bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the efficacy of microdissection of paravebous sinus meningiomas invading large venous sinuses
Authors: Ji Chengyuan , Zhao Jiashuo , Xing Weixin , Liu Jiangang
Published: May 2023

Objective

The management of paravebous sinus meningiomas that invade major venous sinuses is a subject of debate, particularly concerning the necessity of complete resection of the tumor and reconstruction of the venous sinus. This article aims to demonstrate the outcomes of total removal of the lesion (including the invading venous sinus portion) and the effects of restoring or not restoring venous circulation in terms of recurrence of the tumor, mortality, and post-operative complications.

Methods

The authors conducted a study involving 68 patients with paravebous sinus meningiomas. Of the 60 parasagittal meningiomas, 23 were located in the anterior third, 30 in the middle third, and 7 in the posterior third. Additionally, 3 lesions were located in the sinus confluence area, and 5 in the transverse sinus. All patients underwent surgery, and the degree of venous sinus involvement was classified into six types. For type I meningiomas, the outer layer of the sinus wall was stripped off. For types II to VI, two strategies were employed: non-constitutional, wherein the tumor and affected venous sinuses were removed without repair, and reconstructive, wherein the tumor was completely removed and the venous sinuses were sutured or repaired. Karnofsky Performance Status (KPS) scale and Magnetic Resonance Venography (MRV) were utilized to assess the outcomes of the surgical procedures.

Results

The study group of 68 patients underwent complete tumor resection in 97.1%, with sinus reconstruction attempted in 84.4% of cases with sinus wall and sinus cavity invasion. The recurrence rate of this group was 5.9%, with follow-up ranging from 33 to 57 months. It was found that the recurrence rate was significantly higher in cases with incomplete resection than in those with complete resection. The overall mortality rate was 4.4%, with all cases resulting from malignant brain swelling due to the failure to perform venous reconstruction after resectioning of the meningioma type VI. Furthermore, 10.3% of patients experienced worsening symptoms of neurological deficits or complete loss of neurological function, with a significantly higher incidence in those without venous reconstruction than in the venous reconstruction group (P < 0.0001, Fisher test). No statistically significant pre-operative and post-operative KPS differences were observed in patients with type I to V. However, in patients with type VI (who did not receive venous reconstruction), the post-operative KPS score was significantly worse.

Conclusion

The results of this study suggest the necessity of a complete resection of the tumor, including the invasive venous sinus component, as the recurrence rate was found to be relatively low at 5.9%. Moreover, patients who did not undergo venous reconstruction showed significant deterioration in their clinical condition compared to other subgroups, thus highlighting the importance of venous sinus reconstruction.
The status of low anterior resection syndrome: data from a single-center in China
Authors: Su Jing , Liu Qianhui , Zhou Dagui , Yang Xiaofeng , Jia Guiru , Huang Lijun , Tang Xiao , Fang Jiafeng
Published: May 2023

Aim

The incidence and risk factors of low anterior resection syndrome (LARS) largely variate in different studies. In addition, there is lack of study on how patients evaluate the therapeutic effect of LARS. This single-center retrospective study aims to investigate the status of LARS in Chinese patients undergoing laparoscopic low anterior resection (LAR).

Methods

Consequent patients undergoing laparoscopic LAR and free from disease recurrence from January 2015 to May 2021 were issued with both LARS questionnaire and satisfaction survey. Related data were collected and analyzed.

Results

Both LARS questionnaires and self-made satisfaction survey were received from 261 eligible patients. The overall incidence of LARS was 47.1% (minor in 19.5%, major in 27.6%), decreased with the passage of postoperative time (64.7% within 12 months, and 41.7% within 12–36 months), and became stable 36 months later (39.7%). The most common symptoms were defecation clustering (n = 107/261, 41.0%) and defecation urgency (n = 101/261, 38.7%). According to the multivariable regression analysis, risk factors of major LARS were: 1 year increase in age (OR 1.035, 95% CI 1.004–1.068), protective stoma (OR 2.656, 95% CI 1.233–5.724) and T3 − 4 stage (OR 2.449, 95% CI 1.137–5.273). Most patients complained defecation disorder (87.3%) to doctors and 84.5% got suggestions or treatments for it. However, only 36.8% patients thought the treatments worked for them.

Conclusions

LARS frequently occurs after laparoscopic LAR, while the therapeutic effect is not satisfying. Elder, advanced T-stage and protective stoma were risk factors for postoperative major LARS.
Risk factors analysis of surgical complications of hepatic hemangioma: a modified Clavien-Dindo classification-based study
Authors: Yang Kai , Ma Yan , Yang Zelong , Yang Yanling , Song Wenjie , Chen Weigang , Lv Weihao , Zhang Ruohan , Chen Yong , Qiao Hongyu
Published: May 2023

Purpose

There are few studies on the risk factors of postoperative complications after surgical treatment of hepatic hemangioma (HH). This study aims to provide a more scientific reference for clinical treatment.

Methods

The clinical characteristics and operation data of HH patients undergoing surgical treatment in the First Affiliated Hospital of Air Force Medical University from January 2011 to December 2020 were retrospectively collected. All enrolled patients were divided into two groups based on the modified Clavien-Dindo classification: Major group (Grade II/III/IV/V) and Minor group (Grade I and no complications). Univariate and multivariate regression analysis was used to explore the risk factors for massive intraoperative blood loss (IBL) and postoperative Grade II and above complications.

Results

A total of 596 patients were enrolled, with a median age of 46.0 years (range, 22–75 years). Patients with Grade II/III/IV/V complications were included in the Major group (n = 119, 20%), and patients with Grade I and no complications were included in the Minor group (n = 477, 80%). The results of multivariate analysis of Grade II/III/IV/V complications showed that operative duration, IBL, and tumor size increased the risk of Grade II/III/IV/V complications. Conversely, serum creatinine (sCRE) decreased the risk. The results of multivariate analysis of IBL showed that tumor size, surgical method, and operative duration increased the risk of IBL.

Conclusions

Operative duration, IBL, tumor size, and surgical method are independent risk factors that should be paid attention to in HH surgery. In addition, as an independent protective factor for HH surgery, sCRE should attract more attention from scholars.
Laparoscopic assisted trans-scrotal orchiopexy versus traditional orchiopexy for inguinal cryptorchidism: a retrospective study based on 154 patients
Authors: Guo Qiang , Zhang Yifei , Lai Huajian , Zhong WenWen , Qiu Jianguang , Wang Dejuan
Published: May 2023

Background

The purpose of this study was to investigate the clinical effect of laparoscopic assisted trans-scrotal orchiopexy versus traditional orchiopexy for inguinal cryptorchidism.

Methods

A retrospective analysis of cryptorchidism patients who were admitted to our hospital from July 2018 to July 2021. The patients were divided into the laparoscopic assisted trans-scrotal surgery group (n = 76) and the traditional surgery group (n = 78) according to the surgical method.

Results

All patients were successfully operated. There was no significant difference in operation time between the laparoscopic assisted trans-scrotal group and the traditional group (P>0.05). Although there was no significant difference in the postoperative hospital stay between the two groups, the time of postoperative hospital stay of the laparoscopic assisted trans-scrotal surgery group was lower than that in the traditional surgery group (P = 0.062). Additionally, there was no significant difference in discharge rate on the first day after surgery between the two groups, but the discharge rate on the first day after surgery was more than 90% in both groups. In terms of postoperative complications, there were no cases of testicular retraction, testicular atrophy, inguinal hernia, or hydrocele that occurred in both groups. There was no significant difference in the incidence of scrotal hematoma between the two groups(P>0.05). Although there was no significant difference in the incidence of poor wound healing between the two groups(P>0.05), the incidence in the laparoscopic assisted trans-scrotal surgery group was lower than that in the traditional surgery group (2.6% vs. 6.4%).

Conclusion

Laparoscopic assisted trans-scrotal surgery is as safe and effective method as traditional surgery for patients with inguinal cryptorchidism, and could also provide a good appearance.
Diode laser in management of loss of taste sensation in patients with post-COVID syndrome: a randomized clinical trial
Authors: Shabaan Alshaimaa Ahmed , Kassem Islam , Mahrous Aliaa Ibrahium , aboulmagd Inass , Badrah Mai , Attalla Mohamed , Refahee Shaimaa Mohsen
Published: May 2023

Objective

Loss of taste (ageusia) is a symptom observed following recovery from COVID-19 infection. The loss of taste and smell sensation may negatively affect patients’ quality of life (QoL). The present study aimed to evaluate the effectiveness of the Diode Laser in managing loss of taste sensation in patients with post-COVID syndrome versus the placebo.

Material and method

The study sample was 36 patients who complained of persistent loss of taste sensation following COVID-19. The patients were randomly assigned to one of the two groups according to the received treatment: Group I (laser treatment) and Group II (light treatment), with each patient receiving a diode laser treatment or placebo from the same operator. Taste sensation was subjectively measured after treatment for four weeks.

Results

The results demonstrated a significant difference between both groups regarding taste restoration after one month (p = 0.041), with Group II having a significantly higher percentage of cases 7 (38.9%) with partial taste restoration. In contrast, a significantly higher proportion of Group I 17 cases (94.4%) had complete taste restoration (p < 0.001).

Conclusion

The present study concluded that using a Diode laser 810 nm aided in a more rapid recovery from loss of taste dysfunction.
A narrative review of evidence to support increased domestic resource mobilization for family planning in Nigeria
Authors: Mbachu Chinyere Ojiugo , Agu Ifunanya Clara , Ekwueme Chinazom N. , Ndu Anne , Onwujekwe Obinna
Published: May 2023

Background

Family planning (FP) is an important public health intervention that is proven to reduce unplanned pregnancies, unsafe abortions, and maternal mortality. Increasing investments in FP would ensure stability and better maternal health outcomes in Nigeria. However, evidence is needed to make a case for more domestic investment in family planning in Nigeria. We undertook a literature review to highlight the unmet needs for family planning and the situation of its funding landscape in Nigeria. A total of 30 documents were reviewed, including research papers, reports of national surveys, programme reports, and academic/research blogs. The search for documents was performed on Google Scholar and organizational websites using predetermined keywords. Data were objectively extracted using a uniform template. Descriptive analysis was performed for quantitative data, and qualitative data were summarized using narratives. Frequencies, proportions, line graphs and illustrative chart were used to present the quantitative data.

Although total fertility rate declined over time from 6.0 children per woman in 1990 to 5.3 in 2018, the gap between wanted fertility and actual fertility increased from 0.2 in 1990 to 0.5 in 2018. This is because wanted fertility rate decreased from 5.8 children per woman in 1990 to 4.8 per woman in 2018. Similarly, modern contraceptive prevalence rate (mCPR) decreased by 0.6% from 2013 to 2018, and unmet need for family planning increased by 2.5% in the same period. Funding for family planning services in Nigeria comes from both external and internal sources in the form of cash or commodities. The nature of external assistance for family planning services depends on the preferences of funders, although there are some similarities across funders. Irrespective of the type of funder and the length of funding, donations/funds are renewed on annual basis. Procurement of commodities receives most attention for funding whereas, commodities distribution which is critical for service delivery receives poor attention.

Conclusion

Nigeria has made slow progress in achieving its family planning targets. The heavy reliance on external donors makes funding for family planning services to be unpredictable and imbalanced. Hence, the need for more domestic resource mobilization through government funding.
Protective effects of the Terminalia bellirica tannin-induced Nrf2/HO-1 signaling pathway in rats with high-altitude pulmonary hypertension
Authors: Aimaier Salamaiti , Tao Yang , Lei Fang , Yupeng Zhang , Wenhui Shi , Aikemu Ainiwaer , Maimaitiyiming Dilinuer
Published: May 2023

Background

Oxidative stress and endothelial cell dysfunction induced by high-altitude hypoxia have important roles in the pathological process of high-altitude pulmonary hypertension (HAPH). Tannins present in Terminalia bellirica (Gaertn.) Roxb. (TTR) have pharmacological activities that produce oxidation resistance and exert anti-inflammatory effects. Whether TTR exerts a protective effect on HAPH remains unknown.

Methods

A rat model of HAPH was established. The mean pulmonary arterial pressure (mPAP) of the animals was measured, the serum levels of SOD, MDA, and GSH-Px were measured using ELISA, and the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in the lung tissue of each group of rats was measured using Western blotting. Pathological changes in the lung tissue were also observed. A model of damage to H2O2-induced pulmonary artery endothelial cells (PAECs) was generated, and cell proliferation was measured using CCK-8 assays. Flow cytometry was used to measure ROS levels in PAECs. Western blotting was used to detect the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in PAECs.

Results

The hemodynamic and pathologic findings showed that the mPAP of HAPH rats increased markedly, and the vascular wall thickness increased (P < 0.05). TTR reduced mPAP, alleviated or slowed pulmonary arterial remodeling, increased GSH-Px and SOD activity, lowered the level of MDA (P < 0.05), and downregulated the expression of Bax in the lung tissues of HAPH rats, while the expression of Bcl-2, Nrf2, and HO-1 was upregulated (P < 0.05). The results of the cell experiments showed that TTR inhibited H2O2-induced PAEC apoptosis and ROS production (P < 0.05), downregulated the expression of Bax in PAECs, and upregulated the expression of Bcl-2, Nrf2, and HO-1 (P < 0.05).

Conclusion

The results suggest that TTR reduces pulmonary arterial pressure, decreases oxidative stress during HAPH, and exerts protective effects in rats with HAPH and that its mechanism of action is related to regulation of the Nrf2/HO-1 signaling pathway.
The PEST (Pathology, Epidemiology, Severity, Treatment) approach to optimizing antimicrobial therapy
Authors: Davar Kusha , Vijayan Tara
Published: May 2023

Background

Selecting an empiric antimicrobial regimen can be difficult for early learners and misuse of antibiotics can lead to adverse events and antimicrobial resistance. There have been few interventions that have focused on improving antibiotic decision making, as a form of therapeutic reasoning, for post-graduate trainees. We describe here an approach to aid internal medicine interns in their therapeutic reasoning, particularly when it comes to diagnosing and empirically treating infections.

Methods

The PEST (pathology, epidemiology, severity, treatment) model was created as a four-step approach to therapeutic reasoning and choosing an appropriate antimicrobial regimen for a given infectious disease syndrome. In February 2020, we conducted two independent teaching sessions for interns on the PEST approach. We assessed pre-and post-teaching responses to five clinical vignette-based questions. Results were presented as a percentage of interns who chose an appropriate antibiotic and provided sufficient therapeutic reasoning as defined by using at least three out of the four PEST criteria. Statistical analysis occurred via Fischer’s exact test to determine the level of statistical significance between responses.

Results

Twenty-seven interns participated in the activity. At baseline, several interns had incorporated aspects of the PEST approach in their pre-teaching responses. Ten interns commented on the usefulness of such a systematic approach. While there was no statistically significant difference in antibiotic selection, the teaching session demonstrated a trend towards significance in improving therapeutic reasoning as defined by the PEST strategy.

Conclusion

Our results suggested an improvement in using a structured cognitive tool such as the PEST approach to reinforce therapeutic reasoning, but the method did little to improve antibiotic selection. Some interns used select “PEST” concepts prior to the intervention suggesting that the PEST approach may enhance prior knowledge or clinical reasoning skills. Continued incorporation of the PEST approach using a case-based framework may solidify conceptual and practical knowledge of antimicrobial selection. Further studies are needed to assess the impact of such teaching interventions.
Symptom prevalence, severity, distress and management among patients with chronic diseases
Authors: ALHosni Fatima , Al Qadire Mohammad , Omari Omar Al , Al Raqaishi Huda , Khalaf Atika
Published: May 2023

Background

Advanced knowledge, technology, and treatment approaches resulted in longer survival rates for patients suffering from chronic diseases. However, symptoms of these diseases persist and affect the individual’s entire life and normal functioning.

Aim

To assess symptoms prevalence, severity, distress, and management among patients with chronic obstructive pulmonary diseases (COPD), chronic heart failure (CHF), and end-stage renal disease (ESRD) in Oman.

Design

A descriptive cross-sectional design was used.

Sample and settings

The study sample comprised 340 participants who were recruited between May and December 2021 from two referral hospitals and one large dialysis unit in the Sultanate of Oman, Muscat Governate using a convenience sampling technique.

Results

The highly prevalent symptoms among patients with selected chronic diseases were lack of energy (60.9%), pain (57.4%), numbness (53.2%), difficulty sleeping (49.4%), and shortness of breath (45.9%). The most severe symptoms were shortness of breath (53.2%), problems with urination (51.9%), constipation (50.8%), difficulty sleeping (49.7%), and pain (46.2%). The symptom “problems with sexual interests or activity” was found to be the most frequently occurring and highly distressing symptom out of all reported symptoms.

Conclusions

The current study’s findings showed that symptoms were prevalent and that some symptoms were frequent, severe, and highly distressing. In addition, patients perceived symptom treatment as inadequate. Psychological symptoms received less treatment attention compared with physical symptoms. One of the mainstays for managing symptoms can be the introduction of palliative care. Providing palliative care to these patients can alleviate their suffering and improve their quality of life. In addition, designing chronic disease self-management programmes can make a difference in patients’ life.
Nurses’ clinical competency and its correlates: before and during the COVID-19 outbreak
Authors: Hui Tian , Zakeri Mohammad Ali , Soltanmoradi Yaser , Rahimi Neda , Hossini Rafsanjanipoor Sayed Mortaza , Nouroozi Majid , Dehghan Mahlagha
Published: May 2023

Background

Clinical competency is the ability to integrate knowledge, skills, attitudes and values into a clinical situation and it is very important in nursing education, clinical settings, nursing management, and crises. This study aimed to investigate nurses’ professional competence and its correlates before and during the COVID-19 pandemic.

Methods

We conducted this cross-sectional study before and during the COVID-19 outbreak and recruited all nurses working in hospitals affiliated to Rafsanjan University of Medical Sciences, southern Iran, so we included 260 and 246 nurses in the study before and during the COVID-19 epidemic, respectively. Competency Inventory for Registered Nurses (CIRN) was used to collect data. After inputting the data into SPSS24, we analysed them using descriptive statistics, chi-square and multivariate logistic tests. A significant level of 0.05 was considered.

Results

The mean clinical competency scores of nurses were 156.97 ± 31.40 and 161.97 ± 31.36 before and during the COVID-19 epidemic, respectively. The total clinical competency score before the COVID-19 epidemic was not significantly different from that during the COVID-19 epidemic. Interpersonal relationships (p = 0.03) and desire for research/critical thinking (p = 0.01) were significantly lower before the COVID-19 outbreak than during the COVID-19 outbreak. Only shift type had an association with clinical competency before the COVID-19 outbreak, while work experience had an association with clinical competency during the COVID-19 epidemic.

Conclusion

The clinical competency among nurses was moderate before and during the COVID-19 epidemic. Paying attention to the clinical competence of nurses can improve the care conditions of patients, and nursing managers should improve the clinical competence of nurses in different situations and crises. Therefore, we suggest further studies identifying factors improving the professional competency among nurses.
The Alberta Neonatal Abstinence Syndrome Mother-Baby Care ImprovEmeNT (NASCENT) program: protocol for a stepped wedge cluster randomized trial of a hospital-level Neonatal Abstinence Syndrome rooming-in intervention
Authors: Wine Osnat , McNeil Deborah , Kromm Seija K. , Foss Karen , Caine Vera , Clarke Denise , Day Nathaniel , Johnson David W. , Rittenbach Katherine , Wood Stephen , Hicks Matt
Published: May 2023

Background

Neonatal Abstinence Syndrome (NAS), a problem common in newborns exposed to substances in-utero, is an emerging health concern. In traditional models of care, infants with NAS are routinely separated from their mothers and admitted to the Neonatal Intensive Care Unit (NICU) with long, expensive length of stay (LOS). Research shows a rooming-in approach (keeping mothers and infants together in hospital) with referral support is a safe and effective model of care in managing NAS. The model’s key components are facilitating 24-h care by mothers on post-partum or pediatric units with support for breastfeeding, transition home, and access to Opioid Dependency Programs (ODP). This study will implement the rooming-in approach at eight hospitals across one Canadian Province; support practice and culture shift; identify and test the essential elements for effective implementation; and assess the implementation’s impact/outcomes.

Methods

A stepped wedge cluster randomized trial will be used to evaluate the implementation of an evidence-based rooming-in approach in the postpartum period for infants born to mothers who report opioid use during pregnancy. Baseline data will be collected and compared to post-implementation data. Six-month assessment of maternal and child health and an economic evaluation of cost savings will be conducted. Additionally, barriers and facilitators of the rooming-in model of care within the unique context of each site and across sites will be explored pre-, during, and post-implementation using theory-informed surveys, interviews, and focus groups with care teams and parents. A formative evaluation will examine the complex contextual factors and conditions that influence readiness and sustainability and inform the design of tailored interventions to facilitate capacity building for effective implementation.

Discussion

The primary expected outcome is reduced NICU LOS. Secondary expected outcomes include decreased rates of pharmacological management of NAS and child apprehension, increased maternal ODP participation, and improved 6-month outcomes for mothers and infants. Moreover, the NASCENT program will generate the detailed, multi-site evidence needed to accelerate the uptake, scale, and spread of this evidence-based intervention throughout Alberta, leading to more appropriate and effective care and use of healthcare resources.

Trial registration

ClinicalTrials.gov, NCT0522662. Registered February 4th, 2022.
Down-regulation of WWP2 aggravates Type 2 diabetes mellitus-induced vascular endothelial injury through modulating ubiquitination and degradation of DDX3X
Authors: You Shilong , Xu Jiaqi , Yin Zeyu , Wu Boquan , Wang Pengbo , Hao Mingjun , Cheng Cheng , Liu Mengke , Zhao Yuanhui , Jia Pengyu , Jiang Hongkun , Li Da , Cao Liu , Zhang Xingang , Zhang Ying , Sun Yingxian , Zhang Naijin
Published: May 2023

Background

Endothelial injury caused by Type 2 diabetes mellitus (T2DM) is considered as a mainstay in the pathophysiology of diabetic vascular complications (DVCs). However, the molecular mechanism of T2DM-induced endothelial injury remains largely unknown. Here, we found that endothelial WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) act as a novel regulator for T2DM-induced vascular endothelial injury through modulating ubiquitination and degradation of DEAD-box helicase 3 X-linked (DDX3X).

Methods

Single-cell transcriptome analysis was used to evaluate WWP2 expression in vascular endothelial cells of T2DM patients and healthy controls. Endothelial-specific Wwp2 knockout mice were used to investigate the effect of WWP2 on T2DM-induced vascular endothelial injury. In vitro loss- and gain-of-function studies were performed to assess the function of WWP2 on cell proliferation and apoptosis of human umbilical vein endothelial cells. The substrate protein of WWP2 was verified using mass spectrometry, coimmunoprecipitation assays and immunofluorescence assays. The mechanism of WWP2 regulation on substrate protein was investigated by pulse-chase assay and ubiquitination assay.

Results

The expression of WWP2 was significantly down-regulated in vascular endothelial cells during T2DM. Endothelial-specific Wwp2 knockout in mice significantly aggravated T2DM-induced vascular endothelial injury and vascular remodeling after endothelial injury. Our in vitro experiments showed that WWP2 protected against endothelial injury by promoting cell proliferation and inhibiting apoptosis in ECs. Mechanically, we found that WWP2 is down-regulated in high glucose and palmitic acid (HG/PA)-induced ECs due to c-Jun N-terminal kinase (JNK) activation, and uncovered that WWP2 suppresses HG/PA-induced endothelial injury by catalyzing K63-linked polyubiquitination of DDX3X and targeting it for proteasomal degradation.

Conclusion

Our studies revealed the key role of endothelial WWP2 and the fundamental importance of the JNK-WWP2-DDX3X regulatory axis in T2DM-induced vascular endothelial injury, suggesting that WWP2 may serve as a new therapeutic target for DVCs.
Benchmark dose calculations for PFAS exposure based on two data sets on immunotoxic effects
Authors: Budtz-Jørgensen Esben , Grandjean Philippe
Published: May 2023

Background

Exposure to perfluorinated alkylate substances (PFAS) is associated with harmful effects on human health, including developmental immunotoxicity. This outcome was chosen as the critical effect by the European Food Safety Authority (EFSA), which calculated a new joint reference dose for four PFAS using a Benchmark Dose (BMD) analysis of a study of 1-year old children. However, the U.S. Environmental Protection Agency (EPA) recently proposed much lower exposure limits.

Methods

We explored the BMD methodology for summary and individual data and compared the results with and without grouping for two data sets available. We compared the performance of different dose-response models including a hockey-stick model and a piecewise linear model. We considered different ways of testing the assumption of equal weight-based toxicity of the four PFAS and evaluated more flexible models with exposure indices allowing for differences in toxicity.

Results

Results relying on full and decile-based data were in good accordance. However, BMD results for the larger study were lower than observed by EFSA for the smaller study. EFSA derived a lower confidence limit for the BMD of 17.5 ng/mL for the sum of serum-PFAS concentration, while similar calculations in the larger cohort yielded values of about 1.5 ng/mL. As the assumption of equal weight-based toxicity of the four PFAS seems questionable, we confirmed dose-dependencies that allowed potency differences between PFAS. We also found that models linear in the parameters for the BMD analysis showed superior coverage probabilities. In particular, we found the piecewise linear model to be useful for Benchmark analysis.

Conclusions

Both data sets considered could be analyzed on a decile basis without important bias or loss of power. The larger study showed substantially lower BMD results, both for individual PFAS and for joint exposures. Overall, EFSA’s proposed tolerable exposure limit appears too high, while the EPA proposal is in better accordance with the results.
Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer
Authors: Xu Xu , Wang Xiaona , Chen Qihui , Zheng Aman , Li Donglu , Meng Ziqi , Li Xinran , Cai Hanchen , Li Wangzhi , Huang Shiyuan , Wang Fan
Published: May 2023

Background

Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear.

Methods

The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo.

Results

Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells.

Conclusions

Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer.
SARS-CoV-2 envelope protein triggers depression-like behaviors and dysosmia via TLR2-mediated neuroinflammation in mice
Authors: Su Wenliang , Ju Jiahang , Gu Minghui , Wang Xinrui , Liu Shaozhuang , Yu Jiawen , Mu Dongliang
Published: May 2023

Background

Depression and dysosmia have been regarded as primary neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that the SARS-CoV-2 envelope (E) protein is a pro-inflammatory factor sensed by Toll-like receptor 2 (TLR2), suggesting the pathological feature of E protein is independent of viral infection. In this study, we aim to ascertain the role of E protein in depression, dysosmia and associated neuroinflammation in the central nervous system (CNS).

Methods

Depression-like behaviors and olfactory function were observed in both female and male mice receiving intracisternal injection of E protein. Immunohistochemistry was applied in conjunction with RT-PCR to evaluate glial activation, blood–brain barrier status and mediators synthesis in the cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein-related depression-like behaviors and dysosmia in mice.

Results

Intracisternal injection of E protein evoked depression-like behaviors and dysosmia in both female and male mice. Immunohistochemistry suggested that the E protein upregulated IBA1 and GFAP in the cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-1β, TNF-α, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-1β, IL-6 and CCL2 were upregulated in the olfactory bulb. Furtherly, inhibiting microglia, rather than astrocytes, alleviated depression-like behaviors and dysosmia induced by E protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in the cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression-like behaviors and dysosmia induced by E protein.

Conclusions

Our study demonstrates that envelope protein could directly induce depression-like behaviors, dysosmia, and obvious neuroinflammation in CNS. TLR2 mediated depression-like behaviors and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.
Role of combined use of mean platelet volume-to-lymphocyte ratio and monocyte to high-density lipoprotein cholesterol ratio in predicting patients with acute myocardial infarction
Authors: Cao Jianlei , Li Rui , He Tao , Zhang Lin , Liu Huixia , Wu Xiaoyan
Published: May 2023

Background

Atherosclerosis and thrombosis play important roles in the pathophysiology of acute coronary syndrome, with platelet activation and inflammation as the key and initiative factors. Recently mean platelet volume-to-lymphocyte ratio (MPVLR) and monocyte to high-density lipoprotein cholesterol ratio (MHR) have emerged as new prognostic indicators of cardiovascular diseases. However, the predicting effect of the combination of MPVLR and MHR in myocardial infarction has not been reported.

Objective

The aim of this study was to investigate the usefulness of combination of MPVLR and MHR in predicting patients with AMI.

Methods

375 patients who had chest pain or stuffiness were retrospectively enrolled in this study. According to the results of coronary angiography and cardiac troponin, patients were divided into AMI group (n = 284) and control group (n = 91). MPVLR, MHR, Gensini score and Grace score were calculated.

Results

MPVLR and MHR were significantly higher in AMI group than that in control group (6.47 (4.70–9.58) VS 4.88 (3.82–6.44), 13.56 (8.44–19.01) VS 9.14 (7.00–10.86), P < 0.001, respectively). Meanwhile, both were positively correlated with Gensini score and Grace score. Patients with a high level of MPVLR or MHR had an increased risk for AMI (odds ratio (OR) = 1.2, 95% confidence interval (CI) 1.1–1.4, OR = 1.2, 95% CI 1.2–1.3). Combination of MPVLR and MHR identified a greater ROC area than its individual parameters (P < 0.001).

Conclusion

Both MPVLR and MHR are independent predictors of AMI. Combination of MPVLR and MHR had higher predicting value in AMI, and thus appears to be a new risk factor and biomarker in the evaluation of risk and severity of atherosclerosis in AMI.
The short- and long-term effects of cognitive behavioral therapy on the glycemic control of diabetic patients: a systematic review and meta-analysis
Authors: Dong Na , Wang Xiaowei , Yang Liu
Published: May 2023

Background

Glycemic control is an important issue in the treatment of diabetic patients. However, traditional methods, such as medication (the usual treatment), have limitations. Cognitive behavioral therapy (CBT) might be a useful option to help control the glycemic condition. The effects can be revealed by systemic review or meta-analysis of randomized clinical trials (RCT).

Methods

A systematic search and a meta-analysis for the RCT were done of the short- and long-term effects of CBT on the glycemic control of diabetic patients in a comparison with the usual treatment. Nineteen RCT studies and 3,885 diabetic patients were enrolled in this meta-analysis. Subgroup analyses of types 1 and 2 diabetes and individual and group CBT were also performed.

Results

Patients treated with CBT showed no significant difference in HbA1c when compared to the usual treatment within six months. However, CBT was more effective in reducing HbA1c when compared to usual treatment with at least six months of treatment duration [standardized mean difference: -0.44 (95% confidence interval (CI): -0.63 ~ -0.25), Z = 4.49]. Subgroup analysis of type 1 and 2 diabetic patients supported a long-term effect of CBT on glycemic control [standardized mean difference: -0.85 (95% CI: -1.19 ~ -0.10), Z = 2.23, standardized mean difference: -0.33 (95% CI:-0.47 ~ -0.19), Z = 4.52, respectively].

Conclusions

CBT would be a useful option for improving the glycemic control of diabetic patients undergoing long-term treatment. The advantages of the long-term effects of CBT should be considered by clinicians and staff.
The effect on incisional hernia of absorbable barbed suture for midline fascial closure in minimally invasive surgery for colorectal and gastric cancers: study protocol for a randomized controlled trial
Authors: Lee Sejin , Han Se Wung , Lee Min Ro , Kim Chan-Young , Ha Gi Won
Published: May 2023

Background

Incisional hernia following abdominal surgery is a frequent complication of midline laparotomy. This complication is strongly associated with the technique and material used for suture. While a monofilament absorbable suture is recommended to prevent incisional hernia, it can lead to suture loosening or surgical-knot breakage. Although barbed sutures can be an alternative suture material in abdominal fascial closure, evidence for its safety and effectiveness is lacking. Therefore, we designed a prospective randomized trial to evaluate the safety and efficacy of absorbable barbed sutures for midline fascia closure in minimally invasive surgery for colorectal and gastric cancers in comparison with conventional absorbable monofilament sutures.

Methods

A total of 312 patients who underwent minimally invasive surgery for colorectal and gastric cancers will be randomly allocated to either the absorbable barbed or monofilament suture group for abdominal fascia closure in a 1:1 ratio. The primary outcome is incisional hernia rate within 3 years after surgery, as verified by physical examination and computed tomography. Postoperative complications, including surgical site infection, postoperative pain, and quality of life, will be compared between two groups as secondary outcomes. The investigator will examine the patients until discharge and at 6, 12, 18, 24, and 36 months postoperatively.

Discussion

This is the first randomized controlled trial to compare absorbable barbed sutures with monofilament sutures for midline fascia closure in minimally invasive surgery. If absorbable barbed sutures demonstrate superior results to those of monofilament sutures, this type of suture material may be recommended as an alternative option for abdominal fascia closure.

Trial registration

KCT0007069. Registered on January 30, 2023
Evaluation of a community-based integrated care model (CIE) for frail older people in rural Foshan, China: study protocol for a stepped-wedge cluster randomized controlled trial {1}
Authors: Xie Fengjiao , Wen Shuang , Deng Aiwen , Chen Jianhao , Xiong Ribo
Published: May 2023

Background

While community-based eldercare has proven to be effective in qualitative studies, there is limited evidence on the effectiveness of this geriatric care model in rural communities where caring for older people is traditionally the responsibility of family members, but a formal long-term care was recently introduced in China. CIE is a rural community-embedded intervention using multidisciplinary team, to provide evidenced-based integrated care services for frail older people including social care services and allied primary healthcare and community-based rehabilitation services.

Methods

CIE is a prospective stepped-wedge cluster randomized trial conducted at 5 community eldercare centers in rural China. The multifaceted CIE intervention, guided by chronic care model and integrated care model, consists of five components: comprehensive geriatric assessment, individualized care planning, community-based rehabilitation, interdisciplinary case management, and care coordination. The intervention is rolled out in a staggered manner in these clusters of centers at an interval of 1 month. The primary outcomes include functional status, quality of life, and social support. Process evaluation will also be conducted. Generalized linear mixed model is employed for binary outcomes.

Discussion

This study is expected to provide important new evidence on clinical effectiveness and implementation process of an integrated care model for frail older people. The CIE model is also unique as the first registered trial implementing a community-based eldercare model using multidisciplinary team to promote individualized social care services integrated with primary healthcare and community-based rehabilitation services for frail older people in rural China, where formal long-term care was recently introduced.

Trial registration {2a}

China Clinical Trials Register (http://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR2200060326). May 28th, 2022.
Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer’s disease
Authors: Sommerer Yasmine , Dobricic Valerija , Schilling Marcel , Ohlei Olena , Sabet Sanaz Sedghpour , Wesse Tanja , Fuß Janina , Franzenburg Sören , Franke Andre , Parkkinen Laura , Lill Christina M. , Bertram Lars
Published: May 2023

Background

Studies on DNA methylation (DNAm) in Alzheimer’s disease (AD) have recently highlighted several genomic loci showing association with disease onset and progression.

Methods

Here, we conducted an epigenome-wide association study (EWAS) using DNAm profiles in entorhinal cortex (EC) from 149 AD patients and control brains and combined these with two previously published EC datasets by meta-analysis (totaln = 337).

Results

We identified 12 cytosine-phosphate-guanine (CpG) sites showing epigenome-wide significant association with either case–control status or Braak’s tau-staging. Four of these CpGs, located in proximity toCNFN/LIPE,TENT5A, PALD1/PRF1,andDIRAS1, represent novel findings. Integrating DNAm levels with RNA sequencing-based mRNA expression data generated in the same individuals showed significant DNAm-mRNA correlations for 6 of the 12 significant CpGs. Lastly, by calculating rates of epigenetic age acceleration using two recently proposed “epigenetic clock” estimators we found a significant association with accelerated epigenetic aging in the brains of AD patients vs. controls.

Conclusion

In summary, our study represents the hitherto most comprehensive EWAS in AD using EC and highlights several novel differentially methylated loci with potential effects on gene expression.
Transcriptomic analysis of cave, surface, and hybrid samples of the isopod Asellus aquaticus and identification of chromosomal location of candidate genes for cave phenotype evolution
Authors: Lomheim Haeli J. , Reyes Rodas Lizet , Mulla Lubna , Freeborn Layla , Sun Dennis A. , Sanders Sheri A. , Protas Meredith E.
Published: May 2023

Background

Transcriptomic methods can be used to elucidate genes and pathways responsible for phenotypic differences between populations. Asellus aquaticus is a freshwater isopod crustacean with surface- and cave-dwelling ecomorphs that differ greatly in multiple phenotypes including pigmentation and eye size. Multiple genetic resources have been generated for this species, but the genes and pathways responsible for cave-specific characteristics have not yet been identified. Our goal was to generate transcriptomic resources in tandem with taking advantage of the species’ ability to interbreed and generate hybrid individuals.

Results

We generated transcriptomes of the Rakov Škocjan surface population and the Rak Channel of Planina Cave population that combined Illumina short-read assemblies and PacBio Iso-seq long-read sequences. We investigated differential expression at two different embryonic time points as well as allele-specific expression of F1 hybrids between cave and surface individuals. RNAseq of F2 hybrids, as well as genotyping of a backcross, allowed for positional information of multiple candidate genes from the differential expression and allele-specific analyses.

Conclusions

As expected, genes involved in phototransduction and ommochrome synthesis were under-expressed in the cave samples as compared to the surface samples. Allele-specific expression analysis of F1 hybrids identified genes with cave-biased (cave allele has higher mRNA levels than the surface allele) and surface-biased expression (surface allele has higher mRNA levels than the cave allele). RNAseq of F2 hybrids allowed for multiple genes to be placed to previously mapped genomic regions responsible for eye and pigmentation phenotypes. In the future, these transcriptomic resources will guide prioritization of candidates for functional analysis.
Cryptococcus neoformans osteomyelitis of the tibia: a case report and review of the literature
Authors: Papadakis Stamatios A. , Gourtzelidis Georgios , Pallis Dimitrios , Ampadiotaki Margarita-Michaela , Tatakis Fotios , Tsivelekas Konstantinos , Georgousi Kleoniki , Kokkinis Constantinos , Diamantopoulou Kalliopi , Lelekis Moyssis
Published: May 2023

Introduction

Osteomyelitis is a bone inflammation that can be related to various infectious agents. As with any other type of inflammation, the prevailing symptoms and signs may include redness, swelling, pain, and heat. Fungal osteomyelitis is rare and usually found in immune-compromised patients.

Case presentation

A non-human immunodeficiency virus immunocompromised Greek female patient, 82 years old, visited the emergency department due to a 3 day pain located mainly over the left tibia’s anterior surface, accompanied by swelling and redness. There was also a subcutaneous lesion of her left breast. Medical history revealed that the patient had an unmasked close contact with pigeons, a main host of the disease. Initial x-ray imaging showed an osteolytic area in the upper third of the tibial diaphysis. The patient was admitted and underwent a computed tomography-guided biopsy. The specimen revealed a Cryptococcus neoformans infection of the bone and the breast. She was treated with 400 mg fluconazole twice a day for 3 weeks while in hospital and 200 mg twice a day upon discharge for 9 months. After that, she underwent surgical debridement because of lasting local irritation. She was closely monitored in our outpatient office, and in her last visit, 1 year after the initial admission, inflammatory signs had regressed vastly.

Conclusions

To our knowledge, this is the ninth cryptococcal osteomyelitis of the tibia to be recorded since 1974, and the most unusual finding was the bifocal nature of the infection, affecting both the tibia and the breast.