bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of anticoagulant and platelet inhibition on the risk of bacteremia among patients with acute pyelonephritis: a retrospective cohort study
Authors: Steiner Svava E. , Edgren Gustaf , Melican Keira , Richter-Dahlfors Agneta , Brauner Annelie
Published: May 2022

Background

An increasing number of patients are being prescribed anticoagulants and platelet inhibitors (antithrombotic treatment). Basic research has suggested an association between antithrombotic treatment and bacteremia during kidney infection. Here, we investigated the association between antithrombotic treatment, bacteremia and acute kidney injury in patients with acute pyelonephritis.

Methods

A retrospective cohort study was conducted in a large university hospital in Sweden. Data were retrieved from electronic medical records for adult patients with acute pyelonephritis in 2016. The main outcome was bacteremia and secondary outcome acute kidney injury. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated through multiple logistic regression. Treatment with different groups of antithrombotic agents were compared to no antithrombotic treatment.

Results

1814 patients with acute pyelonephritis were included, in whom bacteremia developed in 336 (18.5%). Low-molecular-weight heparin (LMWH) at prophylactic doses was associated with a lower risk of bacteremia, compared to no antithrombotic treatment (OR 0.5; 95% CI 0.3–0.7). Other antithrombotic treatments were not associated with a risk of bacteremia. Additionally, patients with prophylactic doses of LMWH had a lower risk of acute kidney injury (OR 0.5; 95% CI 0.3–0.8).

Conclusions

We found no association between antithrombotic treatment and an increased risk of bacteremia during acute pyelonephritis. Conversely, patients with prophylactic doses of LMWH had a slightly reduced risk of bacteremia. LMWH at prophylactic doses was also associated with a lower risk of acute kidney injury. Our results suggest that it is safe to continue antithrombotic treatment during acute pyelonephritis, in regards to bacteremia and acute kidney injury risk.
Tescalcin promotes highly invasive papillary thyroid microcarcinoma by regulating FOS/ERK signaling pathway
Authors: Zou Xiuhe , Zhou Qian , Nie Yan , Gou Junhe , Yang Jing , Zhu Jingqiang , Li Zhihui , Gong Yanping
Published: May 2022

Background

Part of papillary thyroid microcarcinoma (PTMC) has a high risk of tumor invasion and metastasis, which may occur in the regional lymph node metastasis or distant metastasis, severely threatening the life of patients. Invasion and metastasis are tightly involved in the proliferation, migration and invasion in cancer. This study aimed to investigate the role of tescalcin (TESC) in the proliferation, migration and invasion of PTMC.

Methods

The expressions of TESC in PTMC tissues and cells were detected by immunohistochemistry or qRT-PCR. Then, TPC-1 and BHT101 cells transfected with TESC-RNAi were used for the transcriptome sequencing. The proliferation, apoptosis, migration and invasion of TPC-1 and BHT101 cells were detected by CCK-8, colony formation, flow cytometric assay, transwell migration and scratch test. Moreover, TESC-RNAi transfected TPC-1 and BHT101 cells were subcutaneously injected into mice. Tumor volume and weight were calculated, and the positive rate of Ki-67 was determined by immunohistochemistry. Finally, the levels of c-Fos, ERK1/2 and p-ERK1/2 were determined by western blot.

Results

The expressions of TESC in PTMC tissues and cell lines were prominently enhanced. Transcriptome sequencing results showed that c-Fos was decreased in TPC-1 and BHT101 cells transfected with TESC-RNAi, which was associated with multiple different signaling pathways including the MAPK signaling pathway. Furthermore, TESC promoted the progress of PTMC by regulating the expression of c-Fos, which might be associated with the ERK signaling pathway.

Conclusions

TESC promoted the growth and metastasis of PTMC through regulating c-Fos/ERK1/2.
An investigation of the Sustainability of Village Savings and Loans Associations (VSLAs) amidst Covid-19 and its impact on household income levels: lessons from Malawi, Sub-Saharan Africa
Authors: Chidimbah Munthali George N. , Wu Xuelian , Nambiro Woleson Dzimbiri Mastano , Zolo Amon , K.B Mushani John , Banda Lazarus Obed Livingstone
Published: May 2022

Background

Food security, malnutrition, and poverty are some of the challenges that most of the sub-Saharan African countries have been historically facing. With the coming of Covid-19 pandemic, the sustainability of the Village Savings and Loans Association which are formed to counter fight these challenges is questioned.

Aim

This study aimed to assess factors associated with the Sustainability of VSLAs amidst Covid-19 and its impacts on households' income levels.

Methods

An online cross-sectional design was conducted from November to January 2021, targeting VSLAs members in Mzuzu. A snowball and respondent-driven sampling technique were used to recruit the needful participants using a referral approach. IBM SPSS version 23 was used to perform descriptive statistics, Chi-Square, and binary logistic regression with unstandardized Beta (β), Odds Ratios (OR), and 95% Confidence Interval (CI) being taken into account with P-value set at 0.1, 0.05 and 0.01 significance levels.

Results

Our study finds that household income declined by 54% for those earnings belonged to ˂ MK5,000, as compared to 38% and 15% for medium (MK5,000 ≥ MK10,000) and higher (> MK10,000) income bands respectively. Our study shows that gender (β = 0.437, p = 0.094), age-group (β = 1.317, p = 0.000), education (β = 2.181, p = 0.047), share contributions (β = 1.035, p = 0.008), meetings (β = 0.572, p = 0.021), occupation (β = -0.453, p = 0.106), and frequency of meeting (β = -0.507, p = 0.049) were positively and negatively statistically significant predictors.

Conclusion

According to the findings of this study, households with lower income earners, which is one of the indicators of poverty, are more affected by the pandemic than their counterparts. We urge that the Malawi governments should maintain and, if they haven't already, implement programs that support low-income households, such as transfer payments, which have been shown to uplift people out of income poverty in many developing countries.
Range of invasive meningococcal disease sequelae and health economic application – a systematic and clinical review
Authors: Shen Jing , Begum Najida , Ruiz-Garcia Yara , Martinon-Torres Federico , Bekkat-Berkani Rafik , Meszaros Kinga
Published: May 2022

Background

Invasive meningococcal disease (IMD) is uncommon, life-threatening, with many diverse sequelae. The aims were to: 1) comprehensively characterise the sequelae; 2) have a systematic application for sequelae impact in economic evaluation (EE).

Methods

Sequelae categorised as physical/neurological or psychological/behavioural were identified from a systematic review of IMD observational studies (OS) and EEs in high-income countries (published 2001–2020). A comprehensive map and EE-relevant list, respectively, included physical/neurological sequelae reported in ≥2OS and ≥ 2OS + 2EE (≥1OS and ≥ 1OS + 1EE for psychological/behavioural). Sequelae proportions were selected from the highest quality studies reporting most sequelae. Three medical experts independently evaluated the clinical impact of findings.

Results

Sixty-Six OS and 34 EE reported IMD sequelae. The comprehensive map included 44 sequelae (30 physical/neurological, 14 psychological/behavioural), of which 18 (14 physical/neurological and 4 psychological/behavioural) were EE-relevant. Experts validated the study and identified gaps due to limited evidence, underreporting of psychological/behavioural sequelae in survivors/their families, and occurrence of multiple sequelae in the acute phase and long-term.

Conclusions

The considerable burden of IMD sequelae on survivors and their families is potentially underestimated in EE, due to underreporting and poorly-defined subtle sequelae. When assessing IMD burden and potential interventions e.g., vaccination, sequelae range and duration, underreporting, and indirect burden on dependents should be considered.
Association between dietary fiber intake and atherosclerotic cardiovascular disease risk in adults: a cross-sectional study of 14,947 population based on the National Health and Nutrition Examination Surveys
Authors: Zhang Shutang , Tian Jie , Lei Min , Zhong Canye , Zhang Yan
Published: May 2022

Background

This study aimed to investigate the association between dietary fiber intake and long-term cardiovascular disease (CVD) risk based on the National Health and Nutrition Examination Survey (NHANES) database.

Methods

A total of 14,947 participants aged 20–79 from the NHANES database were included in this study between 2009 and 2018. The atherosclerotic cardiovascular disease (ASCVD) score was utilized to predict the 10-year risk of CVD in individuals (low, borderline, intermediate, and high risk). Weighted univariate and multinomial multivariate logistic regression analyses were used to analyze the association between dietary fiber intake and long-term CVD risk.

Results

Higher dietary fiber density may be associated with a reduced ASCVD risk in participants with intermediate risk [odds ratio (OR) = 0.76; 95% confidence interval (CI), 0.61–0.94] and high risk (OR = 0.60; 95%CI, 0.45–0.81) compared with those in the group with low risk. Higher total dietary fiber intake may also reduce ASCVD risk in participants with high risk (OR = 0.84; 95%CI, 0.75–0.95). Subgroup analyses showed that higher dietary fiber density may be related to reduced ASCVD risk in intermediate-risk participants aged 20–39 (OR = 0.62; 95%CI, 0.43–0.89) and 40–59 (OR = 0.67; 95%CI, 0.49–0.94). In high-risk participants, higher dietary fiber density may reduce ASCVD risk in 20–39-year-old (OR = 0.38; 95%CI, 0.19–0.77), 40–59-year-old (OR = 0.37; 95%CI, 0.20–0.70), male (OR = 0.47; 95%CI, 0.23–0.97) and female (OR = 0.57; 95%CI, 0.38–0.86) participants.

Conclusion

Higher dietary fiber density and total dietary fiber intake were associated with a lower long-term CVD risk, especially in the 20–39 and 40–59 age groups, where the reduction was most significant.
Levels of HIV/AIDS stigma and associated factors among sexually active Ethiopians: analysis of 2016 Ethiopian Demographic and Health Survey Data
Authors: Feyasa Merga Belina , Gebre Mamo Nigatu , Dadi Teshome Kabeta
Published: May 2022

Background

Stigma and discrimination have fueled the transmission of the disease and dramatically increased its negative public health impact. Even though the disease has extremely ravaged human life, stigma, and discrimination attached to it are not well addressed in Ethiopia at the country level. The reduction of stigma and discrimination in a population are important indicators of the success of programs that target HIV prevention and control. This study aimed to assess the level of HIV-related stigma and its determinants among sexually active Ethiopians.

Methods

A public domain data were obtained from 2016 Ethiopian Demographic and Health Survey in which two-stage cross-sectional stratified cluster sampling was applied. A total of 28,371 sexually active Ethiopians were interviewed from both rural and urban parts of Ethiopia. Descriptive Statistics and multilevel ordinal logistic regression (proportional odds model) were used to summarize data and to investigate correlates of HIV-related stigma.

Results

Only 5.1% (95% CI: 4.5%, 5.8%) of sexually active Ethiopians did not have a stigmatizing attitude, whereas, 59.2% (95% CI: 57.3%, 61.1%) and 35.65% (95% CI: 33.5%, 37.9%) of them had a moderate and high level of stigma respectively. Regression results show that residence (AOR = 1.82, 95% CI:1.46, 2.27), education (AOR = 0.65,95% CI: 0.50,0.84), owning mobile (AOR = 0.63,95% CI:0.55,0.72), HIV-testing (AOR = 0.77, 95% CI:0.70,0.84), age (AOR = 0.81, 95% CI: 0.73, 0.91), religion (AOR = 1.53,95% CI:1.33,1.76), and marital status (AOR = 1.38, 95% CI:1.19, 1.61) were significantly associated with HIV-related stigma (p < 0.0001).

Conclusion

Regardless of all efforts put in a place to prevent and control HIV, a significant proportion of sexually active Ethiopians have stigmatizing attitudes. Residence, educational level, owning mobile, HIV test uptake, age, religion, and marital status were determinants of HIV-related stigma. Expanding mobile coverage, promoting HIV counseling and tests, promoting HIV education, and working with religious leaders, among other strategies could be used to minimize the stigma attached to the disease to best prevent and control it.
Implementing community-based Dried Blood Spot (DBS) testing for HIV and hepatitis C: a qualitative analysis of key facilitators and ongoing challenges
Authors: Young James , Ablona Aidan , Klassen Benjamin J. , Higgins Rob , Kim John , Lavoie Stephanie , Knight Rod , Lachowsky Nathan J.
Published: May 2022

Background

In 2018, the Community-Based Research Centre (CBRC) invited gay, bisexual, trans, queer men and Two-Spirit and non-binary people (GBT2Q) at Pride Festivals across Canada to complete in-person Sex Now surveys and provide optional dried blood spot (DBS) samples screening for human immunodeficiency virus (HIV) and hepatitis C virus (HCV). As there is a lack of research evaluating the implementation of DBS sampling for GBT2Q in community settings, we aimed to evaluate this intervention, identifying key facilitators and ongoing challenges to implementing community-based DBS screening for HIV/HCV among GBT2Q.

Methods

We conducted sixteen one-on-one interviews with individuals involved with the community-based DBS collection protocol, including research staff, site coordinators, and volunteer DBS collectors. Most individuals involved with DBS collection were “peers” (GBT2Q-identified). The Consolidated Framework for Implementation Research (CFIR) guided our data collection and analysis.

Results

Interviewees felt that DBS collection was a low-barrier, cost-effective, and simple way for peers to quickly screen a large number of Sex Now respondents. Interviewees also noted that the community and peer-based aspects of the research helped drive recruitment of Sex Now respondents. Most interviewees felt that the provision of results took too long, and that some Sex Now respondents would have preferred to receive their test results immediately (e.g., rapid or point-of-care testing).

Conclusion

Peer-based DBS sampling can be an effective and relatively simple way to screen GBT2Q at Pride Festivals for more than one sexually transmitted and blood borne infection.
Accelerometer-measured physical activity is associated with knee breadth in middle-aged Finns – a population-based study
Authors: Junno Juho-Antti , Keisu Asla , Niemelä Maisa , Modarress Julin Marella , Korpelainen Raija , Jämsä Timo , Niinimäki Jaakko , Lehenkari Petri , Oura Petteri
Published: May 2022

Background

Articular surface size is traditionally considered to be a relatively stable trait throughout adulthood. Increased joint size reduces bone and cartilage tissue strains. Although physical activity (PA) has a clear association with diaphyseal morphology, the association between PA and articular surface size is yet to be confirmed. This cross-sectional study aimed to clarify the role of moderate-to-vigorous PA (MVPA) in knee morphology in terms of tibiofemoral joint size.

Methods

A sample of 1508 individuals from the population-based Northern Finland Birth Cohort 1966 was used. At the age of 46, wrist-worn accelerometers were used to monitor MVPA (≥3.5 METs) during a period of two weeks, and knee radiographs were used to obtain three knee breadth measurements (femoral biepicondylar breadth, mediolateral breadth of femoral condyles, mediolateral breadth of the tibial plateau). The association between MVPA and knee breadth was analyzed using general linear models with adjustments for body mass index, smoking, education years, and accelerometer weartime.

Results

Of the sample, 54.8% were women. Most individuals were non-smokers (54.6%) and had 9—12 years of education (69.6%). Mean body mass index was 26.2 (standard deviation 4.3) kg/m2. MVPA was uniformly associated with all three knee breadth measurements among both women and men. For each 60 minutes/day of MVPA, the knee breadth dimensions were 1.8—2.0% (or 1.26—1.42 mm) larger among women (p < 0.001) and 1.4—1.6% (or 1.21—1.28 mm) larger among men (p < 0.001).

Conclusions

Higher MVPA is associated with larger tibiofemoral joint size. Our findings indicate that MVPA could potentially increase knee dimensions through similar biomechanical mechanisms it affects diaphyseal morphology, thus offering a potential target in reducing tissue strains and preventing knee problems. Further studies are needed to confirm and investigate the association between articulation area and musculoskeletal health.
Correlation between the thyroid hormone levels and nonalcoholic fatty liver disease in type 2 diabetic patients with normal thyroid function
Authors: Zhang Yuanyuan , Li Juyi , Liu Huaizhen
Published: May 2022

Background

The objective of this study is to retrospectively analyze the correlation between the thyroid hormones and nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients with normal thyroid function. Methods: Totally 586 T2DM patients with normal thyroid function participated in this research and were divided into T2DM without NAFLD (240 cases) group and T2DM with NAFLD (346 cases) group. The NAFLD fibrosis score (NFS) > 0.676 was defined as progressive liver fibrosis and used to categorize the patients into T2DM without progressive liver fibrosis group (493 cases) and T2DM with progressive liver fibrosis group (93 cases). Results: The results indicated that the levels of free triiodothyronine (FT3), total triiodomethylamine (TT3) and FT3/free thyroxine ratio (FT3/FT4) were significantly higher while the FT4 level was lower in T2DM with NAFLD group than that in T2DM without NAFLD group (p < 0.05). The levels of FT3, FT4, TT3 and TT4 in patients with progressive liver fibrosis were significantly lower in patients with progressive liver fibrosis than that in patients without progressive liver fibrosis (p < 0.05). Logistic regression analysis showed a positive connection between FT3/FT4 ratio and NAFLD (p = 0.038), a negative relationship between FT4 level and NAFLD (p = 0.026), between the levels of FT4, TT3 and total thyroxine (TT4) and the risk of progressive hepatic fibrosis (p = 0.022, p = 0.007, p = 0.046).

Conclusion

There is a certain correlation between thyroid hormone levels and NAFLD in T2DM patients, suggesting that the assessment of thyroid hormone levels in T2DM patients with normal thyroid function could be helpful in the prevention and treatment of NAFLD.
Clinical diagnostic value of American College of Radiology thyroid imaging report and data system in different kinds of thyroid nodules
Authors: Zhang Ziwei , Lin Ning
Published: May 2022

Background

To evaluate the diagnostic value of American College of Radiology (ACR) score and ACR Thyroid Imaging Report and Data System (TI-RADS) for benign nodules, medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) through comparing with Kwak TI-RADS.

Methods

Five hundred nine patients diagnosed with PTC, MTC or benign thyroid nodules were included and classified into the benign thyroid nodules group (n = 264), the PTC group (n = 189) and the MTC group (n = 56). The area under the curve (AUC) values were analyzed and the receiver operator characteristic (ROC) curves were drawn to compare the diagnostic efficiencies of ACR score, ACR TI-RADS and KWAK TI-RADS on benign thyroid nodules, MTC and PTC.

Results

The AUC values of ACR score, ACR TI-RADS and Kwak TI-RADS for distinguishing malignant nodules from benign nodules were 0.914 (95%CI: 0.886–0.937), 0.871 (95%CI: 0.839–0.899) and 0.885 (95%CI: 0.854–0.911), respectively. In distinguishing of patients with MTC from PTC, the AUC values of ACR score, ACR TI-RADS and Kwak TI-RADS were 0.650 (95%CI: 0.565–0.734), 0.596 (95%CI: 0.527–0.664), and 0.613 (95%CI: 0.545–0.681), respectively. The AUC values of ACR score, ACR TI-RADS and Kwak TI-RADS for the discrimination of patients with MTC, PTC or benign nodules from patients without MTC, PTC or benign nodules were 0.899 (95%CI: 0.882–0.915), 0.865 (95%CI: 0.846–0.885), and 0.873 (95%CI: 0.854–0.893), respectively.

Conclusion

The ACR score performed the best, followed ex aequo by the ACR and Kwak TI-RADS in discriminating patients with malignant nodules from benign nodules and patients with MTC from PTC.
Traditional menstruation practices among Nepalese women living in Japan
Authors: Kawata Rina , Endo Masayuki , Ohashi Kazutomo
Published: May 2022

Background

Traditional menstruation practices in Nepal (Chhaupadi in Nepalese) lack scientific support and undermine women’s health. This study aimed to understand the changes in the traditional menstruation practices due to migration from Nepal to Japan.

Methods

This study included 104 Nepalese women of reproductive age living in an urban area of western Japan. Participants were recruited using snowball sampling, and the method of data collection was a questionnaire survey. To examine how Nepalese women adapt traditional menstruation practices to their living environment, we compared how women followed frequently 17 traditional practices when they lived in Nepal and later in Japan. We examined the relationships among behavioural changes in traditional practices, education level, and caste.

Results

The frequency of 14 of the 17 traditional practices decreased after the women moved to Japan. Among women who reduced the frequency of traditional practices after moving from Nepal to Japan, the reduction was not associated with educational level or caste of the participants.

Conclusions

This study suggests that the attitudes towards the traditional menstruation practices change in response to living circumstances. Future studies should focus on determining living environment factors related to behavioural changes in traditional practices.
Perspectives of general practitioners towards their supervisors over the past ten years in China
Authors: xin Rao , Li Luo , Qiaoli Su , Xingyue Wang , Shuangqing Li
Published: May 2022

Objectives

Doctors who wish to become general practitioners (GPs) in China are required to attend and complete general practice resident training. In the early stages of the standardized GP training system, GP training supervisors play important roles. This study aims to explore how GP residents perceive their GP supervisors, factors that affect GP residents’ satisfaction level, as well as to offer suggestions based on the implications of this study.

Design

We conducted a mixed quantitative and qualitative study. Firstly, with respect to the quantitative research, we conducted a survey to investigate training satisfaction through questionnaires, then extracted and analyzed the factors that influence training satisfaction. In the qualitative study, we conducted in-depth, semistructured interviews using qualitative research criteria (COREQ)––a 32-item checklist for interviews.

Participants

Participants in the quantitative survey included 1172 GPs whose training time wasbetween 2008 and 2017. Afterwards, 100 participants were selected from this sample , filtered by stratified random sampling and by having provided extreme answers on the quantitative survey (less than 5% of the total sample). They were chosen for the qualitative research to conduct a more detailed investigation., This stratified random sampling was based on residents’ grades, regions, and training levels (city level or county level). Extreme answers were identified as answers of “extremely good” or “extremely bad” to questions from the initial comprehensive survey of 1172 participants. Consequently, 30 participants with extreme answers were found, while the remaining 70 participants in the interviews were selected by stratified random sampling. Ultimately, this sample of participants met our information collection and sample estimation requirements.

Results

The results show that satisfaction with GP theoretical training supervisors, GP hospital-based training supervisors, and GP community-based training supervisors differed. Considering long-term averages, the hierarchy of satisfaction is as follows: GP theoretical training supervisors > GP community-based training supervisors > GP hospital-based training supervisors.

GP hospital-based training supervisors need to improve their conception of GPs, teaching methods and conscientiousness. GP community-based training supervisors need to improve their teaching methods, knowledge of clinical theory and practice ability.

Conclusions

On the one hand, teams of GP supervisors in China have gradually been established over time. On the other hand,the satisfaction tendencies of residents with respect to their GP supervisors are quite different, and teams of GP supervisors must be promoted and improved.
Can positive expectations help to improve the learning of risk literacy? A cluster-randomized study in undergraduate medical students
Authors: Benson Sven , Schmidt Katharina , Kleine-Borgmann Julian , Herbstreit Stephanie , Schedlowski Manfred , Hollinderbäumer Anke
Published: May 2022

Background

Risk literacy, i.e., the ability to calculate and apply risk parameters, represents a key competence for risk communication and medical decision making. However, risk literacy is reportedly low in medical students. The successful acquisition of statistical competencies is often difficult, and can be hampered by emotional learning obstacles, calling for interventions to support learning. In this cluster-randomized study, we aimed to translate findings from placebo research to medical education. Specifically, we tested if the acquisition of risk literacy during a seminar unit can be facilitated by positive expectations, induced by a positive and non-threatening framing of the content and learning goals.

Methods

The study took place during a mandatory 2.5-h seminar on “risk literacy” for 2nd year medical students. The seminar teaches both statistical knowledge and its application in patient communication. To test the effects of expectations on risk literacy acquisition, the (otherwise identical) seminar was framed either as “communication training” (positive framing condition) or “statistics seminar” (negative framing condition). All N = 200 students of the semester were invited to participate, and cluster-randomized to the positive or negative framing condition (4 seminar groups each condition). Risk literacy was assessed with the “Quick Risk Test” (QRT) at the beginning and end of the seminar, along with statistics anxiety and subjective learning success using questionnaires.

Results

Data from N = 192 students were included. At the end of the seminar, risk literacy was increased in both framing conditions, with a significantly greater increase in QRT scores in the positive framing condition. Statistics anxiety was significantly decreased in both framing conditions, with no evidence of group differences. Subjective learning success was overall high and comparable between groups.

Conclusions

Supporting our hypothesis, positive framing led to a significantly greater increase in risk literacy (i.e., in QRT scores). Our data offer first support that positive framing of learning goals may help to facilitate the acquisition of statistical knowledge. Expectation-orientated interventions may thus offer a feasible tool to optimize learning settings and framing of learning objectives in medical statistics courses.
Effectiveness of instructional videos for enhancing healthcare provider competencies for hypertension management – a pre-post study in primary healthcare settings, Tanzania
Authors: Edward Anbrasi , Kagaruki Gibson B. , Manase Frank , Appel Lawrence J. , Matsushita Kunihiro
Published: May 2022

Background

Inadequate adherence to hypertension (HT) clinical standards by healthcare providers is one of the major barriers for HT management. We examined the effectiveness of four short instructional training videos on HT management.

Methods

Eighteen primary health care facilities were randomly selected using systematic sampling from five districts in the Dar es Salaam region, Tanzania. Pre-post provider knowledge assessments were conducted six months after training and provider performance was measured using patient observations on 8-10 consecutive adult patients per facility. A Screening Quality Index (SQI), comprised of ten HT screening standards, was used to measure adherence.

Results

Pre-post knowledge scores improved significantly, for, time between blood pressure (BP) readings (28.1% to 72.7%, p=0.01), BP threshold for patients with complications (21.2% to 97.0%, p<0.001), and lifestyle/dietary counseling (from 36.4% to 97.0%, p<0.001). SQI was significantly higher following the training for all provider groups; Nurses (3.0±3.5 to 8.4±1.0, p<0.001), Assistant Medical Officers and Medical Officers (3.5±4.1 to 7.6±2.4, p<0.001), and Assistant Clinical Officers and Clinical Officers (5.4±3.8 to 8.4±2.0, p<0.001). After training, significantly higher adherence was evident for key aspects of managing patients with HT: e.g., counseling on medication (62.1% to 92.7%, p=0.002), side effects (41.4% to 56.1%, p=0.009), reducing caloric intake (69.0 % to 95.1%, p=0.003), reducing cooking salt (65.5% to 97.6%, p<0.01), increasing physical activity (55.2% to 92.7% p<0.001), stopping/reducing cigarette smoking (24.1% to 63.4%, p=0.001), and reducing alcohol consumption (24.1% to 68.3%, p<0.001). SQI was significantly associated with number of years of provider experience (more than 2 years), type of primary healthcare facility (public facility), and exposure to the training intervention.

Conclusion

Training with short instructional videos can improve provider competency and clinical performance for HT management. The strategy has the potential to enhance effective implementation of HT control strategies in primary care clinics in Tanzania and elsewhere.
Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy
Authors: Wang Congcong , Li Ning , Li Yutian , Hou Shasha , Zhang Wenxin , Meng Zhaowei , Wang Shen , Jia Qiang , Tan Jian , Wang Renfei , Zhang Ruiguo
Published: May 2022

Exosomes are nanoscale monolayer membrane vesicles that are actively endogenously secreted by mammalian cells. Currently, multifunctional exosomes with tumor-targeted imaging and therapeutic potential have aroused widespread interest in cancer research. Herein, we developed a multifunctional HEK-293T exosome-based targeted delivery platform by engineering HEK-293T cells to express a well-characterized exosomal membrane protein (Lamp2b) fused to the αv integrin-specific iRGD peptide and tyrosine fragments. This platform was loaded with doxorubicin (Dox) and labeled with radioiodine-131 (131I) using the chloramine-T method. iRGD exosomes showed highly efficient targeting and Dox delivery to integrin αvβ3-positive anaplastic thyroid carcinoma (ATC) cells as demonstrated by confocal imaging and flow cytometry in vitro and an excellent tumor-targeting capacity confirmed by single-photon emission computed tomography-computed tomography after labeling with 131I in vivo. In addition, intravenous injection of this vehicle delivered Dox and 131I specifically to tumor tissues, leading to significant tumor growth inhibition in an 8505C xenograft mouse model, while showing biosafety and no side effects. These as-developed multifunctional exosomes (denoted as Dox@iRGD-Exos-131I) provide novel insight into the current treatment of ATC and hold great potential for improving therapeutic efficacy against a wide range of integrin αvβ3-overexpressing tumors.

Graphical Abstract
Platinum-induced mitochondrial OXPHOS contributes to cancer stem cell enrichment in ovarian cancer
Authors: Sriramkumar Shruthi , Sood Riddhi , Huntington Thomas D. , Ghobashi Ahmed H. , Vuong Truc T. , Metcalfe Tara X. , Wang Weini , Nephew Kenneth P. , O’Hagan Heather M.
Published: May 2022

Background

Platinum based agents—cisplatin and carboplatin in combination with taxanes are used for the treatment of ovarian cancer (OC) patients. However, the majority of OC patients develop recurrent, platinum resistant disease that is uniformly fatal. Platinum treatment enriches for chemoresistant aldehyde dehydrogenase (ALDH) + ovarian cancer stem cells (OCSCs), which contribute to tumor recurrence and disease relapse. Acquired platinum resistance also includes metabolic reprograming and switching to oxidative phosphorylation (OXPHOS). Chemosensitive cells rely on glycolysis while chemoresistant cells have the ability to switch between glycolysis and OXPHOS, depending on which pathway drives a selective advantage for growth and chemoresistance. High expression of genes involved in OXPHOS and high production of mitochondrial ROS are characteristics of OCSCs, suggesting that OCSCs favor OXPHOS over glycolysis. Based on connections between OCSCs, chemoresistance and OXPHOS, we hypothesize that platinum treatment induces changes in metabolism that contribute to platinum-induced enrichment of OCSCs.

Methods

The effect of cisplatin on mitochondrial activity was assessed by JC1 staining and expression of OXPHOS genes by RT-qPCR. Cisplatin-induced changes in Sirtuin 1 (SIRT1) levels and activity were assessed by western blot. Small molecule inhibitors of mitochondrial complex I and SIRT1 were used to determine if their enzymatic activity contributes to the platinum-induced enrichment of OCSCs. The percentage of ALDH + OCSCs in OC cells and tumor tissue from xenograft models across different treatment conditions was analyzed using ALDEFLUOR assay and flow cytometry.

Results

We demonstrate that platinum treatment increases mitochondrial activity. Combined treatment of platinum agents and OXPHOS inhibitors blocks the platinum-induced enrichment of ALDH + OCSCs in vitro and in vivo. Furthermore, platinum treatment increases SIRT1 levels and subsequent deacetylase activity, which likely contributes to the increase in platinum-induced mitochondrial activity.

Conclusions

These findings on metabolic pathways altered by platinum-based chemotherapy have uncovered key targets that can be exploited therapeutically to block the platinum-induced enrichment of OCSCs, ultimately improving the survival of OC patients.
Pentoxifylline alleviates ischemic white matter injury through up-regulating Mertk-mediated myelin clearance
Authors: Zheng Lili , Jia Junqiu , Chen Yan , Liu Renyuan , Cao Runjing , Duan Manlin , Zhang Meijuan , Xu Yun
Published: May 2022

Background

Vascular dementia (VAD) is the second most common type of dementia lacking effective treatments. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, displays protective effects in multiple cerebral diseases. In this study, we aimed to investigate the therapeutic effects and potential mechanisms of PTX in VAD.

Methods

Bilateral common carotid artery stenosis (BCAS) mouse model was established to mimic VAD. Mouse behavior was tested by open field test, novel object recognition test, Y-maze and Morris water maze (MWM) tests. Histological staining, magnetic resonance imaging (MRI) and electron microscopy were used to define white matter integrity. The impact of PTX on microglia phagocytosis, peroxisome proliferator-activated receptors-γ (PPAR-γ) activation and Mer receptor tyrosine kinase (Mertk) expression was assessed by immunofluorescence, western blotting and flow cytometry with the application of microglia-specific Mertk knockout mice, Mertk inhibitor and PPAR-γ inhibitor.

Results

Here, we found that PTX treatment alleviated cognitive impairment in novel object recognition test, Y-maze and Morris water maze tests. Furthermore, PTX alleviated white matter injury in corpus callosum (CC) and internal capsule (IC) areas as shown by histological staining and MRI analysis. PTX-treatment group presented thicker myelin sheath than vehicle group by electron microscopy. Mechanistically, PTX facilitated microglial phagocytosis of myelin debris by up-regulating the expression of Mertk in BCAS model and primary cultured microglia. Importantly, microglia-specific Mertk knockout blocked the therapeutic effects of PTX in BCAS model. Moreover, Mertk expression was regulated by the nuclear translocation of PPAR-γ. Through modulating PPAR-γ, PTX enhanced Mertk expression.

Conclusions

Collectively, our results demonstrated that PTX showed therapeutic potentials in VAD and alleviated ischemic white matter injury via modulating Mertk-mediated myelin clearance in microglia.
Anti-inflammatory effects of recreational marijuana in virally suppressed youth with HIV-1 are reversed by use of tobacco products in combination with marijuana
Authors: Yin Li , Dinasarapu Ashok R. , Borkar Samiksha A. , Chang Kai-Fen , De Paris Kristina , Kim-Chang Julie J. , Sleasman John W. , Goodenow Maureen M.
Published: May 2022

Background

Marijuana’s putative anti-inflammatory properties may benefit HIV-associated comorbidities. How recreational marijuana use affects gene expression in peripheral blood cells (PBC) among youth with HIV-1 (YWH) is unknown.

Approach

YWH with defined substance use (n = 54) receiving similar antiretroviral therapy (ART) were assigned to one of four analysis groups: YWH with detectable plasma HIV-1 (> 50 RNA copies/ml) who did not use substances (H+V+S−), and YWH with undetectable plasma HIV-1 who did not use substances (H+V−S−), or used marijuana alone (H+V−S+[M]), or marijuana in combination with tobacco (H+V−S+[M/T]). Non-substance using youth without HIV infection (H−S−, n = 25) provided a reference group. PBC mRNA was profiled by Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Differentially expressed genes (DEG) within outcome groups were identified by Significance Analysis of Microarrays and used for Hierarchical Clustering, Principal Component Analysis, and Ingenuity Pathways Analysis.

Results

HIV-1 replication resulted in > 3000 DEG involving 27 perturbed pathways. Viral suppression reduced DEG to 313, normalized all 27 pathways, and down-regulated two additional pathways, while marijuana use among virally suppressed YWH resulted in 434 DEG and no perturbed pathways. Relative to H+V−S−, multiple DEG normalized in H+V−S+[M]. In contrast, H+V−S+[M/T] had 1140 DEG and 10 dysregulated pathways, including multiple proinflammatory genes and six pathways shared by H+V+S−.

Conclusions

YWH receiving ART display unique transcriptome bioprofiles based on viral replication and substance use. In the context of HIV suppression, marijuana use, alone or combined with tobacco, has opposing effects on inflammatory gene expression.
Effect of catheter ablation combined with left appendage occlusion for non-valvular atrial fibrillation: a meta-analysis
Authors: Qu Jun , Wang Zhen , Wang Shuhao
Published: May 2022

Objective

To estimate the effect of catheter ablation combined with left appendage occlusion in the treatment of non-valvular atrial fibrillation (NVAF) by a method of meta-analysis.

Methods

Pubmed, Embase, and Cochrane Library were searched for the studies about catheter ablation combined with left appendage occlusion in treating NVAF. The data analysis was performed using R 4.0.5 software. The retrieval time was from inception to May 12, 2021.

Results

A total of 18 published studies were identified in the meta-analysis, including 1385 participants. During the perioperative period of catheter ablation combined with left appendage occlusion in treating NVAF, the pooled incidences of pericardial effusion, major or minor bleeding events, and residual flow documented were 0.5%(95%CI 0.0002–0.0099), 1.42%(95% CI 0.00–0.04), 7.24%(95% CI 0.0447–0.0975), respectively. During the follow-up, the incidences of all-cause mortality, embolism events, and bleeding events were 0.32%(95%CI 0.0000–0.0071), 1.29%(95%CI 0.0037–0.0222), 2.07%(95% CI 0.0075–0.0339), respectively. In the follow-up period of the transesophageal echocardiography, the most complication was residual flow event with an incident rate of 10.80%(95% CI 0.054–0.1620). The maximum occurrence probability of residual flow events was 17.92% (95% CI 0.1133–0.2452). Moreover, the incident rate of NVAF recurrence was 29.23% (95% CI 0.2222–0.3623).

Conclusion

The meta-analysis suggests that the “one-stop” procedure is effective for those patients undergoing NVAF. However, Patients with more residual blood flow have a higher incidence of bleeding complications. More studies are warranted to verify the safety and efficacy of catheter ablation combined with left appendage occlusion in terms of the “one-stop” procedure.
Prompting endogenous repair of brain injury: science fiction or reality?
Authors: de Rus Jacquet Aurelie , Cicchetti Francesca
Published: May 2022

Drug-refractory forms of neurological diseases could find their next breakthrough therapy in non-pharmacological approaches to brain repair. Lentini et al. present the potential of in situ brain regeneration to address neurodegeneration in the epileptic brain.
Depletion of Toxoplasma adenine nucleotide translocator leads to defects in mitochondrial morphology
Authors: Wu Yihan , Ying Zhu , Liu Jing , Sun Zhepeng , Li Shuang , Liu Qun
Published: May 2022

Background

Adenine nucleotide translocase (ANT) is a protein that catalyzes the exchange of ADP/ATP across the inner mitochondrial membrane. Beyond this, ANT is closely associated with cell death pathways and mitochondrial dysfunction. It is a potential therapeutic target for many diseases. The function of the ANT in Toxoplasma gondii is poorly understood.

Methods

The CRISPR/CAS9 gene editing tool was used to identify and study the function of the ANT protein in T. gondii. We constructed T. gondii ANT transgenic parasite lines, including endogenous tag strain, knockout strain and gene complement strain, to clarify the function and location of TgANT. Mitochondrial morphology was observed by immunofluorescence and transmission electron microscopy.

Results

Toxoplasma gondii was found to encode an ANT protein, which was designated TgANT. TgANT localized to the inner mitochondrial membrane. The proliferation of the Δant strain was significantly reduced. More important, depletion of TgANT resulted in significant changes in the morphology and ultrastructure of mitochondria, abnormal apicoplast division and abnormal cytoskeletal daughter budding. In addition, the pathogenicity of the Δant strain to mice was significantly reduced.

Conclusions

Altogether, we identified and characterized the ANT protein of T. gondii. Depletion of TgANT inhibited parasite growth and impaired apicoplast and mitochondrial biogenesis, as well as abnormal parasite division, suggesting TgANT is important for parasite growth.
Physical optimization of cell proliferation and differentiation using spinner flask and microcarriers
Authors: Yang Feng , Wang Shouwei , Li Yingying , Li Shilei , Liu Wenting , Li Yushuang , Hu Haijuan
Published: May 2022

The traditional breeding industry has been increasingly saturated and caused environmental pollution, disease transmission, excessive resource use, and methane emission; however, it still cannot meet the needs of the growing population. To explore other alternatives, researchers focused on cell agriculture and cell-based meat, especially large-scale cell culture. As a prerequisite for production, large-scale culture technology has become an important bottleneck restricting cell-based meat industrialization. In this study, the single-factor variable method was adopted to examine the influence of Cytodex1 microcarrier pretreatment, spinner flask reaction vessel, cell culture medium, serum and cell incubation, and other influencing factors on large-scale cell cultures to identify the optimization parameters suitable for 3D culture environment. Collagen and 3D culture were also prospectively explored to promote myogenesis and cultivate tissue-like muscle fibers that contract spontaneously. This research lays a theoretical foundation and an exploratory practice for large-scale cell cultures and provides a study reference for the microenvironment of myoblast culture in vitro, a feasible direction for the cell therapy of muscular dystrophy, and prerequisites for the industrialized manufacturing of cell-based meat.

Graphical Abstract
Host-dependent impairment of parasite development and reproduction in the acanthocephalan model
Authors: Schmidt Hanno , Mauer Katharina , Hankeln Thomas , Herlyn Holger
Published: May 2022

Background

A central question in parasitology is why parasites mature and reproduce in some host species but not in others. Yet, a better understanding of the inability of parasites to complete their life cycles in less suitable hosts may hold clues for their control. To shed light on the molecular basis of parasite (non-)maturation, we analyzed transcriptomes of thorny-headed worms (Acanthocephala:Pomphorhynchus laevis), and compared developmentally arrested worms excised from European eel (Anguilla anguilla) to developmentally unrestricted worms from barbel (Barbus barbus).

Results

Based on 20 RNA-Seq datasets, we demonstrate that transcriptomic profiles are more similar betweenP. laevismales and females from eel than between their counterparts from barbel. Impairment of sexual phenotype development was reflected in gene ontology enrichment analyses of genes having differential transcript abundances. Genes having reproduction- and energy-related annotations were found to be affected by parasitizing either eel or barbel. According to this, the molecular machinery of male and female acanthocephalans from the eel is less tailored to reproduction and more to coping with the less suitable environment provided by this host. The pattern was reversed in their counterparts from the definitive host, barbel.

Conclusions

Comparative analysis of transcriptomes of developmentally arrested and reproducing parasites elucidates the challenges parasites encounter in hosts which are unsuitable for maturation and reproduction. By studying a gonochoric species, we were also able to highlight sex-specific traits. In fact, transcriptomic evidence for energy shortage in female acanthocephalans associates with their larger body size. Thus, energy metabolism and glycolysis should be promising targets for the treatment of acanthocephaliasis. Although inherently enabling a higher resolution in heterosexuals, the comparison of parasites from definitive hosts and less suitable hosts, in which the parasites merely survive, should be applicable to hermaphroditic helminths. This may open new perspectives in the control of other helminth pathogens of humans and livestock.