Effects of food policy actions on Indigenous Peoples' nutrition-related outcomes: a systematic review.

Abstract:
INTRODUCTION
Indigenous Peoples worldwide endure unacceptable health disparities with undernutrition and food insecurity often coexisting with obesity and chronic diseases. Policy-level actions are required to eliminate malnutrition in all its forms. However, there has been no systematic synthesis of the evidence of effectiveness of food and nutrition policies for Indigenous Peoples around the world. This review fills that gap.

METHODS
Eight databases were searched for peer-reviewed literature, published between 2000 and 2019. Relevant websites were searched for grey literature. Articles were included if they were original studies, published in English and included data from Indigenous Peoples from Western colonised countries, evaluated a food or nutrition policy (or intervention), and provided quantitative impact/outcome data. Study screening, data extraction and quality assessment were undertaken independently by two authors, at least one of whom was Indigenous. A narrative synthesis was undertaken with studies grouped according to the NOURISHING food policy framework.

RESULTS
We identified 78 studies from Canada, Australia, Aotearoa/New Zealand and the USA. Most studies evaluated targeted interventions, focused on rural or remote Indigenous communities. The most effective interventions combined educational strategies with policies targeting food price, composition and/or availability, particularly in retail and school environments. Interventions to reduce exposure to unhealthy food advertising was the only area of the NOURISHING framework not represented in the literature. Few studies examined the impact of universal food policies on Indigenous Peoples' diets, health or well-being.

CONCLUSION
Both targeted and universal policy action can be effective for Indigenous Peoples. Actions that modify the structures and systems governing food supply through improved availability, access and affordability of healthy foods should be prioritised. More high-quality evidence on the impact of universal food and nutrition policy actions for Indigenous Peoples is required, particularly in urban areas and in the area of food marketing.

Browne|Jennifer|J| Lock|Mark|M| Walker|Troy|T| Egan|Mikaela|M| Backholer|Kathryn|K|

systematic review
nutrition
health policy
prevention strategies
public health


Hysteroscopy and contraception.

Abstract: The Essure method is the only available hysteroscopic sterilisation method. A 4-cm device is placed in the fallopian tubes, which then induces an inflammatory reaction that causes occlusion. The method has a high successful placement rate and high effectiveness, and it can be performed in an office setting without anaesthesia. Three months after the procedure, a confirmation test has to be conducted to assure a correct position of the micro-inserts and tubal occlusion. This test can be performed by hysterosalpingography (HSG), plain X-ray or ultrasound. Pregnancies reported after Essure sterilisation are, in a majority, related to non-adherence to the follow-up protocol or misreading of the confirmation test. A majority of the pregnancies occurred after HSGs that were determined to have been misinterpreted, including missed expulsion or perforation of the micro-insert. Other complications such as ectopic pregnancy and allergic reaction to the micro-inserts seem to have been described to be of low incidence.

essure
hysteroscopic sterilisation
confirmation test
adiana
ovabloc


Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies.

Abstract:
OBJECTIVE
Driven by the need of pharmacovigilance centres and companies to routinely collect and review all available data about adverse drug reactions (ADRs) and adverse events of interest, we introduce and validate a computational framework exploiting dominant as well as emerging publicly available data sources for drug safety surveillance.

METHODS
Our approach relies on appropriate query formulation for data acquisition and subsequent filtering, transformation and joint visualization of the obtained data. We acquired data from the FDA Adverse Event Reporting System (FAERS), PubMed and Twitter. In order to assess the validity and the robustness of the approach, we elaborated on two important case studies, namely, clozapine-induced cardiomyopathy/myocarditis versus haloperidol-induced cardiomyopathy/myocarditis, and apixaban-induced cerebral hemorrhage.

RESULTS
The analysis of the obtained data provided interesting insights (identification of potential patient and health-care professional experiences regarding ADRs in Twitter, information/arguments against an ADR existence across all sources), while illustrating the benefits (complementing data from multiple sources to strengthen/confirm evidence) and the underlying challenges (selecting search terms, data presentation) of exploiting heterogeneous information sources, thereby advocating the need for the proposed framework.

CONCLUSIONS
This work contributes in establishing a continuous learning system for drug safety surveillance by exploiting heterogeneous publicly available data sources via appropriate support tools.

Koutkias|Vassilis G|VG|
Lillo-Le Louët|Agnès|A|
Jaulent|Marie-Christine|MC|

D016907:Adverse Drug Reaction Reporting Systems

D064420:Drug-Related Side Effects and Adverse Reactions

D016247:Information Storage and Retrieval

emerging data sources for pharmacovigilance


Omega-3 fatty acid supplementation provides an additional benefit to a low-dust diet in the management of horses with chronic lower airway inflammatory disease.

Abstract:
BACKGROUND
Omega-3 polyunsaturated fatty acid (PUFA) may benefit humans and animals with chronic inflammatory diseases.

HYPOTHESIS
Omega-3 PUFA supplementation improves clinical signs, lung function, and airway inflammation in horses with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD).

ANIMALS
Eight research horses and 35 client-owned horses.

METHODS
A pilot study examined the dose of PUFA that can alter plasma PUFA composition. Then, a randomized, controlled clinical trial was performed in horses with RAO and IAD. Horses were fed a complete pelleted diet with no hay and randomly assigned to 1 of 3 daily treatments for 2 months: 30 or 60 g of the supplement or 30 g of placebo. Clinical signs, lung function, plasma PUFA composition, and bronchoalveolar lavage fluid (BALF) cytology were evaluated. Data were expressed as median (25-75th percentiles). P < .05 was considered significant.

RESULTS
Polyunsaturated fatty acid supplementation resulted in increased plasma docosahexaenoic acid (DHA) that peaked at 4 weeks. Clinical improvement was noted in all horses involved in the clinical trial, but the group that received PUFA had greater improvement in clinical signs (cough score improved 60%), lung function (respiratory effort decreased 48%), and BALF (neutrophils decreased from 23 to 9%) when compared to placebo (cough score improved 33%, respiratory effort decreased 27%, BALF neutrophils increased from 11 to 17%; P < .05).

CONCLUSIONS AND CLINICAL IMPORTANCE
Feeding horses with RAO and IAD a PUFA supplement containing 1.5-3 g DHA for 2 months provides an additional benefit to low-dust diet.

Nogradi|N|N|
Couetil|L L|LL|
Messick|J|J|
Stochelski|M A|MA|
Burgess|J R|JR|

D000824:Animal Nutritional Physiological Phenomena

Recurrent airway obstruction
Inflammatory airway disease
Cough
Poor performance


Tracking the spread of COVID-19 in India via social networks in the early phase of the pandemic.

Abstract:
BACKGROUND
The coronavirus pandemic (COVID-19) has spread worldwide via international travel. This study traced its diffusion from the global to national level and identified a few superspreaders that played a central role in the transmission of this disease in India.

DATA AND METHODS
We used the travel history of infected patients from 30 January to 6 April 6 2020 as the primary data source. A total of 1386 cases were assessed, of which 373 were international and 1013 were national contacts. The networks were generated in Gephi software (version 0.9.2).

RESULTS
The maximum numbers of connections were established from Dubai (degree 144) and the UK (degree 64). Dubai's eigenvector centrality was the highest that made it the most influential node. The statistical metrics calculated from the data revealed that Dubai and the UK played a crucial role in spreading the disease in Indian states and were the primary sources of COVID-19 importations into India. Based on the modularity class, different clusters were shown to form across Indian states, which demonstrated the formation of a multi-layered social network structure. A significant increase in confirmed cases was reported in states like Tamil Nadu, Delhi and Andhra Pradesh during the first phase of the nationwide lockdown, which spanned from 25 March to 14 April 2020. This was primarily attributed to a gathering at the Delhi Religious Conference known as Tabliqui Jamaat.

CONCLUSIONS
COVID-19 got induced into Indian states mainly due to International travels with the very first patient travelling from Wuhan, China. Subsequently, the contacts of positive cases were located, and a significant spread was identified in states like Gujarat, Rajasthan, Maharashtra, Kerala and Karnataka. The COVID-19's spread in phase one was traced using the travelling history of the patients, and it was found that most of the transmissions were local.

COVID-19
international travels
Indian states
Delhi religious conference
local transmission
mass gathering
superspreading event


Macrophage and neutrophil death programs differentially confer resistance to tuberculosis.

Abstract: Apoptosis can potently defend against intracellular pathogens by directly killing microbes and eliminating their replicative niche. However, the reported ability of Mycobacterium tuberculosis to restrict apoptotic pathways in macrophages in vitro has led to apoptosis being dismissed as a host-protective process in tuberculosis despite a lack of in vivo evidence. Here we define crucial in vivo functions of the death receptor-mediated and BCL-2-regulated apoptosis pathways in mediating protection against tuberculosis by eliminating distinct populations of infected macrophages and neutrophils and priming T cell responses. We further show that apoptotic pathways can be targeted therapeutically with clinical-stage compounds that antagonize inhibitor of apoptosis (IAP) proteins to promote clearance of M. tuberculosis in mice. These findings reveal that any inhibition of apoptosis by M. tuberculosis is incomplete in vivo, advancing our understanding of host-protective responses to tuberculosis (TB) and revealing host pathways that may be targetable for treatment of disease.

Stutz|Michael Dominic|MD|
Allison|Cody Charles|CC|
Ojaimi|Samar|S|
Preston|Simon Peter|SP|
Doerflinger|Marcel|M|
Arandjelovic|Philip|P|
Whitehead|Lachlan|L|
Bader|Stefanie M|SM|
Batey|Daniel|D|
Asselin-Labat|Marie-Liesse|ML|
Herold|Marco J|MJ|
Strasser|Andreas|A|
West|Nicholas P|NP|
Pellegrini|Marc|M|

macrophages
apoptosis
Mycobacterium tuberculosis
IAP antagonist
caspase
cell death
pyroptosis


Influence of previous statin therapy on cholesterol-lowering effect of ezetimibe.

Abstract:
BACKGROUND AND OBJECTIVES
The inhibition of cholesterol absorption by ezetimibe increases cholesterol synthesis. The effect of inhibition of cholesterol synthesis on cholesterol absorption is controversial. The influence of these interactions on cholesterol levels is unknown. We investigated on the extent to which cholesterol levels were affected by the reaction of one pathway to the inhibition of the other pathway.

SUBJECTS AND METHODS
This case-controlled study enrolled 198 patients who needed cholesterol-lowering drugs. Ezetimibe (10 mg) was administered to the patients with (n=58) and without on-going statin therapy (n=58). Simvastatin (20 mg) was administered to the patients treated with (n=41) and without ezetimibe (n=41).

RESULTS
Ezetimibe without statin lowered the total cholesterol by 13.3±8.8% (p<0.001) and the low density lipoprotein-cholesterol (LDL-C) by 18.7±15.3% (p<0.001). Ezetimibe added to statin decreased the total cholesterol by 21.1±7.7% (p<0.001) and the LDL-C by 29.9±12.6% (p<0.001). The total cholesterol and LDL-C were reduced more by ezetimibe in patients with statin therapy than in those without statin therapy (p<0.001 and p<0.001, respectively). The differences in the effect of simvastatin on total cholesterol and LDL-C between the patients with and without ezetimibe showed borderline significance (p=0.10 and p=0.055, respectively).

CONCLUSION
A prior inhibition of cholesterol synthesis by statin enhanced the effect of ezetimibe on total cholesterol and LDL-C by 7.8% and 11.2%, respectively. This finding suggests that ezetimibe increased cholesterol synthesis, resulting in a significant elevation of cholesterol levels.

Choi|Young Hwan|YH|
Kim|Young|Y|
Hyeon|Cheol Won|CW|
Hyun|Seonghyup|S|
Kwon|Jee Eun|JE|
Won|Hoyoun|H|
Shin|Seung Yong|SY|
Lee|Wang-Soo|WS|
Lee|Kwang Je|KJ|
Kim|Sang-Wook|SW|
Kim|Tae Ho|TH|
Kim|Chee Jeong|CJ|


The Role of Epidermal Growth Factor Receptor Signaling Pathway during Bovine Herpesvirus 1 Productive Infection in Cell Culture.

Abstract: Accumulating studies have shown that the epidermal growth factor receptor (EGFR) signaling pathway plays an essential role in mediating cellular entry of numerous viruses. In this study, we report that bovine herpesvirus 1 (BoHV-1) productive infection in both the human lung carcinoma cell line A549 and bovine kidney (MDBK) cells leads to activation of EGFR, as demonstrated by the increased phosphorylation of EGFR at Tyr1068 (Y1068), which in turn plays important roles in virus infection. A time-of-addition assay supported that virus replication at post-entry stages was affected by the EGFR specific inhibitor Gefitinib. Interestingly, both phospholipase C-γ1 (PLC-γ1) and Akt, canonical downstream effectors of EGFR, were activated following virus infection in A549 cells, while Gefitinib could inhibit the activation of PLC-γ1 but not Akt. In addition, virus titers in A549 cells was inhibited by chemical inhibition of PLC-γ1, but not by the inhibition of Akt. However, the Akt specific inhibitor Ly294002 could significantly reduce the virus titer in MDBK cells. Taken together, our data suggest that PLC-γ1 is stimulated in part through EGFR for efficient replication in A549 cells, whereas Akt can be stimulated by virus infection independent of EGFR, and is not essential for virus productive infection, indicating that Akt modulates BoHV-1 replication in a cell type-dependent manner. This study provides novel insights on how BoHV-1 infection activates EGFR signaling transduction to facilitate virus replication.

Qiu|Wencai|W| Chang|Long|L| He|Yongming|Y| Zhu|Liqian|L|0000-0002-9579-2252

D000072283:A549 Cells
D000818:Animals
D002417:Cattle
D002460:Cell Line
D066246:ErbB Receptors
D007242:Herpesvirus 1, Bovine
D054884:Host-Pathogen Interactions
D006801:Humans
D051966:Phospholipase C gamma
D010766:Phosphorylation
D051057:Proto-Oncogene Proteins c-akt
D015398:Signal Transduction
D019562:Viral Load
D014779:Virus Replication

epidermal growth factor receptor
bovine herpesvirus 1
phospholipase C-γ1
Akt


Effectiveness and safety of generic version of abacavir/lamivudine and efavirenz in treatment naïve HIV-infected patients: a nonrandomized, open-label, phase IV study in Cali-Colombia, 2011-2012.

Abstract:
BACKGROUND
Generic drug policies are often associated with concerns about the quality and effectiveness of these products. Phase IV clinical trials may be a suitable design to assess the effectiveness and safety of generic drugs. The objective of this study was to describe the effectiveness and the safety of the generic abacavir/lamivudine and efavirenz in treatment-naïve HIV-infected patients.

METHODS
A monocentric, nonrandomized, open-label, phase IV study in treatment naïve HIV-infected patients 18 years or older with indication to receive abacavir/lamivudine and efavirenz were recruited from a program that provides comprehensive outpatient consultation and continuing care. The primary end-point was to achieve viral load <40 copies/mL at 12 months after baseline to assess effectiveness. Secondary end-point of the study were 1) to asses increasing in T-CD4 lymphocytes levels as accompaniment to asses effectiveness, and 2) to assess both gastrointestinal, skin, and central nervous system symptoms, and lipid profile, cardiovascular risk, renal, and hepatic function as safety profile. Data were determined at baseline, 3, 6, and 12 months. Close clinical monitoring and pharmaceutical care were used for data collection. Wilcoxon matched-pairs signed-rank test was used to compare proportions or medians.

RESULTS
Sixty patients were invited to participate in the study; 42 were enrolled and 33 completed the follow-up. Of the nine patients excluded from the study, only one was withdrawn due to adverse events. At 12 months, 31 of 42 patients (73.8 % in intention-to-treat analysis) achieved a viral load of HIV1 RNA <40 copies/mL. There was a significant increase (172 cells/mm3) in the median for CD4 T lymphocyte count. The adverse events were mild and met the safety profile for this antiretroviral regimen, mainly of central nervous system symptoms, skin rash, lipid abnormalities, and an increase of 2 % in the median of the percentage of cardiovascular risk.

CONCLUSIONS
The clinical outcomes of generic version of abacavir/lamivudine and efavirenz in HIV treatment naïve patients showed the expected safety and effectiveness profile of proprietary ARV drugs.

TRIAL REGISTRATION
Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000202 . Registered 19 November 2015.

Galindo|Jaime|J|
Amariles|Pedro|P|
Mueses-Marín|Héctor F|HF|
Hincapié|Jaime A|JA|
González-Avendaño|Sebastián|S|
Galindo-Orrego|Ximena|X|

Phase IV study
Generic drugs
Antiretroviral drugs
HIV/AIDS


The impact of HPV vaccination on the prevention of oropharyngeal cancer: A scoping review.

Abstract:
INTRODUCTION
HPV-associated oropharyngeal cancer (OPC) has one of the most rapidly rising incidences of any cancer in high-income countries. HPV vaccination is being tested to prevent HPV-associated OPC.

OBJECTIVE
To determine the effect of Human Papilloma Virus (HPV) vaccination on the prevention of OPC in adults worldwide.

BASIC RESEARCH DESIGN
Scoping review conducted using PRISMA-ScR Checklist.

METHOD
An electronic literature search identified relevant records. Titles and abstracts were screened to assess eligibility by two researchers, and data from relevant full-text articles were extracted and synthesised.

RESULTS
Three-hundred-and-forty-three studies were identified, with eleven articles meeting the inclusion criteria. The most common study design was cross-sectional (n = 7), the most common location was the US (n = 6) and data collection periods spanned 2004 to 2020. One article found unvaccinated participants had a 19 times increased risk of developing OPC compared with those who had been vaccinated against HPV. The remaining papers showed that prevalence of HPV-vaccine-type oral infection was significantly lower in vaccinated participants than unvaccinated participants, with a reduction of oral HPV detection ranging from 72% to 93%. This reduction varied by sex.

CONCLUSIONS
There is evidence to suggest that HPV vaccination reduces oral HPV infection and decreases the incidence of HPV-associated OPC. There is substantial need for further research which directly examines the relationship between HPV vaccination status and subsequent OPC development.

vaccination
Prevention
review
alphapapillomavirus
oropharyngeal neoplasms


Strategies to address the nursing shortage in Saudi Arabia.

Abstract:
AIM
To investigate the nursing shortage in Saudi Arabia and specifically the shortage of Saudi nurses in the healthcare workforce and to propose solutions.

METHODS
Literature published from 1993 to 2013 providing relevant information on the nursing shortage, cultural traditions and beliefs, and nursing education and policies in Saudi was accessed from multiple sources including Medline, CINAHL Plus and Google Scholar and from official Saudi government document and was reviewed.

RESULTS
Saudi Arabia depends largely on an expatriate workforce, and this applies to nursing. Saudi Arabia is experiencing a nursing shortage in common with most countries in the world and a shortage of Saudi nationals, especially women, in the healthcare workforce. The world shortage of nursing is extrinsic to Saudi, but intrinsic factors include a poor image of the nursing profession in the country that is exacerbated by cultural factors.

CONCLUSIONS/IMPLICATIONS
With the call for the Saudization of the workforce to replace the imported workforce by Saudi nationals, including nurses, through the 1992 Royal Decree, Saudi Arabia faces a problem in attracting and retaining Saudi nationals in the nursing workforce. Solutions are suggested that are aimed at improving the public image of nursing through education and the use of the media and improvements in the workplace by addressing working processes such as teamwork, ensuring adequate staffing levels and addressing some aspects of culture which may make working in nursing more compatible with being a Saudi national.

Nursing Shortage
Saudi Arabia
Nursing Education
Nursing Image
Public Education
Saudization Workforce


Obstetric outcome and incidence of congenital anomalies in 2351 IVF/ICSI babies.

Abstract:
PURPOSE
The aim of this study was to provide a comprehensive follow-up of fetal and perinatal outcome and the incidence of congenital anomalies in babies born after fresh embryo transfers compared to those conceived spontaneously in infertile couples.

METHODS
Retrospective comparative analysis of all clinical pregnancies from fresh cleavage-stage embryo transfer cycles (IVF and ICSI) compared with infertile patients who conceived spontaneously in the same time period (control). Congenital anomalies were classified following the European Surveillance of Congenital Anomalies (EUROCAT) classification.

RESULTS
A total of 2414 assisted reproductive technology (ART) pregnancies were compared to 582 spontaneous conceptions in the control infertile group representing 2306 deliveries. No significant differences were found in pregnancy outcome between the two groups (delivery rate, abortion rate, ectopic pregnancies, medical abortions for fetal anomalies, single and twins mean gestational age, and weight at delivery). A significant difference (p < 0.001) was found in the twin (21.3 vs 2.3 %) and triplet rates (2.3 vs 0 %). A total of 2351 babies were delivered in the ART group and 449 in the control group. A total of 90 babies (3.8 %) were diagnosed with a major congenital anomaly in the ART group and 15 (3.3 %) in the control group (p = ns). The overall rate of major congenital anomalies (105/2800) in ART and spontaneous pregnancies in infertile couples was significantly higher when compared to the EUROCAT 2.0 versus 3.75 % (p = 0.0002).

DISCUSSION
Babies born after ART treatments and from spontaneous conception in infertile couples had rates of congenital anomalies higher than those recorded by the EUROCAT. However, the rates of anomalies were not different within the infertile population whether conceived by ART or spontaneously. These data suggest that the diagnosis of infertility in itself is the common denominator for the increase in the rates of anomalies seen in both ART and spontaneous conceptions.

Levi Setti|Paolo Emanuele|PE|
Moioli|Melita|M|
Smeraldi|Antonella|A|
Cesaratto|Elisa|E|
Menduni|Francesca|F|
Livio|Stefania|S|
Morenghi|Emanuela|E|
Patrizio|Pasquale|P|

IVF
ICSI
ART
Pregnancy outcome
Neonatal anomalies


Determination of herbicides paraquat, glyphosate, and aminomethylphosphonic acid in marijuana samples by capillary electrophoresis.

Abstract: In this work, two methods were developed to determine herbicides paraquat, glyphosate, and aminomethylphosphonic acid (AMPA) in marijuana samples by capillary electrophoresis. For paraquat analysis, sample was extracted with aqueous acetic acid solution and analyzed by capillary zone electrophoresis with direct UV detection. The running electrolyte was 50 mmol/L phosphate buffer (pH 2.50). For glyphosate and AMPA, indirect UV/VIS detection was used, as these substances do not present chromophoric groups. Samples were extracted with 5 mmol/L hydrochloric acid. The running electrolyte was 10 mmol/L gallic acid, 6 mmol/L TRIS, and 0.1 mmol/L CTAB (pH = 4.7). The methods presented good linearity, precision, accuracy, and recovery. Paraquat was detected in 12 samples (n = 130), ranging from 0.01 to 25.1 mg/g. Three samples were positive for glyphosate (0.15-0.75 mg/g), and one sample presented AMPA as well. Experimental studies are suggested to evaluate the risks of these concentrations to marijuana user.

Lanaro|Rafael|R|
Costa|José L|JL|
Cazenave|Silvia O S|SO|
Zanolli-Filho|Luiz A|LA|
Tavares|Marina F M|MF|
Chasin|Alice A M|AA|

paraquat
glyphosate
marijuana
capillary electrophoresis
AMPA
Cannabis
forensic science
forensic toxicology


The Bicycle Drawing Test: What Does It Measure in Developmentally Typical Children?

Abstract: To verify the dimensionality of Bicycle Drawing Test (BDT), we applied the coding system of Greenberg, Rodriguez, and Sesta to bicycle drawings made by 295 boys and 320 girls (6-10 years old) with typical development, and submitted the data to item analysis, exploratory factor analysis, and confirmatory factor analysis. These analyses confirmed only two of the original four dimensions of the BDT: spatial reasoning and visual-motor control. The scores in these two factors were correlated with the Colored Progressive Matrices, the Rey Complex Figure (Copy and Memory) and with the teachers' ratings in mathematics, language, and drawing. The correlations, albeit moderate in magnitude, were consistent with the hypothesized convergent and discriminant validity. After checking for measurement invariance across gender and age, we conducted two analyses of variance, the first of which showed a significant difference between younger children (6-8 years old) and older children (9-10 years old); the analysis of variance by gender did not yield significant differences. These data enhance the usefulness of the BDT as a measure of separate cognitive components, but do not support its use as a measure of mechanical reasoning.

Cannoni|Eleonora|E|
Di Norcia|Anna|A|
Bombi|Anna Silvia|AS|
Di Giunta|Laura|L|

Bicycle Drawing Test
spatial reasoning
childhood
visual-motor ability


Exploring the clinical value of preoperative serum gamma-glutamyl transferase levels in the management of patients with hepatocellular carcinoma receiving postoperative adjuvant transarterial chemoembolization.

Abstract:
BACKGROUND
Preoperative serum gamma-glutamyl transferase (γ-GT) levels is significantly related to the prognosis of hepatocellular carcinoma (HCC), but its clinical value in the management of postoperative adjuvant transarterial chemoembolization (PA-TACE) has rarely been explored. This study aimed to investigate whether γ-GT levels could be taken as a biomarker to guide the management of PA-TACE in resectable HCC.

METHODS
HCC patients receiving radical resection were identified through the primary liver cancer big data (PLCBD) from December 2012 to December 2015. Prognostic factors of overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate cox analyses, and subgroup analysis was conducted between PA-TACE group and non-TACE stratified by γ-GT levels before and after 1:1 propensity score matching (PSM).

RESULTS
γ-GT level was found to be an independent risk factor of OS and DFS in 1847 HCC patients receiving radical resection (both P < 0.05), and patients with elevated γ-GT(> 54.0 U/L) have a shortened median OS and DFS, compared with those with normal γ-GT (both P < 0.001). In the subgroup of patients with normal γ-GT, there were no significant differences between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P > 0.05), and PA-TACE was not a significant prognostic factor of both OS and DFS before and after PSM (all P > 0.05). In the subgroup of patients with elevated γ-GT, significant differences were found between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P < 0.05), and PA-TACE was an independent prognostic factor of both OS and DFS (all P < 0.05).

CONCLUSION
Currently, we concluded that patients with more advanced HCC also have more elevated γ-GT, and these patients with elevated γ-GT would be benefited more from PA-TACE after radical resection.

Ke|Qiao|Q| Xiang|Fu|F| Xiao|Chunhong|C| Huang|Qizhen|Q| Liu|Xiaolong|X| Zeng|Yongyi|Y| Wang|Lei|L| Liu|Jingfeng|J|

Gamma-glutamyl transferase
Hepatocellular carcinoma
Transarterial chemoembolization
Radical resection


Prediction Model and Risk Stratification Tool for Survival in Patients With CKD.

Abstract:
Introduction
Because chronic kidney disease (CKD) adversely affects survival, prediction of mortality risk should help to identify individuals requiring therapeutic intervention. The goal of this project was to construct and to validate a risk scoring system and prediction model of the probability of 2-year mortality in a CKD population.

Methods
We applied the Woodpecker approach to develop prediction equations using linear, exponential, and combined models. A risk indicator R on a scale of 0 to 10 was calculated as follows: starting with 0, add 0.048 for each year of age above 20, 0.45 for male sex, 0.49 for each stage of CKD over stage 2, 1.04 for proteinuria, 0.72 for smoking history, and 0.49 for each significant comorbidity up to 5.

Results
Using R to predict 2-year mortality, the model yielded an area under the receiver operating characterisic curve of 0.83 (95% confidence interval = 0.81-0.86) with 5062 subjects with CKD ≥stage 2 from a National Health and Nutrition Examination Survey cohort (1999-2004) having a 3.2% 2-year mortality. The combined expression offered results closest to most actual outcomes for the entire population and for each CKD stage. For those patients with higher risk (R ≥ 4-5, >5-6, and >6), the predicted 2-year mortality rates were 3.8%, 6.4%, and 13.0%, respectively, compared to observed mortality rates of 2.7%, 4.5%, and 13.3%.

Conclusion
The risk stratification tool and prediction model of 2-year mortality demonstrated good performance and may be used in clinical practice to quantify the risk of death for individual patients with CKD.

Goldfarb-Rumyantzev|Alexander S|AS|
Gautam|Shiva|S|
Dong|Ning|N|
Brown|Robert S|RS|

prediction survival CKD mortality outcome epidemiology


Visual cues for manual control of headway.

Abstract: The ability to maintain appropriate gaps to objects in one's environment is important when navigating through a three-dimensional world. Previous research has shown that the visual angle subtended by a lead/approaching object and its rate of change are important variables for timing interceptions, collision avoidance, continuous regulation of braking, and manual control of headway. However, investigations of headway maintenance have required participants to maintain a fixed distance headway and have not investigated how information about own-speed is taken into account. In the following experiment, we asked participants to use a joystick to follow computer-simulated lead objects. The results showed that ground texture, following speed, and the size of the lead object had significant effects on both mean following distances and following distance variance. Furthermore, models of the participants' joystick responses provided better fits when it was assumed that the desired visual extent of the lead object would vary over time. Taken together, the results indicate that while information about own-speed is used by controllers to set the desired headway to a lead object, the continuous regulation of headway is influenced primarily by the visual angle of the lead object and its rate of change. The reliance on visual angle, its rate of change, and/or own-speed information also varied depending on the control dynamics of the system. Such findings are consistent with an optimal control criterion that reflects a differential weighting on different sources of information depending on the plant dynamics. As in other judgements of motion in depth, the information used for controlling headway to other objects in the environment varies depending on the constraints of the task and different strategies of control.

Hosking|Simon G|SG|
Davey|Catherine E|CE|
Kaiser|Mary K|MK|

manual control
control dynamics
headway regulation
optic cues
visual perception


First case of Roma ethnic origin with Andermann syndrome: A novel frameshift mutation in exon 20 of SLC12A6 gene.

Abstract: Andermann syndrome (AS) is caused by mutation of SLC12A6 gene. It comprises severe progressive sensory and motor neuropathy with early onset, varying degree of agenesis of corpus callosum (ACC) and mental retardation. AS occurs occasionally among population outside the northeastern Quebec-Saguenay-Lac- St-Jean and Charlevoix regions, inhabited by French Canadians. None of the described patients were of Roma ethnic origin. We present an 8-month-old infant of Roma ethnic origin with AS, caused by a novel frame shift mutation c.2604delT,p.(Asp868GlufsTer11) in exon 20 of SLC12A6 gene. Our case presented with several atypical findings: clinical presentation resembling "spinal muscular atrophy plus" syndrome; tongue fasciculations, which are not reported in the literature; early contractures of the wrists; normal motor action potentials and preserved sensory action potentials. Our patient is the first of Roma origin from nonconsanguineous parents, which suggests that this mutation might be widespread in the Roma population, although screening for this mutation in 140 alleles from Roma individuals originating from the same geographic region did not reveal further carriers, implying the mutation is rare. We recommend that Roma patients presenting with the clinical phenotype of AS should be tested for this mutation primarily.

Pacheva|Iliyana|I|0000-0003-0461-9065 Todorov|Tihomir|T| Halil|Zeyra|Z| Yordanova|Ralitsa|R| Todorova|Albena|A| Geneva|Ina|I| Galabova|Fani|F| Ivanov|Ivan|I|

D020022:Genetic Predisposition to Disease

D010523:Peripheral Nervous System Diseases

Andermann syndrome
SLC12A6 gene
agenesis of corpus callosum
Roma population
hereditary neuropathy


Macroevolutionary evidence suggests trait-dependent coevolution between behavior and life-history.

Abstract: Species with fast life-histories typically prioritize current over future reproductive events, compared to species with slow life-histories. These species therefore require greater energetic input into reproduction, and also likely have less time to realize their reproductive potential. Hence, behaviors that increase access to both resources and mating opportunities, at a cost of increased mortality risk, could coevolve with the pace of life-history. However, whether this prediction holds across species, remains untested under standardized conditions. Here, we test how risky behaviors, which facilitate access to resources and mating opportunities (i.e., activity, boldness, and aggression), along with metabolic rate, coevolve with the pace of life-history across 20 species of killifish that present remarkable divergences in the pace of life-history. We found a positive association between the pace of life-history and aggression, but interestingly not with other behavioral traits or metabolic rate. Aggression is linked to interference competition, and in killifishes is often employed to secure mates, while activity and boldness are more relevant for exploiting energetic resources. Our results suggest that the trade-off between current and future reproduction plays a more prominent role in shaping mating behavior, while behaviors related to energy acquisition may be influenced by ecological factors.

Killifish
life-history trade-offs
pace-of-life syndrome (POLS) hypothesis
risk-taking behavior
standard metabolic rate (SMR)


How "it gets better": effectively communicating support to targets of prejudice.

Abstract: What is said when communicating intergroup support to targets of prejudice, and how do targets react? We hypothesized that people not targeted by prejudice reference social connection (e.g., social support) more than social change (e.g., calling for a reduction in prejudice) in their supportive messages. However, we hypothesized that targets of prejudice would be more comforted by social change messages. We content coded naturalistic messages of support for lesbian, gay, bisexual, transgendered, and questioning teenagers from youtube.com (Study 1) and college undergraduates' statements (Study 2a) and found social connection messages more frequent than social change messages. Next, we explored targets' responses (Studies 2b-4b). Lesbian and gay participants rated social connection messages less comforting than social change messages (Study 3). Study 4 showed that only targets of prejudice distinguish social connection from social change messages in this way, versus non-targets. These results highlight the importance of studying the communication, content, and consequences of positive intergroup attitudes.

positive intergroup attitudes
LGBTQ
intergroup relations


Strain, biochemistry, and cultivation-dependent measurement variability of algal biomass composition.

Abstract: Accurate compositional analysis in biofuel feedstocks is imperative; the yields of individual components can define the economics of an entire process. In the nascent industry of algal biofuels and bioproducts, analytical methods that have been deemed acceptable for decades are suddenly critical for commercialization. We tackled the question of how the strain and biochemical makeup of algal cells affect chemical measurements. We selected a set of six procedures (two each for lipids, protein, and carbohydrates): three rapid fingerprinting methods and three advanced chromatography-based methods. All methods were used to measure the composition of 100 samples from three strains: Scenedesmus sp., Chlorella sp., and Nannochloropsis sp. The data presented point not only to species-specific discrepancies but also to cell biochemistry-related discrepancies. There are cases where two respective methods agree but the differences are often significant with over- or underestimation of up to 90%, likely due to chemical interferences with the rapid spectrophotometric measurements. We provide background on the chemistry of interfering reactions for the fingerprinting methods and conclude that for accurate compositional analysis of algae and process and mass balance closure, emphasis should be placed on unambiguous characterization using methods where individual components are measured independently.

Laurens|Lieve M L|LM|
Van Wychen|Stefanie|S|
McAllister|Jordan P|JP|
Arrowsmith|Sarah|S|
Dempster|Thomas A|TA|
McGowen|John|J|
Pienkos|Philip T|PT|

Analytical methods
Lipids
Proteins
Carbohydrates
Biochemical composition
Microalgae


The Teaching Pattern of Law Majors Using Artificial Intelligence and Deep Neural Network Under Educational Psychology.

Abstract: With the increasing attention to the cultivation of legal talents, a new teaching model has been explored through artificial intelligence (AI) technology under educational psychology, which focuses on improving learning initiative, teaching methods, and teaching quality of students. First, the application of AI and deep neural network (DNN) algorithms are reviewed in education, and the advantages and disadvantages of traditional learning material recommendation algorithms are summarized. Then, a personalized learning material recommendation algorithm is put forward based on DNN, together with an adaptive learning system based on DNN. Finally, the traditional user-based collaborative filtering (UserCF) model and lifelong topic modeling (LTM) algorithm are introduced as the control group to verify the performance of the proposed recommendation system. The results show that the best learning rate of model training is 0.0001, the best dropout value is 0.5, and the best batch size is 32. The proposed personalized learning resource recommendation method based on deep learning (DL) still has good stability under various training data scales. The personalized test questions of recommended students are moderately difficult. It is easier to recommend materials according to the acquisition of knowledge points and the practicability of the recommended test questions of students. Personalized learning material recommendation algorithm based on AI can timely feedback needs of students, thereby improving the effect of classroom teaching. Using the combination of AI and DL algorithms in teaching design, students can complete targeted personalized learning assignments, which is of great significance to cultivate high-level legal professionals.

law majors
artificial intelligence
educational psychology
deep learning
teaching design


Medical ethics.

Abstract: Mutual trust and relationship between doctors and patients is an important factor of treatment plan. Changing trends in medical field does affect this relationship. This article reviews the basic code of conduct for every medical practitioner.

medical ethics
Consent
law
medical records


Effects of Share 35 Policy on Liver Transplantation Outcomes for Patients With Nonalcoholic Steatohepatitis.

Abstract:
BACKGROUND
To examine the temporal variation and outcomes of liver transplantation between pre- and post-Share 35 eras for patients with nonalcoholic steatohepatitis.

METHODS
A retrospective analysis was performed among 4380 patients with end-stage liver disease from the United Network for Organ Sharing database from 2009 to 2017 due to primary diagnosis of nonalcoholic steatohepatitis or cryptogenic cirrhosis with body mass index greater than 30. Cox regressions were used to model the effect of Share 35 policy on patient and graft survival comparing the first 3 years of Share 35 policy to an equivalent time period before.

RESULTS
The number of nonalcoholic steatohepatitis-related transplants increased from 232 (14.1%) in 2009 to 266 (20.5%) in 2017. In post-Share 35 era, average waitlist time and cold ischemic time decreased, while Model for End-Stage Liver Disease (MELD) scores increased with higher proportion of recipients having MELD ≥35. No significant difference in average length of hospitalization or survival was found after Share 35.

CONCLUSIONS
The Share 35 policy benefits patients with nonalcoholic steatohepatitis from reduced liver transplantation waiting time. It is also associated with comparable outcomes in 2 eras without increasing cold ischemic time or posttransplant length of hospitalization.

D065626:Non-alcoholic Fatty Liver Disease

share 35 policy
liver transplantation
united network for organ sharing
NASH


Influence of Sensitization Patterns on Fractional Exhaled Nitric Oxide in Asthmatic Children.

Abstract: Fractional exhaled nitric oxide (FeNO) has been suggested as a non-invasive biomarker of airway inflammation, which is increased in atopic subjects. Whether sensitization to particular allergens is a predictive factor for increased FeNO levels is not yet fully understood. We conducted a retrospective cross-sectional study. From October to December in 2015, the medical documents of 127 mild, steroid-naive asthmatic children and 34 healthy age-matched children were enrolled in this study. The results of the FeNO measurements, skin prick test, and the spirometry were collected for analysis. Sensitization patterns to the 18 aeroallergens (5 categories: mites, molds, animal dander, pollen, and other) were determined in study population. A significant increase in FeNO level was observed in poly-sensitized asthmatic children (34.7 part per billion, (ppb) [28.3-41.1 p.p.b]), compared with mono-sensitized asthmatics (30.7 p.p.b [18.3-43.2 p.p.b]) and with non-sensitized asthmatics (17.3 p.p.b [10.8-24.5 p.p.b]). With sensitization to perennial allergens (mites, mold, and animal dander), blood eosinophil counts were significantly associated with increased FeNO (p<0.05 for all). The highest FeNO level was identified in children sensitized to a combination of the perennial, seasonal, and other allergens, when compared with those sensitized to one category of allergen alone (p=0.004). Our study showed that variations in FeNO level were associated with individuals' sensitization patterns. Being sensitized to some particular allergens might contribute to prompt the airway inflammation.

Qing|Miao|M| Wei|Xu|X| Zhen|Li|L| Hui|Guan|G| Xiao-Ying|Liu|L| Hui-Jie|Huang|H| Yan|Wang|W| Yi-Xin|Ren|R| Yong-Ge|Liu|L| Li|Xiang|X|

Sensitization patterns
Exhaled nitric oxide
Skin prick test
Perennial allergens
Asthma
Atopy


Examining bi-directionality between Fear of Missing Out and problematic smartphone use. A two-wave panel study among adolescents.

Abstract:
BACKGROUND
In recent years, the Fear of Missing Out (FoMO) construct has been the object of growing attention in digital technology research with previous studies finding support for the relationship between FoMO and problematic smartphone use (PSU) among adolescents and young adults. However, no previous studies clarified the causal link between FoMO and PSU using a longitudinal design.

METHODS
An auto-regressive, cross-lagged panel design was tested by using a longitudinal dataset with two waves of data collection (T0 and T1, one year apart). Participants included two hundred and forty-two adolescents (109 males and 133 females), with a mean age of 14.16 years, who filled out the Fear of Missing Out scale (FoMOs) and the Smartphone Addiction Scale (SAS). Moreover, participants filled out the Difficulties in Emotion Regulation Scale (DERS), at the first time-point of data collection.

RESULTS
The findings of the study show that FoMO (both FoMO-Fear and FoMO-Control subscales) and PSU are positively related at both time-points (i.e. at a cross-sectional level). However no cross-lagged associations between them were longitudinally supported. Females and older adolescents show higher FoMO-Fear at T1.

CONCLUSIONS
The findings of the present study suggest caution when causal links between FoMO and PSU are inferred.

Lo Coco|Gianluca|G|
Salerno|Laura|L|
Franchina|Vittoria|V|
La Tona|Antonino|A|
Di Blasi|Maria|M|
Giordano|Cecilia|C|

Fear of Missing Out
Adolescents
Smartphone addiction
Emotional regulation
Autoregressive cross-lagged panel
Longitudinal modeling


Evaluating the MESSAGE Communication Strategies in Dementia training for use with community-based aged care staff working with people with dementia: a controlled pretest-post-test study.

Abstract:
AIMS AND OBJECTIVES
The study aims to evaluate the effects of a communication skills training programme on community aged care staff's knowledge of communication support in dementia and on staff's care experience.

BACKGROUND
Dementia can lead to impairments in communication. Therefore, quality community-based dementia care requires that staff be skilled communicators, equipped to facilitate interactions with people with dementia. The current investigation evaluated the effectiveness of the MESSAGE Communication Strategies in Dementia for Care Staff training programme with respect to knowledge of communication support and the staff/caregiver experience.

DESIGN
A multi-centre controlled pretest/post-test design with randomised cohort allocation was used. Outcome measures were completed at baseline, immediately after training (training group only), and at three-month follow-up.

METHODS
Thirty-eight care staff working in community aged care participated and completed all outcome measures (training = 22; control = 16).Training and control groups completed the following outcome measures: knowledge of communication support strategies, self-efficacy, preparedness to provide care, strain in nursing care and attitude to dementia care. Staff in the training group provided written feedback on the training.

RESULTS
A significant improvement in knowledge scores from baseline was found for the training group both immediately after training and at three-month follow-up. There was also a significant training effect for self-efficacy and preparedness to provide care. No significant difference was found for the control group for any measure. No significant training effects were found for measures of strain or attitudes to dementia care. Feedback from staff suggests that the training was well received.

CONCLUSIONS
The MESSAGE training was positively received by staff and had a significant effect on care staff knowledge, and confidence to provide care for people with dementia.

RELEVANCE TO CLINICAL PRACTICE
The easily accessible multimedia training programme is well received by staff and has the potential to improve quality of care.

communication
dementia
aged care
dementia care
community care
education


Structure of the Extracellular Region of the Bacterial Type VIIb Secretion System Subunit EsaA.

Abstract: Gram-positive bacteria use type VII secretion systems (T7SSs) to export effector proteins that manipulate the physiology of nearby prokaryotic and eukaryotic cells. Several mycobacterial T7SSs have established roles in virulence. By contrast, the genetically distinct T7SSb pathway found in Firmicutes bacteria more often functions to mediate bacterial competition. A lack of structural information on the T7SSb has limited the understanding of effector export by this protein secretion apparatus. Here, we present the 2.4 Å crystal structure of the extracellular region of the T7SSb subunit EsaA from Streptococcus gallolyticus. Our structure reveals that homodimeric EsaA is an elongated, arrow-shaped protein with a surface-accessible "tip", which in some species of bacteria serves as a receptor for lytic bacteriophages. Because it is the only T7SSb subunit large enough to traverse the peptidoglycan layer of Firmicutes, we propose that EsaA plays a critical role in transporting effectors across the entirety of the Gram-positive cell envelope.

Klein|Timothy A|TA|
Grebenc|Dirk W|DW|
Gandhi|Shil Y|SY|
Shah|Vraj S|VS|
Kim|Youngchang|Y|
Whitney|John C|JC|

D000072417:Protein Domains
D034367:Streptococcus intermedius
D000069377:Type VII Secretion Systems

type VII secretion
T7SSb
X-ray crystallography
bacterial pathogenesis
bacterial protein secretion
interbacterial antagonism
microbe-microbe interactions
protein structure/function


Pulse pressure does not predict the response of diabetic nephropathy to glucose-lowering therapy.

Abstract: We aimed to study whether pulse pressure (PP) predicts the response of diabetic nephropathy to glucose-lowering treatment. Patients with uncontrolled type 2 diabetes were followed for decrease in albuminuria after insulin/oral-hypoglycemic treatment. A total of 143 patients were followed for a median time of 10.5 months in a cohort study. Fasting blood sugar and HbA1C significantly decreased, while systolic, diastolic and pulse pressures remained constant during intervention. Median albuminuria decreased from 18.4 mg/day [10-40] to 16.4 mg/day [9-28] at the end of study (p-value < 0.005). The number of patients with normo/micro/macro-albuminuria changed from 98/36/9 to 108/31/4 (p-value < 0.001). No significant difference in baseline PP (47.5 ± 1.61 vs. 45.9 ± 1.81 mmHg; p-value = 0.51) or final PP (47.0 ± 2.41 vs. 49.4 ± 2.38 mmHg; p-value = 0.47) existed between those with decreased and increased albuminuria. PP was not a significant predictor of albuminuria changes in receiver operating characteristic curve (p-value = 0.77) and regression (p-value = 0.98) analyses. Benefits of glycemic control in diabetic nephropathy are independent of PP.

Nakhjavani|Manouchehr|M|
Nargesi|Arash Aghajani|AA|
Heidari|Behnam|B|
Ghazizadeh|Zaniar|Z|
Larry|Mehrdad|M|
Esteghamati|Alireza|A|

D000419:Albuminuria
D019540:Area Under Curve
D015415:Biomarkers
D001786:Blood Glucose
D001794:Blood Pressure
D003924:Diabetes Mellitus, Type 2
D003928:Diabetic Nephropathies
D015536:Down-Regulation
D005260:Female
D006801:Humans
D007004:Hypoglycemic Agents
D008297:Male
D008875:Middle Aged
D011237:Predictive Value of Tests
D012372:ROC Curve
D012307:Risk Factors
D013997:Time Factors
D016896:Treatment Outcome

Pulse pressure
nephropathy
type 2 diabetes
albuminuria


Reliability and validity of the SE-HEPA: examining physical activity--and healthy eating-specific self-efficacy among a sample of preadolescents.

Abstract:
OBJECTIVE
The purpose of this study was to examine the psychometric properties of the self-efficacy for healthy eating and physical activity measure (SE-HEPA) for preadolescents.

METHOD
The reliability of the measure was examined to determine if the internal consistency of the measure was adequate (i.e., αs > .70). Next, in an effort to determine if a two-factor model was a better fit than a one-factor model, as hypothesized, an exploratory factor analysis in a confirmatory factor analysis framework was used to determine model fit. Additionally, the criterion-related validity of the measure was evaluated by conducting correlational analyses to determine if SE-HEPA scores were associated with preadolescent body mass index.

RESULTS
Consistent with the hypotheses, Cronbach's alphas indicated good reliability for the measure (i.e., αs > .70) and factor analyses indicated the two-factor model provided a better fit than the one-factor model. Additionally, correlations revealed a significant relationship between the two factors (i.e., healthy eating, physical activity) and preadolescent body mass index.

CONCLUSIONS
The SE-HEPA will allow researchers and clinicians to better understand self-efficacy for behaviors important to weight loss among preadolescents. This could, in turn, inform future efforts aimed at increasing behaviors that promote healthy weight status among this population within the context of family-based weight loss programs.

Steele|Michael M|MM|
Burns|Leonard G|LG|
Whitaker|Brandi N|BN|

self-efficacy
preadolescent
health behavior
obesity
weight management


Managing scientific diving operations in a remote location: the Canadian high Arctic.

Abstract: Global climate change is expected to alter the Arctic bioregion markedly in coming decades. As a result, monitoring of the expected and actual changes has assumed high scientific significance. Many marine science objectives are best supported with the use of scientific diving techniques. Some important keystone environments are located in extremely remote locations where land-based expeditions offer high flexibility and cost-effectiveness over ship-based operations. However, the extreme remoteness of some of these locations, coupled with complex and unreliable land, sea and air communications, means that there is rarely quick access (< 48 h) to any specialized diving medical intervention or recompression. In 2009, a land based expedition to the north end of Baffin Island was undertaken with the specific aim of establishing an inventory of the diversity of seaweeds and their pathogens that was broadly representative of a high Arctic marine environment. This account highlights some of the logistical considerations taken on that expedition; specifically it outlines the non-recompression treatment pathway that would have been adopted in the event of a diver suffering decompression illness.

Sayer|Martin D J|MD|
Küpper|Frithjof C|FC|
van West|Pieter|P|
Wilson|Colin M|CM|
Brown|Hugh|H|
Azzopardi|Elaine|E|

Scientific diving
remote locations
decompression illness
first aid
injuries
medical kits
oxygen


Engagement and Adherence With ezPARENT, an mHealth Parent-Training Program Promoting Child Well-Being.

Abstract: Mobile health (mHealth) interventions use mobile technology (tablets and smartphones) delivery platforms for interventions to improve health outcomes. Despite growing acceptance, there is little understanding of how consumers engage with and adhere to mHealth interventions. This study analyzes usage data from the intervention arm ( n = 42) of a randomized clinical trial testing the efficacy of the ezPARENT program and provides recommendations for using engagement and adherence metrics. Engagement was measured by parent usage (duration, frequency, and activity) of ezPARENT and adherence using an adherence index (the sum of individual modules completed, number of visits to ezPARENT, and maximum time between visits). Parents spent M = 37.15 min per module and had M = 13.55 program visits in the 3-month intervention period. Parents visited the program over a period of M = 69.5 days and completed 82% of the modules. These data provide support that parents will use intervention programs delivered digitally; engagement and adherence metrics are useful in evaluating program uptake.

parenting
intervention research
service delivery


Autoimmune and Rheumatic Manifestations Associated With COVID-19 in Adults: An Updated Systematic Review.

Abstract: Background: Numerous cases of the coronavirus disease 2019 (COVID-19) with autoimmune and rheumatic manifestations have been reported. Despite the available reviews that summarized its autoimmune/rheumatic manifestations, a systematic approach is still lacking. Therefore, we conducted a comprehensive systematic review in order to give an overview upon these rare but clinically significant manifestations. Methods: We performed a literature search of PubMed and EMBASE as of October 9, 2020. All articles relevant to either systemic or organ-specific autoimmune and rheumatic manifestations potentially associated with COVID-19 were collected. The reviewed literature were limited to adults ≥18 years. Results: Although most of the existing evidence was based on case reports or case series without a long-term follow-up, a variety of autoimmune/rheumatic manifestations were associated with COVID-19. The manifestations that have a consistent association with COVID-19 include autoimmune cytopenia, cutaneous vasculitis, encephalitis, and Guillain-Barre syndrome. Such association is conflicting as regards to antiphospholipid syndrome, hemophagocytic lymphohistiocytosis, and myasthenia gravis. Conclusion: Our systematic review indicated the potential of the COVID-19 virus to trigger a myriad of autoimmune and rheumatic manifestations, which should be considered amid global efforts to combat COVID-19.


Targets to increase food production: One Health implications.

Abstract: The increasing world population means that there is a requirement to expand global food production. Looking at the Republic of Ireland as an example, the risks and opportunities associated with the expansion of food production are outlined, particularly in relation to zoonoses transmission. A One Health approach to sustainable food production is required to avert a potential public health problem associated with increased agricultural expansion.

McMahon|Barry J|BJ|
Wall|Patrick G|PG|
Fanning|Séamus|S|
Fahey|Alan G|AG|

food production
One health
zoonoses
ecosystem services


Caesium bis(5-bromosalicylaldehyde thiosemicarbazonato-κ3O,N,S)ferrate(III): supramolecular arrangement of low-spin FeIII complex anions mediated by Cs+ cations.

Abstract: The synthesis and crystal structure determination (at 293 K) of the title complex, Cs[Fe(C(8)H(6)BrN(3)OS)(2)], are reported. The compound is composed of two dianionic O,N,S-tridentate 5-bromosalicylaldehyde thiosemicarbazonate(2-) ligands coordinated to an Fe(III) cation, displaying a distorted octahedral geometry. The ligands are orientated in two perpendicular planes, with the O- and S-donor atoms in cis positions and the N-donor atoms in trans positions. The complex displays intermolecular N-H...O and N-H...Br hydrogen bonds, creating R4(4)(18) rings, which link the Fe(III) units in the a and b directions. The Fe(III) cation is in the low-spin state at 293 K.

Powell|Robyn Elizabeth|RE|
Schwalbe|Carl H|CH|
Tizzard|Graham J|GJ|
Koningsbruggen|Petra J van|PJ|

crystal structure
FeIII coordination compound
caesium salt
low-spin state FeIII
salicylaldehyde thiosemicarbazone
spin-crossover behaviour


Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow-Generated Diazo Compounds and Propargylated Amines.

Abstract: We report herein the asymmetric coupling of flow-generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10-20 minutes with high enantioselectivity (89-98 % de/ee), moderate yields and a wide functional group tolerance.

allenes
diazo compounds
copper
asymmetric catalysis
flow chemistry


Comprehensive assessment of water quality through different approaches: Physicochemical and ecotoxicological parameters.

Abstract: Traditionally, water quality was assessed by physicochemical parameters. However, a more comprehensive analysis is needed to study the effects of polluted water bodies on key species over time. So, the aim of this study was to monitor through physicochemical and ecotoxicological indicators the surface water quality of four study sites with different land uses from the lower Paraná river basin (Argentina) during spring and summer of two years: Morejón stream (S1), De la Cruz stream upstream (S2), downstream (S3) and Arrecifes river (S4). Physicochemical parameters were measured in situ and in laboratory, and a Water Quality Index (WQI) was calculated. Chronic toxicity bioassays were performed with surface water samples using Rhinella arenarum embryos and larvae. Also, oxidative stress (catalase, superoxide dismutase, glutathione S-transferase, reduced glutathione and lipid peroxidation), neurotoxicity (butyrylcholinesterase) and genotoxicity (micronuclei frequency) biomarkers were measured at acute exposure, and an Integrated Biomarkers Response (IBR) index was calculated. The water quality varied between excellent and bad in S1, good and bad in S2 and S3, and bad and marginal in S4. S1 presented the greatest variability of pesticides and S4 the highest number of metals exceeding the limits for the local protection of aquatic life. Mainly, S4 caused lethality in R. arenarum larvae, reaching a maximum mortality of 83.3% at 504 h of exposure. The lethal toxicity of S1 and S2 varied between periods. Water samples from all sites altered the oxidative stress, neurotoxicity and genotoxicity biomarkers, and the IBR was negatively correlated with the WQI. The IBR reflected the effects of the degraded water quality on the exposed organisms. So, the importance of evaluating both physicochemical and ecotoxicological parameters to analyze integrally the water quality of polluted areas is highlighted. A degradation of the studied water bodies and its negative impact to the native amphibian R. arenarum were observed.

Peluso|Julieta|J|
Pérez Coll|Cristina S|CS|
Cristos|Diego|D|
Rojas|Dante E|DE|
Aronzon|Carolina M|CM|

Water quality
Toxicity bioassays
Biomarkers
Amphibians


Conjugated polymers nanostructured as smart interfaces for controlling the catalytic properties of enzymes.

Abstract: The search for new molecular architectures to improve the efficiency of enzymes entrapped in ultrathin films is useful to enhance the effectiveness of biosensors. In this present work, conjugated polymers, based on thiophene and fluorine, were investigated to verify their suitability as matrices for the immobilization of urease. The copolymer poly[(9,9-dioctylfluorene)-co-thiophene], PDOF-co-Th was spread on the air-water interface forming stable Langmuir monolayers as determined by surface pressure-area isotherms, polarization-modulation reflection-absorption infrared spectroscopy (PM-IRRAS), and Brewster angle microscopy (BAM). Urease was incorporated in the floating monolayers being further transferred to solid supports as mixed Langmuir-Blodgett (LB) films. These films were then characterized with transfer ratio, fluorescence spectroscopy, PM-IRRAS and atomic force microscopy, confirming the co-transfer of the enzyme as well as its structuring in β-sheets. The catalytic activity was detected for urease, with a lower reaction rate than that encountered for the homogeneous environment. This was attributed to conformational constraints imposed to the biomacromolecule entrapped in the polymeric matrix.

Barbosa|Camila Gouveia|CG|
Caseli|Luciano|L|
Péres|Laura Oliveira|LO|

Conjugated polymer
Biosensor
Urease
Langmuir-Blodgett
Enzyme activity


Crystal structure of 5-chloro-1,3-bis-[2-(2-oxo-1,3-oxazolidin-3-yl)eth-yl]-1H-benz-imidazol-2(3H)-one.

Abstract: In the title compound, C17H19ClN4O5, the benzimidazole fused-ring system is essentially planar, the maximum deviation from the mean plane being 0.06 (1) Å. Both oxazolidine rings are nearly planar, the maximum deviations from the mean planes are 0.071 (13) and 0.070 (10) Å. The dihedral angle between the mean planes of the oxazolidine rings is 69.9 (7)°. The benzimidazole mean plane makes the dihedral angles of 43.9 (6) and 45.6 (6)° with the two oxazolidine rings. In the crystal, the mol-ecules are linked together by weak C-H⋯O hydrogen bonds building zigzag tapes running along the c axis. The Cl atom is split over two positions with an occupancy ratio of 0.567 (7):0.433 (7). This means that the reaction yields two isomers, A and B; the A component has the Cl-atom substituent in the 5-position of the benzimidazolone ring and the B component has the Cl atom in the 6-position. The two isomers form the disordered co-crystal, with a nearly half Cl atom in each of them, as indicated by the occupancy ratio. The crystal structure was refined as an inversion twin.

Bouayad|Kaoutar|K|
Kandri Rodi|Youssef|Y|
Ouzidan|Youness|Y|
Essassi|El Mokhtar|el M|
Saadi|Mohamed|M|
El Ammari|Lahcen|L|

crystal structure
hydrogen bonding
benzimidazol-2-one derivative


CRUSADE bleeding risk score validation for ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Abstract:
INTRODUCTION
The CRUSADE bleeding risk score (CBRS) accurately predicts major bleeding in non-ST segment elevation myocardial infarction NSTEMI patients. However, little information exists about its application in ST segment elevation myocardial infarction STEMI. We aimed to assess the ability of CBRS to predict in-hospital major bleeding in STEMI patients undergoing primary percutaneous coronary intervention (PPCI).

MATERIALS AND METHODS
We prospectively analyzed consecutive STEMI patients undergoing PPCI. Baseline characteristics, in-hospital complications and mid term mortality were recorded. Major bleeding was defined by the CRUSADE definition. Predictive ability of the CBRS was assessed by logistic regression method and the area under the ROC curve (AUC).

RESULTS
We included 1064 patients (mean age 63years). Mean CBRS value was 24. Most of patients (740/1064 (69.6%)) were in the two lowest risk quintiles of CBRS. Incidence of in-hospital major bleeding was 33/1064 (3.1%). The rates of in-hospital bleeding across the quintiles of risk groups were 0.4% (very low risk), 2.6% (low), 4.6% (moderate), 7.2% (high), and 13.4% (very high) (p 0.001). AUC was 0.80 (95% CI 0.73-0.87 p 0.001). In patients with radial access angiography (n=621) AUC was 0.81 (95% CI: 0.65-0.97). Mean follow up was 344days. Patients with bleeding events had higher mortality during follow up (HR 6.91; 95% CI 3.72-12.82; p 0.001).

CONCLUSIONS
Our patients had a significantly lower bleeding risk as compared to CRUSADE NSTEMI population. CBRS accurately predicted major in-hospital bleeding in this different clinical scenario, including patients with radial artery approach.

Ariza-Solé|Albert|A|
Sánchez-Elvira|Guillermo|G|
Sánchez-Salado|José C|JC|
Lorente-Tordera|Victoria|V|
Salazar-Mendiguchía|Joel|J|
Sánchez-Prieto|Remedios|R|
Romaguera-Torres|Rafael|R|
Ferreiro-Gutiérrez|José L|JL|
Gómez-Hospital|Joan A|JA|
Cequier-Fillat|Angel|A|

Non-ST segment elevation myocardial infarction


Integrating Monitoring of Volume Status and Blood Volume-Controlled Ultrafiltration into Extracorporeal Kidney Replacement Therapy.

Abstract:
Purpose
Volume management in hemodialysis (HD) requires the ability to assess volume status objectively and determine treatment strategies that achieve euvolemia without compromising hemodynamic stability. The aim of this study was to compare dialysis with and without blood volume-controlled ultrafiltration (UF) in combination with body composition monitoring, and to evaluate indicators for adequate dialysis (Kt/V), ultrafiltration volume, fluid status, and the occurrence of intradialytic morbid events (IME).

Patients and Methods
Patients undergoing hemodialysis or on-line hemodiafiltration with support of a blood volume monitor (BVM) - a feedback control device integrated into the 5008 and 6008 HD systems - were enrolled. Patients received treatment for four weeks using the 6008 CAREsystem and the BVM (6008+). Data on dialysis dose (Kt/V), UF volume and predialysis fluid status were documented. This data was also documented retrospectively for four weeks with (5008+) and without (5008-) the use of the BVM with the 5008 system. Comparisons were analyzed using linear mixed models.

Results
Twenty-four patients were enrolled. Kt/V was unaffected by blood volume-controlled UF (5008- vs 5008+: p=0.230) and was equally achieved with both HD systems (5008+ vs 6008+: p=0.922). The UF volume and fluid status achieved were comparable, independent of the use of UF control with BVM (5008- vs 5008+; UF volume: p=0.166; fluid overload: p=0.390) or the HD system (5008+ vs 6008+: UF volume: p=0.003; fluid overload: p=0.838), except for UF volume being higher in the 6008+ phase. IMEs occurred in less than 3% of treatments, with no difference between study phases.

Conclusion
This study demonstrates that a clinical approach to kidney replacement therapy that tracks volume status and manages intradialytic fluid removal by blood volume-controlled UF delivers adequate dialysis without compromising fluid removal. It maintains volume status and ensures low incidence of IMEs.

Zschätzsch|Sebastian|S| Stauss-Grabo|Manuela|M| Gauly|Adelheid|A|0000-0002-2554-0711 Braun|Jennifer|J|

body composition monitoring
fluid status
intradialytic morbid events
blood volume monitoring
dialysis dose


Suppression of Cisplatin-Induced Vomiting by Cannabis sativa in Pigeons: Neurochemical Evidences.

Abstract: Cannabis sativa (CS, family Cannabinaceae) has been reported for its anti-emetic activity against cancer chemotherapy-induced emesis in animal models and in clinics. The current study was designed to investigate CS for potential effectiveness to attenuate cisplatin-induced vomiting in healthy pigeons and to study the impact on neurotransmitters involved centrally and peripherally in the act of vomiting. High-performance liquid chromatography system coupled with electrochemical detector was used for the quantification of neurotransmitters 5-hydroxytryptamine (5HT), dopamine (DA) and their metabolites; Di-hydroxy Phenyl Acetic acid (Dopac), Homovanillic acid (HVA), and 5-hydroxy indole acetic acid (5HIAA) centrally in specific brain areas (area postrema and brain stem) while, peripherally in small intestine. Cisplatin (7 mg/kg i.v.) induce emesis without lethality across the 24 h observation period. CS hexane fraction (CS-HexFr; 10 mg/kg) attenuated cisplatin-induced emesis ∼ 65.85% (P < 0.05); the reference anti-emetic drug, metoclopramide (MCP; 30 mg/kg), produced ∼43.90% reduction (P < 0.05). At acute time point (3rd h), CS-HexFr decreased (P < 0.001) the concentration of 5HT and 5HIAA in the area postrema, brain stem and intestine, while at 18th h (delayed time point) CS-HexFr attenuated (P < 0.001) the upsurge of 5HT caused by cisplatin in the brain stem and intestine and dopamine in the area postrema. CS-HexFr treatment alone did not alter the basal neurotransmitters and their metabolites in the brain areas and intestine except 5HIAA and HVA, which were decreased significantly. In conclusion the anti-emetic effect of CS-HexFr is mediated by anti-serotonergic and anti-dopaminergic components in a blended manner at the two different time points, i.e., 3rd and 18th h in pigeons.

Ullah|Ihsan|I| Subhan|Fazal|F| Alam|Javaid|J| Shahid|Muhammad|M| Ayaz|Muhammad|M|

Cannabis sativa
pigeon
emesis
neurotransmitters
cisplatin


Bioresorbable polyelectrolytes for smuggling drugs into cells.

Abstract: There is ample evidence that biodegradable polyelectrolyte nanocapsules are multifunctional vehicles which can smuggle drugs into cells, and release them upon endogenous activation. A large number of endogenous stimuli have already been tested in vitro, and in vivo research is escalating. Thus, the interest in the design of intelligent polyelectrolyte multilayer (PEM) drug delivery systems is clear. The need of the hour is a systematic translation of PEM-based drug delivery systems from the lab to clinical studies. Reviews on multifarious stimuli that can trigger the release of drugs from such systems already exist. This review summarizes the available literature, with emphasis on the recent progress in PEM-based drug delivery systems that are receptive in the presence of endogenous stimuli, including enzymes, glucose, glutathione, pH, and temperature, and addresses different active and passive drug targeting strategies. Insights into the current knowledge on the diversified endogenous approaches and methodological challenges may bring inspiration to resolve issues that currently bottleneck the successful implementation of polyelectrolytes into the catalog of third-generation drug delivery systems.

endogenous stimuli
drug delivery
active and passive targeting
bioencapsulation
layer-by-layer method


Comparing incidences of infusion site reactions between brand-name and generic vinorelbine in patients with non-small cell lung cancer.

Abstract:
AIM
This study aimed to compare the incidence of infusion site reactions (ISRs) induced by intravenous administration of brand-name and generic vinorelbine (VNR) for treating non-small cell lung cancer.

METHOD
This single-centre retrospective cohort study was conducted by medical chart review of VNR infusions. ISRs were defined as symptoms around the infusion site, including pain, redness and swelling. ISRs requiring treatment were defined as ISRs requiring treatments including steroid ointments, vein repuncture and local steroid injections.

RESULTS
In all, 1973 VNR infusions were administered to 340 patients (brand-name 141 patients, generic 199 patients). ISRs and ISRs requiring treatment were observed in 161 and 100 patients, respectively. The ISR incidence per patient and per injection was significantly higher in generic VNR-treated patients than in brand-name VNR-treated patients (53.3% vs 39.0%, P = 0.0112 and 15.0% vs 9.9%, P = 0.0008, respectively). The frequency of ISRs requiring treatment was also significantly higher in the generic group (per patient 36.7% vs 19.2%, P = 0.0005; per injection 11.3% vs 5.5%, P < 0.0001). Multivariate analysis revealed that generic VNR was significantly associated with an increased risk of ISRs (per patient adjusted odds ratio [AOR] 1.775, P = 0.0155; per injection AOR 1.672, P = 0.004) and ISRs requiring treatment (per patient AOR 2.422, P = 0.0012; per injection AOR 2.286, P = 0.001).

CONCLUSION
Intravenous infusion of generic VNR was associated with an increased risk of ISRs. Further research is needed to elucidate the mechanism underlying the increased incidence of ISRs with generic VNR.

Ozawa|Naoya|N|0000-0002-2833-2125 Hase|Tetsunari|T|0000-0002-9653-8424 Hatta|Takahiro|T| Sagara|Atsunobu|A| Ichikawa|Kazuya|K| Miyazaki|Masayuki|M| Yogo|Naoyuki|N| Ando|Masahiko|M| Hashimoto|Naozumi|N| Yamada|Kiyofumi|K| Hasegawa|Yoshinori|Y|

infusion site reaction
generic vinorelbine
brand-name vinorelbine


Does diabetes mellitus comorbidity affect in-hospital mortality and length of stay? Analysis of administrative data in an Italian Academic Hospital.

Abstract:
AIMS
Hospitalized patients with comorbid diabetes mellitus may have worse outcomes than the others. We conducted a study to assess whether comorbid diabetes affects in-hospital mortality and length of stay.

METHODS
For this population-based study, we analyzed the administrative databases of the Regional Health Information System of the Region Friuli Venezia Giulia, where the Hospital of Udine is located. Hospital discharge data were linked at the individual patient level with the regional Diabetes Mellitus Registry to identify diabetic patients. For each 3-digit ICD-9-CM discharge diagnosis code, we assessed the difference in length of stay and in-hospital mortality between diabetic and non-diabetic patients. We conducted both univariate and multivariate analyses, adjusted for age, sex, Charlson's comorbidity score, and urgency of hospitalization, through linear and logistic regression models.

RESULTS
After adjusting for potential confounders, diabetes significantly increased the risk of in-hospital death among patients hospitalized for bacterial pneumonia (OR = 1.94) and intestinal obstruction (OR = 4.23) and length of stay among those admitted for several diagnoses, including acute myocardial infarction and acute renal failure. Admission glucose blood level was associated with in-hospital death in patients with pneumonia and intestinal obstruction, and increased length of stay for several conditions.

CONCLUSIONS
Patients with diabetes mellitus who are hospitalized for other health problems may have increased risk of in-hospital death and longer hospital stay. For this reason, diabetes should be promptly recognized upon admission and properly managed.

Diabetes mellitus
In-hospital mortality
Length of stay
Administrative data
Hospitalization


Efferent and afferent connections of the olfactory bulb and prepiriform cortex in the pigeon (Columba livia).

Abstract: Although olfaction in birds is known to be involved in a variety of behaviors, there is comparatively little detailed information on the olfactory brain. In the pigeon brain, the olfactory bulb (OB) is known to project to the prepiriform cortex (CPP), piriform cortex (CPi), and dorsolateral corticoid area (CDL), which together are called the olfactory pallium, but centrifugal pathways to the OB have not been fully explored. Fiber connections of CPi and CDL have been reported, but those of other olfactory pallial nuclei remain unknown. The present study examines the fiber connections of OB and CPP in pigeons to provide a more detailed picture of their connections using tract-tracing methods. When anterograde and retrograde tracers were injected in OB, projections to a more extensive olfactory pallium were revealed, including the anterior olfactory nucleus, CPP, densocellular part of the hyperpallium, tenia tecta, hippocampal continuation, CPi, and CDL. OB projected commissural fibers to the contralateral OB but did not receive afferents from the contralateral olfactory pallium. When tracers were injected in CPP, reciprocal ipsilateral connections with OB and nuclei of the olfactory pallium were observed, and CPP projected to the caudolateral nidopallium and the limbic system, including the hippocampal formation, septum, lateral hypothalamic nucleus, and lateral mammillary nucleus. These results show that the connections of OB have a wider distribution throughout the olfactory pallium than previously thought and that CPP provides a centrifugal projection to the OB and acts as a relay station to the limbic system.

bird
olfactory pallium
limbic system
fiber organization


Evaluation of a commercial liquid-chromatography high-resolution mass-spectrometry method for the determination of hepcidin-25.

Abstract:
Introduction
Reliable determination of hepcidin-25, a key regulator of iron metabolism, is important. This study aimed at evaluating the performance of the Hepcidin-25 Liquid Chromatography-Tandem Mass-Spectrometry (LC-MS/MS) Kit (Immundiagnostik AG, Bensheim, Germany) for quantification of the hepcidin-25 protein.

Materials and methods
Precision, accuracy, linearity, and preanalytical requirements of the liquid-chromatography high-resolution mass-spectrometry (LC-HR-MS) method were evaluated. The imprecision and bias acceptance criteria were defined ≤ 15%. We investigated sample stability at room temperature (RT) and after repeated freeze and thaw cycles. Additionally, we assessed serum hepcidin-25 concentrations of 165 healthy adults referred for a medical check-up.

Results
The hepcidin-25 LC-MS/MS assay was linear over the concentration range of 3 - 200 ng/mL. Within- and between-run precision ranged between 1.9 - 8.6% and 5.1 - 12.4%, respectively. The mean bias of the low and high control material was - 2.7% and 2.1%, respectively. At RT, serum samples were stable for 3 h (mean bias + 0.3%). After two and three freeze and thaw cycles, hepcidin-25 concentrations showed a bias of + 8.0 and + 20%, respectively. Of 165 healthy adults, 109 females had a significantly lower median of 8.42 (range: 1.00 - 60.10) ng/mL compared to 56 males with 15.76 (range: 1.50 - 60.50) ng/mL (P = 0.002).

Conclusions
The hepcidin-25 LC-MS/MS kit shows a broad analytical range and meets the imprecision and bias acceptance criteria of ≤ 15%. Serum samples can be stored at RT for 3 h and resist up to two freeze and thaw cycles.

Enko|Dietmar|D| Zelzer|Sieglinde|S| Fauler|Günter|G| Herrmann|Markus|M|

D002851:Chromatography, High Pressure Liquid


Role of CYP3A in regulating hepatic clearance and hepatotoxicity of triptolide in rat liver microsomes and sandwich-cultured hepatocytes.

Abstract: Triptolide (TP) is an active component of Tripterygium wilfordii Hook. F and widely used to treat autoimmune and inflammatory diseases. It has been demonstrated that cytochrome P450 (CYP) are involved in the metabolism of TP. However, the underlying mechanisms of TP-induced toxicity mediated by hepatic CYP have not been well delineated. In this study, rat liver microsomes (RLM) and sandwich-cultured rat hepatocytes (SCRH) were used to identify the mechanism involving the CYP3A inhibition by TP and to evaluate TP-induced liver damage after CYP3A modulation by the known inhibitor, ketoconazole, and the known inducer, dexamethasone. The results showed that TP itself had a time- and concentration-dependent inhibitory effect on CYP3A. When the CYP3A inhibitor and inducer were added, the enzyme activity and hepatotoxicity changed significantly. The enzyme inducer increased CYP3A activity and decreased the metabolic half life (t1/2) of TP when compared to the control group, while the enzyme inhibitor had an opposite effect. Our findings reveal that TP is a weak CYP3A inhibitor involving the time-dependent inhibition mechanism. The induction or inhibition of CYP3A played an important role in TP-induced hepatotoxicity. Clinicians should be aware of the metabolic characteristics of TP to maximize therapeutic efficacy and reduce TP-induced toxicity.

Shen|Guolin|G| Zhuang|Xiaomei|X| Xiao|Weibin|W| Kong|Linglei|L| Tan|Yan|Y| Li|Hua|H|

D065692:Cytochrome P-450 CYP3A Inhibitors

CYP3A
Hepatotoxicity
Triptolide
Liver microsomes
Sandwich-cultured hepatocytes
Metabolism


Amazon forest-to-agriculture conversion alters rhizosphere microbiome composition while functions are kept.

Abstract: The conversion of native forest to agriculture is the main cause of microbial biodiversity loss in Amazon soils. In order to better understand this effect, we used metagenomics to investigate microbial patterns and functions in bulk soil and rhizosphere of soybean, in a long-term forest-to-agriculture conversion. Long-term forest-to-agriculture led to microbial homogenization and loss of diversity in both bulk soil and rhizosphere, mainly driven by decreasing aluminum concentration and increased cations saturation in soil, due to liming and fertilization in long-term no-till cropping. Data revealed that long-term no-till cropping culminated in a decrease in Acidobacteria, Actinobacteria and Proteobacteria abundances. However, α- and β-Proteobacteria abundances were higher in the rhizosphere than in bulk soil, regardless of the time after forest-to-agriculture conversion. Changes in functional potential occurred predominantly in bulk soil, with decreases in functions related to potassium metabolism and virulence, disease and defense, while functions related to nucleic acids metabolism increased. Functions in the soybean rhizosphere remained stable, except for those related to potassium metabolism, which decreased after 20-year no-till cropping. Together, our results show that the soybean root system selects microbial taxa via trade-offs, to maintain functional resilience in the rhizosphere microbiome over time.

Goss-Souza|Dennis|D|
Mendes|Lucas William|LW|
Borges|Clovis Daniel|CD|
Rodrigues|Jorge L M|JLM|
Tsai|Siu Mui|SM|

D003247:Conservation of Natural Resources

metagenomics
homogenization
soybean rhizosphere
Amazon biodiversity
plant microbiome


Systematic review and meta-analysis of efficacy and safety of hydroxychloroquine and chloroquine in the treatment of COVID-19.

Abstract: Repurposed drugs like hydroxycloroquine (HCQ) and chloroquine (CQ) are being tested for potential therapeutic role in COVID-19. We aimed to evaluate efficacy and safety of HCQ and CQ in COVID-19. Using PubMed, EMBASE, medRxiv, Google Scholar, clinicaltrials.gov, electronic search was carried out to identify relevant articles till June 2020 with re-evaluation in last week of November 2020. Observational and interventional clinical studies comparing efficacy of CQ or HCQ to standard management or other drug/s for SARS-CoV-2 infection patients were included. Cochrane review manager version 5.3 was used for synthesis of meta-analysis results. For randomized controlled trials, risk of bias was assessed using Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB-2). ROBINS-I was used for quality assessment of observational studies. Overall evidence quality generated by review was graded as per GRADE Recommendation. A total of 903 studies were screened. Nineteen studies were included in synthesis of meta-analysis with total of 4,693, 1,626, and 6,491 patients in HCQ/CQ, HCQ/CQ + AZ and control groups, respectively. HCQ/CQ treatment was associated with significantly increased rates of virological cure (OR = 2.08, 95%CI = 1.36-3.17; P = 0.0007) and radiological cure (OR = 3.89, 95%CI = 1.35 - 11.23; P = 0.01) compared to control. HCQ/CQ had no difference in unadjusted mortality rate (unadjusted OR = 0.98 95% CI = 0.70-1.37, P = 0.89, random effect model) and adjusted hazard ratio for mortality (adjusted HR = 1.05, 95%CI = 0.86--1.29; P = 0.64). However, a significant increase in odds of disease progression (OR = 1.77, 95%CI = 1.46-2.13; P < 0.00001) and QT prolongation (OR = 11.15, 95%CI = 3.95-31.44; P < 0.00001) was noted. The results with HCQ/CQ and azithromycin combination were similar to HCQ/CQ mono-therapy. In the light of contemporary evidence on effectiveness of HCQ/CQ, judicious and monitored use of HCQ/CQ for treatment of COVID-19 patients is recommended in low to middle income countries with emphasis on no mortality benefit. Registration number of Systematic review. Register in PROSPERO database: cRD42020187710.

Mittal|Niti|N|
Mittal|Rakesh|R|
Gupta|M C|MC|
Kaushal|Jyoti|J|
Chugh|Ankita|A|
Khera|Daisy|D|
Singh|Surjit|S|


Emerging Evidence of Translational Control by AU-Rich Element-Binding Proteins.

Abstract: RNA-binding proteins (RBPs) are key regulators of posttranscriptional gene expression and control many important biological processes including cell proliferation, development, and differentiation. RBPs bind specific motifs in their target mRNAs and regulate mRNA fate at many steps. The AU-rich element (ARE) is one of the major cis-regulatory elements in the 3' untranslated region (UTR) of labile mRNAs. Many of these encode factors requiring very tight regulation, such as inflammatory cytokines and growth factors. Disruption in the control of these factors' expression can cause autoimmune diseases, developmental disorders, or cancers. Therefore, these mRNAs are strictly regulated by various RBPs, particularly ARE-binding proteins (ARE-BPs). To regulate mRNA metabolism, ARE-BPs bind target mRNAs and affect some factors on mRNAs directly, or recruit effectors, such as mRNA decay machinery and protein kinases to target mRNAs. Importantly, some ARE-BPs have stabilizing roles, whereas others are destabilizing, and ARE-BPs appear to compete with each other when binding to target mRNAs. The function of specific ARE-BPs is modulated by posttranslational modifications (PTMs) including methylation and phosphorylation, thereby providing a means for cellular signaling pathways to regulate stability of specific target mRNAs. In this review, we summarize recent studies which have revealed detailed molecular mechanisms of ARE-BP-mediated regulation of gene expression and also report on the importance of ARE-BP function in specific physiological contexts and how this relates to disease. We also propose an mRNP regulatory network based on competition between stabilizing ARE-BPs and destabilizing ARE-BPs.

Otsuka|Hiroshi|H|
Fukao|Akira|A|
Funakami|Yoshinori|Y|
Duncan|Kent E|KE|
Fujiwara|Toshinobu|T|

translational control
RNA-binding proteins
AU-rich element
ARE-binding proteins
mRNA decay


Mayo, Myriad, America Invents Act and BPCIA: how has the United States biopharmaceutical market been affected?

Abstract: This paper discusses how the United States biopharmaceutical market has been affected by recent changes in patent law resulting from United States legislations (Biologics Price Competition and Innovation Act and the Leahy-Smith America Invents Act) and Supreme Court precedents (Mayo Collaborative Services v. Prometheus Laboratories, Inc. and Molecular Pathology v. Myriad Genetics). The authors interviewed eight key opinion leaders from the United States knowledgeable in biopharmaceuticals, including industry veterans, patent counsel, senior scientists and jurists. This paper summarizes the opinions of the key opinion leaders. This paper explains the impact of these Supreme Court decisions - i.e., broadening the exceptions to patent eligibility for law of nature and natural phenomenon - on biopharmaceutical innovations and provides future perspectives.

Finston|Susan K|SK|
Davey|Neil S|NS|
Davé|Elina|E|
Ravichandran|Varsha|V|
Davey|Sonya R|SR|
Davé|Raj S|RS|

D001688:Biological Products
D003955:Diagnostic Tests, Routine
D023281:Genomics
D006801:Humans
D010330:Patents as Topic
D035521:Supreme Court Decisions
D014481:United States

biopharmaceutical
patent eligibility
law of nature and natural phenomenon
BPCIA and AIA
DNA and cDNA
Mayo and Myriad
biologic and biosimilar
protein and peptide


The Impact of Human Pegivirus on CD4 Cell Count in HIV-Positive Persons in Botswana.

Abstract:
Background
Human pegiviruses (HPgV)-formerly known as hepatitis G virus or GB virus C (GBV-C)-are common single-stranded RNA viruses that may have a beneficial impact on slowing HIV disease progression. The data on HPgV in resource-limited regions such as Sub-Saharan Africa are scarce. Thus, we conducted the first study of HPgV in Botswana as part of a natural history study of HIV subtype C disease progression.

Methods
Plasma samples from 133 HIV-positive adults were evaluated for HPgV RNA, and the 5'UTR was sequenced to determine the HPgV genotype.

Results
HPgV RNA was detected in 41 (30.8%) individuals. While the presence of HPgV RNA had no impact on baseline HIV viral load, a significant difference in baseline CD4 cell count was observed. HPgV genotypes were determined for 27 individuals and included 5 individuals (18.5%) with genotype 1 and 22 (81.5%) with genotype 5. Baseline CD4 cell counts were significantly higher for persons infected with HPgV genotype 5 compared with genotype 1.

Conclusions
These data suggest that HPgV infection is common among HIV-positive individuals in Botswana and has a significant impact on CD4 cell count. This difference in CD4 cell count based on HPgV genotype suggests that HPgV genotype should be evaluated as a possible predictor of HIV disease progression and highlights the need for additional studies of this virus in resource-limited settings.

N'Guessan|Kombo F|KF|
Anderson|Motswedi|M|
Phinius|Bonolo|B|
Moyo|Sikhulile|S|
Malick|Alyyah|A|
Mbangiwa|Tshepiso|T|
Choga|Wonderful T|WT|
Makhema|Joseph|J|
Marlink|Richard|R|
Essex|Max|M|
Musonda|Rosemary|R|
Gaseitsiwe|Simani|S|
Blackard|Jason T|JT|

Botswana
hepatitis G virus
HIV
Africa
genotype
GB virus C (GBV-C)
human pegivirus (HPgV)


Kinematics of anterior cruciate ligament-deficient knees in a Chinese population during stair ascent.

Abstract:
BACKGROUND
The purpose of this study was to measure the tibiofemoral kinematics of anterior cruciate ligament (ACL) deficiency in a Chinese population and compare the kinematics with published data about a Caucasian population.

METHODS
Unilateral knees of 18 Chinese ACL-deficient (ACL-D) subjects were studied while subjects ascended stairs. Kinematic alteration was compared between ACL-D knees and contralateral ACL-intact (ACL-I) knees. The kinematic alteration of ACL deficiency was also compared between the Chinese population and published data about a Caucasian population.

RESULTS
A statistical difference was found in the three-dimensional rotations between ACL-D and ACL-I knees. In the sagittal plane, ACL-I knees had a larger flexion angle than ACL-D knees during 40 to 50 % of the activity during stair ascent (P < 0.027) and throughout the gait cycle. A significant difference in rotational motion between ACL-D and ACL-I knees was also observed in the frontal plane during 40 to 60 % (P < 0.017) of the activity and in the transverse plane during 70 to 80 % (P < 0.028) of the activity. A greater tibial varus was demonstrated in the Chinese population while the published data revealed external tibial rotation and a statistical difference in translation in the Caucasian population.

CONCLUSIONS
ACL-D knees show different kinematics than ACL-I knees in the Chinese population. ACL-I knees had a larger flexion angle than ACL-D knees in the middle stage of the activity during stair ascent. A significant difference in rotational motion between ACL-D and ACL-I knees was also observed in the frontal plane during the middle phase and in the transverse plane during the terminal phase of the activity. A greater tibial varus was demonstrated in the Caucasian population while the published data revealed external tibial rotation and a statistical difference in translation in the Caucasian population.

D000070598:Anterior Cruciate Ligament Injuries

Kinematics
Knee
Chinese
Anterior cruciate ligament
Gait


Mass spectrometry characterization of Commiphora leptophloeos leaf extract and preclinical evaluation of toxicity and anti-inflammatory potential effect.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Commiphora leptophloeos (Mart.) J.B. Gillett (Burseraceae) is a medicinal plant native from the brazilian northeast caatinga biome, known popularly as "imburana" or "imburana-de-cambão". The leaves of C. leptophloeos are widely used in folk medicine in the treatment of various inflammatory disorders. However, there is no scientific evidence to justify their popular use.

AIM OF THE STUDY
This approach aimed to characterize the phytochemical profile of hydroethanolic leaf extract, as well as evaluate the anti-inflammatory and antioxidant potential activity and to investigate the acute toxicity with pre-clinical in vitro and in vivo methodologies.

MATERIALS AND METHODS
The phytochemical profile was characterized by UPLC-MS and FIA-ESI-IT-MS/MS. The in vitro anti-inflammatory potential the hydroethanolic extract of C. leptophloeos (1, 10, 100 and 200 μg/mL) was investigated by lipopolysaccharide (LPS) induced nitric oxide assay, in order to analyze the potential decrease of nitric oxide (NO) production. For carrageenan-induced paw edema and zymosan-induced air pouch models, the extract (100, 200 and 400 mg/kg) was administrated by intragastric gavage (i.g.) route and used for evaluating the anti-inflammatory effect in vivo. Related to the first animal model, the antiedematogenic activity and myeloperoxidase (MPO) levels could be investigated. In addition, the zymosan-induced air pouch model allowed the analyses of leukocytes migration, total MPO, malondialdehyde (MDA) and cytokines (TNF-α and IL-10) levels. The toxicity in vitro of the extract (1, 10, 100 and 200 μg/mL) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acute toxicity in vivo was tested using the extract at 2000 mg/kg by i. g. route.

RESULTS
The phytochemical analyses of C. leptophloeos leaf extract pointed the presence of six glycosylated flavonoids, identified as orientin, isoorientin, vitexin and isovitexin, quercetrin and isoquercitrin. A decrease of NO in vitro was noticed by the use of the extract in the LPS-induced nitric oxide assay and an expressive reduction of the paw-edema followed by a decrease of myeloperoxidase activity at doses of 200 and 400 mg/kg. The zymosan-induced air pouch model indicated that the extract, in all doses, significantly reduced the leukocytes migration, total protein concentration, MPO and MDA levels. The levels of cytokines were verified by the administration of extract in this model, revealing a lower of TNF-α level and an increase of the IL-10 production. In the toxicity study, the MTT assay evidenced no cytotoxicity of the tested concentrations and acute toxicity in vivo test did not result in any sign of toxicity and mortality or significant changes on the biochemical parameters.

CONCLUSION
Based on these results, is possible suggest that the anti-inflammatory activity revealed in this approach can be related to the modulating the level of cytokine, decrease of TNF-α, increase of IL-10 in vivo and also the inhibition of the production of nitric oxide RAW 264.7 activated by LPS. These results demonstrate the potential anti-inflammatory effect C. leptophloeos leaf extrat in inflammatory in vivo models, supporting its use in folk medicine for treatment of inflammatory diseases. Finally, glycosylated flavonoids can be responsible, at least in part, for this effect.

Dantas-Medeiros|Renato|R|
Furtado|Allanny Alves|AA|
Zanatta|Ana C|AC|
Torres-Rêgo|Manoela|M|
Guimarães Lourenço|Estela Mariana|EM|
Ferreira Alves|Jovelina Samara|JS|
Galinari|Éder|É|
Alexandre de Oliveira Rocha|Hugo|H|
Bernardo Guerra|Gerlane Coelho|GC|
Vilegas|Wagner|W|
Antônio de Sousa Araújo|Thiago|T|
de Freitas Fernandes-Pedrosa|Matheus|M|
Zucolotto|Silvana Maria|SM|

Commiphora leptophloeos
Toxicity
Imburana
Antioxidant
Flavonoids
Inflammation