Perioperative Oral decontamination and ImmunoNuTrition (POINT) to prevent postoperative pulmonary complications in elderly patients scheduled for elective non-cardiac surgeries: protocol for a multicentre, randomised controlled trial

Introduction
Elderly patients are known to be vulnerable to postoperative pulmonary complications (PPCs), especially pneumonia. Apart from elder age, preoperative pulmonary diseases, anaemia, malnutrition, dysphagia and frailty may all be contributing factors to PPCs. Poor oral hygiene is a risk factor for PPC as well, as oropharyngeal microflora might be introduced to the lower respiratory tract following endotracheal intubation for general anaesthesia during surgery. Immune regulation, nutrition supplementation and improvement of oropharyngeal microflora might regulate immune and stress response and can be beneficial to elderly patients exposed to surgical stress. In this study, we will explore the effects of perioperative oral decontamination and immunonutrition supplementation on the incidence of postoperative pneumonia in high-risk elderly surgical patients.

Methods and analysis
This study is a multicentre, two-by-two factorial randomised controlled trial evaluating the efficacy of immunonutrition supplementation and oral chlorhexidine decontamination. A total of 592 patients aged 65 years and older who are scheduled for elective non-cardiac surgeries in seven tertiary hospitals in China will be recruited. Patients will be excluded if they have contraindications to the intervention. Patients will be randomised into four groups in a 1:1:1:1 ratio (oral decontamination vs routine oral care, immunonutrition supplementation vs routine nutrition advice). The primary outcome is the incidence of PPCs within 7 days after surgery. The secondary outcomes are the incidence of postoperative pneumonia, infectious complications, Comprehensive Complication Index, postoperative functional recovery, length of hospital stay and hospital expenses. Intention to treat principles will be applied to all outcomes. Descriptive analysis will be used to compare patients’ baseline characteristics. Logistic regression will be used to compare the incidence of PPCs within 7 days after surgery between different groups.

Ethics and dissemination
The study protocol has been approved by the Research Ethics Committee of Peking Union Medical College Hospital (I-23PJ953). All participants will provide written informed consent. Study results will be published in peer-reviewed journals and presented at academic conferences.

Trial registration number
NCT05971810.

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METTL3 Is Essential for Exercise Benefits in Diabetic Cardiomyopathy

Circulation, Ahead of Print. BACKGROUND:Exercise improves functional outcomes in patients with diabetic cardiomyopathy (DiaCM). The molecular mechanism underlying cardiac benefits of exercise in DiaCM remains incompletely understood. N6-methyladenosine (m6A) is the most common form of messenger RNA modification in eukaryotes and has been implicated in cardiac development and disease. However, the role of m6A in DiaCM and in the mitigating effects of exercise on this disease are unclear.METHODS:Cardiomyocyte-specific N6-adenosine-methyltransferase-like 3 (METTL3, an m6A methyltransferase) knockout mice and their wild-type littermates were subjected to either chow diet or high-fat diet feeding and injection of streptozotocin to induce DiaCM, followed by an 8-week exercise training and assessment of cardiac function. Some of the mice were injected with adeno-associated viral vector encoding METTL3 to overexpress METTL3 in cardiomyocytes. Cardiac METTL3 expressions were assessed in patients with nonischemic primary dilated cardiomyopathies without or with diabetes. Potential METTL3 downstream effector YBX1 (Y-box binding protein 1) was identified through RNA sequencing. The functional role of YBX1 was examined through adeno-associated viral vector overexpression or knockdown in cardiomyocytes in DiaCM mice.RESULTS:We showed that cardiac METTL3 protein expression and m6A level were downregulated in patient with dilated cardiomyopathy and further downregulated in patients with dilated cardiomyopathy and diabetes. Consistently, cardiac METTL3 and m6A were downregulated in mouse with DiaCM, whereas they were upregulated by exercise. Cardiomyocyte-specific METTL3 knockout eliminated the cardiac benefits of exercise on DiaCM. Conversely, cardiomyocyte-specific METTL3 overexpression improved systolic and diastolic function in 2 DiaCM mouse models. We demonstrated that exercise enhanced cardiac METTL3 expression in DiaCM through signal transducer and activator of transcription 3. Moreover, METTL3 attenuated DiaCM through m6A-depdendent YBX1 upregulation and the subsequent activation of Nrf2. Cardiomyocyte-specific YBX1 overexpression promoted Nrf2 activation and attenuated oxidative stress, resulting in an improvement in cardiac function in DiaCM. In contrast, cardiomyocyte-specific YBX1 gene knockdown abolished the effect of METTL3 on cardiac improvement in mice with DiaCM. Further, pharmacological activation of METTL3 using a small molecule attenuated cardiac dysfunction in DiaCM.CONCLUSIONS:These studies reveal an essential role of METTL3 in the cardiac benefits of exercise and identify METTL3 and YBX1 as promising therapeutic targets for treating DiaCM.

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Scoping review protocol of the use of eye movement desensitisation and reprocessing in the treatment of birth trauma

Introduction
A traumatic childbirth can have severe negative effects on the mental health of the mother and can negatively impact the child and partner. Eye movement desensitisation and reprocessing (EMDR) is a psychological intervention used to treat symptoms of trauma. The National Institute for Health and Care Excellence guidelines for antenatal and postnatal mental health recommend that trauma-focused cognitive behavioural therapy or EMDR should be offered to women who suffer from post-traumatic stress disorder resulting from a traumatic birth. However, the use of EMDR for birth trauma has not been clearly outlined in the literature.

Objectives
The aim of this scoping review is to explore the extent of the currently available research and to identify knowledge gaps in the use of EMDR for treating birth trauma.

Methods and analysis
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines will be followed to provide a comprehensive scoping review of the use of EMDR for birth trauma. Several databases will be searched, such as PsychInfo, Pubmed, the Cochrane Library, Embase, Scopus and CINAHL, from the date the database was developed, until approximately August 2026. The grey literature sources will also be searched, and searches will be limited to include studies written in the English language. Two researchers will independently screen and extract data from both quantitative and qualitative studies, which meet the inclusion criteria. Data will be analysed in a descriptive and thematic manner. Data extraction may include study characteristics, data collection procedures, outcomes and results. Findings will be presented in tabular and narrative formats.

Ethics and dissemination
Ethical Approval is not necessary for this review, as only secondary data will be used. It is expected that the review will be disseminated at psychological conferences and in relevant journal articles.

Trial registration number
This scoping review protocol has been registered on Open Science Framework. The registration DOI is: https://doi.org/10.17605/OSF.IO/UJZ52.

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Scoping review protocol of the use of eye movement desensitisation and reprocessing in the treatment of birth trauma

Introduction
A traumatic childbirth can have severe negative effects on the mental health of the mother and can negatively impact the child and partner. Eye movement desensitisation and reprocessing (EMDR) is a psychological intervention used to treat symptoms of trauma. The National Institute for Health and Care Excellence guidelines for antenatal and postnatal mental health recommend that trauma-focused cognitive behavioural therapy or EMDR should be offered to women who suffer from post-traumatic stress disorder resulting from a traumatic birth. However, the use of EMDR for birth trauma has not been clearly outlined in the literature.

Objectives
The aim of this scoping review is to explore the extent of the currently available research and to identify knowledge gaps in the use of EMDR for treating birth trauma.

Methods and analysis
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines will be followed to provide a comprehensive scoping review of the use of EMDR for birth trauma. Several databases will be searched, such as PsychInfo, Pubmed, the Cochrane Library, Embase, Scopus and CINAHL, from the date the database was developed, until approximately August 2026. The grey literature sources will also be searched, and searches will be limited to include studies written in the English language. Two researchers will independently screen and extract data from both quantitative and qualitative studies, which meet the inclusion criteria. Data will be analysed in a descriptive and thematic manner. Data extraction may include study characteristics, data collection procedures, outcomes and results. Findings will be presented in tabular and narrative formats.

Ethics and dissemination
Ethical Approval is not necessary for this review, as only secondary data will be used. It is expected that the review will be disseminated at psychological conferences and in relevant journal articles.

Trial registration number
This scoping review protocol has been registered on Open Science Framework. The registration DOI is: https://doi.org/10.17605/OSF.IO/UJZ52.

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Relationship between psychosocial problems and satisfaction with GP communication in German primary care practices: a structural equation model based on the cross-sectional GPCare-1 patient study

Objectives
This study examined the relationship between primary care patients’ psychosocial problems, other patient characteristics that are associated with satisfaction with overall care and satisfaction with general practitioner (GP) communication.

Design
A cross-sectional survey was conducted. Patients filled an anonymous two-page questionnaire on various socio-demographic, medical characteristics and their satisfaction with GP communication. Structural equation modelling evaluated associations of various patient characteristics, including psychosocial problems with GP communication.

Setting
General practices in Germany.

Participants
A total of 813 patients from 12 GP practices participated. The survey was conducted in summer 2020 during a COVID-19 lockdown.

Results
The estimated response rate was 24.1%. The prevalence of psychosocial problems in the sample was 30%. The three most frequent problems were excessive stress at work (19%), financial problems/debts (9%) and loneliness (8%). Most patients agreed that their GP takes their problems seriously (71%), feeling comfortable talking about sensitive things (66%), having enough space in communication (62%) and being asked by their GP about personal strains (53%). Higher social support, preference to solve one’s problem without GP help, higher age and better health status predicted more satisfaction with physician–patient communication, while the number of psychosocial problems, gender, years with physician, chronic stress and depression had no influence. According to the Bentler Comparative Fit Index, the pooled structural equation model had a 97.6% better fit than the corresponding model without covariate effects.
Higher social support, preference to solve one’s problem without GP help, higher age and better health status but not the number of psychosocial problems predicted more satisfaction with physician–patient communication.

Conclusions
GPs should be aware of the high occurrence of patients’ psychosocial problems and actively address patients’ social support and self-management preferences which influence patients’ satisfaction with GP communication.

Trial registration number
The General Practice Care-1 study was registered in the German Clinical Trials Register (DRKS00022330).

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Dysbiotic oral microbiota-derived kynurenine, induced by chronic restraint stress, promotes head and neck squamous cell carcinoma by enhancing CD8+ T cell exhaustion

Background
Chronic restraint stress (CRS) is a tumour-promoting factor. However, the underlying mechanism is unknown.

Objective
We aimed to investigate whether CRS promotes head and neck squamous cell carcinoma (HNSCC) by altering the oral microbiota and related metabolites and whether kynurenine (Kyn) promotes HNSCC by modulating CD8+ T cells.

Design
4-nitroquinoline-1-oxide (4NQO)-treated mice were exposed to CRS. Germ-free mice treated with 4NQO received oral microbiota transplants from either CRS or control mouse donors. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were performed on mouse saliva, faecal and plasma samples to investigate alterations in their microbiota and metabolites. The effects of Kyn on HNSCC were studied using the 4NQO-induced HNSCC mouse model.

Results
Mice subjected to CRS demonstrated a higher incidence of HNSCC and oral microbial dysbiosis than CRS-free control mice. Pseudomonas and Veillonella species were enriched while certain oral bacteria, including Corynebacterium and Staphylococcus species, were depleted with CRS exposure. Furthermore, CRS-altered oral microbiota promoted HNSCC formation, caused oral and gut barrier dysfunction, and induced a host metabolome shift with increased plasma Kyn in germ-free mice exposed to 4NQO treatment. Under stress conditions, we also found that Kyn activated aryl hydrocarbon receptor (AhR) nuclear translocation and deubiquitination in tumour-reactive CD8+ T cells, thereby promoting HNSCC tumourigenesis.

Conclusion
CRS-induced oral microbiota dysbiosis plays a protumourigenic role in HNSCC and can influence host metabolism. Mechanistically, under stress conditions, Kyn promotes CD8+ T cell exhaustion and HNSCC tumourigenesis through stabilising AhR by its deubiquitination.

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Effects of pre-CABG program on discharge readiness and surgery outcomes for patients undergoing elective CABG surgery: a study protocol for a randomised control trial

Introduction
Cardiovascular diseases, a leading cause of death globally, impose significant health and economic burdens, particularly in countries like Iran. Coronary artery bypass grafting (CABG) is a common intervention for ischaemic heart disease, yet it entails a long recovery process with potential complications and psychological impacts. This study aims to evaluate the effectiveness of a prehabilitation programme (pre-CABG) on postoperative outcomes and discharge readiness in patients undergoing elective CABG.

Methods and analysis
This randomised controlled trial involves 60 patients diagnosed with coronary artery disease at Imam Khomeini Hospital Complex, Tehran. Participants will be randomly assigned to either the intervention group, receiving the pre-CABG programme, or the control group, receiving standard care. The pre-CABG programme includes patient education, stress management techniques, respiratory muscle training and nutritional guidance. Primary outcomes include discharge readiness, duration of intubation, Intensive Care Uniy (ICU) stay, occurrence of atelectasis, onset of mobility, hospital stay and levels of anxiety and depression. Secondary outcomes include the rate of 30-day readmissions. Data collection will involve standardised scales and checklists administered at various stages preoperation and postoperation.

Ethics and dissemination
The research study has received approval from the Research Ethics Committee at Tehran University of Medical Sciences’ School of Nursing and Midwifery and Rehabilitation. All participants must provide written consent for their involvement in this study. The findings will be shared with appropriate groups and published in peer-reviewed journals.

Trial registration number
The study is registered with the Iranian Registry of Clinical Trials under the ID IRCT20231019059768N1.

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Study protocol for a multicentre randomised controlled trial using music prehabilitation to reduce preoperative anxiety before oncological colorectal surgery: the MU-PRIOR trial

Introduction
Prehabilitation aims to improve preoperative health before surgery to reduce complications. Reducing anxiety helps prevent postoperative pain, stress and sleep disturbances. Listening to music through headphones or earpieces in the hospital directly preoperatively, intraoperatively and postoperatively has been shown to ameliorate anxiety, stress, pain and sleep disorders. This randomised controlled trial will investigate the effect of active music listening at home 1 week before surgery as a prehabilitation modality on preoperative anxiety compared with standard care.

Methods and analysis
This study is a multicentre randomised controlled trial that will include 116 patients. The study population consists of adults undergoing elective oncological colorectal surgery. The intervention group will be advised to listen to recorded music three times per day for 20 min, starting 1 week prior to surgery, using headphones or earpieces. Both groups will receive standard care during hospitalisation. The primary outcome is patient-reported preoperative anxiety using the State-Trait Anxiety IndexInventory 6. Secondary outcomes are patient-reported stress, delirium incidence, medication usage, postoperative pain, complication rate, length of stay, adherence to the intervention, quality of life and healthcare-related costs.

Ethics and dissemination
This study protocol has been approved by the Medical Ethical Review Board of Erasmus Medical Center on 15 December 2022 (MEC-2022-9415). The trial will be carried out following the updated Declaration of Helsinki principles and Good Clinical Practice guidelines. Study results will be published and reported in a peer-reviewed journal according to the Consolidated Standards of Reporting Trials guidelines.

Trial registration number
NCT05982184.

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Prevalence of anxiety, depression and post-traumatic stress disorder among the caregivers of children and adolescents diagnosed with cancer in Oman: a multicentre, prospective cohort study

Objectives
To assess the prevalence of anxiety, depression and post-traumatic stress disorder (PTSD) and their associated factors among the caregivers of children diagnosed with cancer in Oman and explore the changes in psychological outcomes over time.

Design
A multicentre, prospective, cohort study.

Setting
The National Oncology Centre of the Royal Hospital, the Sultan Qaboos University Hospital and the Sultan Qaboos Comprehensive Cancer Care and Research Centre in Muscat, Oman.

Participants
Caregivers of Omani children and adolescents diagnosed with cancer at the three primary cancer referral centres in Oman.

Outcome measures
Validated Arabic versions of the State-Trait Anxiety Inventory, the Centre for Epidemiologic Studies Depression Scale and the Impact of Event Scale-Revised were used to screen for symptoms of anxiety, depression and PTSD, respectively. The first assessment (T1) was conducted any time within the first 3 months of the child’s diagnosis, while the second assessment (T2) was conducted 3–6 months after T1. Multivariate linear regression models were used to investigate the association between socio-demographic and clinical characteristics and average anxiety, depression and PTSD scores.

Results
Of the 92 caregivers of Omani children and adolescents diagnosed with cancer, 45.7%, 53.3%, 45.7% and 68.5% exhibited state anxiety, trait anxiety, depression and PTSD at T1. Subsequently, prevalence rates of these conditions decreased to 32.6%, 42.4%, 33.7% and 55.4%, respectively, at T2. Between T1 and T2, the prevalence of state anxiety decreased significantly, as did average state anxiety and PTSD scores (p

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