bluuebunny/crossref_metadata_2025 huggingface dataset:
The prognostic utility of GRACE risk score in predictive adverse cardiovascular outcomes in patients with NSTEMI and multivessel disease
Authors: Chen Xiaokang , Wu Hao , Li Liangpeng , Zhao Xiaofang , Zhang Chao , Wang Wei Eric
Published: December 2022

Background

GRACE risk score models are capable of predicting all-cause mortality of non-ST elevation myocardial infarction (NSTEMI) patients. However, its utility for evaluating major adverse cardiovascular events (MACE) in NSTEMI patients with multivessel disease (MVD) remains unclear.

Methods and results

This study was designed as a retrospective cohort study that recruited patients with NSTEMI and multivessel disease between September 2013 and December 2018 in Daping Hospital, Chongqing, China. The primary outcome was a composite outcome that included all-cause mortality, recurrent angina, non-fatal myocardial infarction, coronary re-vascularization, and non-fatal strokes. Of the 827 patients with NSTEMI, 32 did not complete follow-up and 430 were excluded because of single-vessel disease. The remaining 365 NSTEMI patients with MVD had a median follow-up of 3.0 (IQR 2.6–3.3) years, 78 patients experienced outcomes. The GRACE risk score predicted the MACE (hazard ratio 1.014, 95% CI 1.006–1.021, P < 0.001). The GRACE risk score performed well in predicting all-cause mortality (c-statistic 0.72, 95% CI 0.59–0.85, P = 0.001) in MVD but was less powerful in predicting MACE (c-statistic 0.69, 95% CI 0.62–0.75, P < 0.001). When combining the GRACE risk score with the SYNTAX score, and blood urea nitrogen for predicting all-cause mortality and MACE events, the c-statistic value increased to 0.82 and 0.81 (P < 0.001).

Conclusion

In NSTEMI patients with MVD, the GRACE score showed an acceptable predictive value for all-cause mortality, but it was less powerful in predicting MACE. Blood urea nitrogen may be valuable in assessing long-term cardiovascular events in patients with MVD.
Epidemiological pattern of trauma patients based on the mechanisms of trauma: trends of a regional trauma center in Midwest of Iran
Authors: Roshanaei Ghodratollah , Khoshravesh Sahar , Abdolmaleki Sajjad , Bathaei Tayebeh , Farzian Mahnaz , Saatian Mohammadreza
Published: December 2022

Introduction

Trauma is one of the important issues in public health because it is responsible for 90% of mortality in Low and Middle-Income Countries (LIMCs). The present study aimed to determine the epidemiological pattern of trauma patients in a regional trauma center in the Midwest of Iran from 2014 to 2020.

Methods

This study was a retrospective study that was performed on 29,804 trauma patients admitted to Be′sat Hospital in Hamadan from January 2014 to December 2020. Data was collected using Health Information Management (HIM) Center of the Be′sat Hospital. For investigating the relationship of the characteristics of trauma patients and the mechanisms of trauma, Multiple Multinomial Logistic Regression (MMNLR) model was used. All statistical analyses were performed using the IBM SPSS Statistics version 24.

Results

The mean age of all patients was 35.4 (SD = 21.9) years. Most of them were men (71.7%). The most common mechanism of trauma was road traffic accidents (RTAs) (39.6%) followed by falls (30.2%), other (19.7%), violence (6.2%), and burn (4.4%). 1.5% of the trauma patients expired. The results of multiple multinomial logistic regression indicated that significant affected factor on odds referring because of RTAs compared to other mechanism were: season and hospital length of stay (LOS); in falls and violence: age, sex, season, and LOS; and in burn: age, sex, season, evening time, and LOS (p < 0.05).

Conclusion

Based on the investigation of 29,804 trauma patients, in Iran as a developing country, RTAs and falls were two common mechanisms of trauma. It seems that as a short-term plan, it is possible to focus on road safety, to improve the quality of vehicles, to hold training courses for drivers. Also, as a long-term goal, considering that the elderly population in Iran is increasing, it is necessary to pay attention to fall reduction programs.
Common laboratory blood test immune panel markers are useful for grading ulcerative colitis endoscopic severity
Authors: Cui Jiawei , Li Xiujuan , Zhang Zhiqiang , Gao Hongliang , Li Jian
Published: December 2022

Background

At present, many indicators reflect the clinical disease activity of ulcerative colitis (UC). However, commonly used inflammatory markers do not show good utility for indicating endoscopic disease activity. The purpose of this study was to evaluate high sensitivity C-reactive protein (hs-CRP), C-reactive protein to albumin ratio (CAR), inflammatory markers, and complete blood count (CBC) related parameters in patients with UC as simple, non-invasive, and independent markers of endoscopic activity (EA).

Methods

We retrospectively collected extensive data from the hospital medical records of 386 patients who presented with UC to the First Affiliated Hospital of Xinjiang Medical University (Urumqi, China) from 2018 to 2022 January. The Mayo endoscopic score (MES) was used to evaluate endoscopic disease activity. All included patients were defined as the MES-All group; those with extensive colitis (E3) were defined as the MES-E3 group. Demographics, laboratory parameters, endoscopic results, the extent of disease, and drug history were recorded and analyzed.

Results

For patients in the MES-All or MES-E3 group, hs-CRP, CAR, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were significantly higher in EA UC patients than in those with mucosal healing. The mean platelet volume (MPV) and lymphocyte to monocyte ratio were significantly lower in active disease than in the patient’s remission (p < 0.001). ROC analysis showed that in the MES-All and MES-E3 groups, the cutoff values of hs-CRP activity under endoscopy were 5.32 mg/L (AUC 0.850, sensitivity 77.6%, specificity 81.9%) and 5.16 mg/L (AUC 0.902, sensitivity 86.9%, specificity 85.4%) respectively, and the cutoff values of CAR were 0.14 (AUC 0.853, sensitivity 76.8%, specificity 84.8%) and 0.18 (AUC 0.904, sensitivity 81.8%, specificity 89.6%) respectively. Multivariate logistic regression analysis showed that hs-CRP, CAR, NLR, and PLR identified UC EA, while decreased MPV reflected inflammatory activity in the UC mucosa.

Conclusion

Especially in patients with extensive colitis, hs-CRP and CAR are closely related to EA and show a higher diagnostic value compared to the related CBC parameters. The aforementioned indicators are simple and non-invasive independent markers that reflect the EA in UC.
SARS-CoV-2 outbreaks in secondary school settings in the Netherlands during fall 2020; silent circulation
Authors: Jonker Lotte , Linde Kimberly J. , de Hoog Marieke L. A. , Sprado Robin , Huisman Robin C. , Molenkamp Richard , Oude Munnink Bas B. , Dohmen Wietske , Heederik Dick J. J. , Eggink Dirk , Welkers Matthijs R. A. , Vennema Harry , Fraaij Pieter L. A. , Koopmans Marion P. G. , Wouters Inge M. , Bruijning-Verhagen Patricia C. J. L.
Published: December 2022

Background

In fall 2020 when schools in the Netherlands operated under a limited set of COVID-19 measures, we conducted outbreaks studies in four secondary schools to gain insight in the level of school transmission and the role of SARS-CoV-2 transmission via air and surfaces.

Methods

Outbreak studies were performed between 11 November and 15 December 2020 when the wild-type variant of SARS-CoV-2 was dominant. Clusters of SARS-CoV-2 infections within schools were identified through a prospective school surveillance study. All school contacts of cluster cases, irrespective of symptoms, were invited for PCR testing twice within 48 h and 4–7 days later. Combined NTS and saliva samples were collected at each time point along with data on recent exposure and symptoms. Surface and active air samples were collected in the school environment. All samples were PCR-tested and sequenced when possible.

Results

Out of 263 sampled school contacts, 24 tested SARS-CoV-2 positive (secondary attack rate 9.1%), of which 62% remained asymptomatic and 42% had a weakly positive test result. Phylogenetic analysis on 12 subjects from 2 schools indicated a cluster of 8 and 2 secondary cases, respectively, but also other distinct strains within outbreaks. Of 51 collected air and 53 surface samples, none were SARS-CoV-2 positive.

Conclusion

Our study confirmed within school SARS-CoV-2 transmission and substantial silent circulation, but also multiple introductions in some cases. Absence of air or surface contamination suggests environmental contamination is not widespread during school outbreaks.
The relationship between smartphone addiction and aggression among Lebanese adolescents: the indirect effect of cognitive function
Authors: Fekih-Romdhane Feten , Malaeb Diana , Sarray El Dine Abir , Obeid Sahar , Hallit Souheil
Published: December 2022

Background

Despite a large body of research has shown that smartphone addiction (SA) is associated with aggressive behaviors, only a few mediators have been previously examined in this relationship among early adolescent students. No previous studies have explored, to our knowledge, the indirect role of cognitive function despite its great importance during this life period. This study is intended to verify whether cognitive function have indirect effects on the relationship between SA and aggression among high-school students in the context of Lebanese culture.

Methods

This was a cross-sectional designed study, conducted between January and May 2022, and enrolling 379 Lebanese adolescent students (aged 13–17 years). The Cognitive Functioning Self-Assessment Scale, the Buss–Perry Aggression Questionnaire-Short Form, and the Smartphone Addiction Scale-Short form were used.

Results

The bivariate analysis results revealed that higher SA and worse cognitive function were significantly associated with more physical aggression, verbal aggression, anger and hostility. The mediation analyses found that cognitive function mediated the association between SA and physical aggression, verbal aggression, anger and hostility. Higher SA was significantly associated with worse cognitive function and more physical aggression, verbal aggression, anger and hostility. Finally, worse cognitive function was significantly associated with more physical aggression, verbal aggression, anger and hostility.

Conclusion

Our findings cautiously suggest that, to reduce adolescent students’ aggression, interventions that promote cognitive performance may be effective. Particularly, students who are addicted to smartphones and show aggressive tendencies require interventions designed to improve cognition function.
Development of the Chinese preschooler dietary index: a tool to assess overall diet quality
Authors: Wang Xiaoyu , Xu Yujie , Tan Bingbing , Duan Ruonan , Shan Shufang , Zeng Linan , Zou Kun , Zhao Li , Xiong Jingyuan , Zhang Lingli , Rong Shuang , Cheng Guo
Published: December 2022

Background

Diet quality in early childhood has a long-term impact on health outcomes. However, there are scarce dietary indexes for Chinese preschool children, and the existing indexes had limited validity and reliability. This study thus aimed to develop a dietary index for preschool children based on the Chinese Dietary Guideline and Chinese Dietary Reference Intakes and to assess their overall diet quality using the China Health and Nutrition Survey (CHNS).

Methods

The Chinese Preschooler Dietary Index (CPDI) included 11 components, covering 9 food group components and two nutrient components. The total scores of CPDI ranged from 0 to 90, with a higher score indicating greater diet quality. This study assessed the diet quality of 1742 preschoolers aged two to five years old from CHNS using the CPDI. Dietary intake data were obtained using three-day 24-h diet recalls, and sociodemographic information was also collected. Cochran-Mantel-Haensel (CMH) test was used to explore the association between demographic and CPDI total scores. The principal component analysis, correlation analysis and Cronbach’s alpha were used to evaluate the relative reliability and validity of the CPDI. Finally, a stepwise multiple regression analysis was performed to explore potential influencing factors of CPDI.

Results

Among the 1742 CHNS preschool children, more than 70% resided in rural areas and 41.2% of the sample were raised in a low-income family. The mean CPDI score of the preschoolers was 38.8 ± 12.9. Higher diet scores were correlated with higher energy and nutrient intake. Children with higher age (β = 0.93, SE = 0.26,P = 0.0003), raised in a home with higher household income (β = 3.11, SE = 0.27,P < 0.0001) or living in urban areas (β = -4.44, SE = 0.66,P < 0.0001) were associated with higher CPDI scores.

Conclusions

The CPDI is useful in evaluating the diet quality of preschool children. Based on the CPDI, the diet quality of Chinese preschoolers needs to be improved, especially in rural areas.
Comparing enhancements to well-child visits in the prevention of obesity: ENCIRCLE cluster-randomized controlled trial
Authors: Bailey-Davis Lisa , Moore Amy M. , Poulsen Melissa N. , Dzewaltowski David A. , Cummings Stacey , DeCriscio Laina R. , Hosterman Jennifer Franceschelli , Huston Daniel , Kirchner H. Lester , Lutcher Shawnee , McCabe Carolyn , Welk Gregory J. , Savage Jennifer S.
Published: December 2022

Background

Obesity disproportionally impacts rural, lower-income children in the United States. Primary care providers are well-positioned to engage parents in early obesity prevention, yet there is a lack of evidence regarding the most effective care delivery models. The ENCIRCLE study, a pragmatic cluster-randomized controlled trial, will respond to this gap by testing the comparative effectiveness of standard care well-child visits (WCV) versus two enhancements: adding a patient-reported outcome (PRO) measure (PRO WCV) and PRO WCV plus Food Care (telehealth coaching and a grocery store tour).

Methods

A total of 2,025 parents and their preschool-aged children (20–60 months of age) will be recruited from 24 Geisinger primary care clinics, where providers are randomized to the standard WCV, PRO WCV, or PRO WCV plus Food Care intervention arms. The PRO WCV includes the standard WCV plus collection of the PRO—the Family Nutrition and Physical Activity (FNPA) risk assessment—from parents. Parents complete the PRO in the patient-portal or in the clinic (own device, tablet, or kiosk), receive real-time feedback, and select priority topics to discuss with the provider. These results are integrated into the child’s electronic health record to inform personalized preventive counseling by providers. PRO WCV plus Food Care includes referrals to community health professionals who deliver evidence-based obesity prevention and food resource management interventions via telehealth following the WCV. The primary study outcome is change in child body mass index z-score (BMIz), based on the World Health Organization growth standards, 12 months post-baseline WCV. Additional outcomes include percent of children with overweight and obesity, raw BMI, BMI50, BMIz extended, parent involvement in counseling, health behaviors, food resource management, and implementation process measures.

Discussion

Study findings will inform health care systems’ choices about effective care delivery models to prevent childhood obesity among a high-risk population. Additionally, dissemination will be informed by an evaluation of mediating, moderating, and implementation factors.

Trial registration

ClinicalTrials.gov identifier (NCT04406441); Registered May 28, 2020.
Comparison of antibacterial effect of plantaricin 149 suspension and traditional root canal irrigation solutions in root canal infections in vitro
Authors: Wang Ying , Chen Keda , Lin Xiaolong
Published: December 2022

Dental pulp and periapical diseases are common conditions in stomatology, caused by various pathogenic microorganisms. Antimicrobial peptides, as new antibiotics, offer promising applications in the irrigation and disinfection medicaments for root canals.

One patient with chronic periapical periodontitis was selected to extract the clinical pathogenic bacteria.Porphyromonas gingivalis(Pg) (ATCC 33,277),Streptococcus mutans(Sm) (ATCC 25,175), andPrevotella intermedius(Pi) (ATCC 25,611) were used as test strains. The effects of plantaricin (Pln) 149 on the biofilm formation and growth in infected root canals were evaluated by RT-PCR, laser confocal scanning microscopy, and bacterial diversity analysis. In addition, the cytotoxicity of Pln 149 (100 µg/mL) to human dental pulp stem cells (hDPSCs) was assessed using an MTT assay. Pln 149 exhibited significant inhibitory effects on Pg Sm and Pi (P < 0.05), with significant differences in the biofilm images of the laser confocal scanning microscope (P < 0.05). There were no significant differences in hDPSCs viability or proliferation between the Pln 149 and control groups. Considering the excellent antimicrobial effects and low cytotoxicity, we suggest that Pln 149 might be a promising option for root canal irrigation solutions.
The relationship among pregnancy-related anxiety, perceived social support, family function and resilience in Chinese pregnant women: a structural equation modeling analysis
Authors: Huang Jingui , Xu Lingli , Xu Zhen , Luo Yexin , Liao Bizhen , Li Yan , Shi Yumei
Published: December 2022

Background

Accumulating evidence suggests that pregnancy-related anxiety (PRA) has adverse impacts on maternity health and infant development. A substantial body of literature has documented the important influence of family function, perceived social support and resilience on PRA. However, research identifying the mediating mechanisms underlying this relationship in China are still lacking. Therefore, the current study aimed to investigate the prevalence of PRA under the three-child policy in China, and also explore the interrelationships among perceived social support, family function, resilience, and PRA.

Methods

In this cross-sectional study, a convenient sampling method was used to select 579 pregnant women who underwent prenatal examination at the maternity outpatient departments of the First Affiliated Hospital of Chongqing Medical University in China from December 2021 to April 2022. Participants were required to complete the following questionnaires: the demographic form, the Chinese Pregnancy-related Anxiety scale, the 10-item Connor-Davidson Resilience Scale, the APGAR Family Care Index Scale, and Multidimensional Scale of Perceived Social Support. Pearson correlation analysis was utilized to examine the rudimentary relationship among the study variables. Bootstrapping analyses in the structural equation modeling were applied to identify the significance of indirect effects.

Results

There were 41.4% of pregnant Chinese women indicating PRA. Correlational analyses indicated that perceived social support, family function and resilience were negatively associated with PRA (r = − 0.47, P < 0.01; r = − 0.43, P < 0.01; r = − 0.37, P < 0.01, respectively). The results of bootstrapping analyses demonstrated significant indirect effects of perceived social support (β = − 0.098, 95% CI [− 0.184, − 0.021]) and family function (β = − 0.049, 95% CI [− 0.103, − 0.011]) on PRA via resilience.

Conclusions

Chinese pregnant women are suffering from high levels of PRA. Better family function and perceived social support might reduce the occurrence of PRA, as well as by the mediating effects of resilience. Healthcare providers must be concerned about PRA and perform corresponding actions to reduce it. By strengthening social support and improving family function, antenatal care providers could effectively reduce or prevent PRA. And more importantly, implementing resilience-promoting measures are also essential to relieve anxiety and support mental health in pregnant women.
Cross-cultural adaptation and validation of the Chinese version of the revised surveys on patient safety culture™ (SOPS®) hospital survey 2.0
Authors: Wu Yinghui , Hua Wenzhe , Zhu Daqiao , Onishi Ryo , Yang Yanna , Hasegawa Tomonori
Published: December 2022

Background

Surveys on Patient Safety Culture™ (SOPS®) Hospital Survey (HSOPS 1.0), developed by the U.S. Agency for Healthcare Research and Quality in 2004, has been widely adopted in the United States and internationally. An updated version, the SOPS Hospital Survey 2.0 (HSOPS 2.0), released in 2019, has not yet been applied in China. The aim of the present study was to translate HSOPS 2.0 into Chinese version with cross-cultural adaptations and test its psychometric properties.

Methods

A convenience sample was used. Hospital nurses (N = 1013) and a sub-set (n = 200) was invited for the re-test. A three-stage study was conducted. Firstly, the HSOPS 2.0 was translated by a panel. Secondly, the content validity was tested using the two-round Delphi method and cognitive interview. Next, the construct validity was tested by the confirmatory factor analysis and further demonstrated by the convergent validity, discriminant validity, and correlations with the outcome of patient safety. Thirdly, the reliability was tested by internal consistency reliability and re-test reliability.

Results

The “float or PRN” and “manager” words were deleted as considered unfitted for the Chinese health care system. The content validity index provided evidence of strong content validity (I-CVI = 0.84 ~ 1.00, S-CVI = 0.98). Confirmatory factor analysis revealed a good model fit (χ2/df = 4.05, RMSEA = 0.06, CFI = 0.94) and acceptable factor loadings (0.41 ~ 0.97). Convergent validity, and discriminant validity supported the factorial structure of the Chinese version of HSOPS 2.0. Further evidence for the construct validity was derived from correlations with the outcome of patient safety (r = 0.10 ~ 0.41). A good internal consistency (Cronbach’sα = 0.68 ~ 0.93, McDonald’s omega = 0.84 ~ 0.96) and test-retest reliability (ICC = 0.78 ~ 0.95) showed acceptable reliability. Additionally, Chinese nurses reported markedly lower scores for three dimensions, including “Response to Error”, “Communication Openness”, and “Reporting Patient Safety Events”, when comparing the findings of this study with those from U.S. research utilizing the HSOPS 2.0.

Conclusion

The Chinese version of HSOPS 2.0 demonstrated good validity and reliability in a Chinese sample of hospital nurses, which suggests that it can be used to measure nurse-perceived patient safety culture in future research and practice. Psychometric properties of the Chinese version of HSOPS 2.0 among other Chinese healthcare professionals remain to be confirmed.
Tailoring a complex intervention to reduce antidepressants in institutionalized older persons with dementia
Authors: Hølmkjær Pernille , Vermehren Charlotte , Holm Anne , Rozing Maarten Pieter , Høj Kirsten , Overbeck Gritt
Published: December 2022

Introduction

First-line treatment for behavioral and psychiatric symptoms of dementia is non-pharmacological. Still, psychotropic medication is widely used, despite its limited effect and harmful side-effects. More than half of all nursing home residents with dementia receive antidepressants, even though deprescribing is safe and feasible. Interventions to promote deprescribing of antidepressants in nursing homes are few and complex. To optimize the deprescribing process through an intervention, transparency for the development of the intervention is needed. We aim to describe the steps in the development and tailoring of an intervention targeting GPs, nursing home staff, and relatives to enhance collaboration on reducing the use of antidepressants in institutionalized older persons with dementia in Denmark.

Method

A step-wise process guided by the core elements in the Medical Research Council constituted the tailoring process. Five steps were included; 1) a literature search, 2) interviews with stakeholders, 3) drafting the intervention prototype, 4) professionals’ assessment of the intervention, and 5) refinement of the intervention. The steps were conducted from June 2020 to June 2022.

Results

Based on the literature search, interviews with stakeholders, and professionals’ assessment of the intervention, four main themes were identified; 1) focusing on antidepressants, 2) importance of professional qualifications, 3) collaboration and communication, and 4) patient and relative involvement. They guided intervention development and refinement of the final intervention, which included 1) a case-based training course and 2) a dialog tool including a symptom assessment scale to be used in a structured consultation at the nursing home.

Conclusion

This study presents a detailed account of the tailoring process for a complex intervention to optimize deprescribing of antidepressants for older persons with dementia at nursing homes. By presenting a thorough development process, we expect to achieve increased adherence to the intervention which is currently being tested in an ongoing cluster randomized controlled trial. The transparency of the process will also increase the future development of other similar complex interventions.
Prevalence, motivation, and outcomes of clinic transfer in a clinical cohort of people living with HIV in North West Province, South Africa
Authors: Leslie Hannah H. , Mooney Alyssa C. , Gilmore Hailey J. , Agnew Emily , Grignon Jessica S. , deKadt Julia , Shade Starley B. , Ratlhagana Mary Jane , Sumitani Jeri , Barnhart Scott , Steward Wayne T. , Lippman Sheri A.
Published: December 2022

Introduction

Continuity of care is an attribute of high-quality health systems and a necessary component of chronic disease management. Assessment of health information systems for HIV care in South Africa has identified substantial rates of clinic transfer, much of it undocumented. Understanding the reasons for changing sources of care and the implications for patient outcomes is important in informing policy responses.

Methods

In this secondary analysis of the 2014 – 2016 I-Care trial, we examined self-reported changes in source of HIV care among a cohort of individuals living with HIV and in care in North West Province, South Africa. Individuals were enrolled in the study within 1 year of diagnosis; participants completed surveys at 6 and 12 months including items on sources of care. Clinical data were extracted from records at participants’ original clinic for 12 months following enrollment. We assessed frequency and reason for changing clinics and compared the demographics and care outcomes of those changing and not changing source of care.

Results

Six hundred seventy-five (89.8%) of 752 study participants completed follow-up surveys with information on sources of HIV care; 101 (15%) reported receiving care at a different facility by month 12 of follow-up. The primary reason for changing was mobility (N=78, 77%). Those who changed clinics were more likely to be young adults, non-citizens, and pregnant at time of diagnosis. Self-reported clinic attendance and ART adherence did not differ based on changing clinics. Those on ART not changing clinics reported 0.66 visits more on average than were documented in clinic records.

Conclusion

At least 1 in 6 participants in HIV care changed clinics within 2 years of diagnosis, mainly driven by mobility; while most appeared lost to follow-up based on records from the original clinic, self-reported visits and adherence were equivalent to those not changing clinics. Routine clinic visits could incorporate questions about care at other locations as well as potential relocation, particularly for younger, pregnant, and non-citizen patients, to support existing efforts to make HIV care records portable and facilitate continuity of care across clinics.

Trial registration

The original trial was registered with ClinicalTrials.gov, NCT02417233, on 12 December 2014.
Stress hyperglycemia ratio and in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes
Authors: Zhou Yiling , Liu Li , Huang Hongmei , Li Nan , He Jidong , Yao Heling , Tang Xiaochi , Chen Xiangyang , Zhang Shengzhao , Shi Qingyang , Qu Furong , Wang Si , Wang Miye , Shu Chi , Zeng Yuping , Tian Haoming , Zhu Ye , Su Baihai , Li Sheyu ,   The WECODe Study Group
Published: December 2022

Objective

To evaluate the impact of stress hyperglycemia on the in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes.

Research design and methods

We identified non-surgical hospitalized patients with heart failure and type 2 diabetes from a large electronic medical record-based database of diabetes in China (WECODe) from 2011 to 2019. We estimated stress hyperglycemia using the stress hyperglycemia ratio (SHR) and its equation, say admission blood glucose/[(28.7 × HbA1c)− 46.7]. The primary outcomes included the composite cardiac events (combination of death during hospitalization, requiring cardiopulmonary resuscitation, cardiogenic shock, and the new episode of acute heart failure during hospitalization), major acute kidney injury (AKI stage 2 or 3), and major systemic infection.

Results

Of 2875 eligible Chinese adults, SHR showed U-shaped associations with composite cardiac events, major AKI, and major systemic infection. People with SHR in the third tertile (vs those with SHR in the second tertile) presented higher risks of composite cardiac events ([odds ratio, 95% confidence interval] 1.89, 1.26 to 2.87) and major AKI (1.86, 1.01 to 3.54). In patients with impaired kidney function at baseline, both SHR in the first and third tertiles anticipated higher risks of major AKI and major systemic infection.

Conclusions

Both high and low SHR indicates poor prognosis during hospitalization in non-surgical patients with heart failure and type 2 diabetes.
Fecal microbiota transplantation and replenishment of short-chain fatty acids protect against chronic cerebral hypoperfusion-induced colonic dysfunction by regulating gut microbiota, differentiation of Th17 cells, and mitochondrial energy metabolism
Authors: Su Shao-Hua , Wu Yi-Fang , Lin Qi , Zhang Lin , Wang Da-Peng , Hai Jian
Published: December 2022

Background

Little is known about the association between gut microbiota and intestinal injury under a state of chronic cerebral hypoperfusion (CCH). Here, the effects of gut microbiota and short-chain fatty acids (SCFAs), as important metabolic products, on intestinal function and potential mechanisms after CCH were investigated.

Methods

Rats were subjected to bilateral common carotid artery occlusion (BCCAo) to induce CCH. The gut microbiota and metabolites of SCFAs were assessed by 16S rRNA sequencing and targeted metabolomics, respectively. Transcriptomic analysis of colon tissues was also conducted. Subsequently, potential molecular pathways and differentially expressed genes were verified by western blot, immunoprecipitation, and immunofluorescence analyses. Furthermore, the integrity of the colonic barrier was evaluated by hematoxylin and eosin and mucin 2 staining and expression levels of tight junction proteins. Besides, colonic inflammation was further assessed by flow cytometry and expression levels of inflammatory cytokines. In addition, colonic mitochondrial dysfunction was analyzed via membrane potential, reactive oxygen species, electron transport chain (ETC) activities, adenosine triphosphate content, and mitochondrial ultrastructure.

Results

CCH modified gut microbial composition and microbial metabolism of SCFAs, which may be associated with inhibition of mitochondrial ETC activities and oxidative phosphorylation, leading to dysregulation of mitochondrial energy metabolism. Furthermore, CCH induced differentiation of pathogenic Th17 cells, promoted the formation of complexes of interferon regulatory factor 4 and signal transducer and activator of transcription 3 (STAT3), and increased the phosphorylation of STAT3. This was associated with an impairment of colonic barrier function and chronic colonic inflammation. In contrast, FMT and SCFA replenishment ameliorated CCH-induced gut microbial dysbiosis by increasing the intestinal content of Ruminococcus_sp_N15_MGS_57 and modulating microbial metabolism of SCFAs by increasing acetic acid contents associated with an improvment of the balance between Tregs and Th17 cells, mitochondrial ETC activities, and oxidative phosphorylation to prevent colonic inflammation and dysregulation of mitochondrial energy metabolism.

Conclusion

These findings indicate that FMT and SCFA replenishment present a promising therapeutic strategy against colonic dysfunction under a state of chronic cerebral ischemia.
Exosomes derived from miR-338-3p-modified adipose stem cells inhibited inflammation injury of chondrocytes via targeting RUNX2 in osteoarthritis
Authors: Li ChunLiang , Li Wei , Pu GengZang , Wu JingWen , Qin Feng
Published: December 2022

Background

Osteoarthritis (OA) is a chronic degenerative disease that is one of the main causes of disability in middle-aged and elderly people. Adipose stem cell (ASC)-derived exosomes (ASC-Exo) could repair cartilage damage and treat OA. MiRNA-338-3p expression was confirmed to play a role in inhibiting proinflammatory cytokines. Herein, we aimed to explore the mechanism by which exosomes derived from miR-338-3p overexpressing ASCs protects chondrocytes from interleukin (IL)-1β-induced chondrocyte change.

Methods

Exosomes were extracted from ASCs transfected with miR-338-3p or its antisense inhibitor. The ASC-Exos (miR-338-3p silencing/overexpression) were incubated with IL-1β-induced ATDC5 cells, followed by evaluation of the chondrocyte proliferation, degradation, and inflammation injury.

Results

In vitro results revealed that ASC-Exos inhibited the expression of prostaglandin E2 (PGE2), IL-6, IL-1β, and TNF-α, as well as promoted the proliferation of ATDC5 cells. Moreover, ASC-Exos inhibited inflammation injury and degradation of ATDC5 cells by transferring miR-338-3p. Luciferase reporter assays showed that RUNX2 was a target gene of miR-338-3p. Additionally, RUNX2 overexpression in ATDC5 cells reversed the protective effect of miR-338-3p on chondrocytes. Taken together, this study demonstrated that exosomes secreted from miR-338-3p-modified ASCs were effective in the repair of IL-1β-induced chondrocyte change by inhibiting RUNX2 expression.

Conclusions

Our result provided valuable data for understanding the mechanism of ASC-Exos in OA treatment.

Graphical abstract
Divergent impacts on the gut microbiome and host metabolism induced by traditional Chinese Medicine with Cold or Hot properties in mice
Authors: Li Bingbing , Tao Xin , Sheng Lili , Li Yan , Zheng Ningning , Li Houkai
Published: December 2022

Background

Traditional Chinese Medicine (TCM) has been practiced and developed in China over thousands of years under the guidance of a series of complicated traditional theories. Herbs within TCM usually are classified according to their different properties ranging from cold, cool, warm to hot, which are simplified as Cold and Hot properties. TCM with either Cold or Hot properties are used in various formulae designed for the purpose of restoring the balance of patients. Emerging evidence has highlighted that an altered gut microbiota or host metabolism are critically involved in affecting the healing properties of TCM. However, at present the exact influences and crosstalk on the gut microbiota and host metabolism remain poorly understood.

Methods

In the present study, the divergent impacts of six TCMs with either Cold or Hot properties on gut microbiome and host metabolism during short- or long-term intervention in mice were investigated. Six typical TCMs with Hot or Cold properties including Cinnamomi Cortex (rougui, RG), Zingiberis Rhizoma (ganjiang, GJ), Aconiti Lateralis Radix Praeparata (fuzi, FZ), Rhei Radix et Rhizoma (dahuang, DH), Scutellariae Radix (huangqin, HQ), and Copitdis Rhizoma (huanglian, HL) were selected and orally administered to male C57BL/6J mice for a short- or a long-term (7 or 35 days). At the end of experiments, serum and cecal contents were collected for metabolomic and gut microbiome analyses using gas chromatography–tandem mass spectrometry (GC–MS) or 16S ribosomal deoxyribonucleic acid (16S rDNA) sequencing.

Results

The results revealed that the gut microbiome underwent divergent changes both in its composition and functions after short-term intervention with TCM possessing either Cold or Hot properties. Interestingly, the number of changed genus and bacteria pathways was reduced in Hot_LT, but was increased in Cold_LT, especially in the HL group. Increased α diversity and a reduced F/B ratio revealed the changes in Hot_ST, but a reduced Shannon index and increased altered bacteria function was evident in Cold_LT. The serum metabolic profile showed that the influence of TCM on host metabolism was gradually reduced over time. Glycolipid metabolism related pathways were specifically regulated by Hot_ST, but also surprisingly by Cold_LT. Reduced lactic acid in Cold_ST, increased tryptophan concentrations and decreased proline and threonine concentrations in Cold_LT perhaps highlighting the difference between the two natures influence on serum metabolism. These metabolites were closely correlated with altered gut microbiota shown by further correlation analyses.

Conclusion

The results indicated that TCM properties could be, at least partially characterized by an alteration in the gut microbiota and metabolic profile, implying that the divergent responses of gut microbiome and host metabolism are involved in different responses to TCM.

Graphic Abstract
Early neurodevelopmental outcomes in children with asymptomatic congenital CMV infection
Authors: Novelli Maria , Natale Fabio , Di Norcia Anna , Boiani Arianna , Temofonte Sara , Calandriello Francesca , Zitarelli Cristina , Caravale Barbara
Published: December 2022

Background

Approximately 85–90% of congenital cytomegalovirus infections (cCMV) are asymptomatic. Few studies have investigated early and long-term neurodevelopmental outcomes in children with asymptomatic cCMV (acCMV), and the data is contradictory. In the present study, we did investigate the effect of cCMV asymptomatic infection on neurological outcomes and in cognitive, language and motor development at 6 months of age.

Methods

Fifty-six children with cCMV asymptomatic infection were followed for 6 months, as part of a long-term surveillance program, examining their neurological and developmental outcomes. Neurological examination and Bayley-III Scales were performed.

Results

Clinical evaluation revealed that early neurological outcomes were essentially normal, with minor neurological deficits (i.e., tone abnormalities) in a subgroup of patients. Bayley-III scores were substantially in the normal range, with 14% showing a score less than 85 (-1SD) in the Motor Scale. Children's neurological and neurodevelopmental outcomes at 6 months of age did not differ according to the trimester of infection.

Conclusions

Some infants with cCMV asymptomatic infection may present minor neurological abnormalities in early stages of life. It seems useful to monitor this population for early and late neurodevelopmental sequelae.
StudyMe: a new mobile app for user-centric N-of-1 trials
Authors: Zenner Alexander M. , Böttinger Erwin , Konigorski Stefan
Published: December 2022

N-of-1 trials are multi-crossover self-experiments that allow individuals to systematically evaluate the effect of interventions on their personal health goals. Although several tools for N-of-1 trials exist, there is a gap in supporting non-experts in conducting their own user-centric trials. In this study, we present StudyMe, an open-source mobile application that is freely available from https://play.google.com/store/apps/details?id=health.studyu.me and offers users flexibility and guidance in configuring every component of their trials. We also present research that informed the development of StudyMe, focusing on trial creation. Through an initial survey with 272 participants, we learned that individuals are interested in a variety of personal health aspects and have unique ideas on how to improve them. In an iterative, user-centered development process with intermediate user tests, we developed StudyMe that features an educational part to communicate N-of-1 trial concepts. A final empirical evaluation of StudyMe showed that all participants were able to create their own trials successfully using StudyMe and the app achieved a very good usability rating. Our findings suggest that StudyMe provides a significant step towards enabling individuals to apply a systematic science-oriented approach to personalize health-related interventions and behavior modifications in their everyday lives.
A combined miRNA–piRNA signature in the serum and urine of rabbits infected with Toxoplasma gondii oocysts
Authors: Xie Shi-Chen , Zhou Chun-Xue , Zhai Bin-Tao , Zheng Wen-Bin , Liu Guo-Hua , Zhu Xing-Quan
Published: December 2022

Background

Increasing evidence has shown that non-coding RNA (ncRNA) molecules play fundamental roles in cells, and many are stable in body fluids as circulating RNAs. Study on these ncRNAs will provide insights into toxoplasmosis pathophysiology and/or help reveal diagnostic biomarkers.

Methods

We performed a high-throughput RNA-Seq study to comprehensively profile the microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) in rabbit serum and urine after infection withToxoplasma gondiioocysts during the whole infection process.

Results

Total RNA extracted from serum and urine samples of acutely infected [8 days post-infection (DPI)], chronically infected (70 DPI) and uninfected rabbits were subjected to genome-wide small RNA sequencing. We identified 2089 miRNAs and 2224 novel piRNAs from the rabbit sera associated withT. gondiiinfection. Meanwhile, a total of 518 miRNAs and 4182 novel piRNAs were identified in the rabbit urine associated withT. gondiiinfection. Of these identified small ncRNAs, 1178 and 1317 serum miRNAs and 311 and 294 urine miRNAs were identified as differentially expressed (DE) miRNAs in the acute and chronic stages of infections, respectively. A total of 1748 and 1814 serum piRNAs and 597 and 708 urine piRNAs were found in the acute and chronic infection stages, respectively. Of these dysregulated ncRNAs, a total of 88 common DE miRNAs and 120 DE novel piRNAs were found in both serum and urine samples of infected rabbits.

Conclusions

These findings provide valuable data for revealing the physiology of herbivore toxoplasmosis caused by oocyst infection. Circulating ncRNAs identified in this study are potential novel diagnostic biomarkers for the detection/diagnosis of toxoplasmosis in herbivorous animals.

Graphical Abstract
Association of glucagon-like peptide-1 receptor agonists with cardiac arrhythmias in patients with type 2 diabetes or obesity: a systematic review and meta-analysis of randomized controlled trials
Authors: Wu Sijin , Lu Wenzhao , Chen Zhongli , Dai Yan , Chen Keping , Zhang Shu
Published: December 2022

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been highly recommended for glycemic control and weight reduction. However, evidence has accumulated that GLP-1 RAs treatment is related to an increase in heart rate, which could potentially induce cardiac arrhythmias. This study aims to investigate the association of GLP-1 RAs therapy with incident arrhythmias in diabetic and obese patients.

Methods

MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception up to May 25, 2022. Randomized controlled trials (RCTs) comparing GLP-1 RAs with placebo or active control for adults with type 2 diabetes or obesity were included. The outcomes of interest were prespecified as incident atrial fibrillation (AF), atrial flutter (AFL), ventricular arrhythmias (VAs), and sudden cardiac death (SCD). Mantel-Haenszel relative risk (MH-RR) with a corresponding 95% confidence interval (95% CI) was estimated using a fixed-effects model.

Results

A total of 56 RCTs involving 79,720 participants (44,028 GLP-1 RAs vs 35,692 control: mean age 57.3 years) were included from 7692 citations. GLP-1 RAs use overall did not significantly increase the risk of AF (RR 0.97, 95% CI 0.83–1.12), AFL (RR 0.83, 95% CI 0.59–1.17), VAs (RR 1.24, 95% CI 0.92–1.67), and SCD (RR 0.89, 95% CI 0.67–1.19), compared with controls. In further subgroup analyses, we observed an increasing trend toward incident AF with dulaglutide (RR 1.40, 95% CI 1.03–1.90) while an inverse trend with oral semaglutide (RR 0.43, 95% CI 0.21–0.87). Additionally, higher doses of GLP-1 RAs (RR 1.63, 95% CI 1.11–2.40) and higher baseline BMI (RR 1.60, 95% CI 1.04–2.48) might significantly increase the risk of VAs. No significant differences were identified in other subgroup analyses.

Conclusions

GLP-1 RAs therapy was not associated with an overall higher risk of arrhythmias, demonstrating an assuring cardiovascular safety profile. Further studies are required to determine whether the potential antiarrhythmic or arrhythmogenic effect of GLP-1 RAs is drug-specific and varies from doses or baseline BMI.

Trial registration: PROSPERO Identifier: CRD42022339389.
Genome-wide distribution of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: a pilot study with human and in vitro data
Authors: D’Cruz Shereen Cynthia , Hao Chunxiang , Labussiere Martin , Mustieles Vicente , Freire Carmen , Legoff Louis , Magnaghi-Jaulin Laura , Olivas-Martinez Alicia , Rodriguez-Carrillo Andrea , Jaulin Christian , David Arthur , Fernandez Mariana F. , Smagulova Fatima
Published: December 2022

Objective

To assess the genetic and epigenetic effects promoted by Bisphenol A (BPA) exposure in adolescent males from the Spanish INMA-Granada birth cohort, and in human cells.

Methods

DNA methylation was analysed using MEDIP. Repeat number variation in genomic DNA was evaluated, along with the analysis of H3K4me3 by using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Analyses were performed with material extracted from whole blood of the adolescents, complemented by in vitro assessments of human (HeLa) cells exposed to 10 nM BPA, specifically, immunofluorescence evaluation of protein levels, gene expression analysis and ChIP‒qPCR analysis.

Results

Adolescents in the high urinary BPA levels group presented a higher level of Satellite A (SATA) repetitive region copy numbers compared to those in the low BPA group and a tendency towards increase in telomere length. We also observed decreased DNA methylation at the promoters of the imprinted genesH19, KCNQ1,andIGF2; atLINE1retroelements; and at theARID2, EGFRandESRRAandTERTgenes. Genome-wide sequencing revealed increased H3K4me3 occupancy at the promoters of genes encoding histone acetyltransferases, telomeric DNA binding factors and DNA repair genes. Results were supported in HeLa cells exposed to 10 nM BPA in vitro. In accordance with the data obtained in blood samples, we observed higher H3K4me3 occupancy and lower DNA methylation at some specific targets in HeLa cells. In exposed cells, changes in the expression of genes encoding DNA repair factors (ATM, ARID2, TRP53) were observed, and increased expression of several genes encoding telomeric DNA binding factors (SMG7, TERT, TEN1, UPF1, ZBTB48) were also found. Furthermore, an increase in ESR1/ERa was observed in the nuclei of HeLa cells along with increased binding of ESR1 toKAT5, KMT2EandTERF2IPpromoters and decreased ESR1 binding at theRARApromoter. The DNA damage marker p53/TP53 was also increased.

Conclusion

In this pilot study, genome-wide analysis of histone trimethylation in adolescent males exposed to BPA revealed a global impact on the expression of genes encoding telomeric binding proteins and histone acetyltransferase factors with similar results in HeLa cells. Nevertheless, larger studies should confirm our findings.