bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni
Authors: Eissa Maha Mohamed , El-Azzouni Mervat , El-Khordagui Labiba Khalil , Bary Amany Abdel , El-Moslemany Riham Mohamed , Salam Sara Ahmed Abdel 
Published: July 2020

Abstract
Background: The control of schistosomiasis has been centered to date on a single drug, praziquantel, with shortcomings including treatment failure, reinfection, and emergence of drug resistance. Drug repurposing, combination therapy or nanotechnology were explored to improve antischistosomal treatment. The aim of the present study was to utilize a novel combination of the three strategies to improve the therapeutic profile of praziquantel. This was based on a fixed dose nanocombination of praziquantel and miltefosine, an antischistosomal repurposing candidate, co-loaded at reduced doses into lipid nanocapsules, for single dose oral therapy.Methods: Two nanocombinations were prepared to provide 250 mg praziquantel-20 mg miltefosine/kg (higher fixed dose) or 125 mg praziquantel-10 mg miltefosine/kg (lower fixed dose) respectively. Their antischistosomal efficacy in comparison with nontreated control and their praziquantel or miltefosine singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, the 21st and 42nd days post infection. Scanning electron microscopic, parasitological and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukey post hoc test for pairwise comparisons.Results: Lipid nanocapsules (~58 nm) showed high entrapment efficiency of both drugs (>97%). Compared to singly loaded praziquantel-lipid nanocapsules, the higher dose nanocombination showed a significant increase in antischistosomal efficacy in terms of statistically significant decrease in mean worm burden, particularly against invasive and juvenile worms, and amelioration of hepatic granulomas (p ≤0.05). In addition, scanning electron microscopic examination showed extensive dorsal tegumental damage with noticeable deposition of nanostructures. Conclusions: The therapeutic profile of praziquantel could be improved by a novel multiple approach integrating drug repurposing, combination therapy and nanotechnology. Multistage activity and amelioration of liver pathology could be achieved by a new praziquantel-miltefosine fixed dose nanocombination providing 250 mg praziquantel-20 mg miltefosine/kg. To the best of our knowledge, this is the first report of a fixed dose nano-based combinatorial therapy for schistosomiasis mansoni. Further studies are needed to document the nanocombination safety and explore its prophylactic activity and potential to hinder the onset of resistance to the drug components.
A risk score based on pediatric Sequential Organ Failure Assessment predicts 90-day mortality in children with Klebsiella pneumoniae bloodstream infection
Authors: Li Shuang , Liu Jingxian , Chen Feng , Cai Kang , Tan Jintong , Xie Wei , Qian Rong , Liu Xiaoqin , Zhang Wenhong , Liu Ying , Huang Lisu 
Published: July 2020

Abstract
Background: Klebsiella pneumoniae bloodstream infection (Kp-BSI) is a serious threat to pediatric patients. The objective of this study was to explore the risk factors, validate the prediction efficiency of pediatric Sequential Organ Failure Assessment (SOFA) and establish better early predictors of mortality in pediatric patients with Kp-BSI. Methods: All children diagnosed with Kp-BSI were included in this retrospective cohort study from January 2009 to June 2019. Basic characteristics, symptoms and physical examinations, treatments, laboratory statistics, and SOFA at the onset of Kp-BSI were recorded. The Cox proportional hazard model and receiver operating characteristic curves were used to assess the association between the variables and the 90-day mortality and their predictive value. DeLong's test of receiver operating characteristic curves and integrated discrimination improvement index were used to determine the improvement in predictive capacity of the modified SOFA models. A predictive score was developed using multivariate logistic regression. Results: Of the 146 children enrolled, 33 (22.6%) patients died within 90 days. Hospitalization in the last six months, intra-abdominal source of infection, presence of organ failure, and altered levels of blood biomarkers, including C-reactive protein, albumin, and lactate were significant risk factors for 90-day mortality. The area under the curve (AUC) of SOFA for predicting 90-day mortality was 0.80 (95% CI 0.71–0.89). Moreover, we found that a prediction model combining SOFA with two other parameters, namely hospitalization in the last six months and intra-abdominal source of infection, was better at predicting mortality (AUC = 0.89, 95% CI 0.82–0.96; sensitivity = 0.86; specificity = 0.84). According to this novel risk model, we defined three statistically different groups: low-risk, medium-risk and high-risk groups, with an observed 90-day mortality of 5.4%, 35.7%, and 72.0%, respectively. With reference to the low-risk patients, the medium-risk and high-risk groups had a higher mortality, with hazard ratios of 8.36 (95% CI 3.60–27.83) and 20.27 (95% CI 7.47–54.95), respectively. Conclusions: The modified SOFA may be better than the original score to predict 90-day mortality in pediatric patients with Kp-BSI. Future prospective studies are required to validate this novel scoring system in external cohorts.
Can virtual reality improve traditional anatomy education programmes? A mixed-methods study on the use of a 3D skull model
Authors: Chen Shi , Zhu Jiawei , Cheng Cheng , Pan Zhouxian , Liu Lingshan , Du Jianhua , Shen Xinhua , Shen Zhen , Zhu Huijuan , Liu Jihai , Yang Hua , Ma Chao , Pan Hui 
Published: July 2020

Abstract
Background: Realistic, portable, and scalable lectures, cadaveric models, 2D atlases and computer simulations are being combined more frequently for teaching anatomy, resulting in major increases in user satisfaction. However, while digital simulations may be more portable, interesting, or motivating than traditional teaching tools, whether they are superior in terms of student learning remain unclear. This paper presents a study in which the educational effectiveness of a virtual reality (VR) skull model is compared with that of cadaveric skulls and atlases. The purpose of this study was to compare the results of teaching with VR to those of teaching with traditional teaching methods by administering objective questionnaires and perception surveys. Methods: A mixed-methods study with 73 medical students was carried out with three different groups: the VR skull (N=25), cadaveric skull (N=25) and atlas (N=23) groups. Anatomical structures were taught through an introductory lecture and model-based learning. All students completed the pre- and post-intervention tests, which were composed of a theory test and an identification test. Results: The participants in all three groups had significantly higher total scores on the post-intervention test than on the pre-intervention test; the post-interview test score in the VR group was not statistically significantly higher than those of the other groups (VR: 30 [22-33.5], cadaver: 26 [20-31.5], atlas: 28[20-33]; p=0.571). The participants in the VR and cadaver groups provided more positive feedback on their learning models than the atlas group (VR: 26 [19-30], cadaver: 25 [19.5-29.5], atlas: 12 [9-20]; p<0.0001).Conclusions: The skull VLR was equally efficient with cadaver skull and atlas in teaching anatomy structures. Such a model can aid individuals in understanding complex anatomical structures with a higher level of motivation and tolerable adverse effects.
Scaled-Up Nutrition Education on Pulse-Cereal Complementary Food Practice in Ethiopia: A Cluster-Randomized Trial
Authors: Teshome Getenesh Berhanu , Whiting Susan J. , Green Timothy J. , Mulualem Demelash , Henry Carol J. 
Published: July 2020

Abstract
Background

Improving children's weight status through nutrition education (NE) for mothers about using pulses in complementary feeding has been demonstrated in pilot studies, but no effect on stunting was reported. The aim of the study was to evaluate the effectiveness of a 9-month pulse-nutrition education program on mothers' knowledge, attitude, and practices (KAP) towards pulses, as well as its impact on children's dietary diversity, and nutritional status. The NE was delivered by Health Extension Workers (HEWs).

Methods

A cluster randomized study was employed for the community-based interventional study. Twelve randomly selected villages in Sidama Zone, Southern Ethiopia were included in the study. A total of 772 mother-child pairs involved in the study; where 386 mother-child pairs in the intervention group received additional messages about pulse-cereal complementary food, and 386 pairs (the control) received only routine health education for 9 months. A survey on mothers’ KAP and anthropometric measurements of the children were taken at baseline, midline, and endline.

Results

At baseline and endline, maternal KAP and the dietary diversity score of the children (mean age at endline 18.8 ± 2.9 mo) were assessed. Results : Intervention mothers’ KAP improved ( p <0.001) at midline and endline compared to that of the control group, as did frequency of pulse consumption and DDS among children. At 9 months, the prevalence of stunting, wasting, and underweight was significantly reduced in the intervention group compared to the control group ( p =0.001).

Conclusions

NE delivered by HEWs improved KAP of mothers regarding pulse consumption and dietary diversity of children led to improved nutritional status of the children. Training HEWs on the use of pulses for CF may be an effective way to improve the health of children in Ethiopian communities.
Influences on NHS Health Check behaviours: a systematic review
Authors: Atkins Lou , Stefanidou Chryssa , Chadborn Tim , Thompson Katherine , Michie Susan , Lorencatto Fabi 
Published: July 2020

Abstract
Background

National Health Checks were introduced in the English National Health Service (NHS) in 2009 to reduce cardiovascular disease (CVD) risks and events. Following Public Health England’s (PHE’s) 2017 Digital review, NHS Health Checks were identified as a Digital Exemplar for PHE forming part of the Predictive Prevention programme, setting out the government’s vision for putting prevention at the heart of the nation’s health. This study applied behavioural science frameworks to: i) identify behaviours and actors relevant to uptake, delivery and follow up of NHS Health Checks and influences on these behaviours and; ii) signpost to example intervention content, with a focus on digital intervention development.

Methods

A systematic review of studies reporting NHS Health Check-related behaviours of patients, health care professionals (HCPs) and commissioners. Influences on behaviours were coded using theory-based models: COM-B and Theoretical Domains Framework (TDF). Potential intervention types and behaviour change techniques (BCTs) were suggested to target key influences.

Results

We identified 37 studies reporting nine behaviours and influences for eight of these. The most frequently identified influences were physical opportunity including HCPs having space and time to deliver NHS Health Checks and patients having money to adhere to recommendations to change diet and physical activity. Other key influences were motivational, such as beliefs about consequences about the value of NHS Health Checks and behaviour change, and social, such as influences of others on behaviour change. The following techniques are suggested for websites or smartphone apps: Adding objects to the environment, e.g. provide HCPs with electronic schedules to guide timely delivery of Health Checks to target physical opportunity, Social support (unspecified) , e.g. include text suggesting patients to ask a colleague to agree in advance to join them in taking the ‘healthy option’ lunch at work; Information about health consequences , e.g. quotes and/or videos from patients talking about the health benefits of changes they have made.

Conclusions

Through the application of behavioural science we identified key behaviours and their influences which informed recommendations for digital intervention content. To ascertain the extent to which this reflects existing interventions we recommend a review of relevant evidence.
Does a ketogenic diet have beneficial effects on quality of life, physical activity or biomarkers in patients with breast cancer: A randomized controlled clinical trial.
Authors: khodabakhshi adeleh , Seyfried Thomas N. , Kalamian Miriam , mahmoudi maryam , Davoodi Sayed Hossein 
Published: July 2020

Abstract
Introduction: Despite recent interest in the use of ketogenic diets (KDs) for cancer, evidence of beneficial effects is lacking. This study examined the impact of a randomly assigned KD on quality of life, physical activity and biomarkers in patients with breast cancer.Method: A total of 80 patients with locally advanced or metastatic breast cancer and without a history of renal disease or diabetes were randomly assigned to either a KD or a control group for this 12-week trial. Concurrent with the first, third, and fifth chemotherapy sessions, quality of life, physical activity, and biomarkers (thyroid function tests, electrolytes, albumin, ammonia, ALP, lactate and serum ketones) were assessed. Dietary intake was also recorded on admission and the end of the treatment.Results: No significant differences were seen in quality of life or physical activity scores between the two groups after 12 weeks; however, the KD group showed higher global quality of life and physical activity scores compared to the control group at 6 weeks (P=0.02 P= 0.01). Also, serum lactate and ALP levels decreased significantly in the KD group compared to the control group at the end of the intervention (10.7±3 vs 13.3±4, 149±71 vs 240±164, P=0.02 and P=0.007, respectively). A significant inverse association was observed between total carbohydrate intake and serum beta-hydroxybutyrate at 12 weeks (r= -0.77 P <0.001). No significant differences between groups were observed in thyroid hormones, electrolytes, albumin, LDH or ammonia. Compliance among KD subjects ranged from 66.7% to 79.2% as assessed by dietary intake and serum ketones levels of >0.5.Conclusion: According to our results, besides a higher global quality of life and physical activity scores compared to the control group at 6 weeks, KD diet combined to chemotherapy in patients with breast cancer does not bring additional benefit about quality of life and physical activity at 12 weeks. However, decreases seen in levels of lactate and ALP in the KD group suggest that a KD may benefit patients with breast cancer.
Investigating the healthcare pathway through patient’s experience and profiles: implications for the breast cancer healthcare providers
Authors: CHERIF Emna , VERDIER Elisabeth MARTIN , ROCHETTE Corinne 
Published: July 2020

Abstract
Background Healthcare systems are facing many changes. Particularly, patients are more engaged in the care process. The medical perspective of the process is insufficient to provide patients with high quality care and service personalisation. This research presents an attempt to complete this medical perspective through an experiential perspective, especially for chronic diseases such as cancer. We investigated patients’ experiences and profiles to reach a deeper understanding of their needs and expectations when they confront the disease.The objectives of this research were to model the key stages underling the patient pathway and to identify the challenging touch points of the interactions between patients and healthcare providers. Bringing together findings of patient experience, pathway, and profiles would help all the stakeholders involved to develop better practices for the healthcare process.Methods A qualitative observational nethnography on a French specialized forum for breast cancer patients “les Impatientes” was conducted. A total of 967 reviews were collected over a complete year period from all over France. Thematic and lexicometric content analysis were performed according to the experience dimensions, the pathway stages and touch points, as well as the patients’ profiles.Results Data analysis shows that the healthcare pathway experienced by the patients is built around three stages. The discovery stage is closely related to the emotional dimension regarding the patient and physician relationship. The examination stage is characterized by a more technical and informational needs for the types of treatments. The follow-up and survivorship stage illustrates the patients’ need to assess the treatments’ effectiveness and the quality of the follow-up. Moreover, three profiles of patients were identified. The newcomers, the altruists and the autonomous are characterized by different attitudes depending on the stage of the healthcare pathway they were living.Conclusions Our research presents an original modelling of the patient pathway and profiles beyond the medical process. It gives practical tracks to improve the healthcare pathway. Patients expect healthcare providers to integrate and strengthen several challenging touch points in order to create satisfactory patient experiences and high quality service.
High insecticide resistances levels in Anopheles gambiaes s.l. in northern Uganda and its relevance for future malaria control
Authors: Echodu Richard , Iga Julius , Oyet William Sam , Mireji Paul , Anena Juliet , Onanyang David , Iwiru Tereza , Lutwama Julius Julian , Opiyo Elizabeth Auma 
Published: July 2020

Abstract
Objective: The aim of the study was to determine the level of insecticide resistance and diversity in Anopheles mosquitoes in northern Uganda. Standard WHO insecticide susceptibility test assays were used to test for susceptibility to 0.5% malathion, 0.1% bendiocarb, 0.05% deltamethrin and 0.75% permethrin on 3-5 day old generation one progeny. We also screened for species diversity and knockdown resistance using PCR assay.Results: Anopheles gambiae s.s. is the predominant malaria vector in northern Uganda followed by An. arabiensis. An. gambiae s.s. was susceptible to malathion and bendiocarb with the observed mortality rate of 100% and 98-100% observed respectively while very high resistance was observed with deltamethrin and permethrin. Minimal KDR-eastern variant homozygous forms of 8.3% in An. gambiae s.s. were detected in Oyam district. In conclusion, this study confirms that An. gambiae s.s. females are susceptible to malathion and bendiocarb while high intensity of resistance was observed with deltamethrin and permethrin in the same area. Use of carbamate and organophosphate insecticides bendiocarb and malathion for indoor residual spraying activities in northern Uganda is highly recommended since high levels of pyrethroids resistance (deltamethrin & permethrin) was detected in the area.
Transcriptome Analysis of Aedes aegypti Aag2 Cells in Response to Dengue Virus-2 Infection
Authors: Li Man-jin , Lan Ce-jie , Gao He-ting , Xing Dan , Gu Zhen-yu , Su Duo , Zhao Tong-yan , Yang Hui-ying , Li Chun-xiao 
Published: July 2020

Abstract
Background: Dengue virus (DENV) is a flavivirus transmitted by mosquitoes that is prevalent in tropical and subtropical countries and has four serotypes (DENV1-4). Aedes aegypti, as the main transmission vector of DENV, exhibits strong infectivity and transmission. With the aim of obtaining a better understanding of the Ae. aegypti-DENV interaction, the transcriptome changes in DENV-2-infected Aag2 cells were studied to describe the immune responses of mosquitoes using the Ae. aegypti Aag2 cell line as a model.Methods: RNAseq technology was used to sequence the transcripts of the Ae. aegypti Aag2 cell line before and after infection with DENV-2. A bioinformatics analysis was then performed to assess the biological functions of the differentially expressed genes, and the sequencing data were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: The transcriptome analysis generated 8,866 unigenes that were found in both groups, 225 unigenes that were only found in the infection group, and 683 unigenes that only existed in the control group. A total of 1199 differentially expressed genes, including 1014 upregulated and 185 downregulated genes, were identified. The bioinformatics analysis showed that the differentially expressed genes were mainly involved in the longevity regulating pathway, circadian rhythm, DNA replication, and peroxisome, purine, pyrimidine, and drug metabolism. The qRT-PCR verification results showed the same trend, which confirmed that the expression of the differentially expressed genes had changed and that the transcriptome sequencing data were reliable.Conclusions: This study investigated the changes in the transcriptome levels in the DENV-2-infected Ae. aegypti Aag2 cell line, which provides a faster and effective method for discovering genes related to Ae. aegypti pathogen susceptibility. The findings provide basic data and directions for further research on the complex mechanism underlying host-pathogen interactions.
Clinical features of gingivostomatitis due to primary infection of Herpes simplex virus in children
Authors: Huang Chen-Wei , Hsieh Chi-Hsien , Lin Ming-Ru , Huang Yhu-Chering 
Published: July 2020

Abstract
Background

Primary herpetic gingivostomatitis (PHGS) in children, though usually self-limited, might mimic bacterial and enteroviral pharyngitis clinically. We conducted a study to define the clinical features of PHGS in children.

Methods

Between January 2012 to December 2016, 282 inpatients aged less than 19 years with cell culture-confirmed herpes simplex virus (HSV) infection in a medical center were identified from the virologic laboratory logbook. Clinical data were retrospectively collected.

Results

Among the 282 inpatients, 185 cases were considered as PHGS and included for analysis. 99.5% had fever. The mean duration of fever was 5.11 days (±2.24) with the longest being 17 days. The common oral manifestations included oral ulcers (84.3%), which equally resided in the anterior and posterior part of the oral cavity (65.4% vs. 63.2%), gum swelling and/or bleeding (67.6%), and exudate coated tonsils (16.8%). Leukocytosis (WBC count >15,000/uL3) was noted in 52 patients (28.1%) and a serum C-reactive protein level >40 mg/L in 55 patients (29.7%). 65 patients (35%) were diagnosed as PHGS on admission and were significantly more likely to have ulcers over the anterior oral cavity (76.1% vs. 26.7%) and gum swelling/bleeding (76.2% vs. 7.5%, p-value all <0.001) on admission and were significantly less likely to receive antibiotic treatment (16.9 vs. 36.7%, p-value < 0.01) than others. 46 patients (25%) undiagnosed as PHGS on discharge were significantly more likely to have exudate coated on tonsils, receive antibiotic treatment and significantly less likely to have gum swelling/bleeding and oral ulcers (all p values < 0.01).

Conclusions

Meticulously identifying specific oral manifestations of gum swelling/bleeding and ulcers over the anterior oral cavity in children can differentiate PHGS from both bacterial and enteroviral pharyngitis and subsequently reduce unnecessary prescription of antibiotics.