bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world use of ACEI/ARB in diabetic hypertensive patients before the initial diagnosis of obstructive coronary artery disease: patient characteristics and long-term follow-up outcome
Authors: Zhang Yue , Ding Xiaosong , Hua Bing , Liu Qingbo , Chen Hui , Zhao Xue-Qiao , Li Weiping , Li Hongwei
Published: February 2020

Background: Current guidelines recommend angiotensin-converting-enzyme inhibitors (ACEI) /angiotensin receptor blockers (ARB) as a first-line therapy in diabetic hypertensive patients and for secondary prevention in patients with obstructive coronary artery disease (OCAD). However, the effects of using ACEI/ARB before the initial diagnosis of OCAD on major adverse cardiac and cerebral event (MACCE) in diabetic hypertensive patients remain unclear. This study investigated whether using ACEI/ARB before the initial diagnosis of OCAD could be associated with improved clinical outcomes in diabetic hypertensive patients. Methods: A total of 2501 patients with hypertension and diabetes, who were first diagnosed with OCAD by coronary angiography, were included in the analysis. Of the 2501 patients, 1300 did not used ACEI/ARB before the initial diagnosis of OCAD [the ACEI/ARB(-) group]; 1201 did [the ACEI/ARB(+) group]. Propensity score matching at 1:1 was performed to select 1050 patients from each group. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, heart function, and subsequent MACCE during a median of 25.4-month follow-up were determined and compared between the 2 groups. Results: Compared with the ACEI/ARB(-) group, the ACEI/ARB(+) group had significantly lower incidence of AMI (22.5% vs. 28.4%, p=0.002), smaller infarct size in patients with AMI (pTNI: 5.7 vs. 6.8 ng/ml, p=0.044; pCKMB: 21.7 vs. 28.7 ng/ml, p=0.028), better heart function (LVEF: 60.0 vs. 58.5%, p=0.002), and lower incidences of non-fatal stroke (2.4% vs. 4.6%, p=0.015) and composite MACCE (23.1% vs. 29.7%, p=0.026). No prior ACEI/ARB therapy was significantly and independently associated with non-fatal stroke and composite MACCE. Conclusions: In diabetic hypertensive patients, treatment with ACEI/ARB before the initial diagnosis with OCAD was associated with decreased incidence of AMI, smaller infarct size, improved heart function, and lower incidences of non-fatal stroke and composite MACCE. Trial registration: retrospectively registered.
Idenfication of a novel signature based on mTORC1 pathway for hepatocellular carcinoma.
Authors: Mo Zhuomao , Luo Shaoju , Cao Zhirui , Hu Hao , Yu Ling , Zhang Shijun
Published: February 2020

Background mTORC1 signal pathway play a role in the initiation and progression of hepatocellular carcinoma (HCC), but no relevant gene signature was developed. This research aimed to explore the potential correlation between mTORC1 signal pathway and HCC and establish the related genes signature. Methods HCC cases were retrieved from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. The genes to be included in mTORC1-assiociated signature were selected by performing univariate, multivariate Cox regression analysis and lasso regression analysis. Then, the signature was verified by survival analysis and multiple receiver operating characteristic (ROC) curve. Furthermore, a nomogram was established and evaluated by C-index, calibration plot and ROC curve. Results The signature was established with the six genes ( ETF1, GSR, SKAP2, HSPD1, CACYBP and PNP ). Under the grouping from signature, patients in the high- risk group showed worse survival than those in the low-risk group in both three datasets. The univariate and multivariate Cox regression analysis indicated that mTORC1 related signature can be the potential independent prognostic factor in HCC. Conclusion The mTORC1 associated gene signature established and validated in our research could be used as a potential prognostic factor in HCC.
A "global" network dysfunction in the mirror neuron system in autism is modulated by task complexity and age: A meta-analysis of neuroimaging studies
Authors: Chan Mei Yan Melody , Han Yvonne M.Y.
Published: February 2020

Background Impaired imitation has been found to be an important factor contributing to social communication deficits in individuals with autism spectrum disorder (ASD). It has been hypothesized that the neural correlates of imitation, the mirror neuron system (MNS), are dysfunctional in ASD, resulting in imitation impairment as one of the key behavioral manifestations in ASD. Previous MNS studies produced inconsistent results, leaving the debate of whether mirror neurons are “broken” in ASD unresolved.Methods This meta-analysis aimed to explore the differences in MNS activation patterns between typically developing (TD) and ASD individuals when they observe/imitate biological motions with/without emotional components. Effect-size signed differential mapping (ES-SDM) was adopted to synthesize the available fMRI data. Results The MNS is dysfunctional in ASD; not only the brain regions containing mirror neurons were affected, the brain regions supporting MNS functioning were also impaired. Second, MNS dysfunction in ASD is modulated by task complexity; differential activation patterns during the presentation of “cold” and “hot” stimuli might be a result of atypical functional connectivity in ASD. Third, MNS dysfunction in ASD individuals is modulated by age. MNS regions were found to show delayed maturation; abnormal lateralization development in some of the brain regions also contributed to the atypical development of the MNS in ASD. Limitations We have attempted to include a comprehensive set of original data for this analysis. However, whole brain analysis data were not obtainable from some of the published papers, these studies could not be included as a result. Moreover, the results indicating the age effect on MNS in ASD could only be generalized to individuals aged 11-37, as MNS activation remains unstudied for populations beyond this age range. Also, the ES-SDM linear regression modelling might not be ideal to illustrate the associations between age and MNS activation; the meta-regression results should be treated with caution. Conclusion There is a “global” rather than a “local” network dysfunction, which may underlie the imitation impairments in individuals with ASD. Task complexity and age modulate the functioning of the MNS, which may explain the previous peculiar results contributing to the unresolved “broken mirror neuron” debate.
Determinants of stunting and underweight among children aged 6 to 59 months in Bussi Islands of Wakiso District, Uganda: a cross-sectional study
Authors: Nsubuga Edirisa Juniour , Muzafaru Ssenyondo , Isunju John Bosco , Mayega Roy William
Published: February 2020

Background: Child malnutrition in rural hard to reach areas of Uganda is higher than that in urban areas and it leads to increased risk of death. It is assumed that the condition is worse in Islands, however, limited research has been conducted on the prevalence and determinants of stunting and underweight among children in the Islands of Uganda. This study assessed the prevalence and determinants of stunting and underweight among children aged 6 to 59 months in Bussi Islands of Wakiso District in Uganda.Methods: A cross-sectional survey using quantitative methods was conducted in the Islands of Wakiso District. 409 households and 409 caretaker-child pairs of children aged 6 to 59 months were got using simple random sampling. Modified poisson regression generated Unadjusted and Adjusted Prevalence Ratios with 95% confidence intervals.Results: Prevalence of stunting and underweight among children was 29.8% and 16.1% respectively. Determinants of stunting were child age of 12 to 23 months and 24 to 35 months (APR: 2.28; 95% CI: 1.29, 4.03 and APR: 1.97; 95% CI: 1.09, 3.56 respectively); household food insecurity (APR: 1.67; 95% CI: 1.15, 2.43); utilisation of more than 80 litres of water in a day by a household (APR: 0.48; 95% CI: 0.24, 0.95); suffering from diarrhoea (APR: 1.79; 95% CI: 1.28, 2.50); receiving of deworming tablets every six months by children (APR: 0.58; 95% CI: 0.42, 0.81) and not suffering from measles (APR: 0.62; 95% CI: 0.42, 0.92). Determinants of underweight were child age of 24 to 35 months (APR: 2.30; 95% CI: 1.13, 5.33), suffering from diarrhoea (APR: 2.06; 95% CI: 1.30, 3.27) and having more than nine household members (APR: 3.18; 95% CI: 1.10, 10.6).Conclusions: Child stunting and underweight are public health problems in Bussi Islands of Wakiso District. Therefore, nutrition interventions in the Islands should focus on the determinants that were identified by this study.
Integrated analyses of rice dark response and leaf color control reveal links with porphyrin and chlorophyll metabolism
Authors: Wang Tianxingzi , Chen Yue , Zhu Zheng , Liu Yuqing , Yan Gaowei , Xu Shan , Xu Haiqing , Yang Ming , Dou Shijuan , Li Liyun , Liu Guozhen
Published: February 2020

Background: Light is a key regulatory signal for rice growth and development. Under dark stress, rice shows leaf yellowing. Whole genome transcriptomic analysis will identify differentially expressed genes (DEG) in dark-treated rice seedlings and DEG-enriched metabolic pathways. Rice leaf color is an essential agronomic trait. Traditional genetic experiments have reported over a hundred of leaf color control (LCC) genes and some of them were also regulated by light signal. Thus, an integrated analysis for the two set of data will be helpful for illustration of the mechanism for both dark-response and leaf color control.Results: Transcriptome changes in response to dark treatment were surveyed by RNA-Seq analysis. About 13,115 differentially expressed genes (DEGs) were identified. One hundred and fifty rice LCC genes were collected. It was found that 102 LCC genes (68.0%) were also dark-response DEGs, which suggests an overlap between dark response and LCC networks. Fifty DEG overlapped LCC genes was associated with chloroplast development. KEGG analysis revealed enrichment of LCC genes in porphyrin and chlorophyll metabolism (PCM) (18/44, 40.9%). Of the 18 LCC genes in the PCM pathway, 15 were dark-response DEGs (83.3%). More interestingly, all of them are involved in a central PCM sub-pathway, chlorophyll biosynthesis.Conclusions: Integrated analysis for dark stress-response and leaf color control identified the correlation between the two processes and mutually supported evidences were obtained. It was found that PCM pathway, particularly chlorophyll biosynthesis process, plays important roles in rice LCC and dark stress-response. This study provides important clues for understanding the mechanisms of dark response and leaf color control and identifying additional LCC genes.
Association Between Intensive Care Unit Occupancy at Discharge, Afterhours Discharges, & Clinical Outcomes: An Historical Cohort Study
Authors: Fergusson Nicholas A , Ahkioon Steve , Ayas Najib , Dhingra Vinay K , Chittock Dean R , Sekhon Mypinder S , Mitra Anish R , Griesdale Donald EG
Published: February 2020

Background: There is a paucity of contemporary, patient-level data evaluating the association between discharge occupancy in the intensive care unit (ICU) and clinical outcomes such as readmission and mortality. Additionally, it is unknown whether increased occupancy at discharge may modify the timing of discharge (i.e. increased afterhours discharge) and further provoke negative clinical consequences. The objective of this single-center historical cohort study was to explore the association between ICU occupancy on the day of discharge and afterhours discharges, 72-hour readmission and 30-day mortality. Methods: This was a historical cohort study of a single large quaternary ICU in Canada. Discharge occupancy was defined as the number of hours of patient care delivered on the day of discharge divided by the total amount of hours of care available for that day (number of funded beds x 24 hours). Afterhours discharge was defined as a discharge between 22:00 and 6:59. Logistic regression models controlling for important covariates were constructed. Adjusted restricted cubic spline models were also created to control for non-linear relationships. Results: A total of 8,862 ICU discharges, representing 7,288 individual patients, between April 1, 2010 and August 10, 2017 were included in this analysis. A total of 1180 (13.3%) afterhours discharges, 408 (4.6%) 72-hour readmissions, and 574 (6.5%) 30-day post discharge deaths occurred. In the adjusted analysis, greater discharge occupancy was associated with afterhours discharges (per 10% increase; adjusted odds ratio (aOR) 1.12, 95% 1.03-120, p = 0.005). Discharge occupancy was not associated with 72-hour readmission (per 10% increase; aOR 0.97, 95% CI 0.87-1.09, p= 0.624) or 30-day mortality (per 10% increase; aOR 1.05, 95% CI 0.95-1.16, p= 0.323). Afterhours discharge was not associated with neither 72-hour readmission (aOR 1.15, 95% CI 0.86-1.54, p= 0.341) nor 30-day mortality (aOR 1.05, 95% CI 0.82-1.36, p= 0.691). Conclusions: Greater ICU occupancy on the day of discharge was associated with a significant increase in afterhours discharges. However, neither discharge occupancy nor afterhours discharge were associated with 72-hr readmission or 30-day mortality. Keywords: Intensive care unit; occupancy; capacity strain; process-of-care; afterhours discharge; readmission; mortality
Computed tomography in the assessment of aneurysmal subarachnoid haemorrhage for clinical outcome: an observational cohort study
Authors: Couret David , Boussen Salah , Cardoso Dan , Alonzo Audrey , Madec Sylvain , Reyre Anthony , Brunel Hervé , Girard Nadine , Graillon Thomas , Dufour Henry , Bruder Nicolas , Simeone Pierre , Meilhac Olivier , Velly Lionel J
Published: February 2020

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications such as delayed cerebral infarction (DCI) or acute hydrocephalus and poor neurological outcome. DCI occurs most frequently 7 days after aSAH and can last for a prolonged period. The ability to predict these complications would allow the neuro-intensivist to identify patients at risk and select the most appropriate unit for hospitalization. Methods: A 3-year single-centre retrospective cohort study was conducted in our neuroscience critical care unit. Initial computed tomography (CT) scans in patients hospitalized for aSAH were blindly assessed using eight grading systems: the Fisher scale, modified Fisher scale, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score, and LeRoux score. We evaluated and compared these radiological scales for the early prediction of DCI, acute hydrocephalus, and poor neurological outcome at 3 months. Results: Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval [CI], 0.74–0.85). The ideal cut-off score for all patients was 20/42, with a sensitivity of 85% (95% CI, 75%–94%) and specificity of 63% (95% CI, 54%–71%). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROC AUC of 0.85 (95% CI, 0.79–0.89). In multivariate analysis, the Hijdra scale was the only independent predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10–1.27). Conclusions: Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice.
Innovative solutions to enhance safe and green environments for ageing well using stakeholder co-design.
Authors: Hatton Anna L , Haslam Catherine , Bell Sarah , Langley Joe , Woolrych Ryan , Cory Corrina , Brownjohn James MW , Goodwin Victoria A
Published: February 2020

Background There is a need to develop innovative solutions to enhance safe and green physical environments, which optimise health, wellbeing and community participation among older adults. In order to develop solutions that meet the needs of a diverse ageing population, an interdisciplinary approach is needed. Our aim was to identify the needs of older people in relation to ageing well in the environment by bringing together knowledge from different stakeholder and interdisciplinary perspectives. Methods An international consortium (Retrofit living For ageing well through Understanding and Redesign of Built environments consortium: ReFURB) was established in April 2018, including ten core members, to (i) explore cutting-edge solutions to safe living for ageing populations and (ii) develop innovative approaches to everyday physical environments, which bring about health benefits. We used a co-design, interdisciplinary framework involving older adults, carers, physiotherapists, geriatricians, engineers, human movement experts, geographers and psychologists from the UK and Australia. This engaged people in a one day workshop that comprised a series of presentations from international speakers on urban design, social connectedness, hazards and injury prevention, and the physical environment. Small group discussions (facilitated by consortium members) followed presentations to consider the opportunities, challenges and barriers encountered with ageing, which included the use of creative engagement activities (LEGO® Serious Play, mind maps, poster gallery walk), to help participants share personal stories and reflect on the issues raised. Thematic coding was used to synthesise the outputs of the small group work. Results Five themes emerged across the workshops, comprising: access and transport; involvement of the whole community; restoration rather than redesign; assistive and digital technology; and intergenerational approaches. These dimensions related to the physical, social and nature-based qualities of everyday environments, as they pertain to ageing well. Conclusions Co-design was a valuable tool that helped understand the perceptions of stakeholders and essential to develop effective interventions and solutions. Participants highlighted several issues affecting people as they age and key environmental considerations to promote wellbeing, activity, and participation. The consortium identified gaps in the existing evidence base and are now planning activities to further develop research ideas in collaboration with our co-design participants.
Neuroprotective effects of dexmedetomidine against the ketamine-induced disturbance of proliferation and differentiation of developing neural stem cells in the subventricular zone
Authors: Sha Huanhuan , Peng Peipei , Li Bing , Wei Guohua , Wang Juan , Wu Yuqing , huang he
Published: February 2020

Background: Recent years, the number of neonatal patients receiving surgery under general anesthesia is increasing. Previous studies have indicated that ketamine can disturb the proliferation and differentiation of developing neural stem cells (NSCs). Therefore, the safe use of ketamine in pediatric anesthesia has drawn great concern among anesthesiologists and children’s parents. Dexmedetomidine (DEX) is widely used in sedation, antianxiety and analgesia. Recent studies have shown that DEX could provide neuroprotection against anesthetic-induced neurotoxicity in the developing brain. The aim of this in vivo study was to investigate whether DEX had neuroprotective effects on the proliferation and differentiation of NSCs in the subventricular zone (SVZ) following neonatal ketamine exposure. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley rats were equally divided into the following 5 groups: Control group (n=8), ketamine group (n=8), 1 μg/kg DEX+ketamine group (n=8), 5 μg/kg DEX+ketamine group (n=8) and 10 μg/kg DEX+ketamine group (n=8). The proliferation and differentiation of NSCs in the SVZ were assessed by immunostaining with BrdU incorporation. Results: Neonatal ketamine exposure significantly inhibited NSC proliferation and astrocytic differentiation in the SVZ, and neuronal differentiation was markedly promoted. Furthermore, DEX pretreatment reversed the ketamine-induced disturbances in the proliferation and differentiation of NSCs at moderate (5 μg/kg) or high doses (10 μg/kg). Conclusion: Our findings demonstrate that DEX may have neuroprotective effects on NSCs in the SVZ of neonatal rats in a repeated ketamine anesthesia model.
Brain structural abnormalities in migraine patients: an observational study
Authors: Bonanno Lilla , Buono Viviana Lo , Corallo Francesco , Ruvolo Claudio , Torre Viviana , Bramanti Placido , Marino Silvia
Published: February 2020

Background: Migraine is a common neurological disorder, characterized by a complex physiopathology. We analyzed brain structural differences in migraine and the possible pathogenetic mechanism underlying this disease.Methods: We assessed brain structure in migraine patients, 14 with aura (MA) and 14 migraine without aura, (MO) compared with health subjects (HS) by using (VBM) approach.Results: Total cerebral GMV showed a significant difference between MA and HS (p=0.03), and between MO and HS (p=0.003). In addition, there was a significative difference trend between MA and MO (p=0.05) groups. We found three clusters of regions which showed significant GMV reduction in MA compared with MO. MA subjects showed a decrease of GMV in 4 clusters if compared with HS, and MO subjects showed a decrease of GMV in 3 clusters if compared with HS. We observed that MA and MO patients had a significant reduction of GMV in the frontal and temporal lobe and the cerebellum, if compared to HS. The bilateral fusiform gyrus and the cingulate gyrus were increased in MO patients compared with HS.Conclusion: Our findings could provide a new instrumental approach to understand possible differences in the pathogenesis of 2 type of migraine.
Yüzeyi Kimyasal Buhar Biriktirme Yöntemiyle Grafen Kaplanmış Gümüş Yüzeyin Yansıtma ve Islatılabilme Özelliklerinin İncelenmesi
Authors: AYHAN Muhammed Emre , GÜR Bahri
Published: February 2020

Malzemelerin yüzey özelliklerinin korunmasında grafen kritik bir nanomalzeme vazifesi görmektedir. Özellikle kimyasal olarak reaktif davranan metal yüzeylerin korozyon dirençlerinin artırılması endüstriyel uygulamalarda önem arz etmektedir. Yapılan çalışmalar pürüzsüz bir atomik yapıya sahip, kimyasal olarak inert, mekanik ve termal kararlılığa sahip olan grafen filmlerin üstün bir korozyon ve oksidasyon bariyeri görevi gördüğünü ispatlamıştır. Gümüş metali, yüksek elektrik ve ısı iletkenliği ile beraber bütün metaller içerisinde en yüksek yansıtma kabiliyeti başta olmak üzere, yüzey plazmon rezonansı gibi birçok üstün optik özelliklere sahip olan bir metaldir. Atmosfer ortamında gümüş her ne kadar oksitlenmese de havada bulunan kükürt içerikli gazlar sebebiyle gümüş yüzeyinde gümüş sülfür (Ag2S) tabakası oluşur ve kararmalar meydana gelir. Oluşan bu tabaka elektriksel, optik ve ıslatılabilirlik gibi yüzey özelliklerini olumsuz etkiler. Bu çalışmada optik ve elektronik uygulamalarda yaygın olarak kullanılan gümüş yüzeylerin kimyasal buhar biriktirme yöntemiyle sentezlenmiş grafen ile kaplanmasının yüzey özelliklerine etkisi, özellikle de ıslatılabilirlik ve yansıtma özelliklerine olan etkileri araştırılmıştır. Bu çalışmada Ag altlık üzerine büyütülen birkaç tabakalı grafen filmlerin temas açıları 96.7o olarak tespit edilmiştir. Yapılan yüzey kaplamaları taramalı elektron mikroskobu (SEM), geçirimli elektron mikroskobu (TEM) ve Raman spektroskopisi çalışmaları ile karakterize edilmiştir.
An investigation on using MDCs for an efficient desalination process as pretreatment of reverse osmosis
Authors: Habibi Avin , Abbaspour Madjid , Javid Amir H. , Hassani Amir H.
Published: February 2020

Microbial desalination cell (MDC) is a new bio-electrochemical technique which converts chemical energy into electrical energy, and at the same time desalinates water and treats wastewater. In this study, MDC performance and water biofouling conditions were tested as an efficient pretreatment desalination process of reverse osmosis (RO). The experiments were designed in a three-chamber reactor to compare the performance of batch and continuous fed modes, using bio-cathode and synthetic wastewater in four different hydraulic retention times and 17 and 35 g/L NaCl concentrations. According to the results, maximum salt removal of about 52.3% was obtained in the continuously fed MDC at 35 g/L NaCl concentration. The maximum salt removal at 17 g/L NaCl was also observed in continuous mode. The anolyte pH in both batch and continuous modes dropped from 7 to 6.32, 6.47 and 6.37, 6.48 in 17 and 35 g/L NaCl concentrations respectively. The chemical oxygen demand (COD) removal values in the continuous mode were 61 and 65% in the anolyte and catholyte respectively, higher than those of fed-batch MDC. The biofouling of the middle chamber solution was confirmed by conducting bio-microbial tests. Our results suggest that the type of hydraulic flow can improve the performance of MDC in different concentrations of NaCl.
Context and intentions: practical associations for fecal sludge management in rural low-income Cambodia
Authors: Harper James , Bielefeldt Angela , Javernick-Will Amy , Veasna Toeur , Nicoletti Chris
Published: February 2020

Finite storage capacities of household pit latrines make safely managing fecal sludge a recurring challenge for 2.7 billion people globally. Frequently without guidance from standards or regulation, rural latrine owners choose how to manage their own fecal sludge. However, their intentions – what behavioral science says are the best predictors of future behaviors – when pits fill are poorly understood, inhibiting the development of safe fecal sludge management (FSM) solutions and deteriorating public and environmental health. Using survey data commonly measured by development practitioners, we analyze response frequencies and their associations with contextual factors, such as location, month that the survey was administered, and poverty level. We also use binomial logistic regression to determine if contextual factors can be used to predict the intentions of rural Cambodian latrine owners when pits fill. We found that four in ten rural latrine owners intend to manage their fecal sludge unsafely (41%), and one in six did not have a plan (16%). Desirable FSM intentions increased markedly after rice harvest and varied markedly across provinces. Many predictors of desirable FSM intentions, such as location and satisfaction with the household's latrine, were also identified. Associations between FSM intentions and contextual factors can be used to help predict FSM behaviors and improve FSM service delivery, behavior change campaigns, and product design. However, future work should seek to characterize the complete decision-making processes of rural latrine owners when pits fill.

This article has been made Open Access thanks to the generous support of a global network of libraries as part of the Knowledge Unlatched Select initiative.
Seawater intrusion vulnerability evaluation and prediction: a case study of Qeshm Island, Iran
Authors: Zeynolabedin Amin , Ghiassi Reza , Dolatshahi Pirooz Moharram
Published: February 2020

Seawater intrusion is one of the most serious issues to threaten coastal aquifers. Tourian aquifer, which is selected as the case study, is located in Qeshm Island, Persian Gulf. In this study, first the vulnerability of the region to seawater intrusion is assessed using chloride ion concentration value, then by using the autoregressive integrated moving average (ARIMA) model, the vulnerability of the region is predicted for 14 wells in 2018. The results show that the Tourian aquifer experiences moderate vulnerability and the area affected by seawater intrusion is wide and is in danger of expanding. It is also found that 0.95 km2 of the region is in a state of high vulnerability with Cl concentration being in a dangerous condition. The prediction model shows that ARIMA (2,1,1) is the best model with mean absolute error of 13.3 mg/L and Nash–Sutcliffe value of 0.81. For fitted and predicted data, mean square error is evaluated as 235.3 and 264.3, respectively. The prediction results show that vulnerability is increasing through the years.
Biofilms in premise plumbing systems as a double-edged sword: microbial community composition and functional profiling of biofilms in a tropical region
Authors: De Sotto Ryan , Tang Rena , Bae Sungwoo
Published: February 2020

To understand distributions of opportunistic premise plumbing pathogens (OPPPs) and microbial community structures governed by sample location, pipe materials, water temperature, age of property and type of house, 29 biofilm samples obtained from faucets, pipes, and shower heads in different households in Singapore were examined using next-generation sequencing technology. Predictive functional profiling of the biofilm communities was also performed to understand the potential of uncultivated microorganisms in premise plumbing systems and their involvement in various metabolic pathways. Microbial community analysis showed Proteobacteria, Bacteroidetes, Acidobacteria, Nitrospira, and Actinobacteria to be the most abundant phyla across the samples which was found to be significantly different when grouped by age of the properties, location, and the type of house. Meanwhile, opportunistic premise plumbing pathogens such as Mycobacterium, Citrobacter, Pseudomonas, Stenotrophomonas, and Methylobacterium were observed from the samples at 0.5% of the total reads. Functional prediction using 16S gene markers revealed the involvement of the biofilm communities in different metabolic pathways like nitrogen metabolism, biodegradation of xenobiotics, and bacterial secretion implying diverse functionalities that are yet to be studied in this environment. This study serves as a preliminary survey on the microbial communities harboring premise plumbing systems in a tropical region like Singapore.

This article has been made Open Access thanks to the generous support of a global network of libraries as part of the Knowledge Unlatched Select initiative.
Water management in the high mountain watersheds of the Sierra Nevada National Park (southern Spain). An example of ancestral Integrated Water Management
Authors: Martos-Rosillo Sergio , González-Ramón Antonio , Ruiz-Constán Ana , Marín-Lechado Carlos , Guardiola-Albert Carolina , Moral Martos Francisco , Jódar Jorge , Pedrera Parias Antonio
Published: February 2020

Sierra Nevada is the main mountain range in the southern Iberian Peninsula and has been catalogued as a Biosphere Reserve (1986), a Natural Park (1989) and a National Park (1999). Apart from its ecological, geomorphological and landscape singularities, there are other remarkable hydrological, historical and cultural features, such as the ancestral water management performed at the headwaters of the rivers. A dense network channels excavated in the ground, the so-called acequias de careo, allows the derivation of melt water from of the river water head towards the higher zone of the hillsides, where it infiltrates. It slowly flows down through the weathered zone of the metamorphic rocks, until reaching the rivers and springs used for supply and irrigation. This water management system, implemented since the Muslim conquest of southern Spain (VIII century), has led to a remarkable transformation of the landscape, where agricultural terraces and pastures coexist with ecosystems of high ecological value. This paper describes the careos water-management technique in a pilot basin, the Bérchules watershed, recently studied during 2014 and 2015 by the Geological Survey of Spain. Migration, the abandonment of cultivated lands and, consequently, of the acequias de careo are affecting the dynamics of the rivers, endangering the delicate balance reached between man and  nature in the Sierra Nevada, after many centuries of harmonious coexistence.
Geology and Hydrogeology Aspects of El Palmar National Park, Entre Ríos, Argentina
Authors: Silva Busso Adrián , Machado Patricio
Published: February 2020

The El Palmar National Park located in the El Palmar Basin (Entre Ríos, Argentina) is a natural reserve of a relictic nature. As a protected area, its importance lies in the population of Yatay palm trees (Butia yatay). This type of palm tree is restricted to the area of the national park and its surroundings and it is uncommon to observe them in other locations on the platense coast. In the area there are outcrops of units of Cretaceous age represented by the Puerto Yeruá formation on which were deposited the clastic sediments of the Salto Chico formation of Plio-Pleistocene age (no outcrops) and the Ubajay formation of Holocene age in net contact. We identified two types of aquifers in the area, one fissured aquifer contained in Puerto Yeruá and two clastic aquifers contained in the Salto Chico and Ubajay formations. The first is of very thin and low permeability and the second of comparable permeability but thicker. The proposed hydrostratigraphic model has allowed us to understand the lateral and vertical variations of the aquifer units involved.
Recent Advances and Perspectives in the Silver-catalyzed Multi-component Reactions
Authors: Treesa G. S. Susan , Saranya Salim , Meera Gopinadh , Anilkumar Gopinathan
Published: February 2020

The catalytic activity of silver and its salts in various reactions leads to a vast variety of organic compounds having significant applications in organic synthesis. This review gives a comprehensive study on silver-catalyzed multi-component reactions that attracted the interest of the scientific world through ecofriendly, atom-economic and mild conditions. The silver-catalyzed multi-component synthesis of organic compounds including aliphatic, aromatic and heterocycles are divided into subsections based on the types of bond formed and covers literature up to 2019.
Development of Poly (Methyl vinyl ether-alt-maleic acid) Microneedles for Transdermal Delivery of Atorvastatin Calcium
Authors: Castañeda Pablo S. , Domínguez Delgado Clara L. , Cruz Isabel M.R. , Contreras Luz M.M. , Trinidad Eva M.M. , Cervantes Miriam L. , Escobar-Chávez José J.
Published: February 2020

Aims:

Biodegradable polymeric microneedles containing atorvastatin calcium were developed
in order to improve the percutaneous absorption of the drug, useful for the treatment of hypercholesterolemia.

Background:

The use of physical enhancers like microneedles have shown good results to increase the
delivery of drugs through the skin, the use of microneedles has very important advantages for transdermal
drug delivery, for example, they are painless, easy to use and safe, they increase time interval
of drug activity, dose, and reductions in adverse reactions, they also offer, the facility to remove the
system instantly of the skin.

Objective:

Develop polymer microneedles loaded with a calcium atorvastatin and evaluate them by
Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), bioadhesion, postwetting-
bioadhesion, breaking strength, drug release test and in vitro percutaneous absorption studies
to demonstrate the use of microneedles atorvastatin is able to cross the skin.

Methods:

The microneedles were made with poly (methyl vinyl ether-alt-maleic acid) as biodegradable
polymer using the technique of casting in solution in a mold. After solidification these microneedles
were characterized by Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy
(SEM), bioadhesion, post-wetting-bioadhesion, breaking strength, drug release test and in vitro percutaneous
absorption studies.

Results:

In general, the performances were satisfactory for optimal formulation in terms of DSC with
no interactions between drug and excipients, SEM shows microneedles with a conical shape, bioadhesion
of 1570 g.f, post wetting-bioadhesion of 1503.4 g.f, breaking strength of 1566.7g.f that is sufficient
to disrupt Stratum corneum, good drug release and a flux of 33.4 μg/cm2*h with a tLag of 15.14
h for the in vitro percutaneous absorption.

Conclusion:

The results indicate that it is possible to generate microneedles to increase the percutaneous
absorption of calcium atorvastatin transdermally, with the potential to be used as an alternative to
the oral route for the treatment of dyslipidemias.
Feasibility Study for Bedside Production of Recombinant Human Acid α-Glucosidase: Technical and Financial Considerations
Authors: Aldosari Mohammed H. , den Hartog Marcel , Ganizada Hubertina , Evers Martijn J.W. , Mastrobattista Enrico , Schellekens Huub
Published: February 2020

Objective:

The high cost of orphan drugs limits their access by many patients, especially in
low- and middle-income countries. Many orphan drugs are off-patent without alternative generic or biosimilar
versions available. Production of these drugs at the point-of-care, when feasible, could be a
cost-effective alternative.

Methods:

The financial feasibility of this approach was estimated by setting up a small-scale production
of recombinant human acid alpha-glucosidase (rhGAA). The commercial version of rhGAA is
Myozyme™, and Lumizyme™ in the United States, which is used to treat Pompe disease. The rhGAA
was produced in CHO-K1 mammalian cells and purified using multiple purification steps to obtain a
protein profile comparable to Myozyme™.

Results:

The established small-scale production of rhGAA was used to obtain a realistic cost estimation
for the magistral production of this biological drug. The treatment cost of rhGAA using bedside
production was estimated at $3,484/gram, which is 71% lower than the commercial price of Myozyme
™.

Conclusion:

This study shows that bedside production might be a cost-effective approach to increase
the access of patients to particular life-saving drugs.
Endocannabinoid Receptors in the CNS: Potential Drug Targets for the Prevention and Treatment of Neurologic and Psychiatric Disorders
Authors: Estrada José Antonio , Contreras Irazú
Published: February 2020

:

The endocannabinoid system participates in the regulation of CNS homeostasis and functions,
including neurotransmission, cell signaling, inflammation and oxidative stress, as well as
neuronal and glial cell proliferation, differentiation, migration and survival. Endocannabinoids are
produced by multiple cell types within the CNS and their main receptors, CB1 and CB2, are expressed
in both neurons and glia. Signaling through these receptors is implicated in the modulation
of neuronal and glial alterations in neuroinflammatory, neurodegenerative and psychiatric conditions,
including Alzheimer’s, Parkinson’s and Huntington’s disease, multiple sclerosis, amyotrophic
lateral sclerosis, stroke, epilepsy, anxiety and depression. The therapeutic potential of endocannabinoid
receptors in neurological disease has been hindered by unwelcome side effects of current drugs
used to target them; however, due to their extensive expression within the CNS and their involvement
in physiological and pathological process in nervous tissue, they are attractive targets for drug
development. The present review highlights the potential applications of the endocannabinoid system
for the prevention and treatment of neurologic and psychiatric disorders.
History of Alcohol Consumption and HIV Status Related to Functional Connectivity Differences in the Brain During Working Memory Performance
Authors: Bryant Vaughn E. , Gullett Joseph M. , Porges Eric C. , Cook Robert L. , Bryant Kendall J. , Woods Adam J. , Williamson John , Ennis Nicole , Cohen Ronald A.
Published: February 2020

Background:

Poorer working memory function has previously been associated with alcohol
misuse, Human Immunodeficiency Virus (HIV) positive status, and risky behavior. Poorer working
memory performance relates to alterations in specific brain networks.

Objective:

The current study examined if there was a relationship between brain networks involved
in working memory and reported level of alcohol consumption during an individual’s period of
heaviest use. Furthermore, we examined whether HIV status and the interaction between HIV and
alcohol consumption was associated with differences in these brain networks.

Methods:

Fifty adults, 26 of whom were HIV positive, engaged in an n-back working memory task
(0-back and 2-back trials) administered in a magnetic resonance imaging (MRI) scanner. The Kreek-
McHugh-Schluger-Kellogg (KMSK) scale of alcohol consumption was used to characterize an individual’s
period of heaviest use and correlates well with their risk for alcohol dependence. Connectivity
analyses were conducted using data collected during n-back task.

Results:

Functional connectivity differences associated with greater alcohol consumption included
negative connectivity, primarily from parietal attention networks to frontal networks. Greater alcohol
consumption was also associated with positive connectivity from working memory nodes to the precuneus
and paracingulate. HIV positive status was associated with more nodes of negative functional
connectivity relative to alcohol consumption history alone, particularly in the frontoparietal networks.
The HIV positive individuals with heavier drinking history related to negative fronto-parietal connectivity,
along with positive connectivity from working memory nodes to mesolimbic regions.

Conclusion:

Findings allow for a better understanding of brain networks affected by HIV and alcohol
and may provide avenues for interventions.
Evaluating the Relationship Between Serum Level of Interleukin-6 and Rheumatoid Arthritis Severity and Disease Activity
Authors: Rajaei Elham , Mowla Karim , Hayati Qodratollah , Ghorbani Ali , Dargahi-Malamir Mehrdad , Hesam Saeed , Zayeri Zeinab Deris
Published: February 2020

Aim:

The aim of this study was to evaluate the relationship between Interleukin-6 (IL-6)
serum level and the severity and activity of Rheumatoid Arthritis (RA).

Methods:

In this cross-sectional study, 120 RA patients referred to the rheumatology clinic, the patients
were diagnosed by rheumatologists according to ACR / EULAR 2010 criteria. Based on
DAS28 score the patients were divided into 4 groups: Remission, Mild, Moderate and Severe. Each
group contained 30 patients. Serum levels of Erythrocyte Sedimentation Rate (ESR), C-Reactive
Protein (CRP), anti-Cyclic Citrullinated Peptide (anti-CCP) and Rheumatoid Factor (RF) and serum
levels of IL-6, were measured. The relationship between these factors was measured and compared
to the relationship between IL-6 and these factors, and the activity of the disease was evaluated
based on DAS-28.

Results:

This study showed that the serum level of IL-6 has a significant relationship with RA activity
according to DAS-28 (P value <0.001). There is also a significant relationship between the
ESR level, the number of painful joints, and the number of swollen joints, and the severity of the
disease based on VAS.

Conclusion:

Generally the findings of this study indicate that serum level of IL-6 plays an important
role in the severity and activity of RA disease and can be considered as a determining factor in
evaluating the severity of RA in RA patients and it is a good guide for a step up or down of treatment.
Bacterial Profile and Antibiotic Use in Pneumonia Patients at Dr. Soetomo General Hospital
Authors: Yulia Rika , Mariza Josephine Witha , Soedarsono  , Herawati Fauna
Published: February 2020

Background:

Pneumonia is one of the causes of morbidity and mortality in children and
adults worldwide. WHO report in 1999 stated that the main cause of death due to infectious disease
is pneumonia. The rising mortality rate among severe pneumonia patients is because they do not
receive empirical antibiotic treatment according to the infecting pathogens.

Objective:

The purpose of this study is to identify the bacterial profile and the use of antibiotic
treatment on pneumonia patients admitted to the pulmonology ward of Dr. Soetomo General Hospital
in Surabaya, Indonesia.

Methods:

This descriptive observational study used the data from pneumonia patients admitted to the
pulmonology ward of Dr. Soetomo General Hospital, Surabaya, from February to April 2018. The
data was collected from the patients’ medical records, antibiotic use notes, and culture results of
bacterial antibiotic sensitivity test. The total of antibiotic use was calculated using a defined daily
dose (DDD) per 100 bed days. The quality of antibiotics was assessed using Gyssens method. The
microbial mapping was acquired from a sputum culture test result.

Results:

The most prevalent bacteria in pneumonia patients were the Gram-negative bacteria and the
most common species was Acinetobacter baumannii followed by Klebsiella pneumoniae. In contrast,
the most common Gram-positive bacteria species was Streptococcus viridans. The total antibiotic use
was 35.53 DDD/100 bed days, and ceftriaxone was the most commonly used antibiotic with 9.23
DDD/100 bed days. Fifty percent of the antibiotic use was in category wise use of antibiotic.

Conclusion:

The Gram-negative bacteria were the most common cause of pneumonia and
ceftriaxone was the most commonly used antibiotic for its cure. Fifty percent of the patients received
ceftriaxone appropriately.
Gums from Indigenous Plants of Iran: A Review on Physicochemical, Rheological and Functional Properties
Authors: Ebrahimi Behzad , Rad Aziz H. , Ghanbarzadeh Babak
Published: February 2020

Background:

Recently, public interests have increased to study novel and vernacular
polysaccharides due to their various uses, especially in food formulations as well as pharmaceuticals
and herbal medicines. Plant-based gums are commercially produced from a large number of plants
that include complex polysaccharides.

Scope and Approach:

he present study has summarized physicochemical, rheological and functional
properties of tragacanth, basil seed and balangu gums from indigenous plants of Iran.

Conclusion:

The results of this review study demonstrate that the highlighted gums are commonly
used as dietary fibers, thickening agents, emulsifiers, stabilizers and drug delivery agents. The general
appearance of gums varies from dark-brown to whitish in color. At various concentrations, pH
and ionic strengths, aqueous dispersions show great variations in their rheological behavior. In conclusion,
industrial applications of these gums are possible as a result of their strong thickening properties.
Additionally, significant surface activity and emulsification capacity enable their application
in the food, pharmaceutical and/or cosmetic industries.
Design and Synthesis of New Antifungals Based on N-Un-substituted Azoles as 14α Demethylase Inhibitor
Authors: Davood Asghar , Rahimi Aneseh , Iman Maryam , Azerang Parisa , Sardari Soroush , Mahboubi Arash
Published: February 2020

Objective(s):

Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit
cytochrome P450 sterol 14α-demethylase (CYP51). Nearly all azole antifungal agents are Nsubstituted
azoles. In addition, an azolylphenalkyl pharmacophore is uniquely shared by all azole
antifungals. Due to the importance of nitrogen atom of azoles (N-3 of imidazole and N-4 of triazole)
in coordination with heme in the binding site of the enzyme, here a group of N- un-substituted
azoles in which both nitrogen are un-substituted was reported.

Materials and Methods:

Designed compounds were synthesized by reaction of imidazole-4-carboxaldehyde with appropriate arylamines and subsequently reduced to desired amine derivatives. Antifungal activity against Candida albicans and Saccharomyces cervisiae were done using a broth micro-dilution assay. Docking studies were done using AutoDock.

Results:

Antimicrobial evaluation revealed that some of these compounds exhibited moderate antimicrobial
activities against tested pathogenic fungi, wherein compounds 3, 7, and 8 were potent.
Docking studies propose that all of the prepared azoles interacted with 14α-DM, wherein azoleheme
coordination played the main role in drug-receptor interaction.

Conclusion:

Our results offer some useful references for molecular design performance or modification
of this series of compounds as a lead compound to discover new and potent antimicrobial agents.