bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancies after vaginal radical trachelectomy (RT) in patients with early invasive uterine cervical cancer: results from a single institute
Authors: Shinkai Shota , Ishioka Shinichi , Mariya Tasuku , Fujibe Yuya , Kim Miseon , Someya Masayuki , Saito Tsuyoshi
Published: April 2020

Background

Radical tracheletomy (RT) with pelvic lymphadenectomy has become an option for young patients with early invasive uterine cervical cancer who desire to maintain their fertility. However, this operative method entails a high risk for the following pregnancy due to its radicality.

Methods

We have performed vaginal RT for 71 patients and have experienced 28 pregnancies in 21 patients. They were followed up carefully according to the follow-up methods we reported previously. Their pregnancy courses and prognoses after the pregnancy were retrospectively reviewed.

Results

All the vaginal RTs were performed safely without serious complications, including 6 patients who underwent the operation during pregnancy. The median time to be pregnant after RT was 29.5 months. 13 patients (46%) became pregnant without artificial insemination by husband or assisted reproductive technology. Cesarean section was performed for all of them. The median time of pregnancy was 34 weeks, and emergent cesarean section was performed for 7 pregnancies (25%). The median birth weight was 2156 g. Four patients had trouble with cervical cerclage, and they suffered from sudden premature preterm rupture of the membrane (pPROM) during the second trimester of pregnancy. We underwent transabdominal cerclage (TAC) for all of them and careful management for the prevention of uterine infection was performed. One patient had a recurrence of cancer during pregnancy.

Conclusions

Both the obstetrical prognosis and oncological prognosis after vaginal RT have become favorable for pregnant patients after vaginal RT.
Low-dose peripheral blood stem cell graft after high-dose chemotherapy - an evaluation of hematopoietic reconstitution
Authors: Sauer Sandra , Pavel Petra , Schmitt Anita , Cremer Martin , Kriegsmann Mark , Bruckner Thomas , Jordan Karin , Wuchter Patrick , Müller-Tidow Carsten , Kriegsmann Katharina
Published: April 2020

Background

High-dose (HD) chemotherapy followed by autologous blood stem-cell transplantation (ASCT) is the standard treatment for multiple myeloma (MM) patients. However, the collection of sufficient peripheral blood stem cell (PBSC) grafts can be challenging, and the question arises whether reinfusion of low-dose grafts will lead to a hematopoietic recovery.

Methods

The hematopoietic recovery of 148 MM patients who underwent HD melphalan chemotherapy and received PBSC transplants with varying CD34+ cells doses (3–4 × 106 [n = 86], 2–2.5 × 106 [n = 53], < 2 × 106 [n = 9] per kg body weight [bw]) was analyzed in this retrospective single-center study.

Results

All patients reached hematopoietic reconstitution, even those who received < 2 × 106 CD34+ cells/kg bw. 62 (42%) patients received granulocyte-colony-stimulating factor (G-CSF). The median duration to leukocyte recovery ≥1.0 × 109/L was 12 days in every group. The median duration to platelet recovery ≥20 × 109/L was 11, 13 and 13 days, respectively. In the multivariate analysis, a low number of reinfused CD34+ cells was associated with prolonged time until leukocyte reconstitution (p = 0.010, HR 0.607) and platelet recovery (p < 0.001, HR 0.438). G-CSF support significantly accelerated leukocyte (p < 0.001, HR 16.742) but not platelet reconstitution.

Conclusion

In conclusion, reinfusion of low- and even very-low-dose PBSC grafts leads to sufficient hematopoietic reconstitution. No severe adverse events were observed during or after HD chemotherapy and ASCT in the analyzed cohort. While the impact of CD34+ cell dose is marginal, G-CSF significantly accelerates the leukocyte recovery.
Life review therapy for holocaust survivors (LRT-HS): study protocol for a randomised controlled trial
Authors: Forstmeier Simon , van der Hal Elisheva , Auerbach Martin , Maercker Andreas , Brom Danny
Published: April 2020

Background

The Holocaust was one of the most traumatic catastrophes in recorded human history. Survivors seeking psychotherapeutic help today, now in their seventies and older, often show symptoms of a posttraumatic stress disorder (PTSD), depression, or prolonged grief disorder. Established psychological treatments for PTSD (e.g. cognitive behaviour therapy, psychodynamic therapies) have been tested and assessed mainly with young and middle-aged adults; only very few studies examined them in old age. There is no therapy outcome study known to us for any treatment mode for Holocaust survivors. Moreover, there is a need for an age group-specific treatment of PTSD and other stress-related mental disorders. A narrative approach including life-review and narrative exposure seems to meet very well the natural need of older people to review their lives and is highly effective. However, most studies on the efficacy of life review therapy (LRT) focus on late-life depression. There is a lack of efficacy studies evaluating the effect of LRT on PTSD symptoms in older individuals that have experienced traumatic events.

Methods

The main goal of this study is to evaluate the effect of LRT for Holocaust survivors (LRT-HS) on symptoms of PTSD and related mental health problems (depression, anxiety, prolonged grief), compared to a supportive control group. A secondary goal is to identify the characteristics of participants that seem to especially benefit from the treatment. The proposed study is a randomised, controlled follow-up trial including Holocaust survivors with one or more trauma-related disorders. The LRT treatment consists of 20–25 sessions. Before and after the treatment phase, participants in both conditions will be assessed. Follow-up will take place 6 months after the treatment. A sample size of 80 is required (drop-out rate included).

Discussion

Efficacious treatments for trauma-related disorders in older people are of high importance, also because the probability of traumatisation and loss increases with age. Because this study is conducted with this specific group of multiply traumatised people, we are convinced that the results can easily transfer to other samples.

Trial registration

ISRCTN, ISRCTN12823306. Registered 31 March 2018 – Retrospectively registered (first participant 22 December 2017).
Socioeconomic status and survival after stroke – using mediation and sensitivity analyses to assess the effect of stroke severity and unmeasured confounding
Authors: Lindmark Anita , Norrving Bo , Eriksson Marie
Published: April 2020

Background

Although it has been established that low socioeconomic status is linked to increased risk of death after stroke, the mechanisms behind this link are still unclear. In this study we aim to shed light on the relationship between income level and survival after stroke by investigating the extent to which differences in stroke severity account for differences in survival.

Methods

The study was based on patients registered in Riksstroke (the Swedish stroke register) with first time ischemic stroke (n = 51,159) or intracerebral hemorrhage (n = 6777) in 2009–2012. We used causal mediation analysis to decompose the effect of low income on 3-month case fatality into a direct effect and an indirect effect due to stroke severity. Since causal mediation analysis relies on strong assumptions regarding residual confounding of the relationships involved, recently developed methods for sensitivity analysis were used to assess the robustness of the results to unobserved confounding.

Results

After adjustment for observed confounders, patients in the lowest income tertile had a 3.2% (95% CI: 0.9–5.4%) increased absolute risk of 3-month case fatality after intracerebral hemorrhage compared to patients in the two highest tertiles. The corresponding increase for case fatality after ischemic stroke was 1% (0.4–1.5%). The indirect effect of low income, mediated by stroke severity, was 1.8% (0.7–2.9%) for intracerebral hemorrhage and 0.4% (0.2–0.6%) for ischemic stroke. Unobserved confounders affecting the risk of low income, more severe stroke and case fatality in the same directions could explain the indirect effect, but additional adjustment to observed confounders did not alter the conclusions.

Conclusions

This study provides evidence that as much as half of income-related inequalities in stroke case fatality is mediated through differences in stroke severity. Targeting stroke severity could therefore lead to a substantial reduction in inequalities and should be prioritized. Sensitivity analysis suggests that additional adjustment for a confounder of greater impact than age would be required to considerably alter our conclusions.
Daily almond consumption in cardiovascular disease prevention via LDL-C change in the U.S. population: a cost-effectiveness analysis
Authors: Wang Jifan , Lee Bravatti Michelle A. , Johnson Elizabeth J. , Raman Gowri
Published: April 2020

Background

Heart disease is the leading cause of death in the United States. The U.S. Food and Drug Administration approved the health claim that 1.5 oz (42.5 g) of nut intake may reduce the risk of cardiovascular disease. Previous studies have focused on the cost-effectiveness of other foods or dietary factors on primary cardiovascular disease prevention, yet not in almond consumption. This study aimed to examine the cost-effectiveness of almond consumption in cardiovascular disease primary prevention.

Perspective & Setting

This study assessed the cost-effectiveness of consuming 42.5 g of almond from the U.S. healthcare sector perspective.

Methods

A decision model was developed for 42.5 g of almond per day versus no almond consumption and cardiovascular disease in the U.S. population. Parameters in the model were derived from the literature, which included the probabilities of increasing low-density lipoprotein cholesterol, developing acute myocardial infarction and stroke, treating acute myocardial infarction, dying from the disease and surgery, as well as the costs of the disease and procedures in the U.S. population, and the quality-adjusted life years. The cost of almonds was based on the current price in the U.S. market. Sensitivity analyses were conducted for different levels of willingness-to-pay, the probabilistic sensitivity analysis, ten-year risk prevention, different costs of procedures and almond prices, and patients with or without cardiovascular disease.

Results

The almond strategy had $363 lower cost and 0.02 higher quality-adjusted life years gain compared to the non-almond strategy in the base-case model. The annual net monetary benefit of almond consumption was $1421 higher per person than no almond consumption, when the willingness to pay threshold was set at $50,000 for annual health care expenditure. Almond was more cost-effective than non-almond in cardiovascular disease prevention in all the sensitivity analyses.

Conclusion

Consuming 42.5 g of almonds per day is a cost-effective approach to prevent cardiovascular disease in the short term and potentially in the long term.
An observational study of system-level changes to improve the recording of very brief advice for smoking cessation in an inpatient mental health setting
Authors: Spaducci Gilda , Richardson Sol , McNeill Ann , Pritchard Megan , Sanyal Jyoti , Healey Andy , Yates Mary , Robson Debbie
Published: April 2020

Background

Smoking prevalence among people with psychosis remains high. Providing Very Brief Advice (VBA) comprising: i) ASK, identifying a patient’s smoking status ii) ADVISE, advising on the best way to stop and iii) ACT (OFFER), offering a referral to specialist smoking cessation support, increases quit attempts in the general population. We assessed whether system-level changes in a UK mental health organisation improved the recording of the provision of ASK, ADVISE, ACT (OFFER) and consent to referral to specialist smoking cessation support (ACT (CONSENT)).

Methods

We conducted a study using a regression discontinuity design in four psychiatric hospitals with patients who received treatment from an inpatient psychosis service over 52 months (May 2012–September 2016). The system-level changes to facilitate the provision of VBA comprised: A) financially incentivising recording smoking status and offer of support (ASK and ACT (OFFER)); B) introduction of a comprehensive smoke-free policy; C) enhancements to the patient electronic healthcare record (EHCR) which included C1) a temporary form to record the financial incentivisation of ASK and ACT (OFFER) C2) amendments to how VBA was recorded in the EHCR and C3) the integration of a new electronic national referral system in the EHCR. The recording of ASK, ADVISE, ACT (OFFER/CONSENT) were extracted using a de-identified psychiatric case register.

Results

There were 8976 admissions of 5434 unique individuals during the study period. Following A) financial incentive, the odds of recording ASK increased (OR: 1.56, 95%CI: 1.24–1.95). Following B) comprehensive smoke-free policy, the odds of recording ADVICE increased (OR: 3.36, 95%CI: 1.39–8.13). Following C1) temporary recording form, the odds of recording ASK (OR:1.99, 95%CI:1.59–2.48) and recording ACT (OFFER) increased (OR: 4.22, 95%CI: 2.51–7.12). Following C3) electronic referral system, the odds of recording ASK (OR:1.79, 95%CI: 1.31–2.43) and ACT (OFFER; OR: 1.09, 95%CI: 0.59–1.99) increased. There was no change in recording VBA outcomes following C2) amendments to VBA recording.

Conclusions

Financial incentives and the recording of incentivised outcomes, the comprehensive smoke-free policy, and the electronic referral system, were associated with increases in recording individual VBA elements, but other changes to the EHCR were not. System-level changes may facilitate staff recording of VBA provision in mental health settings.
Adverse influence of multilevel socioeconomic status on physical activity: results from a national survey in Vietnam
Authors: Vu Thi Hoang Lan , Bui Thi Tu Quyen , Nguyen Thi Kim Ngan , Hoang Van Minh
Published: April 2020

Background

This study aims to explore associations of individual- and provincial-level socioeconomic status (SES) and the combined interaction among these SES with individual physical activity (PA).

Method

This analyze used data of 3068 Vietnamese people aged 18–65 years from the national representative STEPS survey in 2015 (STEPS2015). The survey collected PA-related data using the Global PA Questionnaire Version 2 and those on provicial-level characteristics from two surveys in 2014, namely the Intercensal Population and Housing Survey (IPHS) and The Vietnam Household Living Standard Survey (VLSS2014). Multilevel linear analyze was performed with individual and provincial characteristics as independent variables and the metabolic equivalent (MET) score – the indicator of individual PA – as the dependent variable.

Results

Male and female participants with insufficient PA accounted for 20.2 and 35.7%, respectively. Both individual- and provicial-level SES were inversely associated with the individual PA level. As the provincial-level monthly income increased by 1 million Vietnam Dongs, the total PA score of individuals residing in that province reduced by 1900 METS. A buffering effect was reported between provincial and individual SES, as the provincial average income increased, the differences in PA scores between different SES groups decreased.

Conclusion

Our data suggest that Vietnamese individuals in low SES groups tended to be more physically active than those in high SES groups because their PA was largely related to work.
Composition of weekly physical activity in adolescents by level of physical activity
Authors: Groffik Dorota , Fromel Karel , Badura Petr
Published: April 2020

Background

Physical activity (PA) in adolescence is crucial for lifelong healthy lifestyle, and attention is needed to adolescents at health risk due to insufficient PA. This study investigates the composition of weekly PA in adolescents by PA level and provides a rationale for change in their lifestyles.

Methods

The research was conducted at 66 schools in Poland between 2009 and 2016, among 949 girls and 650 boys aged 15–18 years. We used pedometers to monitor weekly PA with data assessed using the Indares web app. The participants were split into three groups by mean daily step count (lower, < 9000; middle, 9000–12,999; and higher, ≥ 13,000 steps/day), as a reliable and non-expensive indicator of PA.

Results

We did not observe statistically significant differences in composition of 7-day PA between participants with varying levels of PA, regardless of their gender (F(12,9558) = 0.60; p = 0.841; ηp2 > 0.000). The smallest differences in daily step counts by PA level were found on Mondays and the biggest on Fridays and Saturdays, in boys and girls; the differences between average school and average weekend days were most pronounced in less active girls (1677 steps/day) and boys (1886 steps/day). During the school week, the highest proportion of less active girls met the 11,000 steps/day recommendation on Fridays (21.9%), statistically significantly less than on other school days (p < 0.001). Similarly, less active boys (22.2%) had significantly less activity on Fridays than on other school days, except for Mondays (p = 0.143) Analogous pattern was apparent also in more active adolescents.

Conclusions

Less active adolescents have comparable composition of weekly PA to the more active ones but they can hardly meet the generally accepted PA recommendations. Better understanding of weekly PA composition and rates of meeting PA recommendations by day of the week can lead to more efficient interventions improving lifestyles. The recommendation of 9000 steps/day most days of the week, thus, appears appropriate for less active adolescents, as a motivating achievable goal.
Effect of mechanical ventilation versus spontaneous breathing on abdominal edema and inflammation in ARDS: an experimental porcine model
Authors: Marchesi Silvia , Hedenstierna Göran , Hata Aki , Feinstein Ricardo , Larsson Anders , Larsson Anders Olof , Lipcsey Miklós
Published: April 2020

Background

Mechanical ventilation (MV), compared to spontaneous breathing (SB), has been found to increase abdominal edema and inflammation in experimental sepsis. Our hypothesis was that in primary acute respiratory distress syndrome (ARDS) MV would enhance inflammation and edema in the abdomen.

Methods

Thirteen piglets were randomized into two groups (SB and MV) after the induction of ARDS by lung lavage and 1 h of injurious ventilation.

1. SB: continuous positive airway pressure 15 cmH2O, fraction of inspired oxygen (FIO2) 0.5 and respiratory rate (RR) maintained at about 40 cycles min− 1 by titrating remifentanil infusion.

2. MV: volume control, tidal volume 6 ml kg− 1, positive end-expiratory pressure 15 cmH2O, RR 40 cycles min− 1, FIO2 0.5.

Main outcomes: abdominal edema, assessed by tissues histopathology and wet-dry weight; abdominal inflammation, assessed by cytokine concentration in tissues, blood and ascites, and tissue histopathology.

Results

The groups did not show significant differences in hemodynamic or respiratory parameters. Moreover, edema and inflammation in the abdominal organs were similar. However, blood IL6 increased in the MV group in all vascular beds (p < 0.001). In addition, TNFα ratio in blood increased through the lungs in MV group (+ 26% ± 3) but decreased in the SB group (− 17% ± 3).

Conclusions

There were no differences between the MV and SB group for abdominal edema or inflammation. However, the systemic increase in IL6 and the TNFα increase through the lungs suggest that MV, in this model, was harmful to the lungs.
Effect of bisphosphonate treatment of titanium surfaces on alkaline phosphatase activity in osteoblasts: a systematic review and meta-analysis
Authors: Wehner Christian , Lettner Stefan , Moritz Andreas , Andrukhov Oleh , Rausch-Fan Xiaohui
Published: April 2020

Background

Bisphosphonate coating of dental implants is a promising tool for surface modification aiming to improve the osseointegration process and clinical outcome. The biological effects of bisphosphonates are thought to be mainly associated with osteoclasts inhibition, whereas their effects on osteoblast function are unclear. A potential of bisphosphonate coated surfaces to stimulate osteoblast differentiation was investigated by several in vitro studies with contradictory results. The purpose of this systematic review and meta-analysis was to evaluate the effect of bisphosphonate coated implant surfaces on alkaline phosphatase activity in osteoblasts.

Methods

In vitro studies that assessed alkaline phosphatase activity in osteoblasts following cell culture on bisphosphonate coated titanium surfaces were searched in electronic databases PubMed/MEDLINE, Scopus and ISI Web of Science. Animal studies and clinical trials were excluded. The literature search was restricted to articles written in English and published up to August 2019. Publication bias was assessed by the construction of funnel plots.

Results

Eleven studies met the inclusion criteria. Meta-analysis showed that coating of titanium surfaces with bisphosphonates increases alkaline phosphatase activity in osteoblasts after 3 days (n = 1), 7 (n = 7), 14 (n = 6) and 21 (n = 3) days. (7 days beta coefficient = 1.363, p-value = 0.001; 14 days beta coefficient = 1.325, p-value < 0.001; 21 days beta coefficient = 1.152, p-value = 0.159).

Conclusions

The meta-analysis suggests that bisphosphonate coatings of titanium implant surfaces may have beneficial effects on osteogenic behaviour of osteoblasts grown on titanium surfaces in vitro. Further studies are required to assess to which extent bisphosphonates coating might improve osseointegration in clinical situations.
Quality improvement education for medical students: a near-peer pilot study
Authors: McGeorge Elizabeth , Coughlan Charles , Fawcett Martha , Klaber Robert Edward
Published: April 2020

Background

Quality improvement (QI) is an essential component of modern clinical practice. Front-line professionals offer valuable perspectives on areas for improvement and are motivated to deliver change. In the UK, all junior doctors are expected to participate in QI in order to advance to the next stage of their training. However, UK undergraduates receive no standardized training in QI methods. This is perpetuated within medical schools by a lack of teaching capacity and competing priorities, and may lead to tokenistic engagement with future QI projects.

Methods

We describe a near-peer teaching programme designed to introduce students to QI methods. This pilot study was conceived and delivered in full by junior doctors and used existing resources to ensure high quality teaching content. 111 fifth-year medical students from the University of Cambridge were taught in interactive, participative workshops that encourage them to develop their own QI change ideas and projects. Core topics included the model for improvement, driver diagrams, stakeholder engagement, measurement for improvement and analysing and presenting data. Students completed surveys before and immediately after this intervention to assess their understanding of and confidence in utilizing QI methods. Questionnaires were also completed by junior doctor tutors.

Results

Analysis of questionnaires completed before and immediately after the intervention revealed statistically significant improvements in students’ self-reported understanding of QI (p < 0.05) and confidence in applying techniques to their own work (p < 0.05). Students expressed a preference for QI teaching delivered by junior doctors, citing a relaxed learning environment and greater relevance to their stage of training. Tutors reported increased confidence in using QI techniques and a greater willingness to engage with QI in future.

Conclusions

In this single-centre study, near-peer teaching produced significant improvements in students’ self-reported understanding of QI and confidence in applying QI methods. Near-peer teaching may constitute a sustainable means of teaching essential QI skills at undergraduate level. Future work must evaluate objective measures of student engagement with and competence in conducting QI.
Development and validation of data quality rules in administrative health data using association rule mining
Authors: Peng Mingkai , Lee Sangmin , D’Souza Adam G. , Doktorchik Chelsea T. A. , Quan Hude
Published: April 2020

Background

Data quality assessment presents a challenge for research using coded administrative health data. The objective of this study is to develop and validate a set of coding association rules for coded diagnostic data.

Methods

We used the Canadian re-abstracted hospital discharge abstract data coded in International Classification of Disease, 10th revision (ICD-10) codes. Association rule mining was conducted on the re-abstracted data in four age groups (0–4, 20–44, 45–64; ≥ 65) to extract ICD-10 coding association rules at the three-digit (category of diagnosis) and four-digit levels (category of diagnosis with etiology, anatomy, or severity). The rules were reviewed by a panel of 5 physicians and 2 classification specialists using a modified Delphi rating process. We proposed and defined the variance and bias to assess data quality using the rules.

Results

After the rule mining process and the panel review, 388 rules at the three-digit level and 275 rules at the four-digit level were developed. Half of the rules were from the age group of ≥65. Rules captured meaningful age-specific clinical associations, with rules at the age group of ≥65 being more complex and comprehensive than other age groups. The variance and bias can identify rules with high bias and variance in Alberta data and provides directions for quality improvement.

Conclusions

A set of ICD-10 data quality rules were developed and validated by a clinical and classification expert panel. The rules can be used as a tool to assess ICD-coded data, enabling the monitoring and comparison of data quality across institutions, provinces, and countries.
Qualitative exploration of perceived benefits of care and barriers influencing HIV care in trans Nzoia, Kenya
Authors: Naanyu V. , Ruff J. , Goodrich S. , Spira T. , Bateganya M. , Toroitich-Ruto C. , Otieno-Nyunya B. , Siika A. M. , Wools-Kaloustian K.
Published: April 2020

Background

Substantial efforts have been made to ensure people living with HIV (PLHIV) are linked to and retained in care but many challenges deter care utilization. We report perceived benefits of seeking HIV care and barriers to HIV care that were identified through a formative assessment conducted to advise the development of an alternative care model to deliver antiretroviral treatment therapy (ART) in Trans Nzoia County, Kenya.

Methods

Data were collected in 2015 through key informant interviews (KIIs), in-depth interviews (IDIs), and focus group discussions (FGDs). The study involved 55 participants of whom 53% were female. Ten KIIs provided community contextual information and viewpoints on the HIV epidemic in Trans Nzoia County while 20 PLHIV (10 male and 10 female) participated in IDIs. Twenty-five individuals living with HIV participated in four FGDs - two groups for men and two for women. Key informants were purposively selected, while every third patient above 18 years at the Kitale HIV Clinic was invited to share their HIV care experience through IDIs or FGDs. Trained research assistants moderated all sessions and audio recordings were transcribed and analyzed thematically.

Results

Findings showed that PLHIV in Trans Nzoia County used both conventional and complementary alternative care for HIV; however, public health facilities were preferred. Popular perceived benefits of adopting care were relief from symptoms and the chance to live longer. Benefits of care uptake included weight gain, renewed energy, and positive behavior change. Individual-level barriers to HIV care included lack of money and food, use of alternative care, negative side effects of ART, denial, and disclosure difficulties. At the community level, stigma, limited social support for conventional HIV treatment, and poor means of transport were reported. The health system barriers were limited supplies and staff, long distance to conventional HIV care, and unprofessional providers.

Conclusions

Diverse individual, community and health system barriers continue to affect HIV care-seeking efforts in Kenya. Appreciation of context and lived experiences allows for development of realistic care models.
Five novel PRNP gene polymorphisms and their potential effect on Scrapie susceptibility in three native Ethiopian sheep breeds
Authors: Teferedegn Eden Yitna , Yaman Yalcin , Un Cemal
Published: April 2020

Background

Classical scrapie susceptibility in sheep has been linked to three polymorphisms at codon 136, 154, and 171 in the prion protein gene (PRNP) whereas atypical scrapie susceptibility is related to polymorphisms at codon 141. Many other variants over the length of the PRNP have been reported. Some of the variants may play crucial roles in fighting against the emergence of a new form of scrapie disease. Scrapie surveillance, scrapie associated genotyping and PRNP characterization studies have been conducted across the globe. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breed’s PRNP gene has socioeconomic and scientific merits. This study aimed to identify PRNP variants in three native Ethiopian sheep breeds and their potential effect on scrapie susceptibility.

Results

Five novel variants were identified in the PRNP gene of three native Ethiopian sheep breeds. Four non-synonymous heterozygous substitutions i.e. H99Q (CAC-- > CAA), H99L (CAC-- > CTA), A116E (GCA-- > GAA), A116T (GCA-- > ACA), and one synonymous N103 N (AAC-- > AAT) were detected. In addition to the novel variants, polymorphisms at codon 126,127,138,142,146,231, and 237 were also identified. The haplotype ARR was observed in Menz and Afar breeds at frequencies of 0.02 and 0.05 respectively. Neither ARR/ARR nor VRQ/VRQ genotypes were identified in the population under study.

Conclusion

Two of the novel variants at codon 99 and 103 that are placed closer to the proteinase K cleavage site and the variant at codon 116 in the palindrome region along with variants at codon 127 in glycine repeat domain may influence the conformational flexibility of prion protein. The rarity of ARR haplotype and the abundance of 141 L variant demonstrated that the present study population was less resistant to classical scrapie and less predisposed to genotype associated atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies during interbreeding, crossbreeding and help to take precautionary measures against scrapie.
Milk exosome-derived miRNAs from water buffalo are implicated in immune response and metabolism process
Authors: Chen Zujing , Xie Yueqin , Luo Junyi , Chen Ting , Xi Qianyun , Zhang Yongliang , Sun Jiajie
Published: April 2020

Background

Buffalo milk is rich in various nutritional components and bioactive substances that provide more essential health benefits to human body. Recently, exosome identified in the breast milk has been reported as a neotype nutrient and can mediate intercellular communication with exosomal miRNAs. In the present study, we therefore hypothesized that exosome-derived miRNAs from buffalo milk would play the potential physiological importance of consumption of buffalo milk.

Results

We isolated exosomes from buffalo and cow milk samples that were obtained at mid-lactation period, and the exosomal miRNA profiles were then generated using miRNA-seq. In addition, miRNAomes of pig, human and panda milk exosomes were downloaded from GEO database. Finally, a total of 27 milk exosomal miRNA profiles that included 4 buffalo, 4 cow, 8 pig, 4 human and 7 panda were analyzed using the miRDeep2 program. A total of 558 unique miRNA candidates existed across all species, and the top 10 highly expressed miRNA were evolutionarily conserved across multiple species. Functional analysis revealed that these milk enriched miRNAs targeted 400 putative sites to modulate disease resistance, immune responsiveness and basic metabolism events. In addition, a total of 32 miRNAs in buffalo milk were significantly up-regulated compared with non-buffalo milks, while 16 were significantly down-regulated. Of interest, functional analysis showed that up-regulated miRNAs were mainly related to host metabolism processes, while the predicted functions of down-regulated miRNAs were enriched in immune response.

Conclusion

In this study, we explored the exosomal miRNAome differences between milks of different animals, expanding the theoretical basis for potential applications of the miRNA-containing vesicles.
Comparison of the effects of twice-daily exenatide and insulin on carotid intima-media thickness in type 2 diabetes mellitus patients: a 52-week randomized, open-label, controlled trial
Authors: Zhang Jie , Xian Tong-Zhang , Wu Ming-Xiao , Li Chen , Pan Qi , Guo Li-Xin
Published: April 2020

Background

Exenatide, a glucagon like peptide 1 analog, has been suggested to reduce the cardiovascular disease risk factors, such as body weight, blood pressure and subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). This was the first randomized, open-label, controlled trial to compare the effects of exenatide versus insulin on subclinical atherosclerosis, as assessed by carotid-intima media thickness (CIMT), in patients with T2DM.

Methods

A total of 66 patients with T2DM admitted from March 10, 2015 to June 20, 2017 in the Department of Endocrinology, Beijing Hospital were randomized to receive twice-daily exenatide or aspartate 70/30 insulin for 52 weeks. The primary endpoint was change from baseline in CIMT, and secondary endpoints included changes at week 52 from baseline in body weight, glycemic markers, lipid metabolism markers, blood pressure, C-reactive protein, fibrinogen, 8-hydroxydeoxyguanosine, irisin, and brain natriuretic peptide.

Results

Exenatide more significantly reduced the CIMT from baseline compared with insulin after 52 weeks, with a mean difference of − 0.14 mm (95% interval confidence: − 0.25, − 0.02; P = 0.016). Weight and body mass index were both significantly reduced in the exenatide group over 52 weeks. Exenatide reduced total lipoprotein and low-density lipoprotein cholesterol levels more significantly than insulin at weeks 16 and 40. Correlation analyses showed that CIMT was positively correlated with low-density lipoprotein cholesterol.

Conclusions

Twice-daily exenatide could prevent atherosclerosis progression in patients with T2DM over a 52-week treatment period compared with insulin therapy.

Trial registration Chinese Clinical Trial Registry ChiCTR-1800015658
Co-production of gallic acid and a novel cell-associated tannase by a pigment-producing yeast, Sporidiobolus ruineniae A45.2
Authors: Kanpiengjai Apinun , Khanongnuch Chartchai , Lumyong Saisamorn , Haltrich Dietmar , Nguyen Thu-Ha , Kittibunchakul Suwapat
Published: April 2020

Background

Gallic acid has received a significant amount of interest for its biological properties. Thus, there have been recent attempts to apply this substance in various industries and in particular the feed industry. As opposed to yeasts, fungi and bacteria and their tannases have been well documented for their potential bioconversion and specifically for the biotransformation of tannic acid to gallic acid. In this research, Sporidiobolus ruineniae A45.2 is introduced as a newly pigment-producing and tannase-producing yeast that has gained great interest for its use as an additive in animal feed. However, there is a lack of information on the efficacy of gallic acid production from tannic acid and the relevant tannase properties. The objective of this research study is to optimize the medium composition and conditions for the co-production of gallic acid from tannic acid and tannase with a focus on developing an integrated production strategy for its application as a feed additive.

Results

Tannase produced by S. ruineniae A45.2 has been classified as a cell-associated tannase (CAT). Co-production of gallic acid obtained from tannic acid and CAT by S. ruineniae A45.2 was optimized using response surface methodology and then validated with the synthesis of 11.2 g/L gallic acid from 12.3 g/L tannic acid and the production of 31.1 mU/mL CAT after 48 h of cultivation in a 1-L stirred tank fermenter. Tannase was isolated from the cell wall, purified and characterized in comparison with its native form (CAT). The purified enzyme (PT) revealed the same range of pH and temperature optima (pH 7) as CAT but was distinctively less stable. Specifically, CAT was stable at up to 70 °C for 60 min, and active under its optimal conditions (40 °C) at up to 8 runs.

Conclusion

Co-production of gallic acid and CAT is considered an integrated and green production strategy. S. ruineniae biomass could be promoted as an alternative source of carotenoids and tannase. Thus, the biomass, in combination with gallic acid that was formed in the fermentation medium, could be directly used as a feed additive. On the other hand, gallic acid could be isolated and purified for food and pharmaceutical applications. This paper is the first of its kind to report that the CAT obtained from yeast can be resistant to high temperatures of up to 70 °C.
Silencing of microRNA-135b inhibits invasion, migration, and stemness of CD24+CD44+ pancreatic cancer stem cells through JADE-1-dependent AKT/mTOR pathway
Authors: Zhou Jingyang , Wang Haihong , Che Jinhui , Xu Lu , Yang Weizhong , Li Yunjiu , Zhou Wuyuan
Published: April 2020

Background

Recent studies have emphasized determining the ability of microRNAs (miRNAs) as crucial regulators in the occurrence and development of pancreatic cancer (PC), which continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-135b and its associated mechanism to unravel the biological characteristics of tumor growth in pancreatic cancer stem cells (PCSCs).

Methods

Microarray analyses were initially performed to identify the PC-related miRNAs and genes. The expression of miR-135b and PCSC markers in PC tissues and cells was determined by RT-qPCR and western blot analysis, respectively. The potential gene (JADE-1) that could bind to miR-135b was confirmed by the dual-luciferase reporter assay. To investigate the tumorigenicity, migration, invasion, and stemness of PC cells, several gain-of-function and loss-of-function genetic experiments were conducted. Finally, tumor formation in nude mice was conducted to confirm the results in vivo.

Results

miR-135b was highly-expressed in PC tissues and PCSCs, which was identified to specifically target JADE-1. The overexpression of miR-135b promoted proliferation, migration, and invasion of PCSC, inhibited cell apoptosis and increased the expression of stemness-related factors (Sox-2, Oct-4, Nanog, Aldh1, and Slug). Moreover, miR-135b could promote the expression of phosphorylated AKT and phosphorylated mTOR in the AKT/mTOR pathway. Additionally, miR-135b overexpression accelerated tumor growth in nude mice.

Conclusions

Taken together, the silencing of miR-135b promotes the JADE-1 expression, which inactivates the AKT/mTOR pathway and ultimately results in inhibition of self-renewal and tumor growth of PCSCs. Hence, this study contributes to understanding the role of miR-135 in PCSCs and its underlying molecular mechanisms to aid in the development of effective PC therapeutics.
Proactive community case management in Senegal 2014–2016: a case study in maximizing the impact of community case management of malaria
Authors: Gaye Seynabou , Kibler Janelle , Ndiaye Jean Louis , Diouf Mame Birame , Linn Annē , Gueye Alioune Badara , Fall Fatou Ba , Ndiop Médoune , Diallo Ibrahima , Cisse Moustapha , Ba Mady , Thwing Julie
Published: April 2020

The Senegal National Malaria Control Programme (NMCP) introduced home-based malaria management for all ages, with diagnosis by rapid diagnostic test (RDT) and treatment with artemisinin-based combination therapy (ACT) in 2008, expanding to over 2000 villages nationwide by 2014. With prise en charge à domicile (PECADOM), community health workers (CHWs) were available for community members to seek care, but did not actively visit households to find cases. A trial of a proactive model (PECADOM Plus), in which CHWs visited all households in their village weekly during transmission season to identify fever cases and offer case management, in addition to availability during the week for home-based management, found that CHWs detected and treated more cases in intervention villages, while the number of cases detected weekly decreased over the transmission season. The NMCP scaled PECADOM Plus to three districts in 2014 (132 villages), to a total of six districts in 2015 (246 villages), and to a total of 16 districts in 2016 (708 villages). A narrative case study with programmatic results is presented. During active sweeps over approximately 20 weeks, CHWs tested a mean of 77 patients per CHW in 2014, 89 patients per CHW in 2015, and 90 patients per CHW in 2016, and diagnosed a mean of 61, 61 and 43 patients with malaria per CHW in 2014, 2015 and 2016, respectively. The number of patients who sought care between sweeps increased, with a 104% increase in the number of RDTs performed and a 77% increase in the number of positive tests and patients treated with ACT during passive case detection. While the number of CHWs increased 7%, the number of patients receiving an RDT increased by 307% and the number of malaria cases detected and treated by CHWs increased 274%, from the year prior to PECADOM Plus introduction to its first year of implementation. Based on these results, approximately 700 additional CHWs in 24 new districts were added in 2017. This case study describes the process, results and lessons learned from Senegal’s implementation of PECADOM Plus, as well as guidance for other programmes considering introduction of this innovative strategy.
RETRACTED ARTICLE: The effect of probiotics supplementation on blood pressure: a systemic review and meta-analysis
Authors: Qi Dan , Nie Xiao-Lu , Zhang Jian-Jun
Published: April 2020

Background

Fermented milk has over the last decade been intensively studied because of the putative antihypertensive effect. The aim of our study is to investigate the role of probiotics support therapy in blood pressure and, as a kind of convenient and economic drugs for prevention and auxiliary treatment of hypertension.

Materials and methods

We performed a systemic review and meta-analysis to examine the effect of probiotics consumption on blood pressure. Databases including MEDLINE, EMBASE, Clinical trials, CNKI and the Cochrane library were searched. Also, the grey literature and references were searched.

Results

Twenty-three randomized controlled trials (RCTs) involving 2037 participants met the inclusion criteria and were included. Probiotic consumption significantly changed systolic blood pressure (SBP) by − 3.05 mmHg (95%CI: − 4.67, − 1.44; P < 0.001) and diastolic blood pressure (DBP) by − 1.51 mmHg (95%CI: − 2.38, − 0.65; P = 0.001). Subgroup analysis indicated that the benefit effect of probiotics supplementation in SBP was only observed in hypertension [weight mean difference (WMD) = − 3.31 mmHg, 95%CI: − 5.71, − 0.92; P = 0.007] or type 2 diabetes (WMD = -4.85 mmHg, 95%CI: − 9.28, − 0.42; P = 0.032) patients, and the decreased DBP level by probiotics supplementation was only observed in hypertension patients (WMD = -2.02 mmHg, 95%CI: − 3.68, − 0.36; P = 0.017).This effect could only last for a short-term time of 8 or 10 weeks, but not for a long-term time.

Conclusion

This meta-analysis found a moderate and statistically significant reduction for either SBP or DBP with probiotics supplement compared with controls. Thus, probiotics is a potential for the dietary treatment of hypertension.
MiRNA-494 enhances M1 macrophage polarization via Nrdp1 in ICH mice model
Authors: Shao Gaohai , Zhou Changlong , Ma Kunlong , Zhao Wang , Xiong Qijiang , Yang Ling , Huang Zhongyan , Yang Zhao
Published: April 2020

Background

Ubiquitination-mediated M1/M2 macrophage polarization plays important roles in the pathogenesis of immune disease. However, the regulatory mechanism of ubiquitination during M1/M2 macrophage polarization following intracerebral hemorrhage (ICH) has not been well studied.

Methods

In the experiment, macrophages were administered with erythrocyte lysates, and then miR-494-, Nrdp1-, and M1/M2-related markers were analyzed. Brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed.

Results

We found that miR-494 levels increased while Nrdp1 levels decreased in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3′-untranslated region. MiR-494 attenuated C/EBP-β activation and downstream proinflammatory factor production. Upregulation of Nrdp1 in macrophages significantly promoted M2 macrophage polarization via ubiquitinating and activating C/EBP-β. Moreover, the results indicated that miR-494 could enhance M1 macrophage polarization, promote brain edema, and impair neurological functions in ICH mice.

Conclusions

Taken together, our results demonstrated that Nrdp1 contributed to M1/M2 macrophage polarization and neuroinflammation via ubiquitination and activation of C/EBP-β in ICH. miR-494 may provide a promising therapeutic clue for ICH.
Growth and elongation of axons through mechanical tension mediated by fluorescent-magnetic bifunctional Fe3O4·Rhodamine 6G@PDA superparticles
Authors: Wang Yang , Li Binxi , Xu Hao , Du Shulin , Liu Ting , Ren Jingyan , Zhang Jiayi , Zhang Hao , Liu Yi , Lu Laijin
Published: April 2020

Background

The primary strategy to repair peripheral nerve injuries is to bridge the lesions by promoting axon regeneration. Thus, the ability to direct and manipulate neuronal cell axon regeneration has been one of the top priorities in the field of neuroscience. A recent innovative approach for remotely guiding neuronal regeneration is to incorporate magnetic nanoparticles (MNPs) into cells and transfer the resulting MNP-loaded cells into a magnetically sensitive environment to respond to an external magnetic field. To realize this intention, the synthesis and preparation of ideal MNPs is an important challenge to overcome.

Results

In this study, we designed and prepared novel fluorescent-magnetic bifunctional Fe3O4·Rhodamine 6G@polydopamine superparticles (FMSPs) as neural regeneration therapeutics. With the help of their excellent biocompatibility and ability to interact with neural cells, our in-house fabricated FMSPs can be endocytosed into cells, transported along the axons, and then aggregated in the growth cones. As a result, the mechanical forces generated by FMSPs can promote the growth and elongation of axons and stimulate gene expression associated with neuron growth under external magnetic fields.

Conclusions

Our work demonstrates that FMSPs can be used as a novel stimulator to promote noninvasive neural regeneration through cell magnetic actuation.