019

Objective

To explore the composition of urinary stones in the eastern Shandong region of China and discuss its clinical significance.

Methods

A total of 3684 specimens of urinary calculi from the eastern Shandong region were collected in our study. Compositions of stones were analyzed by Automatic Infrared Spectrum Analysis System (type LIIR-20). The results were verified through manual analysis of the spectrogram which is accompanied by polarizing microscopy and chemical analysis if necessary.

Results

Among the 3684 specimens, there were 1767 single-component stones and 1917 mixed-component stones. According to the difference of the main components of the stones, the stones can be divided into the following types: calcium oxalate monohydrate stones (1779, 48.29%), anhydrous uric acid stones (1105, 29.99%), carbonate apatite stones (590, 16.02%), ammonium magnesium phosphate hexahydrate stones (143, 3.88%), calcium oxalate dehydrate stones (36, 0.98%), and cystine stones (31, 0.84%).

Conclusion

There are relatively many uric acid stones in the eastern Shandong region of China. The automatic infrared spectrum analysis system for calculus has the advantages of accuracy and convenience.
Inappropriate child feeding practice and primary health care as major correlates of stunting and underweight among infants and young children 6-23months of age in food insecure households of Amhara and Oromia Regions, Ethiopia. A community based cross sectional study
Authors: Wondimagegne Zelalem Tafese , Alemayehu Fekadu Reta , Adole Anchamo Anato , Yimam Kaleab Baye , Berhan Yifru , Stoecker Barbara J
Published: August 2019

Background: Child undernutrition is a major public health problem in Ethiopia. Even though the highest levels of stunting are found in food insecure areas, insufficient evidence limits effective intervention to improve the situation. Therefore, this study aimed to assess undernutrition and associated factors among infants and young children aged 6–23 mo in food insecure households of Amhara and Oromia Regions, Ethiopia.
Method: A community based cross-sectional study was conducted in productive safety net targeted rural households of Amhara and Oromia Regions from April 25 to June 15, 2018.A total of 464 mother-child dyads were included in the study. Both bivariate and multivariate analyses were used to identify factors associated with stunting, wasting and underweight separately.
Results: The prevalence of stunting, wasting and underweight among children 6-23mo was 42.6%, 12.4% and 27.3% respectively. Age of the child 12-23vs 6-12mo(AOR = 4.21 95% CI: 2.52, 7.05), female (AOR = 1.84 [1.23, 2.75]), higher number of births (AOR = 1.72[1.10, 2.70]), lack of zinc supplement (AOR = 2.41[1.33, 4.38]), inadequate diet diversity (AOR=1.69[1.02, 2.81]) and lack of iodized salt in complementary food (AOR=1.55[1.03, 2.32]) were significantly associated with stunting. Similarly, age of child 12-23 mo (AOR=1.92[1.14, 3.24]), female gender (AOR = 1.88[1.22, 2.90]), higher number of births (AOR= 1.67[1.05, 2.66]), lack of zinc supplement (AOR=2.29[1.14, 4.61]), lower maternal income (AOR= 2.34[1.18, 4.65]), and inadequate diet diversity (AOR= 2.34[1.27, 4.33]) showed significant association with underweight.

Conclusion: The magnitude of child undernutrition was found to be very high in the study areas. Child nutrition intervention strategies should take into account nutrition education on appropriate child feeding and iodized salt utilization. In addition, improving zinc supplementation and economic empowerment of women are important to address the high prevalence child undernutrition in the study area.

Key words: Stunting, zinc, iodized salt, diet diversity, maternal income, food insecurity
Multicenter investigation of pediatric alimentary tract magnets ingestion in China
Authors: Wang Kai , Zhang Dan , Li Xianling , Wang Zengmeng , Hou Guangjun , Jia Xinjian , Niu Huizhong , Qi Shiqin , Deng Qingqiang , Jiang Bin , Bian Hongqiang , Yang Heying , Chen Yajun
Published: August 2019

Purpose: To describe the incidence and management of alimentary tract Buckyball ingestion in Chinese pediatric patients, and discuss the precautionary measures through multicenter investigation.
Methods: Medical records of 74 pediatric patients from 9 large Chinese hospitals were included in this study. Questionnaires were distributed online, and medical records were reviewed. Follow-up was through telephone and outpatient service.
Results: Among the 74 cases were 50 boys (68%) and 24 girls (32%). The age was 36.00 (21.75, 77.00) months, range from 7 months to 11 years old, and it showed two peaks, between one and three years old, and from six to eleven years old. The annual case number showed sharp increase, and the total case number in the last 2 years of 2017 and 2018 showed a 9.25 folds increase than the first 2 years of 2013 and 2014. Only 3 of them had exact reasons for the swallowing, the rest 71 patients had no intension for the ingestion. From onset to the emergency time was 2.00 (1.00, 5.25) days, varied from 4 hours to 40 days. Twenty-one patients had no symptoms, and the rest cases had abdominal pain, vomiting, fever, abdominal distension, fiercely crying, melena, and flatus and defecation stopped. Gastroscope, coloscope, laparoscopic operation, and laparotomy operation were adopted according to the algorithm. Gastrointestinal mucosa erosion, ischemia and necrosis, perforation, and abdominal abscess, ileus, fistula was found in the patients. The numbers of Buckyball ingested was 4 (2, 8), with a range from 1 to 39. During the follow-up period of 6 (1, 15) months, three patients had ileus, and one suffered a second operation. The remaining 71 patients were uneventful. None of the 74 patients reported a second swallowing of foreign bodies.
Conclusions: The incidence of pediatric alimentary tract magnets ingestion in China is still increasing. Management of such patients should follow the algorithm. Precautionary measures toward the issue should be taken from three levels.
Keywords: Pediatric, Alimentary tract, Magnetic foreign body, Buckball
Determinants Of Long-Acting Reversible Contraceptive Methods Utilization Among Married Women Of Reproductive Age Group In Ambo Town, Oromia Region, West Ethiopia, 2016: A Case Control Study
Authors: Soboka Dawit Regassa , Tessema Fasil , Nigatu Mamo
Published: August 2019

Background

Long-acting reversible contraceptive methods are highly effective, safe, convenient and cost-effective. The prevalence of long-acting reversible contraceptive methods utilization among married women in the study area was only 10%, which is comparatively low compared to the regional and national targets.

Objective

To identify determinants of long-acting reversible contraceptive methods utilization among married women of the reproductive age group in Ambo town, 2016

Methods

Community based unmatched case-control study was conducted in Ambo town among married women of reproductive age group. 140 cases and 280 controls were randomly included. Bivariable and multivariable logistic regression was used to identify candidate variables and independent predictor variables respectively. Adjusted odds ratios together with their corresponding 95% CI were calculated to assess the strength of association and statistical significance.

Result

139 cases and 279 controls were interviewed giving a response rate of 99%. Moderate level of knowledge on long-acting reversible contraceptive methods (AOR= 8.73, 95%CI: 3.08 - 24.77), Good level of knowledge (AOR=13.99, 95%CI:4.93-39.71), spousal discussion on long-acting reversible contraceptive methods (AOR=2.88, 95%CI:1.3-6.36), attitude toward long-acting reversible contraceptive methods (AOR=7.07, 95% CI: 3.77-13.24), intention to give birth in the future (AOR=0.085, 95%CI: 0.36-0.20), Women from households in the poorest wealth quintile (AOR= 6.83, 95%CI: 2.68-17.38), Women from households in the medium wealth quintile (AOR=5.83, 95%CI: (2.23- 15.23) and woman’s expectation of restriction to methods use (AOR=0.34, 95%CI:0.22-0.53) were significant determinants of long-acting reversible contraceptive methods utilization.

Conclusion & Recommendation

Good knowledge, moderate knowledge, good attitude, wealth index, spousal discussion, intention to give birth in the future and woman’s expectation of restriction to method use were determinants of long-acting reversible contraceptive methods utilization.
Knowledge of Complications of Diabetes Mellitus and its Associated Factors among Type 2 Diabetic Patients Visiting Addis Zemen District Hospital, Northwest Ethiopia
Authors: Belsti Yitayeh , Akalu Yonas , Fekadu Haileab , Animut Yaregal
Published: August 2019

Objectives: To reduce Diabetes mellitus related morbidity and mortality, knowledge about its complications is necessary. However, there is no information about knowledge of diabetic patients on diabetes mellitus complications in Ethiopia. Therefore, the aim of this study was to assess knowledge on diabetes complications and its associated factors among Type 2 diabetic patients at Addis Zemen District Hospital, northwest Ethiopia, 2019. Institution based cross sectional study was conducted among 402 type 2 adult diabetes patients at Addis Zemen District Hospital by using interviewer administered structured questionnaires.
Results: In this study, less than half (48.5%) with 95%CI (43.3, 52.7) of participants had a good knowledge regarding diabetes complications. Being: male (AOR: 4.67, 95% CI (2.53, 8.61), in the age of 31-45years (AOR: 7.30, 95% CI (3.10, 17.17)) educational level of high school and above (AOR: 7.46, 95%CI (3.02, 18.44)), having monthly income of ≥ 2500 Ethiopian birr (AOR: 7.18, 95%CI (1.70, 30.28)) were significantly associated with good knowledge. This must get the attention of health institutions, the government, and all concerned stakeholders in the health sector to design strategies on increasing diabetes complications knowledge among diabetes patients to decrease morbidity and mortality associated with the complications.
IMAGE BEYOND THE FORM. REPRESENTING PERCEPTION OF URBAN ENVIRONMENT
Authors: BAGNOLO Vincenzo , MANCA Andrea
Published: August 2019

Perception, awareness and appreciation of the built environment are essential skills in urban representation and design. Among the different perceptual dimensions, the visual, or more precisely the visual-aesthetic dimension is the field that better expresses its potential in representation. The study, in an analytical-applicative perspective, addresses the reading of the relationship between forms and uses, symbols and meanings of an urban public space characterized by a recent transformation. The architectural stratifications and practices of use lead to the definition of space, in its tangible and intangible components. In this regard the analysis of the historical drifts, traced back through images and drawings, help us to make visible the mutations and the processes helpful to understand and describe its actual order. The aim of the research is to investigate the visual dimension of an urban space, both in its material and immaterial connotations, and its relationship with the stratified or new uses, explored by multiple and diversified tools of urban representation
Инклюзивная образовательная среда как условие развития и социальной адаптации детей с особыми образовательными потребностями
Authors: Ignatova Natalia Petrovna
Published: August 2019

В данной статье отражён положительный опыт деятельности социально- реабилитационного центра по развитию и адаптации детей со сложными дефектами развития. Существующие проблемы изложены последовательно. Акцентированное внимание уделяется понятиям «инклюзивное образование» «социальные пробы», как вариантам адаптации воспитанников с ограниченными возможностями здоровья. Материал статьи даст возможность педагогам осмыслить проблемы организации инклюзивного образования и возможные пути их решения, а также нацелен на педагогических работников социально-реабилитационных центров, педагогов общего и дополнительного образования, студентов педагогических учебных заведений .
Experiências juvenis de individuação:
Authors: Dos Reis Juliana Batista
Published: August 2019

O artigo analisa as experiências socializadoras escolares e familiares de dois jovens adultos que atualmente estão fora da escola. A produção é fruto de uma pesquisa etnográfica com a realização de entrevistas biográficas com jovens moradores/as de uma região periférica da cidade de Belo Horizonte. Através de uma postura metodológica da sociologia dos indivíduos são apresentadas as experiências familiares e escolares de dois sujeitos, um jovem branco e uma jovem negra. As histórias de vida são analisadas através de duas dimensões, necessariamente imbricadas: os processos socializadores e os modos de individuação. As narrativas sublinharam aspectos comuns e singulares das construções identitárias dos indivíduos, atravessadas pela interseccionalidade de gênero e raça, a partir de suas experiências familiares e escolares. O texto busca revelar a importância da compreensão da socialização escolar e familiar, do ponto de vista juvenil, através das singulares escritas da vida.
SpliVert: A Protein Multiple Sequence Alignment Refinement Method Based on Splitting-Splicing Vertically
Authors: Zhan Qing , Fu Yilei , Jiang Qinghua , Liu Bo , Peng Jiajie , Wang Yadong
Published: August 2019

Background:

Multiple Sequence Alignment (MSA) is a fundamental task in bioinformatics and is required for many biological analysis tasks. The more accurate the alignments are, the more credible the downstream analyses. Most protein MSA algorithms realign an alignment to refine it by dividing it into two groups horizontally and then realign the two groups. However, this strategy does not consider that different regions of the sequences have different conservation; this property may lead to incorrect residue-residue or residue-gap pairs, which cannot be corrected by this strategy.

Objective:

In this article, our motivation is to develop a novel refinement method based on splitting- splicing vertically.

Method:

Here, we present a novel refinement method based on splitting-splicing vertically, called SpliVert. For an alignment, we split it vertically into 3 parts, remove the gap characters in the middle, realign the middle part alone, and splice the realigned middle parts with the other two initial pieces to obtain a refined alignment. In the realign procedure of our method, the aligner will only focus on a certain part, ignoring the disturbance of the other parts, which could help fix the incorrect pairs.

Results:

We tested our refinement strategy for 2 leading MSA tools on 3 standard benchmarks, according to the commonly used average SP (and TC) score. The results show that given appropriate proportions to split the initial alignment, the average scores are increased comparably or slightly after using our method. We also compared the alignments refined by our method with alignments directly refined by the original alignment tools. The results suggest that using our SpliVert method to refine alignments can also outperform direct use of the original alignment tools.

Conclusion:

The results reveal that splitting vertically and realigning part of the alignment is a good strategy for the refinement of protein multiple sequence alignments.
Antiviral Activities of Human Host Defense Peptides
Authors: Brice David C. , Diamond Gill
Published: August 2019

Peptides with broad-spectrum antimicrobial activity are found widely expressed throughout nature. As they participate in a number of different aspects of innate immunity in mammals, they have been termed Host Defense Peptides (HDPs). Due to their common structural features, including an amphipathic structure and cationic charge, they have been widely shown to interact with and disrupt microbial membranes. Thus, it is not surprising that human HDPs have activity against enveloped viruses as well as bacteria and fungi. However, these peptides also exhibit activity against a wide range of non-enveloped viruses as well, acting at a number of different steps in viral infection. This review focuses on the activity of human host defense peptides, including alpha- and beta-defensins and the sole human cathelicidin, LL-37, against both enveloped and non-enveloped viruses. The broad spectrum of antiviral activity of these peptides, both in vitro and in vivo suggest that they play an important role in the innate antiviral defense against viral infections. Furthermore, the literature suggests that they may be developed into antiviral therapeutic agents.
Evaluation of Salivary Antioxidants and Oxidative Stress Markers in Male Smokers
Authors: Ahmadi-Motamayel Fatemeh , Falsafi Parisa , Abolsamadi Hamidreza , Goodarzi Mohammad T. , Poorolajal Jalal
Published: August 2019

Background:

Cigarette smoke free radicals can cause cellular damage and different diseases. All the body fluids have antioxidants which protect against free radicals.

Objective:

The aim of this study was to evaluate salivary total antioxidant capacity and peroxidase, uric acid and malondialdehyde levels in smokers and a nonsmoking control group.

Methods:

Unstimulated saliva was collected from 510 males. A total of 259 subjects were current smokers and 251 were non-smokers. The levels of salivary total antioxidant capacity, uric acid, peroxidase and malondialdehyde were measured using standard procedures. Data were analyzed with t test and ANOVA.

Results:

The smokers were younger and dental hygiene index was higher than healthy nonsmoking controls. The mean total antioxidant capacity in smokers and nonsmokers was 0.13±0.07 and 0.21±011, respectively (P=0.001). Smokers had significantly lower peroxidase and uric acid levels than healthy controls. In addition, the mean malondialdehyde levels in the smokers and nonsmokers were 4.55 ±2.61 and 2.79 ±2.21, respectively (P=0.001).

Conclusion:

Cigarette smoke produces free radical and oxidative stress, causing many side effects. Salivary antioxidant levels decreased and malondialdehyde levels increased in smokers, indicating the high oxidative stress among smokers compared to nonsmokers. Cigarette smoke had deleterious effects on main salivary antioxidants levels.
Methotrexate overdose in clinical practice
Authors: Pannu Ashok Kumar
Published: August 2019

Background:

A folic-acid antagonist, methotrexate, is one of the most commonly prescribed drugs with
its expanding use in clinical practice. The drug requires regular monitoring given its wide range of adverse effects
including bone marrow suppression, hepatic or renal dysfunction, gastrointestinal distress, mucocutaneous damage,
and neurotoxicity. The toxicity usually occurs rapidly and leads to severe neutropenia, sepsis, and advanced renal
failure that are difficult to manage.

Methods:

This review is an update for the clinicians to understand the pharmacology, clinical features, laboratory
evaluation, and treatment of patients with methotrexate overdose. High-quality literature of the past six decades was
collected and reviewed in this article. Several landmark articles were reviewed using PubMed, EMBASE Ovid, and
the Cochrane Library, that have important implications in current clinical practice.

Results:

Methotrexate overdose has complex toxicokinetic and produces myriad clinical features mimicking conditions
of lesser severity. Organ dysfunction related to bone marrow, kidney or central nervous system is lifethreatening.
The management should focus on high-quality supportive care, antidotal therapy (folinic acid and carboxypeptidase-
G2) and plasma alkalization.

Conclusion:

In accordance with the dictum “prevention is better than cure”, the author emphasizes on the role of
patient education, regular clinical observation, and laboratory monitoring for prompt recognition and diagnosis of
methotrexate overdosing at the earliest stage.
Association Between CYP3A4 and CYP3A5 Genotypes and Cyclosporine's Blood Levels and Doses among Jordanian Kidney Transplanted Patients
Authors: El-Shair Sahar , Al Shhab Mohammad , Zayed Khaled , Alsmady Moaath , Zihlif Malek
Published: August 2019

Background:

Cyclosporine is used as an immunosuppressive agent in kidney transplantation. It has a narrow therapeutic window. Cyclosporine is predominantly metabolized by CYP3A4 and CYP3A5. The most common Single Nucleotide Polymorphisms (SNPs) affecting cyclosporine metabolism (CYP3A4*1B, CYP3A4*1G, CYP3A4*22 and CYP3A5*3) were investigated among Jordanian kidney transplanted patients to find out the genotypes and allele frequencies of these SNPs. Additionally, this study investigated whether genotypes of CYP3A4 and CYP3A5 affect C2 blood levels, dosing of cyclosporine and the prevalence of acute rejection.

Methods:

Blood samples of 109 adult patients taking cyclosporine as their primary immunosuppressant for kidney transplantation were collected from the Prince Hamzah Hospital, Amman, Jordan. Patients’ first C2 blood levels and their first two given doses were collected. Patients were genotyped for the four SNPs using Polymerase Chain Reaction- restriction Fragment Length Polymorphism (PCR-RFLP) assay method.

Results:

Allele frequencies among Jordanian patients for CYP3A4*1B, CYP3A4*1G, CYP3A4*22 and CYP3A5*3 were 0.037, 0.399, 0.037 and 0.271, respectively. There was a significant association between CYP3A4*22 and mean difference in the second and first given doses (P=0.034). There was a big difference between CYP3A4*22 and the mean of the first C2 blood levels (P=0.063).

Conclusion:

There was a strong association between CYP3A4*22 and the mean difference between the second and first given doses. There was a trend of significant difference between the mean of the first C2 blood levels among heterozygous CYP3A4*22 patients. Pharmacogenomics may hold promise in assisting the prediction of the best cyclosporine dose and C2 blood level among Jordanian kidney transplant patients.
Nanoantibiotics: A Novel Rational Approach to Antibiotic Resistant Infections
Authors: Engin Ayse Basak , Engin Atilla
Published: August 2019

Background:

The main drawbacks for using conventional antimicrobial agents are the development of multiple drug resistance due to the use of high concentrations of antibiotics for extended periods. This vicious cycle often generates complications of persistent infections, and intolerable antibiotic toxicity. The problem is that while all new discovered antimicrobials are effective and promising, they remain as only short-term solutions to the overall challenge of drug-resistant bacteria.

Objective:

Recently, nanoantibiotics (nAbts) have been of tremendous interest in overcoming the drug resistance developed by several pathogenic microorganisms against most of the commonly used antibiotics. Compared with free antibiotic at the same concentration, drug delivered via a nanoparticle carrier has a much more prominent inhibitory effect on bacterial growth, and drug toxicity, along with prolonged drug release. Additionally, multiple drugs or antimicrobials can be packaged within the same smart polymer which can be designed with stimuli-responsive linkers. These stimuli-responsive nAbts open up the possibility of creating multipurpose and targeted antimicrobials. Biofilm formation still remains the leading cause of conventional antibiotic treatment failure. In contrast to conventional antibiotics nAbts easily penetrate into the biofilm, and selectively target biofilm matrix constituents through the introduction of bacteria specific ligands. In this context, various nanoparticles can be stabilized and functionalized with conventional antibiotics. These composites have a largely enhanced bactericidal efficiency compared to the free antibiotic.

Conclusion:

Nanoparticle-based carriers deliver antibiotics with better biofilm penetration and lower toxicity, thus combating bacterial resistance. However, the successful adaptation of nanoformulations to clinical practice involves a detailed assessment of their safety profiles and potential immunotoxicity.
Relationship Between the Japanese Version of the Montreal Cognitive Assessment and PET Imaging in Subjects with Mild Cognitive Impairment
Authors: Eguchi Atsuko , Kimura Noriyuki , Aso Yasuhiro , Yabuuchi Kenichi , Ishibashi Masato , Hori Daiji , Sasaki Yuuki , Nakamichi Atsuhito , Uesugi Souhei , Jikumaru Mika , Sumi Kaori , Shimomura Tsuyoshi , Matsubara Etsuro
Published: August 2019

Background: The Montreal Cognitive Assessment (MoCA) test has high sensitivity and
specificity for detecting mild cognitive impairment or early dementia. How the MoCA score relates to
findings of positron emission tomography imaging, however, remains unclear.

Objective: This prospective study examined the relationship between the Japanese version of the MoCA
(MoCA-J) test and brain amyloid deposition or cerebral glucose metabolism among subjects with mild
cognitive impairment.

Methods: A total of 125 subjects with mild cognitive impairment underwent the MoCA-J test, and amyloid-
and 18F-fluorodeoxyglucose- positron emission tomography. Linear correlation analysis and multiple
linear regression analysis were conducted to investigate the relationship between the MoCA-J score
and demographic characteristics, amyloid deposition, and cerebral glucose metabolism. Moreover, Statistical
Parametric Mapping 8 was used for a voxel-wise regression analysis of the MoCA-J score and
cerebral glucose metabolism.

Results: The MoCA-J score significantly correlated with age, years of education, and the Mini-Mental
State Examination score. After adjusting for age, sex, and education, the MoCA-J score significantly
correlated negatively with amyloid retention (β= -0.174, p= 0.031) and positively with cerebral glucose
metabolism (β= 0.183, p= 0.044). Statistical Parametric Mapping showed that Japanese version of
MoCA score correlated with glucose metabolism in the bilateral frontal and parietal lobes, and the left
precuneus.

Conclusion: The total MoCA-J score correlated with amyloid deposition and frontal and parietal glucose
metabolism in subjects with mild cognitive impairment. Our findings support the usefulness of the
MoCA-J test for screening subjects at high risk for Alzheimer’s disease.
Association of PICALM Gene Polymorphisms with Alzheimer's Disease: Evidence from an Updated Meta-Analysis
Authors: Zeng Fang-Fang , Liu Jun , He Hong , Gao Xu-Ping , Liao Min-Qi , Yu Xiao-Xuan , Liu Yan-Hua , Zhu Sui , Jing Chun-Xia
Published: August 2019

Background:

Previous studies have examined the roles of three polymorphisms (rs3851179,
rs541458, and rs592297) of the PICALM gene in susceptibility to Alzheimer's disease (AD) with inconclusive
findings.

Objective:

We performed a meta-analysis to explore whether these three polymorphisms in the PICALM
gene were associated with susceptibility to AD.

Methods:

Bibliographical searches were conducted in the PubMed, Embase, Web of Science, and China
National Knowledge Infrastructure (CNKI) databases. Summary Odds Ratios (ORs) with 95% Confidence
Intervals (CIs) were used to assess the strength of association in a random effects model. Potential
sources of heterogeneity were identified by subgroup and meta-regression analyses.

Results:

Twenty studies (9,017 cases and 15,448 controls) on rs3851179, 12 studies (8,077 cases and
12,022 controls) on rs541458, and 4 studies (2,106 cases and 2,234 controls) on rs592297 were considered
eligible for meta-analyses. For both rs3851179 and rs541458, the overall ORs were significant under
all genetic models with mild heterogeneity. Compared with G carriers, A carriers of rs3851179 were
associated with a decreased risk of AD (OR = 0.88; 95% CI 0.84, 0.91, P for Z-test <0.001, I2 = 0.0%).
Compared with T carriers, C carriers of rs541458 were inversely associated with AD risk (OR = 0.86;
95% CI 0.81, 0.92, P for Z-test <0.001, I2 = 39.5%). No association was observed for rs592297. Subgroup
and meta-regression analyses indicated that the protective effect of the rs541458 C allele was observed
only among Caucasians, not among Asians (P for interaction: 0.021~<0.001).

Conclusion:

rs3851179 and rs541458 appear to be associated with decreased AD risk. The null associations
for rs592297 with AD risk need further confirmation with a larger number of participants.
Antitumoral Potential of Lansbermin-I, a Novel Disintegrin from Porthidium lansbergii lansbergii Venom on Breast Cancer Cells
Authors: Montealegre-Sánchez Leonel , Gimenes Sarah N.C. , Lopes Daiana S. , Teixeira Samuel C. , Solano-Redondo Luis , de Melo Rodrigues Veridiana , Jiménez-Charris Eliécer
Published: August 2019

Background:

Disintegrins from snake venoms bind with high specificity cell surface integrins,
which are important pharmacological targets associated with cancer development and progression.

Objective:

In this study, we isolated a disintegrin from the Porthidium lansbergii lansbergii venom and
evaluated its antitumoral effects on breast cancer cells.

Methods:

The isolation of the disintegrin was performed on RP-HPLC and the inhibition of platelet aggregation
was evaluated on human platelet-rich plasma. The inhibition of cell adhesion was also evaluated
in vitro on cultures of cell lines by the MTT method as well as the inhibition of breast cancer cell
migration by the wound healing assay. The binding of the disintegrin to integrin subunits was verified by
flow cytometry and confocal microscopy. Finally, inhibition of angiogenesis was assessed in vitro on
HUVEC cells and the concentration of VEGF was measured in the cellular supernatants.

Results:

The disintegrin, named Lansbermin-I, is a low molecular weight protein (< 10 kDa) that includes
an RGD on its sequence identified previously. Lansbermin-I showed potent inhibition of ADP and
collagen-induced platelet aggregation on human plasma and also displayed inhibitory effects on the adhesion
and migration of breast cancer MCF7 and MDA-MB 231cell lines, without affecting nontumorigenic
breast MCF-10A and lung BEAS cells. Additionally, Lansbermin-I prevented MCF7 cells to
adhere to fibronectin and collagen, and also inhibited in vitro angiogenesis on human endothelial HUVEC
cells.

Conclusion:

Our results display the first report on the antitumor and anti-metastatic effects of an RGDdisintegrin
isolated from a Porthidium snake venom by possibly interfering with α2 and/or β1-containing
integrins. Thus, Lansbermin-I could be an attractive model to elucidate the role of disintegrins against
breast cancer development.
Synthesis and Characterization of GO-Chit-Ni Nanocomposite as a Recoverable Nanocatalyst for Reducing Nitroarenes in Water
Authors: Sarvestani Mosayeb , Azadi Roya
Published: August 2019

In the present study, nickel nanoparticles (Ni-NPs) immobilized on graphene oxide-chitosan
(GO-Chit-Ni) have been synthesized and characterized as a catalyst for reduction of nitroarenes in water.
For this purpose, GO has been functionalized with chitosan (GO-Chit). Then, Ni-NPs were immobilized
on the surface of GO-Chit using a simple method. The GO-Chi-Ni nanocomposites were characterized
using Fourier Transforms Infrared Spectroscopy (FT-IR), Transmission Electron Microscopy
(TEM), X-Ray Diffraction Measurements (XRD), and Atomic Adsorption Spectrometry (AAS). The
GO-Chi-Ni nanoparticles demonstrated appropriate catalytic activity in reducing nitroarenes to aryl
amines in the existence of sodium borohydride (NaBH4) aqueous solution as a hydrogen source at
80oC. This catalytic system applies environmentally benign water as a solvent that is cheap, easily accessible,
non-toxic, non-volatile, non-flammable and thermally stable. This type of catalyst can be applied
several times with no considerable change in its performance.
A Validated DBS Method for Quantitation of a Novel Mutant IDH1/2 Inhibitor, Vorasidenib Using 10 μL Mice Blood: Application to a Pharmacokinetic Study in Mice
Authors: Dittakavi Sreekanth , Jat Rakesh Kumar , Mullangi Ramesh
Published: August 2019

Background:

Vorasidenib is a pan-IDH inhibitor, undergoing clinical trials for the treatment
of acute myeloid leukemia.

Methods:

In this paper, we present the data of method validation to quantify vorasidenib in the mice
blood mice using dried blood spot (DBS) method on LC-MS/MS as per FDA bioanalytical method validation
guideline. Using methanol (enriched with internal standard) as an extraction solvent followed by
sonication, vorasidenib was extracted from DBS quality control samples, calibration curve samples and
pharmacokinetic study samples. Baseline separation of vorasidenib and the IS in a 2.0 μL injected sample
was accomplished by delivering 0.2% formic acid and acetonitrile (25:75, v/v) at a constant flowrate
(1.00 mL/min) on a C18 column. The total run time was 2.0 min. Using the transition pair of m/z
415.4→260.4 for vorasidenib and m/z 583.1→186.1 for the IS, the quantitation was performed. The
method linearity range was 1.00-3008.00 ng/mL.

Results:

The recovery of vorasidenib ranged between 71.28%-78.14% across the tested concentrations.
No matrix effect was seen. Intra- and inter-day precisions were ≤7.23% and intra- and inter-accuracies
ranged between 97.1%-107%. Vorasidenib was stable for three freeze/thaw cycles, up to 7 days at room
temperature and for one month at -80°C. Following intravenous and oral administration of vorasidenib
to mice, it was quantifiable up to 72 h. The oral bioavailability was 51.6%.

Conclusions:

All the validation parameters met the acceptance criteria as specified in the FDA regulatory
guideline. The results suggest that validated DBS method can be used for pharmacokinetic studies in
mice to characterize the pharmacokinetic parameters of vorasidenib post intravenous and oral administration.
A Review on Analytical Methods of Irbesartan and its Combinations in Pharmaceutical Dosage Forms
Authors: Nalini Calamur Nagarajan , Mathivanan Nivedhitha
Published: August 2019

Pharmaceutical analysis plays an indispensable role in various stages of drug pipeline including
drug development, fabrication of formulation, stability studies and quality control. It is also used for
characterizing the composition of different dosage forms in quantitative and qualitative ways. Comprehensive
literature survey forms the foundation stone for the focused analysis of research activity.
Irbesartan is a hypertension antagonist chiefly employed in the treatment of high blood pressure which
is an Angiotensin II Receptor blocker. The multiple mixtures of various antihypertensive medicaments
raise challenges in the method development and validation. A genuine venture is undertaken to compile
the literatures related to the antihypertensive drug Irbesartan published in various peer reviewed journals.
HPLC and UV spectrophotometry are the most preferred analytical techniques when compared to
other methods. This present review provides an in-depth assortment of various analytical techniques
published for Irbesartan and its combinations, which will help the researchers in their future endeavors.
Sensitive Detection of Levocetirizine as a new Generation Antihistamine by Stripping Square Wave Voltammetry
Authors: Ozturk Kubra , Bakirhan Nurgul K. , Ozkan Sibel A. , Uslu Bengi
Published: August 2019

Background::

new and selective electrochemical sensor was developed for the determination
of levocetirizine dihydrochloride, which is an antihistaminic drug.

Method::

The investigation was performed by using cyclic, differential pulse and square wave voltammetric
methods on the β-cyclodextrin modified glassy carbon electrode. It is thereby planned to obtain
information about levocetirizine determination and its mechanism.

Result::

The efficiency of experimental parameters including pH, scan rate, and accumulation potential
and time on the anodic response of levocetirizine dihydrochloride was studied. By employing the developed
method and under optimized conditions, the current showed linear dependence with a concentration
in the range between 2 × 10-8 M and 6 × 10-6 M in pH 2.0 Britton Robinson (BR) buffer.

Conclusion::

The achieved limits of detection and quantification were found as 3.73 × 10-10 M and
1.24 × 10-9 M, respectively. In addition, the possibility of applying the developed sensor for real sample
analysis was investigated, so β-cyclodextrin modified glassy carbon electrode was used to determine
levocetirizine dihydrochloride in Xyzal® tablet dosage form. Finally, this sensor was successfully applied
to the real sample as a selective, simple, reproducible, repeatable electrochemical sensor.
Dimeric NGF Mimetic Attenuates Hyperglycaemia and DNA Damage in Mice with Streptozotocin-Induced Early-Stage Diabetes
Authors: Yagubova Svetlana , Zhanataev Aliy , Ostrovskaya Rita , Anisina Еlena , Gudasheva Тatiana , Durnev Аndrey , Seredenin Sergey
Published: August 2019

Background:

NGF deficiency is one of the reasons for reduced β-cells survival in diabetes. Our previous experiments revealed the ability of low-weight NGF mimetic, GK-2, to reduce hyperglycaemia in a model of advanced diabetes. The increase in DNA damage in advanced diabetes was repeatedly reported, while there were no data about DNA damage in the initial diabetes.

Aim:

The study aimed to establish whether DNA damage occurs in initial diabetes and whether GK-2 is able to overcome the damage.

Methods:

The early-stage diabetes was modelled in Balb/c mice by streptozotocin (STZ) (130 mg/kg, i.p.). GK-2 was administered at a dose of 0.5 mg/kg, i.p., subchronically. The evaluation of DNA damage was performed using the alkaline comet assay; the percentage of DNA in the tail (%TDNA) and the percentage of the atypical DNA comets (“ghost cells”) were determined.

Results:

STZ at this subthreshold dose produced a slight increase in glycemia and MDA. Meanwhile, pronounced DNA damage was observed, concerning mostly the percentage of “ghost cells” in the pancreas, the liver and kidneys. GK-2 attenuated the degree of hyperglycaemia and reduced the % of “ghost cells” and %TDNA in all the organs examined; this effect continued after discontinuation of the therapy.

Conclusion:

Early-stage diabetes is accompanied by DNA damage, manifested by the increase of “ghost cells” percentage. The severity of these changes significantly exceeds the degree of hyperglycaemia and MDA accumulation. GK-2 exerts an antihyperglycaemic effect and attenuates the degree of DNA damage. Our results indicate that the comet assay is a highly informative method for search of antidiabetic medicines.