bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study
Authors: Li Nana , Kang Hong , Liu Zhen , Li Lu , Deng Ying , Wang Meixian , Li Yuting , Xu Wenli , Li Xiaohong , Wang Yanping , Zhu Jun , Tao Jing , Yu Ping
Published: February 2024

Background

The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring.

Methods

A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–phthalates exposure interactions.

Results

There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28–2.37; dominant: aOR = 1.86, 95% CI:1.25–2.78; recessive: aOR = 2.50, 95% CI: 1.26–4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54–121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed.

Conclusions

The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.
Critical congenital heart disease: contemporary prenatal screening performance and outcomes in a multi-centre perinatology service
Authors: Cody Fiona , Franklin Orla , Mc Cay Nicola , Molphy Zara , Dicker Patrick , Breathnach Fionnuala M.
Published: February 2024

Background

Prenatal detection of critical congenital heart disease (CCHD) optimises perinatal decision-making and neonatal outcomes. The objective of this study was to determine the prenatal screening performance, care pathways and perinatal outcomes for prenatally and postnatally diagnosed cases of CCHD over a four-year period.

Study design

This retrospective cohort study in a tertiary centre and its two affiliated secondary sites examined all cases of CCHD, including cases of pregnancy termination and in-utero fetal death, neonatal death and liveborn babies that underwent cardiac catheterization or surgery in the first six weeks of life. Prenatal and postnatal data were ascertained from the first trimester assessment for all patients diagnosed prenatally. Cases requiring intervention that were first identified in the postnatal period were included to determine prenatal detection rates. Follow-up for all cases of CCHD continued to one year of age.

Results

In a consecutive cohort of 49,950 pregnancies in a 4-year period 01/2019 to 12/2022, a prenatal diagnosis of CCHD was made in 96 cases, yielding a prevalence of 1.9 per 1000 births. The prenatal detection for right duct-dependant heart pathology and congenital heart block was 100%, 85% for left duct-dependant pathology and 93% for transposition of the great arteries (TGA). In the prenatally diagnosed group, 37% of cases were complicated by extracardiac structural abnormalities, a genetic diagnosis or both. All cases of prenatal detection were identified in the context of routine anatomy screening rather than specialist Fetal Cardiac screening services. Almost half of all pregnancies complicated by CCHD did not undergo neonatal cardiac intervention, by virtue of parental choice determined either prenatally or after birth. An additional eight babies were diagnosed with CCHD in the neonatal period, such that the prenatal detection rate for CCHD was 92% (96/104, 95% CI = 84%-96%). Survival at 1-year for infants deemed suitable for CCHD surgery was 85%.

Conclusion

In a large unselected population, optimal rates of prenatal detection of critical congenital heart disease can be achieved by a protocolised approach to mid-trimester fetal anatomy ultrasound, underpinned by a programme of sonographer education and training. The cardiac abnormalities most likely to evade prenatal detection are left-sided obstructive lesions.
Pancreatic adenocarcinoma third line systemic treatments: a retrospective cohort study
Authors: Gueiderikh A. , Tarabay A. , Abdelouahab M. , Smolenschi C. , Tanguy M. L. , Valery M. , Malka D. , Pudlarz T. , Fuerea A. , Boige V. , Hollebecque A. , Ducreux M. , Boilève A.
Published: February 2024

Background

Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) primarily relies on FOLFIRINOX (LV5FU- irinotecan – Oxaliplatine) and Gemcitabine – Nab-Paclitaxel in the first-line setting. However, second-lines remain less well-defined and there is limited data regarding third-line treatments. The objective of our study was to determine the proportion of patients advancing to third line chemotherapy, to outline the various third-line chemotherapy regimens used in routine practice and to evaluate their respective efficacy.

Methods

A retrospective single-center cohort from 2010-2022 compiled baseline characteristics, treatment outcomes and survival of PDAC patients who received at least one chemotherapy line in a French tertiary-center. Overall survivals (OS) were analyzed using a Cox multivariable model.

Results

In total, 676 patients were included, with a median follow-up time of 69.4 months, (Interquartile Range (IQR) = 72.1). Of these, 251 patients (37%) that proceeded to 3rd-line chemotherapy. The median PFS in 3rd line was 2.03 months, [CI95%: 1.83, 2.36]. The median 3rd line overall survival was 5.5 months, [CI95%: 4.8, 6.3]. In multivariable analysis erlotinib-based chemotherapy was found to be deleterious (HR=2.38, [CI95%: 1.30, 4.34], p=0.005) compared to fluoropyrimidine-based chemotherapy in terms of 3rd line overall survival while gemcitabine monotherapy showed a tendency towards negative outcomes. First and 2nd line chemotherapies sequence didn’t influence 3rd line outcome.

Conclusion

In our cohort, one-third of treated patients proceeded to 3rd line chemotherapy resulting in a 5.5 months median 3rd line OS, consistent with treatments at advanced stage. Our results argue against the use of erlotinib and gemcitabine monotherapy.
Comprehensive knowledge about HIV/AIDS and associated factors among reproductive age women in Liberia
Authors: Seifu Beminate Lemma , Eshun Gilbert , Tesema Getayeneh Antehunegn , Kyei-Arthur Frank
Published: February 2024

Introduction

Acquired Immune Deficiency Syndrome (AIDS) continues to be a deadly pandemic and a serious threat to public health. Globally, reproductive age women are more likely to be infected with Human Immunodeficiency Virus (HIV). Comprehensive knowledge about HIV/AIDS is pivotal in the fight against AIDS. However, comprehensive HIV/AIDS knowledge is low in Sub-Saharan African (SSA) nations including Liberia, which contributes to the high incidence of HIV in these nations. This study assessed the level of comprehensive knowledge about HIV/AIDS and its associated factors among reproductive age women in Liberia.

Methods

The prevalence and associated factors of comprehensive knowledge about HIV/AIDS among reproductive age women in Liberia were determined using secondary data analysis of 2019–2020 Liberia Demographic and Health Surveys (LDHS). Comprehensive knowledge about HIV/AIDS was a composite variable computed from six variables available in the Demographic and Health Survey (DHS). The study included 7,621 reproductive age women in weighted samples. A generalized linear mixed model with robust error variance was used. For the variables included in the final model, adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) were calculated.

Results

The prevalence of comprehensive HIV/AIDS knowledge among Liberian women aged 15–49 was 33.5%. Women’s age and education, and distance to health facility were positively associated with comprehensive knowledge about HIV/AIDS among Liberian reproductive age women. In contrast, community poverty level was negatively associated with comprehensive knowledge about HIV/AIDS.

Conclusion and recommendations

This study demonstrates that the prevalence of good comprehensive HIV/AIDS knowledge was relatively low among reproductive age women in Liberia. Hence, health practitioners and policymakers should strengthen HIV/AIDS sensitization programmes to increase women’s knowledge about HIV/AIDS.
Eosinophilic bronchiectasis increases length and cost of hospitalization: a retrospective analysis in a hospital of southern China from 2012 to 2020
Authors: Lei Chengcheng , Zeng Zhimin , Chen Fengjia , Guo Yubiao , Liu Yangli
Published: February 2024

Background

The concept of eosinophilic bronchiectasis has received clinical attention recently, but the association between blood eosinophil count (BEC) and hospital characteristics has rarely been reported yet. We aim to investigate the clinical impact of BEC on patients with acute bronchiectasis exacerbation.

Methods

A total of 1332 adult patients diagnosed with acute exacerbation of bronchiectasis from January 2012 to December 2020 were included in this retrospective study. A propensity-matched analysis was performed by matching age, sex and comorbidities in patients with high eosinophil count (≥ 300 cell/µL) and low eosinophil count (< 300 cell/µL). Clinical characteristics, length of hospital stay (LOS), hospitalization cost and inflammatory markers were compared between the two groups.

Results

Eosinophilic bronchiectasis occurred in approximately 11.7% of all patients. 156 propensity score–matched pairs were identified with and without high eosinophil count. Eosinophilic bronchiectasis presented with a longer LOS [9.0 (6.0–12.5) vs. 5.0 (4.0–6.0) days, p < 0.0001] and more hospitalization cost [15,011(9,753–27,404) vs. 9,109(6,402–12,287) RMB, p < 0.0001] compared to those in non-eosinophilic bronchiectasis. The median white blood cell (WBC), lymphocyte, platelet (PLT) and C-reactive protein (CRP) levels in eosinophilic bronchiectasis were significantly increased. Multivariate logistic regression analysis confirmed that the high levels of eosinophil count (OR = 13.95, p < 0.0001), worse FEV1% predicted (OR = 7.80, p = 0.0003) and PLT (OR = 1.01, p = 0.035) were independent prognostic factors for length of hospital (LOS) greater than 7 days.

Conclusion

Eosinophilic bronchiectasis patients had longer length of hospital stay and more hospitalization cost compared to those in non-eosinophilic bronchiectasis group, which might be associated with the stronger inflammatory reaction.
Phenotypes of osteoarthritis-related knee pain and their transition over time: data from the osteoarthritis initiative
Authors: Ye Jing , Xie Dongxing , Li Xiaoxiao , Lu Na , Zeng Chao , Lei Guanghua , Wei Jie , Li Jiatian
Published: February 2024

Background

Identification of knee osteoarthritis (OA) pain phenotypes, their transition patterns, and risk factors for worse phenotypes, may guide prognosis and targeted treatment; however, few studies have described them. We aimed to investigate different pain phenotypes, their transition patterns, and potential risk factors for worse pain phenotypes.

Methods

Utilizing data from the Osteoarthritis Initiative (OAI), pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. We identified the activity-related pain phenotypes and estimated the transition probabilities of pain phenotypes from baseline to the 24-month using latent transition analysis. We examined the risk factors at baseline with the 24-month pain phenotypes and the transition of pain phenotypes.

Results

In 4796 participants, we identified four distinct knee pain phenotypes at both baseline and 24-month follow-up: no pain, mild pain during activity (Mild P-A), mild pain during both rest and activity (Mild P-R-A), and moderate pain during both rest and activity (Mod P-R-A). 82.9% knees with no pain at baseline stayed the same at 24-month follow-up, 17.1% progressed to worse pain phenotypes. Among “Mild P-A” at baseline, 32.0% converted to no-pain, 12.8% progressed to “Mild P-R-A”, and 53.2% remained. Approximately 46.1% of “Mild P-R-A” and 54.5% of “Mod P-R-A” at baseline experienced remission by 24-month. Female, non-whites, participants with higher depression score, higher body mass index (BMI), higher Kellgren and Lawrence (KL) grade, and knee injury history were more likely to be in the worse pain phenotypes, while participants aged 65 years or older and with higher education were less likely to be in worse pain phenotypes at 24-month follow-up visit. Risk factors for greater transition probability to worse pain phenotypes at 24-month included being female, non-whites, participants with higher depression score, higher BMI, and higher KL grade.

Conclusions

We identified four distinct knee pain phenotypes. While the pain phenotypes remained stable in the majority of knees over 24 months period, substantial proportion of knees switched to different pain phenotypes. Several socio-demographics as well as radiographic lesions at baseline are associated with worse pain phenotypes at 24-month follow-up visit and transition of pain phenotypes.
Optimising surgical anastomosis in ileocolic resection for Crohn’s disease with respect to recurrence and functionality: two international parallel randomized controlled trials comparing handsewn (END-to-end or Kono-S) to stapled anastomosis (HAND2END and the End2End STUDIES)
Authors: Haanappel Anouck E. G. , Bellato Vittoria , Buskens Christianne J. , Armuzzi Alessandro , van der Bilt Jarmila D. W. , de Boer Nanne K. H. , Danese Silvio , van der Does de Willebois Eline M. L. , Duijvestein Marjolijn , van der Horst Daniëlle , Pellino Gianluca , Richir Milan C. , Selvaggi Francesco , Spinelli Antonino , Vignali Andrea , Rosati Riccardo , Bemelman Willem A.
Published: February 2024

Background

The most common intestinal operation in Crohn’s disease (CD) is an ileocolic resection. Despite optimal surgical and medical management, recurrent disease after surgery is common. Different types of anastomoses with respect to configuration and construction can be made after resection for example, handsewn (end-to-end and Kono-S) and stapled (side-to-side). The various types of anastomoses might affect endoscopic recurrence and its assessment, the functional outcome, and costs. The objective of the present study is to compare the three types of anastomoses with respect to endoscopic recurrence at 6 months, gastrointestinal function, and health care consumption.

Methods

This is a randomized controlled multicentre superiority trial, allocating patients either to side-to-side stapled anastomosis as advised in current guidelines or a handsewn anastomoses (an end-to-end or Kono-S). It is hypothesized that handsewn anastomoses do better than stapled, and end-to-end perform better than the saccular Kono-S. Two international studies with a similar setup will be conducted mainly in the Netherlands (End2End) and Italy (HAND2END). Patients diagnosed with CD, aged over 16 years in the Netherlands and 18 years in Italy requiring (re)resection of the (neo)terminal ileum are eligible. The first part of the study compares the two handsewn anastomoses with the stapled anastomosis. To detect a clinically relevant difference of 25% in endoscopic recurrence, a total of 165 patients will be needed in the Netherlands and 189 patients in Italy. Primary outcome is postoperative endoscopic recurrence (defined as Rutgeerts score ≥ i2b) at 6 months. Secondary outcomes are postoperative morbidity, gastrointestinal function, quality of life (QoL) and costs.

Discussion

The research question addresses a knowledge gap within the general practice elucidating which type of anastomosis is superior in terms of endoscopic and clinical recurrence, functionality, QoL and health care consumption. The results of the proposed study might change current practice in contrast to what is advised by the guidelines.

Trial registration

NCT05246917 for HAND2END and NCT05578235 for End2End (http://www.clinicaltrials.gov/).
Impact of a Mediterranean diet on prevention and management of urologic diseases
Authors: Sultan Mark I , Ibrahim Shady A , Youssef Ramy F
Published: February 2024

Compared to a Western diet, the Mediterranean diet moves away from red meat and processed foods. Universally regarded as a healthier dietary alternative, the Mediterranean diet has garnered scientific endorsement for its ability to confer an array of compelling benefits. These health benefits encompass not only a lowered incidence of Type 2 diabetes with a reduction in obesity, but also a robust protective effect on cardiovascular health. Extensive literature exists to corroborate these health benefits; however, the impact of a Mediterranean diet on urologic diseases, specifically sexual dysfunction, lower urinary tract symptoms, stone disease, and urologic cancers are not well studied. Understanding how dietary habits may impact these urologic conditions can contribute to improved prevention and treatment strategies.

A total of 955 papers from PubMed and Embase were systematically reviewed and screened. After exclusion of disqualified and duplicated studies, 58 studies consisting of randomized controlled trials, cohort studies, cross sectional studies, reviews and other meta-analyses were included in this review. 11 primary studies were related to the impact of a Mediterranean diet on sexual dysfunction, 9 primary studies regarding urinary symptoms, 8 primary studies regarding stone disease, and 9 primary studies regarding urologic cancers. All primary studies included were considered of good quality based on a New-Castle Ottawa scale. The results demonstrate a Mediterranean diet as an effective means to prevent as well as improve erectile dysfunction, nephrolithiasis, lower urinary tract symptoms, and urinary incontinence. The review highlights the need for additional research to study the impact of diet on urologic cancers and other urologic conditions such as premature ejaculation, loss of libido, female sexual dysfunction, and overactive bladder.
Assessment of knowledge and practices of additive manufacturing in dentistry among university teaching faculty in Saudi Arabia
Authors: Alanazi Khalid K. , Alzaid Abdulaziz A. , Alotaibi Adel , Almehisni Nora , Alzahrani Ghida , Gufran Khalid
Published: February 2024

Background

In recent era, digitalization in the dental sciences has been observed in wide ranges. This cross-sectional study aimed to assess knowledge and practice of additive manufacturing (AM) in dentistry among university teaching faculty in Saudi Arabia.

Methods

A questionnaire was prepared and validated to distribute to the different dental colleges in Saudi Arabia. The questionnaire was divided into three parts: demographic information, knowledge and practices of AM among the dental teaching faculty. After receiving all the responses, descriptive statistics were used for the frequency distribution of all the responses.

Results

A total of 367 responses were received from the different faculty members. Most of the participants were male (67.30%), holding assistant professor (52.50%) positions in the field of prosthodontics (23.40%). In terms of knowledge, even though most of the participants were aware of AM (64.30%); however, do not understand the AM techniques (33.50). Moreover, 71.90% of the participants had no experience working with AM and only 13.60% of participants used AM in their respective dental colleges.

Conclusion

AM techniques are not commonly used in the field of dentistry in Saudi Arabia; therefore, more platforms should have created to enhance the knowledge and practice of AM in the current population.
Analysis of influencing factors of HPV vaccination willingness of female sex workers in urban entertainment venues based on the IMB model in Guangxi, China
Authors: He Zhi-yan , Wei Jun-hong , Jiang Jian-ming , Hu Rui , Qi Guang-zi
Published: February 2024

Objective

Understanding HPV vaccination willingness and its influencing factors among female sex workers (FSWs) in entertainment venues in an urban area of Guangxi, China.

Methods

From 15 August to 15 October 2022, FSWs in entertainment venues with commercial sex trade in an urban area of Guangxi were selected as the study subjects for the questionnaire survey using the method of intentional sampling. The questionnaire based on the information-motivation-behavior (IMB) skills model was used to collect the basic characteristics, HPV and HPV vaccine-related information and cognition, motivation to vaccinate, behavioral skills and willingness to vaccinate from the research targets. A multifactor logistic regression model was used to analyze the factors influencing the research targets' willingness to receive HPV vaccination.

Results

Of the 921 research targets, 712 (77.31%) were willing to receive HPV vaccination. The higher the level of knowledge regarding HPV and HPV vaccine-related information, the higher the motivation for HPV vaccination. In addition, the higher the behavioral skills score, the higher the willingness of FSWs in entertainment venues to receive HPV vaccination (P<0.001). FSWs in entertainment venues with lower venue grades [OR(95% CI)=0.693 (0.539, 0.891), P=0.004] were more reluctant to receive HPV vaccination. Those who favored the effectiveness of the vaccine in preventing the disease [OR(95% CI)=2.144 (1.449, 3.174), P<0.001] and those who had heard of HPV vaccine [OR(95% CI)=2.105 (1.451, 3.054), P<0.001], were able to perceive the benefits of HPV vaccination [OR(95% CI)=1.134 (1.045, 1.230), P=0.002]. These individuals acquired greater behavioral skills i.e., self-decision making for HPV vaccination [OR(95% CI)=1.130 (1.008, 1.267), P=0.036] and self-efficacy [OR(95% CI)=1.135 (1.081, 1.191), P<0.001] and they were more willing to receive HPV vaccine.

Conclusions

There was a relatively high HPV vaccination willingness among FSWs in entertainment venues in an urban area of Guangxi, China. Attention should be focused on introducing the benefits of primary prevention measures such as the HPV vaccine for individuals and behavioral skills for HPV vaccination in order to increase their willingness to be vaccinated thus increasing their HPV vaccination rate.
Health-promoting lifestyle in mothers with vaginal childbirth and cesarean section in the postpartum period
Authors: Govahi Motahareh , Behmanesh Fereshteh , Gholinia Hemmat , Omidvar Shabnam , Adib-Rad Hajar
Published: February 2024

Background

In the postpartum period, there are numerous changes in the physical and psychological dimensions of women, which reduce the quality of life of women. The aim of this study was to compare the health-promoting lifestyle of mothers with vaginal delivery and cesarean delivery in the postpartum period.

Methods

This cross-sectional study was conducted on 77 pregnant women who had delivered vaginal or by cesarean section at Shohadaye Behshahr Hospital and were selected based on inclusion criteria. If the women were willing to participate in the study, a demographic questionnaire was completed, and the telephone numbers of the subjects were recorded so that the Porsline health-promoting lifestyle questionnaire could be sent to them. Data were analyzed with SPSS 22 using the T test, chi-square test and Repeated Measure ANOVA.

Results

There was no difference in the average score of health-promoting lifestyle and its dimensions between the two groups of vaginal delivery and cesarean section at two and six weeks after delivery. However, in both groups, the total score of health-promoting lifestyle decreased significantly over time (P < 0.001).

Conclusions

There was no difference in health-promoting lifestyle between mothers with vaginal and mothers with cesarean delivery at two weeks and six weeks after delivery. This requires more attention from policy makers to make vaginal childbirth more convenient, and by reducing complications after vaginal childbirth, they can improve women’s healthy lifestyles and, in turn, families. Also, it seems that the other variables apart from the method of delivery should be considered, and it is necessary to distinguish these variables such as routine episiotomy in order to prevent the decrease in the level of health-promoting behaviors among women during puerperium period.
Exploring the driving forces and scenario analysis for catastrophic and impoverishing health expenditures in Iran
Authors: Hedayati Maryam , Maleki Mohammadreza , Asl Iravan Masoudi , Fazaeli Ali Akbar , Goharinezhad Salime
Published: February 2024

Background

The extent of healthcare expenditure within households stands as a crucial indicator in low and middle-income countries (LMICs). When out-of-pocket healthcare expenses surpass household income or become unduly burdensome, it serves as a significant socio-economic alarm, resulting in a reduced quality of life, a phenomenon referred to as ‘catastrophic health expenditure (CHE).’ Multiple factors can contribute to the occurrence of CHE. The study’s objective was to identify the key uncertainties and driving forces influencing CHE to develop scenarios in Iran on the horizon of 2030.

Methods

This study was conducted between December 2021 and January 2023, data were collected through a literature review, and experts’ opinions were gathered via questionnaires, interviews, and expert panels. The statistical population included experts in the fields of health policy, health economics, and futures studies. Scenario Wizard software and MICMAC analysis were employed for data analysis, providing valuable insights into potential future scenarios of health expenditures in Iran.

Results

Based on the results of the scoping review and semi-structured interview, 65 key factors in the fields of economics, politics, technology, social, and environmental were identified. The findings of the MICMAC analysis presented 10 key variables. Finally, six main scenario spaces are depicted using Scenario Wizard. These scenarios included catastrophic cost crises, sanction relief, selective information access, technological ambiguity, induced demand management, and incremental reforms.

Conclusions

Each of the six drawn scenarios provides images of the future of health expenditure in Iranian households on the horizon of 2030. The worst-case scenario from all scenarios was scenario one, with the most probable and critical features to derive Iran’s health expenditures. The current study is a valuable addition to the literature depicting the key drivers that all developing nations can consider to decrease exposing households to catastrophic and impoverishing health expenditures.
Exploring the influence of a financial incentive scheme on early mobilization and rehabilitation in ICU patients: an interrupted time-series analysis
Authors: Unoki Yoko , Ono Sachiko , Sasabuchi Yusuke , Hashimoto Yohei , Yasunaga Hideo , Yokota Isao
Published: February 2024

Background

Clinical guidelines recommend early mobilization and rehabilitation (EMR) for patients who are critically ill. However, various barriers impede its implementation in real-world clinical settings. In 2018, the Japanese universal healthcare coverage system announced a unique financial incentive scheme to facilitate EMR for patients in intensive care units (ICU). This study evaluated whether such an incentive improved patients’ activities of daily living (ADL) and reduced their hospital length of stay (LOS).

Methods

Using the national inpatient database in Japan, we identified patients admitted to the ICU, who stayed over 48 hours between April 2017 and March 2019. The financial incentive required medical institutions to form a multidisciplinary team approach for EMR, development and periodic review of the standardized rehabilitation protocol, starting rehabilitation within 2 days of ICU admission. The incentive amounted to 34.6 United States Dollars per patient per day with limit 14 days, structured as a per diem payment. Hospitals were not mandated to provide detailed information on individual rehabilitation for government, and the insurer made payments directly to the hospitals based on their claims. Exposure was the introduction of the financial incentive defined as the first day of claim by each hospital. We conducted an interrupted time-series analysis to assess the impact of the financial incentive scheme. Multivariable radon-effects regression and Tobit regression analysis were performed with random intercept for the hospital of admission.

Results

A total of 33,568 patients were deemed eligible. We confirmed that the basic assumption of ITS was fulfilled. The financial incentive was associated with an improvement in the Barthel index at discharge (0.44 points change in trend per month; 95% confidence interval = 0.20–0.68) and shorter hospital LOS (− 0.66 days change in trend per month; 95% confidence interval = − 0.88 – -0.44). The sensitivity and subgroup analyses showed consistent results.

Conclusions

The study suggests a potential association between the financial incentive for EMR in ICU patients and improved outcomes. This incentive scheme may provide a unique solution to EMR barrier in practice, however, caution is warranted in interpreting these findings due to recent changes in ICU care practices.
Direct evidence of cheetah (Acinonyx jubatus) as intermediate host of Toxoplasma gondii through isolation of viable strains
Authors: Zhu Niuping , Ren Hongjie , Yang Liulu , Mao Gaohui , Li Junbao , Su Chunlei , Yang Yurong
Published: February 2024

Toxoplasma gondii causes lifelong infection in most definitive and intermediate hosts. Clinical cases of toxoplasmosis in captive cheetahs have been reported. However, there are few reports of viable T. gondii strains isolated from cheetahs. Here, T. gondii infection was investigated using molecular and serological assays in cheetahs from China. Modified agglutination test (MAT) (cut-off: 1:25) indicated that all six examined cheetahs (n = 6) showed T. gondii antibodies. Toxoplasma gondii DNA was detected in three out of five cheetahs. Two viable T. gondii strains were isolated from the striated muscles of two cheetahs using mice bioassay. They were designated as TgCheetahCHn1 and TgCheetahCHn2. Genetic characterization of DNA derived from tachyzoites was performed using RFLP-PCR of 10 markers. Toxoplasma gondii TgCheetahCHn1 is ToxoDB PCR-RFLP genotype #319, and the alleles of ROP18/ROP5 types were 3/7. TgCheetahCHn2 is ToxoDB genotype #9, and the alleles of ROP18/ROP5 were 3/6. The average survival time of TgCheetahCHn1-infected Swiss mice was 22 ± 1 days (n = 23), and the mice did not have detectable T. gondii-specific antibodies until 117 ± 30 days post-inoculation (n = 8), therefore, TgCheetahCHn1 had intermediate virulence. TgCheetahCHn2 was avirulent for Swiss mice. Few brain tissue cysts (0–50) were observed in the mice inoculated with TgCheetahCHn1 or TgCheetahCHn2. The results provide direct evidence of cheetah as intermediate host of T. gondii.
Causal effects between circulating immune cells and heart failure: evidence from a bidirectional Mendelian randomization study
Authors: Bian Rutao , Xu Xuegong , Li Zishuang
Published: February 2024

Background

Heart failure (HF) is a prevalent cardiac condition characterized by high mortality and morbidity rates. Immune cells play a pivotal role as crucial biomarkers in assessing the overall immune status of individuals. However, the causal relationship between circulating immune cells and the pathogenesis of HF remains an area requiring further investigation.

Objectives

The aim of this study was to investigate the genetic interactions between circulating immune cells and HF, and to further elucidate the genetic associations between different lymphocyte subsets and HF.

Methods

We obtained genetic variants associated with circulating immune cells as instrumental variables (IVs) from the Blood Cell Consortium and publicly available HF summary data. We conducted additional subsets analyses on lymphocyte counts. Our study utilized two-sample and multivariate Mendelian randomization (MVMR) analysis to investigate the causal effect of immune cells on HF. The primary analysis employed inverse variance weighting (IVW) and was complemented by a series of sensitivity analyses.

Results

The findings of the study showed that the IVW model demonstrated a significant correlation between an elevation in lymphocyte count and a decreased risk of HF (OR = 0.97, 95% CI, 0.94 - 1.00, P = 0.032). However, no such correlation was evident in the MVMR analysis for lymphocytes and HF. Furthermore, the examination of the lymphocyte subsets indicated that an increase in CD39+ CD4+ T-cell counts was notably linked to a reduced risk of HF (OR = 0.96, 95% CI, 0.95 - 0.98, P = 0.0002). The MVMR results confirmed that the association between CD39+ CD4+ T-cell counts and HF remained significant. There was no substantial evidence of reverse causality observed between circulating immune cells and HF.

Conclusion

Our MR research provided evidence for a causal relationship between lymphocyte cell and HF. Subsets analyses revealed a causal relationship between CD39+ CD4+ T lymphocytes and HF. These findings will facilitate a future understanding of the mechanisms underlying HF.
Multienzymatic biotransformation of flavokawain B by entomopathogenic filamentous fungi: structural modifications and pharmacological predictions
Authors: Chlipała Paweł , Tronina Tomasz , Dymarska Monika , Urbaniak Monika , Kozłowska Ewa , Stępień Łukasz , Kostrzewa-Susłow Edyta , Janeczko Tomasz
Published: February 2024

Background

Flavokawain B is one of the naturally occurring chalcones in the kava plant (Piper methysticum). It exhibits anticancer, anti-inflammatory and antimalarial properties. Due to its therapeutic potential, flavokawain B holds promise for the treatment of many diseases. However, due to its poor bioavailability and low aqueous solubility, its application remains limited. The attachment of a sugar unit impacts the stability and solubility of flavonoids and often determines their bioavailability and bioactivity. Biotransformation is an environmentally friendly way to improve the properties of compounds, for example, to increase their hydrophilicity and thus affect their bioavailability. Recent studies proved that entomopathogenic filamentous fungi from the genera Isaria and Beauveria can perform O-methylglycosylation of hydroxyflavonoids or O-demethylation and hydroxylation of selected chalcones and flavones.

Results

In the present study, we examined the ability of entomopathogenic filamentous fungal strains of Beauveria bassiana, Beauveria caledonica, Isaria farinosa, Isaria fumosorosea, and Isaria tenuipes to transform flavokawain B into its glycosylated derivatives. The main process occurring during the reaction is O-demethylation and/or hydroxylation followed by 4-O-methylglycosylation. The substrate used was characterized by low susceptibility to transformations compared to our previously described transformations of flavones and chalcones in the cultures of the tested strains. However, in the culture of the B. bassiana KCh J1.5 and BBT, Metarhizium robertsii MU4, and I. tenuipes MU35, the expected methylglycosides were obtained with high yields. Cheminformatic analyses indicated altered physicochemical and pharmacokinetic properties in the derivatives compared to flavokawain B. Pharmacological predictions suggested potential anticarcinogenic activity, caspase 3 stimulation, and antileishmanial effects.

Conclusions

In summary, the study provided valuable insights into the enzymatic transformations of flavokawain B by entomopathogenic filamentous fungi, elucidating the structural modifications and predicting potential pharmacological activities of the obtained derivatives. The findings contribute to the understanding of the biocatalytic capabilities of these microbial cultures and the potential therapeutic applications of the modified flavokawain B derivatives.
Differential contribution of THIK-1 K+ channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia
Authors: Rifat Ali , Ossola Bernardino , Bürli Roland W. , Dawson Lee A. , Brice Nicola L. , Rowland Anna , Lizio Marina , Xu Xiao , Page Keith , Fidzinski Pawel , Onken Julia , Holtkamp Martin , Heppner Frank L. , Geiger Jörg R. P. , Madry Christian
Published: February 2024

Neuroinflammation is highly influenced by microglia, particularly through activation of the NLRP3 inflammasome and subsequent release of IL-1β. Extracellular ATP is a strong activator of NLRP3 by inducing K+ efflux as a key signaling event, suggesting that K+-permeable ion channels could have high therapeutic potential. In microglia, these include ATP-gated THIK-1 K+ channels and P2X7 receptors, but their interactions and potential therapeutic role in the human brain are unknown. Using a novel specific inhibitor of THIK-1 in combination with patch-clamp electrophysiology in slices of human neocortex, we found that THIK-1 generated the main tonic K+ conductance in microglia that sets the resting membrane potential. Extracellular ATP stimulated K+ efflux in a concentration-dependent manner only via P2X7 and metabotropic potentiation of THIK-1. We further demonstrated that activation of P2X7 was mandatory for ATP-evoked IL-1β release, which was strongly suppressed by blocking THIK-1. Surprisingly, THIK-1 contributed only marginally to the total K+ conductance in the presence of ATP, which was dominated by P2X7. This suggests a previously unknown, K+-independent mechanism of THIK-1 for NLRP3 activation. Nuclear sequencing revealed almost selective expression of THIK-1 in human brain microglia, while P2X7 had a much broader expression. Thus, inhibition of THIK-1 could be an effective and, in contrast to P2X7, microglia-specific therapeutic strategy to contain neuroinflammation.

Graphical Abstract
Ultrasonic microbubbles promote mesenchymal stem cell homing to the fibrotic liver via upregulation of CXCR4 expression
Authors: Xu Heming , Huang Yize , Zhang Fasu , Shi Wei , Cheng Yan , Yang Kai , Tian Pingping , Zhou Fei , Wang Yuan , Fang Xueqing , Song Youliang , Liu Bo , Liu Liwei
Published: February 2024

Objective

To investigate the mechanism of ultrasound microbubbles (UTMB) promoting stem cells homing to fibrotic liver.

Methods

Bone marrow derived mesenchymal stem cells (BMSCs) were divided into 5 groups with or without ultrasound microbubbles and continuously irradiated with ultrasound conditions of frequency 1 MHZ and output power 0.6 W/cm2 for different times, and then injected into a mouse model of liver fibrosis through the tail vein with or without ultrasound microbubbles, with sound intensity. The effect of ultrasound microbubbles on MSC expression of CXC chemokine receptor 4 (CXCR4) and homing fibrotic liver was evaluated by flow cytometry (FCM), western blot (WB) and immunohistochemistry (IHC) analysis.

Results

The level of CXCR4 expression was significantly higher in the ultrasound microbubble group than in the non-intervention group (P < 0.05), and the number of MSC and the rate of CXCR4 receptor positivity in the ultrasound microbubble-treated liver tissues were significantly higher than in the non-intervention group (P < 0.01).

Conclusion

Ultrasonic microbubbles can promote the expression of CXCR4 on the surface of MSCs, thus improving the homing rate of MSCs in fibrotic liver.
Predictors of COVID-19 vaccine uptake among people who use substances: a case study in Tehran
Authors: Karimi Salah Eddin , Amadi Sina , Rampisheh Zahra , Tayefi Batool , Soleimanvandiazar Neda , Higgs Peter , Tehrani-Banihashemi Arash , Hajebi Ahmad , Nojomi Marzieh , Karimijavan Gelavizh
Published: February 2024

Background

Vaccination is one of the most effective ways to manage infectious disease epidemics such as Covid-19. However, the low rates of vaccination in populations at risk including people using illicit substances, hinders the effectiveness of preventive vaccines in reducing transmission. The aim of this study was to investigate the rate of Covid-19 vaccination and its related factors among people who use substances in Tehran, Iran.

Methods

Between July and December 2022, 386 people who use substances aged ≥ 18 years old were recruited by convenience street-based sampling in Tehran. The outcome variable in this study was self-reported completion of at least two doses of the Covid-19 vaccine. Logistic regression was used to investigate the factors related to Covid-19 vaccination. Data were analyzed using SPSS software version 20 at the 0.05 level of significance. As a measure of risk, 95% Confidence interval (CI) was used. The level of significance was considered at 0.05.

Results

Almost three-quarters (n = 286) of the participants reported receiving at least two doses of the Covid-19 vaccine (95% CI, 70.2–79.3). Those participants with high school diplomas were 1.17 times more likely than less educated participants to report having had 2 vaccinations (OR of 1.17, CI 95%: 1.03–1.81). Participants with a higher mean score of having a positive attitude towards Covid-19 vaccination were more likely to have received a vaccination (OR of 1.12, CI 95%: 1.08–1.17). Ethnicity was also an influential variable, people with non-Fars ethnicity were less likely to be vaccinated than those of Fars ethnicity (OR of 0.33, CI 95%: 0.13–0.81). People with higher-than-average monthly income were more likely to report vaccination than those with low monthly incomes (OR of 1.27, CI 95%: 1.09–1.8). Also, participants reporting less access to vaccination centers had a lower chance of reporting having been vaccinated than those who reported high access to vaccination centers (OR of .17, CI 95%: .08-.36).

Conclusions

Covid-19 vaccine uptake was found to be relatively high among people using illicit substances in this study. Higher levels of education, Fars ethnicity, higher income levels, having a positive attitude towards vaccination and access to vaccination centers were the most important predictors of Covid-19 vaccination in this study.
MSCT study for adult esophageal diverticulum with secondary broncho-esophageal fistula
Authors: Dong Xin , Pan Ruonan , Duan Lijun , Lu Xiaoqian , Cao Dianbo
Published: February 2024

Background

Broncho-esophageal fistula (BEF) secondary to esophageal diverticulum is a rare clinical condition, which is often misdiagnosed for a long time. The aim of our study is to summarize and clarify the advantages of MSCT in diagnosing BEF secondary to esophageal diverticulum.

Methods

We retrospectively analyzed patients clinically diagnosed with BEF from January 2005 to January 2022 at Jilin University First Hospital. Only those patients with BEF secondary to esophageal diverticulum and complete clinical data met our enrolled standard. All patients’ clinicopathologic characteristics and MSCT features were systemically evaluated.

Results

17 patients were eligible for our cohort study, including male 10 and female 7. The patient’s mean age was 42.3 ± 12.5. The chronic cough occurred in all seventeen patients and bucking following oral fluid intake was documented in nine patients. MSCT distinctly suggested the fistulous tract between the bronchi and the esophagus in all patients. The mean diameter of the orifices in the wall of the esophagus was 4.40 ± 1.81 mm. The orifice in the midthoracic esophagus side was 15 cases and 2 cases at the lower thoracic esophagus. The involved bronchus included 13 cases at the right lower lobe bronchus, 1 at the right middle lobe bronchus and 3 at the left lower lobe bronchus. The contrast agent was observed in the pulmonary parenchyma in 10 of 13 patients who underwent esophagogram. No definite fistula was observed in 3 of 11 who underwent gastroscopy, while the intra-operative findings supported the existence of fistula.

Conclusions

BEF secondary to esophageal diverticulum tends to occur between the midthoracic esophagus and the right lower lobe bronchus. Compared with esophagography and gastroscopy, MSCT shows more comprehensive information about the fistulous shape, size, course and lung involvement, which are helpful for establishing diagnosis and guiding subsequent treatment.
Treatment guidelines for rare, early-onset conditions associated with epileptic seizures: a literature review on Rett syndrome and tuberous sclerosis complex
Authors: Amin S. , Ruban-Fell B. , Newell I. , Evans J. , Vyas K. , Nortvedt C. , Chin R. F.
Published: February 2024

Background

Rett syndrome (RTT) and tuberous sclerosis complex (TSC) are two rare disorders presenting with a range of different epileptic seizures. Seizure management requires careful therapy selection, thereby necessitating development of high-quality treatment guidelines. This targeted literature review (TLR) aimed to characterise country-specific and international treatment guidelines available for pharmacological management of seizures in RTT and TSC.

Methods

A TLR was performed between 25-Jan and 11-Mar 2021. Manual searches of online rare disease and guideline databases, and websites of national heath technology assessment bodies were conducted for the following countries: Australia, Canada, France, Germany, Israel, Italy, Japan, Spain, Switzerland, UK, and US as defined by pre-specified eligibility criteria. Search terms were developed for each condition and translated into local languages where appropriate. Eligible publications were defined as guidelines/guidance reporting pharmacological management of seizures in patients with RTT and TSC. Guideline development methodology, geographical focus, author information and treatment recommendations were extracted from guidelines. An author map was generated using R version 3.5.1 to visualise extent of collaboration between authors.

Results

24 total guidelines were included, of which three and six contained only recommendations for RTT and TSC, respectively (some provided recommendations for ≥ 1 condition). Guideline development processes were poorly described (50% [12 guidelines] had unclear/absent literature review methodologies); reported methodologies were variable, including systematic literature reviews (SLRs)/TLRs and varying levels of expert consultation. Most (83% [20/24]) were country-specific, with guideline authors predominantly publishing in contained national groups; four guidelines were classified as ‘International,’ linking author groups in the US, UK, Italy and France. High levels of heterogeneity were observed in the availability of treatment recommendations across indications, with 13 and 67 recommendations found for RTT and TSC, respectively. For RTT, all treatment recommendations were positive and sodium valproate had the highest number of positive recommendations (Khwaja, Sahin (2011) Curr Opin Pediatr 23(6):633–9). All TSC treatments (21 medications) received either exclusively negative (National Organization for Rare Disorders (2019)) or positive (Chu-Shore et al. (2010) Epilepsia 51(7):1236–41) recommendations; vigabatrin received the highest number of positive recommendations (Kaur, Christodoulou (2019)).

Conclusions

This review highlights the need for the development of international high-quality and comprehensive consensus-based guidance for the management of seizures with pharmacological therapy in RTT and TSC.

Trial registration

Not applicable.