bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal lung epithelium DNA methylation markers for detection of lung damage in liquid biopsies
Authors: Magenheim Judith , Rokach Ariel , Peretz Ayelet , Loyfer Netanel , Cann Gordon , Amini Hamed , Moradi Patriss , Nagaraju Sudharani , Sameer Wafa , Cohen Assaf , Fogel Ophir , Kuint Rottem , Abutbul Avraham , Abu Rmeileh Aiman , Karameh Mutaz , Cohen Goichman Polina , Wald Ori , Korach Amit , Neiman Daniel , Fox-Fisher Ilana , Moss Joshua , Cohen Daniel , Piyanzin Sheina , Ben Ami Roni , Quteineh Ahmad , Golomb Eliahu , Shemer Ruth , Glaser Benjamin , Kaplan Tommy , Fridlender Zvi G. , Dor Yuval
Published: April 2022

Background

Circulating biomarkers for lung damage are lacking. Lung epithelium-specific DNA methylation patterns can potentially report the presence of lung-derived cell-free DNA (cfDNA) in blood, as an indication of lung cell death.

Methods

We sorted human lung alveolar and bronchial epithelial cells from surgical specimens, and obtained their methylomes using whole-genome bisulfite sequencing. We developed a PCR sequencing assay determining the methylation status of 17 loci with lung-specific methylation patterns, and used it to assess lung-derived cfDNA in the plasma of healthy volunteers and patients with lung disease.

Results

Loci that are uniquely unmethylated in alveolar or bronchial epithelial cells are enriched for enhancers controlling lung-specific genes. Methylation markers extracted from these methylomes revealed that normal lung cell turnover probably releases cfDNA into the air spaces, rather than to blood. People with advanced lung cancer show a massive elevation of lung cfDNA concentration in blood. Among individuals undergoing bronchoscopy, lung-derived cfDNA is observed in the plasma of those later diagnosed with lung cancer, and to a lesser extent in those diagnosed with other lung diseases. Lung cfDNA is also elevated in patients with acute exacerbation of COPD compared with patients with stable disease, and is associated with future exacerbation and mortality in these patients.

Conclusions

Universal cfDNA methylation markers of normal lung epithelium allow for mutation-independent, sensitive and specific detection of lung-derived cfDNA, reporting on ongoing lung injury. Such markers can find broad utility in the study of normal and pathologic human lung dynamics.
Respiratory syncytial virus-associated hospitalisation in children aged ≤5 years: a scoping review of literature from 2009 to 2021
Authors: Noble Michael , Khan Rabia Ali , Walker Brodie , Bennett Emma , Gent Nick
Published: April 2022

Introduction

Following the easing of COVID-19 restrictions in many countries, a surge in respiratory syncytial virus (RSV) hospitalisations was reported, surpassing yearly trends pre-pandemic. The changes to RSV epidemiology may have unforeseen effects on healthcare systems and populations globally, adding to the burden generated during the pandemic and placing increased demand on resources. Here we aim to identify recent global trends of RSV hospitalisation amongst children aged ≤5 years, to help inform policy makers in the planning of preventative interventions.

Methods

We conducted a scoping review of published literature between January 2009 and May 2021. Using keywords “Hospital admissions, Respiratory syncytial virus, RSV, Bronchiolitis, Children” we located studies using Medline, EMCARE, CINAHL and HMIC. Studies were eligible if they reported on trends/data for RSV hospitalisation amongst children aged ≤5 years. The articles were reviewed by two independent reviewers.

Findings

We assessed 3310 abstracts, reviewed 70 studies and included 56 studies in the final review. Findings were categorised into themes. The review highlighted that, although RSV incidence has been steadily increasing since 2009, the number of reported RSV hospitalisations decreased during lockdown. The highest numbers of hospitalisations were reported in children <1 year of age, particularly 0–2-month-old infants. Globally, RSV hospitalisations tend to peak in the winter months; however, since COVID-19 restrictions have eased, countries are reporting incidence peaks at different times, in contrast to the trends of previous years.

Conclusion

With greater physical interactions due to the relaxation of COVID-19 restriction measures, RSV-related hospitalisations can be seen to increase amongst children aged ≤5 years, possibly surpassing the numbers reported in previous RSV seasons.
Single-nucleotide polymorphisms in the sulfatase-modifying factor 1 gene are associated with lung function and COPD
Authors: Jarenbäck Linnea , Frantz Sophia , Weidner Julie , Ankerst Jaro , Nihlén Ulf , Bjermer Leif , Wollmer Per , Tufvesson Ellen
Published: April 2022

Single nucleotide polymorphisms (SNPs) in various genes have been shown to associate with COPD, suggesting a role in disease pathogenesis. Sulfatase modifying factor (SUMF1) is a key modifier in connective tissue remodelling, and we have shown previously that several SNPs inSUMF1are associated with COPD. The aim of this study was to investigate the association betweenSUMF1SNPs and advanced lung function characteristics.

Never-, former and current smokers with (n=154) or without (n=405) COPD were genotyped for 21 SNPs inSUMF1and underwent spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO) measurement and impulse oscillometry.

Four SNPs (rs793391, rs12634248, rs2819590 and rs304092) showed a significantly decreased odds ratio of having COPD when heterozygous for the variance allele, together with a lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) ratio and an impaired peripheral resistance and reactance. Moreover, individuals homozygous for the variance allele of rs3864051 exhibited a strong association to COPD, a lower FEV1/FVC, FEV1andDLCO, and an impaired peripheral resistance and reactance. Other SNPs (rs4685744, rs2819562, rs2819561 and rs11915920) were instead associated with impaired lung volumes and exhibited a lower FVC, total lung capacity and alveolar volume, in individuals having the variance allele.

Several SNPs in theSUMF1gene are shown to be associated with COPD and impaired lung function. These genetic variants ofSUMF1may cause a deficient sulfation balance in the extracellular matrix of the lung tissue, thereby contributing to the development of COPD.
Simulated and Experimental Study of Seabed Sediments Sampling Parameters Based on the VOF Method
Authors: He Shudong , Peng Youduo , Jin Yongping , Yan Jian , Wan Buyan
Published: April 2022

Sediments in the seabed hold vital clues to the study of marine geology, microbial communities and history of ocean life, and the remote operated vehicle (ROV) mounted tubular sampling is an important way to obtain sediments. However, sampling in the seabed is a particularly difficult and complicated task due to the difficulty accessing deep water layers. The sampling is affected by the sampler’s structural parameters, operation parameters and the interaction between the sampling tube and sediments, which usually results in low volume and coring rate of sediments obtained. This paper simulated the soft viscous seabed sediments as non-Newtonian Herschel-Bulkley viscoplastic fluids and established a numerical model for the tubular sampling based on the volume of fluid (VOF) method. The influence rules of the sampling tube diameter, drainage area rate, penetration velocity, and sediments dynamic viscosity on coring rate and volume were studied. The results showed that coring volume was negatively correlated with all the parameters except the sampling tube diameter. Furthermore, coring rate decreased with increases in penetration velocity, drainage area rate, and sediments dynamic viscosity. The coring rate first increased and then decreased with increasing of the sampling tube diameter, and the peak value was also influenced by penetration velocity. Then, based on the numerical simulation results, an experimental sampling platform was set up and real-world sampling experiments were conducted. The simulation results tallied with the experimental results, with a maximum absolute error of only 4.6%, which verified that the numerical simulation model accurately reflected real-world sampling. The findings in this paper can provide a theoretical basis for facilitating the optimal design of the geometric structure of the seabed sediments samplers and the parameters in the sampling process.
Pharmacodynamics, toxicology and toxicokinetics of ropivacaine oil delivery depot
Authors: Lu Wu-dang , Hui Min-quan , Gu Jing-liang , Liu Li , Wu Man-li , Yang Yi , Cao Yong-xiao
Published: April 2022

Background

Ropivacaine oil delivery depot (RODD) can be used to treat postoperative incision pain. The aim was to study pharmacodynamics, toxicity and toxicokinetics of RODD.

Methods

The base research of RODD were conducted. Thirty rabbits were randomly divided into saline, solvent, ropivacaine aqueous injection (RAI) 0.9 mg, RODD 0.9 mg and RODD 3 mg groups. The sciatic nerve of rabbits were isolated, dripped with RODD and the effect of nerve block were observed. In toxicity study, the rats were divided into saline, solvent and RODD 75, 150 and 300 mg/kg groups, 30 rats per group. In toxicokinetics, rats were divided into RODD 75, 150 and 300 mg/kg groups, 18 rats per group. The rats were subcutaneously injected drugs.

Results

The analgesic duration of RODD 3 mg and RAI 0.9 mg blocking ischiadic nerve lasted about 20 h and 2 h, respectively, and their blocking intensity was similar. The rats in RODD 75 mg/kg did not show any toxicity. Compared with saline group, in RODD 150 mg/kg group neutrophils and mononuclear cells increased, lymphocytes decreased and albumin decreased(P < 0.05), and pathological examination showed some abnormals. In RODD 300 mg/kg group, 10 rats died and showed some abnormalities in central nerve system, hematologic indexes, part of biochemical indexes, and the weights of spleen, liver, and thymus. However, these abnormal was largely recovered on 14 days after the dosing. The results of toxicokinetics of RODD 75 mg/kg group showed that the Cmax was 1.24 ± 0.59 µg/mL and the AUC(0-24 h) was 11.65 ± 1.58 h·µg/mL.

Conclusions

Subcutaneous injection RODD releases ropivacaine slowly, and shows a stable and longer analgesic effect with a large safety range.
3-Year outcomes in patients with heavily calcified lesions undergoing percutaneous coronary intervention using cutting balloons
Authors: Liu Wei , Yao Yutong , Jiang Zhi , Tian Longhai , Song Bo , Liu Hui , Deng Shiyan , Luo Rui , Wei Fang
Published: April 2022

Background

Percutaneous coronary intervention (PCI) of heavily calcified lesions (HCLs) is associated with higher complication rates and worse clinical outcomes. Cutting balloon (CB) has been widely used for HCLs, but patients’ prognosis had not been fully clarified. The study aimed to compare 3-year clinical outcomes between patients with HCLs that are treated with CBs and those with non-HCLs.

Method

Patients who underwent PCI in Guizhou Provincial People’s Hospital from June 2015 to September 2018 were retrospectively included. HCL was defined as radiopaque and high-pressure undilatable lesions. CBs were routinely used in combination with non-compliant balloons for the HCLs. Major adverse cardiac event (MACE) and target vessel failure (TVF) were assessed at 3-year follow-up.

Result

Among 2432 patients included in the study, 210(8.6%) had HCLs with a procedural success rate of 91.0%. The patients with HCLs had a higher incidence of MACE (23.3% vs. 10.8%, P < 0.001) than those with non-HCLs. By propensity score matching, 172 patients with HCLs were 1:1 paired to those with non-HCLs, and their PCI vessels were exactly matched. The MACE and TVF were significantly higher in the patients with HCLs than those with non-HCLs (MACE: 21.5% vs. 13.4%, P = 0.036; TVF: 19.8% vs. 9.9%, P = 0.008). In the Cox regression analysis, HCL is independently associated with higher risks of MACE [HR: 1.72(1.01–2.94), P = 0.047], TVF [HR: 2.10(1.15–3.81), P = 0.015] and repeat revascularization [HR: 2.20(1.07–4.52), P = 0.032].

Conclusion

Patients with HCLs undergoing PCI using CBs in combination with non-compliant balloons had higher risks of complications, procedural failure, and worse clinical outcomes at 3 years than those with non-HCLs.
Cutaneous infection due to Bacillus cereus: a case report
Authors: Esmkhani Mohammad , Shams Saeed
Published: April 2022

Background

Bacillus cereus is a Gram-positive bacterium that can be found in various natural and human-made environments. It is often involved in gastrointestinal infections and food poisoning; yet, it can rarely cause serious non-gastrointestinal tract infections.

Case presentation

Here we describe a case of B. cereus cutaneous infection of a wound on the hand of a young woman from a rural area in Iran. On admission, she had no systemic symptoms other than a cutaneous lesion. The identification of the causative agent was performed using sequencing of the 16S rRNA gene of the bacteria isolated from the wound. The isolated microorganism was identified as B. cereus. Targeted antibiotic therapy with ciprofloxacin was successful.

Discussion and conclusion

Although non-intestinal infections caused by B. cereus are rare, it should be taken into consideration that this organism might also cause infections in other parts of the body.
Association between effector-type regulatory T cells and immune checkpoint expression on CD8+ T cells in malignant ascites from epithelial ovarian cancer
Authors: Sato Sho , Matsushita Hirokazu , Shintani Daisuke , Kobayashi Yukari , Fujieda Nao , Yabuno Akira , Nishikawa Tadaaki , Fujiwara Keiichi , Kakimi Kazuhiro , Hasegawa Kosei
Published: April 2022

Background

Regulatory T cells (Tregs) play an important role in the antitumor immune response in epithelial ovarian cancer (EOC). To understand the immune-inhibitory networks of EOC, we addressed the association between Tregs and immune checkpoint expression on T cells in the tumor microenvironment of EOC.

Methods

A total of 41 patients with stage IIIC and IV EOC were included in the analysis. We harvested cells from malignant ascites and investigated them using multi-color flow cytometry. We categorized the Tregs into 3 groups: effector-type Tregs, naïve Tregs and non-Tregs, based on the expression patterns of CD45RA and Foxp3 in CD4+ T cells. Furthermore, the relationships between the expression of various immune checkpoint molecules, such as PD-1, on CD8+ T cells and each of the Treg subtypes was also evaluated.

Results

The median frequency of naïve Tregs, effector-type Tregs and non-Tregs were 0.2% (0–0.8), 2.0% (0–11.4) and 1.5% (0.1–6.3) in CD4+ T cells of malignant ascites from EOC patients, respectively. A high frequency of effector-type Tregs was associated with high-grade serous carcinoma compared with the other histotypes. Patients with higher proportions of effector-type Tregs showed a trend towards increased progression-free survival. We also demonstrated a correlation between a higher proportion of effector-type Tregs and increased PD-1 expression on CD8+ T cells. In addition, C–C chemokine receptor 4 expression was also observed in effector-type Tregs.

Conclusion

These data suggest that multiple immune-inhibitory networks exist in malignant ascites from EOC patients, suggesting an approach towards combinational immunotherapies for advanced EOC patients.
Identification of unhealthy alcohol use by self-report and phosphatidylethanol (PEth) blood concentrations in an acute psychiatric department
Authors: Finanger Trine , Vaaler Arne Einar , Spigset Olav , Aamo Trond Oskar , Andreassen Trine Naalsund , Gråwe Rolf Wilhelm , Skråstad Ragnhild Bergene
Published: April 2022

Background

The use of standard screening methods could improve the detection rate of unhealthy alcohol use in patients admitted to psychiatric acute and emergency departments. The aim of the present study was to investigate the ability of the alcohol biomarker phosphatidylethanol (PEth) to identify patients with high levels of alcohol consumption prior to admission.

Methods

The data were prospectively collected at admittance to an acute psychiatric department in the period January 2016 to June 2017. A blood sample for the analysis of PEth was available from 177 patients. We compared the PEth concentrations with the Alcohol Use Disorders Identification Test (AUDIT) scores during the hospital stay, and psychiatric diagnoses at discharge.

Results

A total of 45.8% of the patients had a PEth concentration ≥ 0.03 μmol/L, indicating significant alcohol consumption. AUDIT scores consistent with unhealthy alcohol use were present in 51.7%. There was a significant positive correlation between PEth concentrations and AUDIT scores (r = 0.631, p < 0.001). PEth was above the detection limit of 0.03 μmol/L in 19% of those reporting an average daily intake of zero alcohol units per day during the last week before admission. PEth concentrations were significantly higher among those with an alcohol diagnosis than among those without such a diagnosis (0.82 μmol/L vs. 0.09 μmol/L, p = 0.001).

Conclusion

PEth provides supplementary information on recent alcohol consumption in a psychiatric population and would be particularly helpful in patients unable or unwilling to give such information at admission.
Construction of life-and-death education contents for the elderly: a Delphi study
Authors: Lei Lei , Lu Ya , Zhao Hongyan , Tan Jing , Luo Yu
Published: April 2022

Background

Life-and-death education is intimately related to palliative-and-hospice care. It should be implemented among groups of all ages, especially for the elderly. This study aims to establish expert consensus on a set of scientific and systematic life-and-death education contents for the elderly and provide reference for the practice on the elderly.

Methods

This study designed three rounds of expert consultation by using a Delphi method. A panel of 22 experts from the fields of palliative-and-hospice care, life-and-death education, geriatric nursing, humanities and ethics, and geriatric psychology participated in the study.

Results

This study finally reached expert consensus on the contents of life-and-death education for the elderly, containing 4 first-level items, Life-and-death literacy promotion in the elderly; Life-and-death concept establishment of the elderly; Life-and-death planning of the elderly; Life-and-death thoughts of the elderly with affiliated 9 second-level items, and corresponding 23 detailed third-level items.

Conclusions

The life-and-death education contents for the elderly offer a basis for publicity for health professionals, promote dialogues on death, preparation, and planning for death and dying. The life-and-death education contents system was clear in coherence containing definite and comprehensive contents, which enriched life-and-death education resources globally. The results could assist in the planning of palliative-and-hospice care services to improve quality of death of the elderly.
Preservation of the left colic artery in modified laparoscopic anterior rectal resections without auxiliary abdominal incisions for transanal specimen retrieval
Authors: Liu Yulin , Yu Peng , Li Han , Xia Lijian , Li Xiangmin , Zhang Meijuan , Cui Zhonghui , Chen Jingbo
Published: April 2022

Background

Laparoscopic low anterior rectal resection is the most widely used surgical procedure for middle and low rectal cancer. The aim of this study was to investigate the feasibility and safety of the extracorporeal placement of the anvil in preserving the left colic artery in laparoscopic low anterior rectal resection without auxiliary incisions for transanal specimen retrieval in this research.

Methods

Clinical data and follow-up data of patients undergoing laparoscopic low anterior rectal resection from January 2017 to October 2020 were collected. The resections were modified such that the resisting nail holder was extracorporeally placed for the transanal exenteration of the specimen without using auxiliary abdominal incisions while preserving the left colic artery. By analyzing the data of anastomotic stenosis, anastomotic bleeding and anastomotic fistulas after surgery, the advantages and disadvantages of this surgical method for patients were clarified.

Results

A total of 22 patients were enrolled. Five of 22 patients simultaneously underwent double-barrel terminal ileostomy. The postoperative exhaust time was 2–7 (median, 3) days. Postoperative anastomotic bleeding occurred in one patient, postoperative anastomotic fistula occurred in four patients, and postoperative anastomotic stenosis occurred in six patients. There were four patients with postoperative distant metastasis, of which three had concomitant local recurrence. Seventeen patients had no obvious symptoms or signs of recurrent metastases during follow-up appointments, and one died of liver failure.

Conclusions

Modified laparoscopic low anterior rectal resection, which resects the specimen through anus eversion by inserting the anvil extracorporeally while preserving the left colic artery, is safe and feasible for patients with low rectal cancer.
Robotic surgery contributes to the preservation of bowel and urinary function after total mesorectal excision: comparisons with transanal and conventional laparoscopic surgery
Authors: Miura Takuya , Sakamoto Yoshiyuki , Morohashi Hajime , Suto Akiko , Kubota Shunsuke , Ichisawa Aika , Kuwata Daisuke , Yamada Takahiro , Tamba Hiroaki , Matsumoto Shuntaro , Hakamada Kenichi
Published: April 2022

Background

Determine whether robotic surgery is more effective than transanal and conventional laparoscopic surgery in preserving bowel and urinary function after total mesorectal excision (TME).

Methods

Of 79 lower rectal cancer patients who underwent function-preserving TME between 2016 and 2020, 64 patients consented to a prospective questionnaire-based functional observation study (52 responded). At 6 months post-resection or ileostomy closure, Wexner, low anterior resection syndrome (LARS), modified fecal incontinence quality of life, and international prostate symptom scores were used to evaluate bowel and urinary function, comparing robotic surgery (RTME) with transanal (taTME) or conventional laparoscopic surgery (LTME).

Results

RTME was performed in 35 patients (54.7%), taTME in 15 (23.4%), and LTME in 14 (21.9%). While preoperative bowel/urinary functions were similar in all three procedures, and the distance from the anal verge to tumor was almost the same, more hand-sewn anastomoses were performed and the anastomotic height from the anal verge was shorter in taTME than RTME. At 2 years post-resection, 8 patients (12.5%) had a permanent stoma; RTME showed a significantly lower rate of permanent stoma than taTME (2.9% vs. 40%, p < 0.01). Despite no significant difference, all bowel function assessments were better in RTME than in taTME or LTME. Major LARS was observed in all taTME and LTME cases, but only 78.8% of RTME. No clear difference arose between RTME and taTME in urinary function; urinary dysfunction was more severe in LTME than RTME (36.4% vs. 6.1%, p = 0.02).

Conclusions

In function-preserving TME for lower rectal cancer, robotic surgery was suggested to be more effective than transanal and conventional laparoscopic surgery in terms of bowel and urinary functions.
Respectful delivery care and associated factors among mothers delivered in public health facilities of Dessie city, Northeast Ethiopia: a cross-sectional study
Authors: Yalew Melaku , Nigatu Dabere , Yasin Toyeb , Kefale Bereket , Damtie Yitayish
Published: April 2022

Background

The government of Ethiopia has been implementing compassionate, respectful, and caring strategies to increase institutional delivery and decrease maternal mortality in recent years. There is limited evidence on respectful delivery care and associated factors in low-income countries like Ethiopia. Therefore, this study aimed to assess the proportion of respectful delivery care and associated factors among mothers delivered in the health facilities of Dessie city, Northeast Ethiopia.

Methods

A health facility-based cross-sectional study was conducted among a total of 390 mothers from April 16 to May 30, 2018. A pretested structured interviewer-administered questionnaire was used to collect the data. The data were entered into Epidata and analyzed using Stata/SE 14. Binary logistic regression analysis was used to identify associated factors. Variables having P-value less than 0.2 in the bivariable regression were selected as a candidate for multi-variable regression. Adjusted odds ratio (AOR) with 95% confidence interval (CI) was estimated to measure the strength and direction of the association respectively.

Results

The proportion of respectful delivery care among mothers delivered in public health facilities of Dessie city was 43.4%, 95% CI (39.1%, 47.6%). It was found to be 34.9% in hospital and 74.1 in health center. Respectful delivery care was associated with day time delivery [AOR = 2.23, 95% CI (1.30, 3.82)], any maternal and/or fetal complications [AOR = 0.50, 95% CI (0.27, 0.94)], gave birth in health center [AOR = 3.22, 95% CI (1.61, 6.46)] and educated mothers [AOR = 2.87, 95% CI (1.18, 7.01)].

Conclusions

The proportion of respectful delivery care in the study area was low as compared to the government emphasis and other works of literature. This study indicated that any maternal and/or newborn complications, daytime delivery, giving birth in a health center, and maternal education were associated with respectful delivery care. Women empowerment through education could be a recalled intervention for respectful care.
Key stakeholders’ views, experiences and expectations of patient and public involvement in healthcare professions’ education: a qualitative study
Authors: Cullen Megan , Cadogan Cathal , George Susmi , Murphy Siobhan , Freeney Siobhan , Fitzpatrick Robbie , Strawbridge Judith
Published: April 2022

Background

Patients and the public have an integral role in educating healthcare professionals. Authentic partnerships between higher education institutions and patients and the public are essential. This study examined key stakeholders’ views, experiences and expectations of patient and public involvement (PPI) including the nature of the involvement and requirements for partnership.

Methods

Purposive and snowball sampling was used to recruit key stakeholders, including patients and members of the public involved in health professions education, and academics interested in PPI. Focus groups were held with patient and public participants, providing the opportunity to gain multiple perspectives in an interactive group setting. Academics with an interest in PPI were interviewed using a semi-structured approach. Topic guides were derived from the literature and piloted prior to data collection. Focus groups and interviews were conducted until data saturation was achieved. All data was audio-recorded, transcribed, anonymised and thematically analysed.

Results

Four focus groups were conducted involving 23 patient and public participants (median number of participants per focus group of 6). Nine interviews were conducted with academics (face-to-face [n = 8] or by telephone [n = 1]). Five themes were developed: previous experiences of PPI, training requirements, challenges/barriers to PPI, facilitators of PPI and future ideas for PPI. All participants held positive views of the value of PPI. Participants had mixed views in terms of training, which depended on the level of involvement, but similar views on the challenges and facilitators for PPI in education. There was agreement that PPI requires institutional vision and investment to build strong relationships and a culture of PPI best practice.

Conclusions

There is a need for more strategic and formal involvement of patients and the public to ensure that that PPI becomes sustainably embedded in health professions education.
A healthy dietary metabolic signature is associated with a lower risk for type 2 diabetes and coronary artery disease
Authors: Smith Einar , Ericson Ulrika , Hellstrand Sophie , Orho-Melander Marju , Nilsson Peter M. , Fernandez Céline , Melander Olle , Ottosson Filip
Published: April 2022

Background

The global burden of cardiovascular disease and type 2 diabetes could be decreased by improving dietary factors, but identification of groups suitable for interventional approaches can be difficult. Reporting of dietary intake is prone to errors, and measuring of metabolites has shown promise in determining habitual dietary intake. Our aim is to create a metabolic signature that is associated with healthy eating and test if it associates with type 2 diabetes and coronary artery disease risk.

Methods

Using plasma metabolite data consisting of 111 metabolites, partial least square (PLS) regression was used to identify a metabolic signature associated with a health conscious food pattern in the Malmö Offspring Study (MOS, n = 1538). The metabolic signature’s association with dietary intake was validated in the Malmö Diet and Cancer study (MDC, n = 2521). The associations between the diet-associated metabolic signature and incident type 2 diabetes and coronary artery disease (CAD) were tested using Cox regression in MDC and logistic regression in Malmö Preventive Project (MPP, n = 1083). Modelling was conducted unadjusted (model 1), adjusted for potential confounders (model 2) and additionally for potential mediators (model 3).

Results

The metabolic signature was associated with lower risk for type 2 diabetes in both MDC (hazard ratio: 0.58, 95% CI 0.52–0.66, per 1 SD increment of the metabolic signature) and MPP (odds ratio: 0.54, 95% CI 0.44–0.65 per 1 SD increment of the metabolic signature) in model 2. The results were attenuated but remained significant in model 3 in both MDC (hazard ratio 0.73, 95% CI 0.63–0.83) and MPP (odds ratio 0.70, 95% CI 0.55–0.88). The diet-associated metabolic signature was also inversely associated with lower risk of CAD in both MDC and MPP in model 1, but the association was non-significant in model 3.

Conclusions

In this proof-of-concept study, we identified a healthy diet-associated metabolic signature, which was inversely associated with future risk for type 2 diabetes and coronary artery disease in two different cohorts. The association with diabetes was independent of traditional risk factors and might illustrate an effect of health conscious dietary intake on cardiometabolic health.
Prediction of residual ischemic risk in ticagrelor-treated patients with acute coronary syndrome
Authors: Zou Yuting , Wang Yuyan , Wu Yangxun , Zhang Shizhao , Liu Haiping , Yin Tong
Published: April 2022

Background

Despite strong antiplatelet therapy with ticagrelor, serious ischemic events still occur in patients with acute coronary syndrome (ACS). The predictability of platelet reactivity to the residual risk of ischemic events during ticagrelor treatment remains uncertain.

Objectives

We aimed to investigate the predictability of the thromboelastography (TEG)-measured adenosine disphosphate (ADP)-induced platelet inhibition rate (ADP%) to the ischemic events in ticagrelor-treated patients with ACS.

Methods

A cohort of ticagrelor-treated patients with ACS were consecutively recruited. ADP% was measured by TEG after 3 days of ticagrelor maintenance treatment. The primary ischemic event was defined as rehospitalization for unstable angina (UA) within 1 year, and the secondary ischemic event was a composite of the primary ischemic event plus all-cause death, nonfatal myocardial infarction (MI), stent thrombosis, stroke, and unplanned revascularization within 1 year.

Results

A total of 751 eligible patients with ACS were included in the analysis, with 336 patients randomly assigned to the derivation group and 415 to the validation group. The overall rates of primary and secondary ischemic events were 14.51% (n = 109) and 16.91% (n = 127), respectively. Compared to the patients without ischemic events, those with ischemic events had a significantly lower ADP% both in the derivation group (for primary ischemic events: 66.05% vs. 92.80%, p < 0.001; for secondary ischemic events: 66.05% vs. 93.20%, p < 0.001) and in the validation group (for primary ischemic events: 66.40% vs. 89.20%, p < 0.001; for secondary ischemic events: 66.90% vs. 89.20%, p < 0.001). Receiver operating characteristic curve (ROC) analysis showed that an ADP% < 76% was the optimal cut-off value for predicting 1-year primary ischemic events, with an area under the curve (AUC) of 0.80 (95% CI: 0.72–0.86, p < 0.001) in the derivation group and 0.77 (95% CI: 0.69–0.85, p < 0.001) in the validation group. The multivariate Cox regression hazard analysis consistently identified an ADP% < 76% as an independent predictor of primary ischemic events in the derivation group (HR: 8.21, 95% CI: 4.82–13.99, p < 0.001) and in the validation group (HR: 6.34 95% CI: 3.32–12.11, p < 0.001). There was also a strong association between an ADP% < 76 and the occurrence of secondary ischemic events in the derivation group (HR: 7.33, 95% CI: 4.47–12.00, p < 0.001) and in the validation group (HR: 4.76, 95% CI: 2.73–8.32, p < 0.001).

Conclusion

The ADP-induced platelet inhibition rate measured by TEG could predict ischemic events in ticagrelor-treated patients with ACS.
Quadruple term gestation of quadri-chorionic quadri-amniotic pregnancy after artificial insemination: a case report
Authors: Caballero-Reyes Mauricio , Medina-Rivera Diana , Alas-Pineda César , Mejía-Raudales Beatriz , Gaitán-Zambrano Kristhel , Valle Rubí Tesla
Published: April 2022

Background

To solve infertility, modern science has promoted assisted reproduction techniques such as in vitro fertilization, ovulation induction, and artificial insemination. Quadruple-type multiple pregnancies occur in 1 of every 500,000 pregnancies, and it is estimated that 90% occur due to assisted reproductive techniques, which often lead to numerous complications.

Case presentation

Here we present a case of a 33-year-old woman, who desired pregnancy, but had a history of primary infertility diagnosed by hysterosalpingography, and endometriosis, which was treated by fulguration and medical management. Concomitantly, the patient was anovulatory. To fulfill her wish, she underwent homologous artificial insemination, after treatment, she successfully conceived quadri-chorionic quadri-amniotic infants, who were born at 37.2 weeks, without perinatal or maternal complications.

Conclusion

This paper presented the parameters of prenatal care, appropriate management approach, and successful resolution without maternal–fetal complications despite the inherent risks of this type of pregnancy.
Consequences of nano and microplastic exposure in rodent models: the known and unknown
Authors: da Silva Brito Walison Augusto , Mutter Fiona , Wende Kristian , Cecchini Alessandra Lourenco , Schmidt Anke , Bekeschus Sander
Published: April 2022

The ubiquitous nature of micro- (MP) and nanoplastics (NP) is a growing environmental concern. However, their potential impact on human health remains unknown. Research increasingly focused on using rodent models to understand the effects of exposure to individual plastic polymers. In vivo data showed critical exposure effects depending on particle size, polymer, shape, charge, concentration, and exposure routes. Those effects included local inflammation, oxidative stress, and metabolic disruption, leading to gastrointestinal toxicity, hepatotoxicity, reproduction disorders, and neurotoxic effects. This review distillates the current knowledge regarding rodent models exposed to MP and NP with different experimental designs assessing biodistribution, bioaccumulation, and biological responses. Rodents exposed to MP and NP showed particle accumulation in several tissues. Critical responses included local inflammation and oxidative stress, leading to microbiota dysbiosis, metabolic, hepatic, and reproductive disorders, and diseases exacerbation. Most studies used MP and NP commercially provided and doses higher than found in environmental exposure. Hence, standardized sampling techniques and improved characterization of environmental MP and NP are needed and may help in toxicity assessments of relevant particle mixtures, filling knowledge gaps in the literature.
Review of a frugal cooling mattress to induce therapeutic hypothermia for treatment of hypoxic-ischaemic encephalopathy in the UK NHS
Authors: Dallera Giulia , Skopec Mark , Battersby Cheryl , Barlow James , Harris Matthew
Published: April 2022

Hypoxic ischaemic encephalopathy (HIE) is a major cause of neonatal mortality and disability in the United Kingdom (UK) and has significant human and financial costs. Therapeutic hypothermia (TH), which consists of cooling down the newborn’s body temperature, is the current standard of treatment for moderate or severe cases of HIE. Timely initiation of treatment is critical to reduce risk of mortality and disability associated with HIE. Very expensive servo-controlled devices are currently used in high-income settings to induce TH, whereas low-income settings rely on the use of low-tech devices such as water bottles, ice packs or fans. Cooling mattresses made with phase change materials (PCMs) were recently developed as a safe, efficient, and affordable alternative to induce TH in low-income settings. This frugal innovation has the potential to become a reverse innovation for the National Health Service (NHS) by providing a simple, efficient, and cost-saving solution to initiate TH in geographically remote areas of the UK where cooling equipment might not be readily available, ensuring timely initiation of treatment while waiting for neonatal transport to the nearest cooling centre. The adoption of PCM cooling mattresses by the NHS may reduce geographical disparity in the availability of treatment for HIE in the UK, and it could benefit from improvements in coordination across all levels of neonatal care given challenges currently experienced by the NHS in terms of constraints on funding and shortage of staff. Trials evaluating the effectiveness and safety of PCM cooling mattresses in the NHS context are needed in support of the adoption of this frugal innovation. These findings may be relevant to other high-income settings that experience challenges with the provision of TH in geographically remote areas. The use of promising frugal innovations such as PCM cooling mattresses in high-income settings may also contribute to challenge the dominant narrative that often favours innovation from North America and Western Europe, and consequently fight bias against research and development from low-income settings, promoting a more equitable global innovation landscape.
Circulating cell free DNA and citrullinated histone H3 as useful biomarkers of NETosis in endometrial cancer
Authors: Ronchetti Livia , Terrenato Irene , Ferretti Margherita , Corrado Giacomo , Goeman Frauke , Donzelli Sara , Mandoj Chiara , Merola Roberta , Zampa Ashanti , Carosi Mariantonia , Blandino Giovanni , Conti Laura , Lobascio Anna Maria , Iacobelli Marcello , Vizza Enrico , Piaggio Giulia , Gurtner Aymone
Published: April 2022

Background

Cancer mortality is mainly caused by organ failure and thrombotic events. It has been demonstrated that NETosis, a chromatin release mechanism implemented by neutrophils, may contribute to these lethal systemic effects. Our aim was to investigate NETosis biomarkers in endometrial cancer (EC).

Methods

The experiments were conducted on 21 healthy subjects (HS) with no gynecological conditions, and on 63 EC patients. To assess the presence of NETosis features, IHC and IF was performed using antibodies against citrullinated histone H3 (citH3), neutrophil elastase (NE) and histone 2B. Serum levels of cell free DNA (cfDNA), cell free mitochondrial DNA (cfmtDNA) and citH3 were measured by qPCR using one microliter of deactivated serum, and by ELISA assay respectively. Fragmentation pattern of serum cfDNA was analyzed using the Agilent 2100 Bioanalyzer and High Sensitivity DNA Chips. Receiver operating characteristic (ROC) analysis was used to identify a cut off for cfDNA and cfmtDNA values able to discriminate between ECs and HSs. Correlation analysis and multiple correspondence analysis (MCA) between cfDNA, mtcfDNA, citH3 and blood parameters were used to identify the potential association among serum parameters in EC grades.

Results

We demonstrated the presence of NETosis features in tissues from all EC grades. Serum cfDNA and cfmtDNA levels discriminate ECs from HSs and a direct correlation between citH3 and cfDNA content and an inverse correlation between cfmtDNA and citH3 in EC sera was observed, not detectable in HSs. MCA indicates cfDNA, cfmtDNA and citH3 as features associated to G1 and G2 grades. A correlation between increased levels of cfDNA, citH3 and inflammation features was found. Finally, serum nucleosomal cfDNA fragmentation pattern varies in EC sera and correlates with increased levels of cfDNA, citH3, lymphocytes and fibrinogen.

Conclusion

Our data highlight the occurrence of NETosis in EC and indicate serum cfDNA and citH3 as noninvasive biomarkers of tumor-induced systemic effects in endometrial cancer.
Tolvaptan versus fluid restriction in acutely hospitalised patients with moderate-profound hyponatraemia (TVFR-HypoNa): design and implementation of an open-label randomised trial
Authors: Warren Annabelle M. , Grossmann Mathis , Hoermann Rudolf , Zajac Jeffrey D. , Russell Nicholas
Published: April 2022

Background

Current hyponatraemia guidelines are divided on the use of tolvaptan in hospitalised patients with moderate to severe hyponatraemia, due to an uncertain risk-benefit ratio. We will conduct a randomised trial to test the hypothesis that early use of tolvaptan improves the rate of serum sodium correction and clinical outcomes compared with current standard first-line therapy, restriction of fluid intake, without increasing the risk of serum sodium overcorrection.

Methods

We will enrol hospitalised patients with euvolaemic or hypervolaemic hyponatraemia and serum sodium of 115–130 mmol/L at Austin Health, a tertiary care centre in Melbourne, Australia. Participants will be randomised 1:1 to receive either tolvaptan (initial dose 7.5 mg) or fluid restriction (initial limit 1000 ml per 24 h), with titration of therapy based on serum sodium response according to a pre-determined protocol over a 72-h intervention period.

The primary endpoint will be the between-group change in serum sodium over time, from study day 1 to day 4. Secondary endpoints include serum sodium increment in the first 24 and 48 h, proportion of participants with normalised serum sodium, length of hospital stay, requirement for serum sodium re-lowering with intravenous dextrose or desmopressin, cognitive and functional measures (Confusion Assessment Method Short form, Timed Up and Go test, hyponatraemia symptom questionnaire), 30-day readmission rate, treatment satisfaction score and serum sodium 30 days after discharge. The trial will be overseen by an independent Data Safety Monitoring Board. Serum sodium will be monitored every 6–12 h throughout the study period, with pre-specified thresholds for commencing intravenous 5% dextrose if serum sodium rise targets are exceeded.

Discussion

We seek to inform future international guidelines with high-quality data regarding the utility and safety of tolvaptan compared to standard therapy fluid restriction in patients with moderate-severe hyponatraemia in hospital. If tolvaptan use in this patient group is endorsed by our findings, we will have established an evidence-based framework for tolvaptan initiation and monitoring to guide its use.

Trial registration

Australia and New Zealand Clinical Trials Registry ACTRN12619001683123. Registered on December 2 2019
Effectiveness of Tai Chi Yunshou motor imagery training for hemiplegic upper extremity motor function in poststroke patients: study protocol for a randomized clinical trial
Authors: Jiang Lin Hong , Zhao Li Juan , Liu Yang , Zhang Hong , Zhang Si Cong , Cong Wei Qin , Qi Rui
Published: April 2022

Background

Evidence concerning the effect of Tai Chi Yunshou motor imagery training (TCY-MIT) on upper extremity motor function (UE-MF) recovery in poststroke patients is lacking, and few studies have examined the neural mechanisms of MIT. The study was designed to assess the effectiveness of TCY-MIT and its possible neural mechanisms.

Methods/design

The study is an assessor-blinded, parallel, superiority, randomized clinical trial. A total of 78 eligible participants will be randomly assigned to 2 groups in a 1:1 ratio. Participants in the control group will receive (conventional rehabilitation therapies) CRTs for 40 min per day, 6 days per week, for 3 weeks. Participants in the intervention group will receive CRTs combined with TCY-MIT (30 min per day, 6 days per week, for 3 weeks). The primary outcome measure is the Fugl-Meyer Assessment of Upper Extremity. Secondary outcome measures are the Box and Block Test, muscle strength test, modified Barthel index, and Pearson correlation coefficients. All outcomes will be assessed at baseline, after completion of the intervention (1, 2, and 3 weeks), and at the end of follow-up (2 months). The outcome assessor will be blinded to the group allocation of the participants.

Discussion

We expect this assessor-blinded, parallel, superiority, randomized clinical trial to explore the effectiveness of TCY-MIT combined with CRTs compared with CRTs alone for UE-MF in poststroke patients.

Trial registration

Chinese Clinical Trial Registry ID: ChiCTR2100048868. Registered on 19 July 2021