bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of body composition and fat distribution with dysmobility syndrome in community-dwelling older adults: Bushehr Elderly Health (BEH) program
Authors: Khaleghi Mohammad Mehdi , Emamat Hadi , Marzban Maryam , Farhadi Akram , Jamshidi Ali , Ghasemi Negin , Falahatzadeh Azar , Jalaliyan Zahrasadat , Malekizadeh Hasan , Nabipour Iraj , Larijani Bagher
Published: October 2023

Background and objective

Dysmobility Syndrome (DS) is characterized as an accumulation of clinical risk factors for functional disability, such as osteoporosis, sarcopenia, and obesity. Neurological disorders that affect the motor and sensory systems can also contribute to the condition, resulting in gait and muscle strength disturbances, as well as a history of falls and fractures. The study aimed to determine the association between fat distribution in different body areas and the odds of older adults developing DS, as there is still uncertainty about the accumulation of fat in which area is most closely linked to the condition.

Methods

This cross-sectional study was conducted according to the data from the second phase of the Bushehr Elderly Health Cohort (BEH). Dysmobility Syndrome was defined based on the co-occurrence of at least three outcomes of its criteria. Body composition was measured using dual-energy X-ray absorptiometry (DXA) and anthropometric studies. For evaluating the relationship, multivariate logistic regression and adjusted univariate linear regression were used.

Results

Of 2,359 who were recruited in the study, 1,277 participants (54.13%) had DS. According to the final logistic regression model in the limb region, FM and FM to FFM ratios were significantly associated with DS [OR (95%CI) = 1.04 (1.02 to 1.05), and 3.42 (1.95 to 5.99), respectively]. Also, In the trunk region, the FM and FM to FFM ratio were significantly related to the odds of DS, although this relationship was weaker than in the limbs region [OR (95%CI) = 1.02 (1.00 to 1.03), and 2.45 (1.36 to 4.39), respectively].

Conclusion

Our findings indicate that a higher regional and whole-body amount of fat mass rather than fat-free mass is closely linked to an increased risk of DS, particularly in the elderly population. Notably, higher fat mass in the limbs (especially in the legs) is associated with greater odds of DS, while a higher android-to-gynoid fat mass ratio is associated with lower DS risk. Screening fat mass distribution in older individuals can be a valuable strategy for promptly diagnosing DS, implementing interventions to prevent disabilities, and improving their quality of life.
Surgical outcomes of laparoscopic proximal gastrectomy for upper-third gastric cancer: esophagogastrostomy, gastric tube reconstruction, and double-tract reconstruction
Authors: Chen Jianhua , Wang Fei , Gao Shuyang , Yang Yapeng , Zhao Ziming , Shi Jiahao , Wang Liuhua , Ren Jun
Published: October 2023

Background

There is no consensus on the optimal reconstruction technique after proximal gastrectomy. The purpose of this study was to retrospectively compare the surgical outcomes among esophagogastrostomy (EG) anastomosis, gastric tube (GT) reconstruction and double-tract (DT) reconstruction in patients who underwent laparoscopic proximal gastrectomy (LPG) to clarify the superior reconstruction method.

Methods

This study enrolled 164 patients who underwent LPG at the Northern Jiangsu People's Hospital in Jiangsu between January 2017 to January 2022 (EG: 51 patients; GT: 77 patients; DT: 36 patients). We compared the clinical and pathological characteristics, surgical features, postoperative complications, nutritional status, and quality of life (QOL) among the above three groups.

Results

Mean operative time was longer with the DT group than the remaining two groups (p = 0.001). With regard to postoperative complications, considerable differences in the postoperative reflux symptoms (p = 0.042) and reflux esophagitis (p = 0.040) among the three groups were found. For the nutritional status, total protein, hemoglobin and albumin reduction rates in the GT group were significantly higher than the other two groups at 12 months postoperatively. In the PGSAS-45, three assessment items were better in the DT group significantly compared with the esophageal reflux subscale (p = 0.047, Cohen’s d = 0.44), dissatisfaction at the meal (p = 0.009, Cohen’s d = 0.58), and dissatisfaction for daily life subscale (p = 0.012, Cohen’s d = 0.56).

Conclusions

DT after LPG is a valuable reconstruction technique with satisfactory surgical outcomes, especially regarding reduced reflux symptoms, improving the postoperative nutritional status and QOL.
Physical intimate partner violence and prenatal oral health experiences in the United States
Authors: Testa Alexander , Lee Jacqueline G. , Jackson Dylan B. , Mungia Rahma , Ganson Kyle T. , Nagata Jason M.
Published: October 2023

Background

Intimate partner violence (IPV) is a significant public health issue, and when experienced during pregnancy, IPV substantially harms maternal health. Still, limited research has examined how IPV may influence prenatal oral health and dental care utilization. This study investigates the relationship between IPV during pregnancy and women’s oral health experiences.

Data

Data are from 31 states from 2016–2019 in the United States that participated in the Pregnancy Risk Assessment Monitoring System (N = 85,289)—a population-based surveillance system of live births conducted annually by the Centers for Disease Control and Prevention and state health departments. Multivariable logistic regression analyses were used to examine the association between physical IPV during pregnancy (measured by being pushed, hit, slapped, kicked, choked, or physically hurt any other way by a current or ex-husband/partner) and various oral health experiences.

Findings

Women who experienced prenatal physical IPV reported worse oral health experiences during pregnancy, including being more likely to report not knowing it was important to care for their teeth, not talking about dental health with a provider, needing to see a dentist for a problem, going to see a dentist for a problem, as well as having more unmet dental care needs.

Conclusions

Together, these findings indicate that women who experience physical IPV during pregnancy have lower knowledge of prenatal oral health care, more oral health problems, and greater unmet dental care needs. Given the risk of IPV and oral health problems for maternal and infant health, the study findings point to greater attention toward the oral health needs of IPV-exposed pregnant women.
Attitudes towards and engagement in self-directed learning among paramedics in New South Wales, Australia: a cross sectional study
Authors: Bryant Jamie , Zucca Alison , Turon Heidi , Sanson-Fisher Robert , Morrison Alan
Published: October 2023

Background

Australian paramedics must engage in continuing professional development (CPD), including self-directed learning (SDL). This study aimed to examine paramedics’ attitudes towards training and learning activities and perceptions about what could increase engagement in self-directed CPD.

Methods

A cross-sectional survey was conducted with New South Wales Ambulance paramedics. The 48-item survey examined learning attitudes, attitudes towards SDL and socio-demographic and professional characteristics.

Results

Most of the 149 participants (19% consent rate) were male (74.5%) and worked full-time (96.5%). All participants agreed that paramedics should reflect on the quality of their practice (100%) and most were committed to undertaking learning to improve their skills and capability (95.2%). However, 26.3% of participants did not feel motivated to undertake learning and 58.9% did not feel supported. Paramedics reported neutral to modestly positive attitudes towards SDL. Most participants agreed they would be more likely to engage in SDL if they had access to training equipment at their station (91%) and dedicated time during work hours (90.4%).

Conclusion

Paramedics are highly committed to undertaking CPD. Increased engagement may be supported by providing SDL materials at work locations and ensuring dedicated time for learning during work hours.
Community-based nursing: a concept analysis with Walker and Avant’s approach
Authors: Zeydani Arezoo , Atashzadeh-Shoorideh Foroozan , Hosseini Meimanat , Zohari-Anboohi Sima
Published: October 2023

Background

Community-based nursing in recent years has received much attention from nursing schools in different countries as a suitable solution in response to existing and future problems and challenges, but there is yet no comprehensive and correct understanding of this concept and considering its importance, the present study was conducted to the aim of analyzing the concept of community-based nursing.

Methods

Concept analysis was done using Walker and Avant's 8-step approach. Nursing dictionary, Persian dictionary, research articles, journals and conferences articles, dissertations, thesis, books, and other sources related to the concept of research were investigated through search engines and available databases using the keywords of nursing, community-based, concept analysis and Walker and Avant from 1990 to 2023. Finally, 54 articles related to the concept were reviewed and analyzed.

Results

The results showed that community-based nursing has attributes such as individual-oriented/ family-oriented/ community-oriented, social partnership with the communities and stakeholders, social justice, and group and interprofessional cooperation, the community as the main activity setting, providing services based on cultural diversity, providing services according to the context, conditions and community needs, caring for individuals and families with health problems throughout life, responding to the community needs, community-based experiences and facing real-life issues in the context of community, using a problem-based and service-based approach, providing context-based care and considering factors affecting health. In this regard, borderline and related cases (community health nursing, community-oriented nursing, population-based nursing, and public health nursing) were also presented to clarify the concept. Antecedents of community-based nursing included: determining the position of community-based nursing, making infrastructure and structure, the partnership between university, hospital and community, identifying all settings, the presence of educators proficient in education, survey of community needs, having knowledge, communication and community-based skills, expanding the role of the nurse, stakeholders' attitude towards community-oriented nursing and management and financial support. Consequences of community-based nursing included: competence development in nurses, solving community-based nursing challenges, meeting the health needs of individuals, families and communities, social justice, and increasing access to health care services.

Conclusion

The results of this study can provide an objective and understandable image of the use of community-based nurses and their education in practice. Conducting more quantitative and qualitative studies about community-based nursing is also recommended.
Understanding the facilitators and barriers to barcode medication administration by nursing staff using behavioural science frameworks. A mixed methods study
Authors: Grailey Kate , Hussain Rabia , Wylleman Elisa , Ezzat Ahmed , Huf Sarah , Franklin Bryony Dean
Published: October 2023

Introduction

Barcode medication administration (BCMA) technology helps ensure correct medications are administered by nursing staff through scanning of patient and medication barcodes. In many hospitals scanning rates are low, limiting the potential safety benefits. We aimed to explore the barriers and facilitators to BCMA use in a London hospital.

Methods

In this mixed methods study we used local quantitative data on BCMA scanning rates to identify clinically similar wards (in terms of patient acuity and workload) with different scanning rates for qualitative exploration. Interviews designed to elicit barriers to using BCMA technology were conducted with nursing staff, supported by observations of medication administration. Qualitative data were analysed inductively and a thematic framework constructed housing key themes, subsequently categorised into barriers and facilitators. To explore patient perspectives of BCMA scanning, a purposive sample of patients were also interviewed. These patient data were analysed deductively according to the thematic framework. Themes were mapped to behavioural science frameworks to further understand the behaviours involved.

Results

BCMA was operational on 15 wards, with only six having medication scan rates of more than 10% of scannable doses. Of three wards selected for qualitative investigation, the lowest scan rate was 6.7%. Twenty-seven nurses and 15 patients were interviewed. Eleven key themes were identified, encompassing both barriers and facilitators to BCMA use. Barriers included poor trolley ergonomics and perceived time inefficiency. Facilitators included a streamlined process and thorough training. All nurses described BCMA as positive for patient safety. Patients described BCMA as making them “feel safer”. Behavioural science frameworks highlighted the importance of professional role and an individual’s belief in their capability.

Conclusion

We present a novel exploration of facilitators and barriers to BCMA use from the viewpoint of both patients and nursing staff, highlighting a strong perception that BCMA enhances safety. Barriers were reported on both high and low usage wards, demonstrating the importance of behaviours and motivations. These findings provide a detailed understanding from which to design interventions to support behaviour change and increase BCMA use.
Patient’s experiences of diabetes care at a tertiary health facility in Lilongwe, Malawi
Authors: Nkambule Ellen , Wella Kondwani , Msosa Annie , Mbakaya Balwani Chingatichifwe , Chilemba Evelyn , Msiska Gladys
Published: October 2023

Background

Little is known about experiences of rural people with diabetes care at a tertiary health facility in low-income settings. Understanding their experiences is essential for developing effective diabetes care interventions.

Methods

The study employed a qualitative narrative inquiry. Participants were identified at a diabetes clinic at a tertiary-level healthcare facility. Ten participants from the rural areas attending the diabetes clinic were purposively selected. Data were collected through in-depth interviews in the privacy of the homes of the study participants and analysis was done using the Riessman approach to thematic narrative analysis.

Results

In this study, the following four themes emerged: (1) the long pathway to a diagnosis of diabetes; (2) Poverty-related hardships and diabetic clinic attendance; (3) The impact of health worker attitudes and behavior on diabetes care; and (4) Low resources and their impact on self-management.

Conclusions

Rural-based patients living with diabetes encounter enormous challenges as they access diabetes care. One of the challenges is delayed diagnosis of diabetes. There is a need to introduce point-of-care (POC) testing to improve diabetes diagnosis. In addition, there is a need to strengthen awareness campaigns among the population so that people are well informed about the signs and symptoms of diabetes to promote early diagnosis. Diabetes care must be decentralized from tertiary hospitals to primary health centers. This will improve access to diabetes care and reduce the burden associated with traveling a long distance to access diabetes care in Malawi.
Challenges in recruiting frequent users of ambulance services for a community paramedic home visit program
Authors: Plishka Mikayla , Angeles Ricardo , Pirrie Melissa , Marzanek Francine , Agarwal Gina
Published: October 2023

Background

The Community Paramedicine at Home (CP@home) program is a health promotion program where community paramedics conduct risk assessments with frequent 9-1-1 callers in their homes, with a goal of reducing the frequency of 9-1-1 calls in this vulnerable population. The effectiveness of the CP@home program was investigated through a community-based RCT conducted in four regions in Ontario, Canada. The purpose of this current recruitment study is to examine the challenges met when recruiting for a community randomized control trial on high frequency 9-1-1 callers.

Methods

Eligible participants were recruited from one of four regions participating in the CP@home program and were randomly assigned to an intervention group (n = 1142) or control group (n = 1142). Data were collected during the recruitment process from the administrative database of the four paramedic services. Whether they live alone, their parental ethnicity, age, reason for calling 9-1-1, reason for not participating, contact method, and whether they were successfully contacted were recorded. Statistical significance was calculated using the Chi-Squared Test and Fisher’s Exact Test to evaluate the effectiveness of the recruitment methods used to enroll eligible participants in the CP@home Program.

Results

Of the people who were contacted, 48.0% answered their phone when called and 53.9% answered their door when a home visit was attempted. In Total, 110 (33.1%) of people where a contact attempt was successful participated in the CP@home program. Most participants were over the age of 65, even though people as young as 18 were contacted. Older adults who called 9-1-1 for a lift assist were more likely to participate, compared to any other individual reason recorded, and were most often recruited through a home visit.

Conclusions

This recruitment analysis successfully describes the challenges experienced by researchers when recruiting frequent 9-1-1 callers, which are considered a hard-to-reach population. The differences in age, contact method, and reason for calling 9-1-1 amongst people contacted and participants should be considered when recruiting this population for future research.
Caspase 6 promotes innate immune activation by functional crosstalk between RIPK1-IκBα axis in liver inflammation
Authors: Lin Yuanbang , Sheng Mingwei , Qin Hua , Zhang Peng , Wang Chunli , Fu Wei , Meng Xiangjun , Wang Duowei , Hou Yachao
Published: October 2023

Background

Caspase 6 is an essential regulator in innate immunity, inflammasome activation and host defense. We aimed to characterize the causal mechanism of Caspase 6 in liver sterile inflammatory injury.

Methods

Human liver tissues were harvested from patients undergoing ischemia-related hepatectomy to evaluate Caspase 6 expression. Subsequently, we created Caspase 6-knockout (Caspase 6KO) mice to analyze roles and molecular mechanisms of macrophage Caspase 6 in murine models of liver ischemia/reperfusion (IR) injury.

Results

In human liver biopsies, Caspase 6 expression was positively correlated with more severe histopathological injury and higher serum ALT/AST level at one day postoperatively. Moreover, Caspase 6 was mainly elevated in macrophages but not hepatocytes in ischemic livers. Unlike in controls, the Caspase 6-deficient livers were protected against IR injury, as evidenced by inhibition of inflammation, oxidative stress and iron overload. Disruption of macrophage NF-κB essential modulator (NEMO) in Caspase 6-deficient livers deteriorated liver inflammation and ferroptosis. Mechanistically, Caspase 6 deficiency spurred NEMO-mediated IκBα phosphorylation in macrophage. Then phosphorylated-inhibitor of NF-κBα (p-IκBα) co-localized with receptor-interacting serine/ threonine-protein kinase 1 (RIPK1) in the cytoplasm to degradate RIPK1 under inflammatory conditions. The disruption of RIPK1-IκBα interaction preserved RIPK1 degradation, triggering downstream apoptosis signal-regulating kinase 1 (ASK1) phosphorylation and inciting NIMA-related kinase 7/NOD-like receptor family pyrin domain containing 3 (NEK7/NLRP3) activation in macrophages. Moreover, ablation of macrophage RIPK1 or ASK1 diminished NEK7/NLRP3-driven inflammatory response and dampened hepatocyte ferroptosis by reducing HMGB1 release from macrophages.

Conclusions

Our findings underscore a novel mechanism of Caspase 6 mediated RIPK1-IκBα interaction in regulating macrophage NEK7/NLRP3 function and hepatocytes ferroptosis, which provides therapeutic targets for clinical liver IR injury.

Graphical Abstract
AXL receptor tyrosine kinase modulates gonadotropin-releasing hormone receptor signaling
Authors: Mohammadzadeh Pardis , Roueinfar Mina , Amberg Gregory C.
Published: October 2023

Background

Gonadotropin-releasing hormone (GnRH) receptors are essential for reproduction and are expressed in numerous urogenital, reproductive, and non-reproductive cancers. In addition to canonical G protein-coupled receptor signaling, GnRH receptors functionally interact with several receptor tyrosine kinases. AXL is a receptor tyrosine kinase expressed in numerous tissues as well as multiple tumors. Here we tested the hypothesis that AXL, along with its endogenous ligand Gas6, impacts GnRH receptor signaling.

Methods

We used clonal murine pituitary αT3-1 and LβT2 gonadotrope cell lines to examine the effect of AXL activation on GnRH receptor-dependent signaling outcomes. ELISA and immunofluorescence were used to observe AXL and GnRH receptor expression in αT3-1 and LβT2 cells, as well as in murine and human pituitary sections. We also used ELISA to measure changes in ERK phosphorylation, pro-MMP9 production, and release of LHβ. Digital droplet PCR was used to measure the abundance of Egr-1 transcripts. A transwell migration assay was used to measure αT3-1 and LβT2 migration responses to GnRH and AXL.

Results

We observed AXL, along with the GnRH receptor, expression in αT3-1 and LβT2 gonadotrope cell lines, as well as in murine and human pituitary sections. Consistent with a potentiating role of AXL, Gas6 enhanced GnRH-dependent ERK phosphorylation in αT3-1 and LβT2 cells. Further, and consistent with enhanced post-transcriptional GnRH receptor responses, we found that Gas6 increased the abundance of Egr-1 transcripts. Suggesting functional significance, in LβT2 cells, Gas6/AXL signaling stimulated LHβ production and enhanced GnRH receptor-dependent generation of pro-MMP9 protein and promoted cell migration.

Conclusions

Altogether, these data describe a novel role for AXL as a modulator of GnRH receptor signaling.
Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer
Authors: He Xing , Peng Yaorong , He Gui , Ye Huilin , Liu Liqiang , Zhou Qixian , Shi Juanyi , Fu Sha , Wang Jie , Zhou Zhenyu , Li Wenbin
Published: October 2023

Background

The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC.

Methods

We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance.

Results

We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors.

Conclusions

Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC.
Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib
Authors: Wang Wei , Wang Wei , Peng Siming , Gao Sihao , Quan Meiying , Gou Lijuan , Wang Changyan , Sun Zhixing , Li Zhuo , Lian Dongmei , Song Hongmei
Published: October 2023

Background

Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression.

Case presentation

We describe a 7-year-old Chinese boy who developed symptoms at the age of 6 months. He presented with a chilblain-like rash, leukopenia, neutropenia, elevated liver enzymesgrowth retardation, microcephaly, elevated acute phase reactants, intracranial calcification and leukodystrophy. At the age of 3 years old, whole-exome sequencing confirmed a de novo heterozygous gain-of-function mutation, c.1016 C > A (p.Ala339Asp), in the IFIH1 gene, and he was diagnosed with AGS7. He was treated with ruxolitinib accompanied by steroids and thalidomide for about four years. The rash, hematological manifestations, and the liver function were all improved, but the erythrocyte sedimentation rate remained consistently elevated until the addition of tocilizumab, a monoclonal antibody against interleukin 6.

Conclusions

Ruxolitinib was not successful in suppressing the inflammatory process, and tocilizumab produced highly encouraging results in reducing the inflammatory reaction of AGS. The study makes a significant contribution to the literature because we may found a potential alternative therapeutic option for AGS.
Effects of reduced kinematic and social play experience on affective appraisal of human-rat play in rats
Authors: Liu Quanxiao , Ilčíková Tereza , Radchenko Mariia , Junková Markéta , Špinka Marek
Published: October 2023

Background

Play is a common and developmentally important behaviour in young mammals. Specifically in Norway rats (Rattus norvegicus), reduced opportunity to engage in rough-and-tumble (RT) play has been associated with impaired development in social competence. However, RT play is a complex behaviour having both a kinematic aspect (i.e., performing complex 3D manoeuvres during play fights) and a social aspect (interacting with a playful partner). There has been little research so far on disentangling the two aspects in RT play, especially on how these two aspects affect the affective appraisal of the intense physical contact during play.

Results

To examine the developmental effects of kinematic and social play reduction on affective appraisal in rats, we subjected male Long-Evans rats from 21 days old to RT play experience that was reduced either kinematically (through playing in a low ceiling environment) or socially (through playing with a less playful Fischer-344 rat). Starting at 35 days, we measured their production of positively (50-kHz) and negatively (22-kHz) valenced ultrasonic vocalisations (USVs) in a 2-min standardised human-rat play procedure that mimicked the playful sequences of nape contact, pinning, and belly stimulation (‘tickling’) for ten days. We hypothesised that the rats with kinematically or socially reduced play would perceive the ‘tickling’ less positively and thus emit positive ultrasonic vocalisations at lower rates compared to control rats with non-reduced play experience. Our results confirmed that each of the treatments reduced play differently: while the kinematic reduction abolished playful pinnings entirely, the social reduction decreased the pinnings and made play highly asymmetric. During the tickling procedure, rats mostly produced 50 kHz USV, indicating that they appraised the procedure as positive. There was a wide inter individual variance and high individual consistency in rats’ USV responses to ‘tickling’. Crucially, neither the kinematically nor the socially reduced play experience affected either type of USV production when rats were ‘tickled’.

Conclusions

This finding indicates that the ability to appraise play-like interactions as positive remains unaffected even when the kinematic or the social aspect of play experience was substantially curtailed.
Impact of prophylactic donor heart tricuspid valve annuloplasty on outcomes in heart transplantation
Authors: Nishida Hidefumi , Jeevanandam Valluvan , Salerno Christopher , Nemoto Atsushi , Song Tae , Onsager David , Nguyen Ann , Grinstein Jonathan , Chung Bow , Sarswat Nitasha , Kim Gene , Pinney Sean , Ota Takeyoshi
Published: October 2023

Background

Tricuspid regurgitation(TR) following heart transplantation could adversely affect clinical outcomes. In an effort to reduce the incidence of TR, prophylactic donor heart tricuspid valve annuloplasty has been performed during heart transplantation in our institution. We assessed early and long-term outcomes.

Methods

Between August 2011 and August 2021, 349 patients who underwent prophylactic tricuspid valve annuloplasty were included. Tricuspid valve annuloplasty was performed using the DeVega annuloplasty technique. The clinical outcomes of the interests included complete atrioventricular block requiring pacemaker implantation, the occurrence of significant TR(defined as moderate or greater), and survival. Long-term survival was compared in patients with and without significant TR using the Kaplan-Meier method. The Cox proportional hazards regression with time-dependent covariate analysis was used to see if significant TR affected the long-term survival.

Results

There was one patient(0.3%) who required pacemaker implantation for complete atrioventricular block. No patients developed tricuspid valve stenosis that required intervention. Significant TR developed in 31 patients(8.9%) during the follow-up period. The survival rate of patients who developed significant TR was significantly lower than that of those who did not(log rank < 0.01). Significant TR was associated with the long-term mortality(HR2.92, 95%CI 1.47–5.82, p < 0.01).

Conclusions

Prophylactic donor heart tricuspid valve annuloplasty has the potential to reduce the occurrence of significant TR and can be performed safely. The significant TR that developed in patients with prophylactic annuloplasty negatively affected survival and was an independent predictor of long-term mortality.
Jin-Gui-Shen-Qi Wan ameliorates diabetic retinopathy by inhibiting apoptosis of retinal ganglion cells through the Akt/HIF-1α pathway
Authors: Liang Dan , Qi Yulin , Liu Lu , Chen Zhaoxia , Tang Shiyun , Tang Jianyuan , Chen Nianzhi
Published: October 2023

Background

Jin-Gui-Shen-Qi Wan (JGSQ) has been used in China for thousands of years to treat various ailments, including frequent urination, blurred vision, and soreness in the waist and knees. It has traditional therapeutic advantages in improving eye diseases.

Aim of the study

Clinical studies have confirmed the therapeutic efficacy of JGSQ in improving diabetes and vision; however, its efficacy and pharmacological effects in treating diabetic retinopathy (DR) remain unclear. Therefore, the aim of this study was to investigate the specific pharmacological effects and potential mechanisms of JGSQ in improving DR through a db/db model.

Materials and methods

db/db mice were given three different doses of orally administered JGSQ and metformin for 8 weeks, and then PAS staining of the retinal vascular network patch, transmission electron microscopy, H&E staining, and TUNEL staining were performed to determine the potential role of JGSQ in improving DR-induced neuronal cell apoptosis. Furthermore, network pharmacology analysis and molecular docking were carried out to identify the main potential targets of JGSQ, and the efficacy of JGSQ in improving DR was evaluated through western blotting and immunofluorescence staining, revealing its mechanism of action.

Results

According to the results from H&E, TUNEL, and PAS staining of the retinal vascular network patch and transmission electron microscopy, JGSQ does not have an advantage in improving the abnormal morphology of vascular endothelial cells, but it has a significant effect on protecting retinal ganglion cells from apoptosis. Through network pharmacology and molecular docking, AKT, GAPDH, TNF, TP53, and IL-6 were identified as the main core targets of JGSQ. Subsequently, through western blot and immunofluorescence staining, it was found that JGSQ can inhibit HIF-1α, promote p-AKT expression, and inhibit TP53 expression. At the same time, inhibiting the release of inflammatory factors protects retinal ganglion cells and improves apoptosis in DR.

Conclusion

These results indicated that in the db/db DR mouse model, JGSQ can inhibit the expression of inflammatory cytokines and protect retinal ganglion cells from apoptosis, possibly by modulating the Akt/HIF-1α pathway.

Graphical Abstract
Generalized pairwise comparisons of prioritized outcomes are a powerful and patient-centric analysis of multi-domain scores
Authors: Deltuvaite-Thomas Vaiva , De Backer Mickaël , Parker Samantha , Deneux Marie , Polgreen Lynda E. , O’Neill Cara , Salvaggio Samuel , Buyse Marc
Published: October 2023

Background

Generalized pairwise comparisons (GPC) can be used to assess the net benefit of new treatments for rare diseases. We show the potential of GPC through simulations based on data from a natural history study in mucopolysaccharidosis type IIIA (MPS IIIA).

Methods

Using data from a historical series of untreated children with MPS IIIA aged 2 to 9 years at the time of enrolment and followed for 2 years, we performed simulations to assess the operating characteristics of GPC to detect potential (simulated) treatment effects on a multi-domain symptom assessment. Two approaches were used for GPC: one in which the various domains were prioritized, the other with all domains weighted equally. The net benefit was used as a measure of treatment effect. We used increasing thresholds of clinical relevance to reflect the magnitude of the desired treatment effects, relative to the standard deviation of the measurements in each domain.

Results

GPC were shown to have adequate statistical power (80% or more), even with small sample sizes, to detect treatment effects considered to be clinically worthwhile on a symptom assessment covering five domains (expressive language, daily living skills, and gross-motor, sleep and pain). The prioritized approach generally led to higher power as compared with the non-prioritized approach.

Conclusions

GPC of prioritized outcomes is a statistically powerful as well as a patient-centric approach for the analysis of multi-domain scores in MPS IIIA and could be applied to other heterogeneous rare diseases.
Dynamic DNA methylation turnover in gene bodies is associated with enhanced gene expression plasticity in plants
Authors: Williams Clara J. , Dai Dawei , Tran Kevin A. , Monroe J. Grey , Williams Ben P.
Published: October 2023

Background

In several eukaryotes, DNA methylation occurs within the coding regions of many genes, termed gene body methylation (GbM). Whereas the role of DNA methylation on the silencing of transposons and repetitive DNA is well understood, gene body methylation is not associated with transcriptional repression, and its biological importance remains unclear.

Results

We report a newly discovered type of GbM in plants, which is under constitutive addition and removal by dynamic methylation modifiers in all cells, including the germline. Methylation at Dynamic GbM genes is removed by the DRDD demethylation pathway and added by an unknown source of de novo methylation, most likely the maintenance methyltransferase MET1. We show that the Dynamic GbM state is present at homologous genes across divergent lineages spanning over 100 million years, indicating evolutionary conservation. We demonstrate that Dynamic GbM is tightly associated with the presence of a promoter or regulatory chromatin state within the gene body, in contrast to other gene body methylated genes. We find Dynamic GbM is associated with enhanced gene expression plasticity across development and diverse physiological conditions, whereas stably methylated GbM genes exhibit reduced plasticity. Dynamic GbM genes exhibit reduced dynamic range in drdd mutants, indicating a causal link between DNA demethylation and enhanced gene expression plasticity.

Conclusions

We propose a new model for GbM in regulating gene expression plasticity, including a novel type of GbM in which increased gene expression plasticity is associated with the activity of DNA methylation writers and erasers and the enrichment of a regulatory chromatin state.
Factors that influence women’s enrolment and ongoing participation in a partially decentralised randomised controlled dermatology trial: a qualitative interview study with participants in the SAFA (Spironolactone for Adult Female Acne) trial
Authors: Boxall Cherish , Renz Susanne , Eminton Zina , Nuttall Jacqueline , Saji Alan , Cluff Charlotte , Wilcox Christopher , Muller Ingrid , Layton Alison M. , Soulsby Irene , Santer Miriam
Published: October 2023

Background

The use of decentralised clinical trials (which bring trials to patients through remote processes and technology versus central on-site visits) has been thought to be a potential solution to common recruitment and retention barriers. However, there is a lack of evidence to understand the experiences, needs and preferences of the public to inform trial methodologies that appeal to different populations. We report participant experiences of SAFA, a partially decentralised randomised clinical trial, to inform the methodology used in future dermatology trials that aim to appeal to women aged 18 and over.

Methods

Participants of the SAFA (Spironolactone for Adult Female Acne) trial were invited to take part in a qualitative semi-structured interview to explore their experience and perspectives of taking part in the trial. Questions focused on their experience of using decentralised methods to access and enrol in the trial (e.g. social media advertising), in addition to the decentralised trial visit and data collection methods used throughout. Interviews were conducted remotely, recorded, and transcribed. Data were analysed using reflexive thematic analysis.

Results

Twelve SAFA participants (all women, age range 22–36 years) were interviewed. Initially, participants were influenced to enrol by trusted online information, the feeling of validation the trial provided, and the convenience and flexibility offered by the decentralised methods and research staff made participants feel valued and enabled them to engage in the trial with minimal interference to existing commitments. SAFA participants were generally accepting of trial demands, such as the text-heavy paperwork and on-site visits for blood collection and highlighted several areas relevant for trial conduct going forwards including where decentralised methods may (and may not) be accepted and how trial accessibility and understanding could be improved.

Conclusions

The study has shown that decentralised methods used by responsive and approachable staff were widely accepted in the SAFA trial. Interviewees found the methods adopted in the SAFA trial helped the trial to fit with their needs and promoted a sense of feeling valued that encouraged ongoing trial engagement. Decentralised methods should be considered favourably when designing a dermatology trial as they can potentially enhance both recruitment and retention.

Trial registration number

ISRCTN 12892056. Registered on October 15, 2018.
An integrated personalized assistive devices approach to reduce the risk of foot ulcer recurrence in diabetes (DIASSIST): study protocol for a multicenter randomized controlled trial
Authors: Vossen Lisa E. , van Netten Jaap J. , Bakker Chantal D. , Berendsen Heleen A. , Busch-Westbroek Tessa E. , Peters Edgar J. G. , Sabelis Louise W. E. , Dijkgraaf Marcel G. W. , Bus Sicco A.
Published: October 2023

Background

Preventing foot ulcers in people with diabetes can increase quality of life and reduce costs. Despite the availability of various interventions to prevent foot ulcers, recurrence rates remain high. We hypothesize that a multimodal treatment approach incorporating various footwear, self-management, and education interventions that matches an individual person’s needs can reduce the risk of ulcer recurrence with beneficial cost-utility. The aim of this study is to assess the effect on foot ulcer recurrence, footwear adherence, and cost-utility of an integrated personalized assistive devices approach in high-risk people with diabetes.

Methods

In a parallel-group multicenter randomized controlled trial, 126 adult participants with diabetes mellitus type 1 or 2, loss of protective sensation based on the presence of peripheral neuropathy, a healed plantar foot ulcer in the preceding 4 years, and possession of any type of custom-made footwear will be included. Participants will be randomly assigned to either enhanced therapy or usual care. Enhanced therapy consists of usual care and additionally a personalized treatment approach including pressure-optimized custom-made footwear, pressure-optimized custom-made footwear for indoor use, at-home daily foot temperature monitoring, and structured education, which includes motivational interviewing and personalized feedback on adherence and self-care. Participants will be followed for 12 months. Assessments include barefoot and in-shoe plantar pressure measurements; questionnaires concerning quality of life, costs, disease, and self-care knowledge; physical activity and footwear use monitoring; and clinical monitoring for foot ulcer outcomes. The study is powered for 3 primary outcomes: foot ulcer recurrence, footwear adherence, and cost-utility, the primary clinical, patient-related, and health-economic outcome respectively.

Discussion

This is the first study to integrate multiple interventions for ulcer prevention into a personalized state-of-the-art treatment approach and assess their combined efficacy in a randomized controlled trial in people with diabetes at high ulcer risk. Proven effectiveness, usability, and cost-utility will facilitate implementation in healthcare, improve the quality of life of high-risk people with diabetes, and reduce treatment costs.

Trial registration

ClinicalTrials.gov NCT05236660. Registered on 11 February 2022.
Effect of music breathing, a program based on mindful breathing and music listening therapy for promoting sense of coherence in young people: study protocol for a randomized controlled trial
Authors: Cheng Winnie Lai-Sheung , Tang Anson Chui-Yan , Tsang Mark Cheuk-Man , Wong Lokki Lok-Ki , Körlin Dag
Published: October 2023

Background

The negative impacts of the COVID-19 pandemic on public health have affected people socially, psychologically, and physically. Young people particularly are having to adjust many aspects of their personal lives: including transitions to work, college, and independent living. Personal resources are important in mitigating stress and improve mental well-being during pandemic. Sense of coherence—an orientation to life—could be considered as a personal resource. Currently, a number of interventions have been developed to target the reduction of stress in young people. Little emphasis has been placed on developing sense of coherence to reduce stress and promote mental well-being among young people. Young people consider music as a preferred leisure activity and an important means of stress relief in their daily lives. However, little research concerning music therapy and sense of coherence exists.

Methods

In the proposed randomized controlled trial, a sample of 290 young people (aged 18–30) will be recruited and allocated randomly into one of two groups: the experimental group and the control group. Participants in the experimental group will participate in a 6-week Music Breathing program that will include music listening and mindful breathing guided by a certified music therapist. Participants in the control group will receive a control condition for 6 weeks Mental Health Education Programme. The primary outcome of the study will be measured using Sense of Coherence Scale. The secondary outcomes will be measured using the Coping Self-Efficacy Scale, Difficulties in Emotion Regulation Scale, Mindful Attention Awareness Scale, Depression Anxiety Stress Scales, BBC Subjective Well-being scale, and salivary cortisol levels. Repeated measures analysis will be used to compare the outcomes between the two groups.

Discussion

The results will inform practice in coping with stress through promoting sense of coherence. Individuals will benefit from the long-term effect of this intervention to enhance their sense of coherence to cope with stressful events and promote better mental well-being.

Trial registration

ClinicalTrials.gov Identifier: NCT05655234. Registered on December 8, 2022.
Synergistic roles of CBX4 chromo and SIM domains in regulating senescence of primary human osteoarthritic chondrocytes
Authors: Chen Yu-Hsiu , Zhang Xin , Attarian David , Kraus Virginia Byers
Published: October 2023

Background

Cellular senescence is a critical factor contributing to osteoarthritis (OA). Overexpression of chromobox homolog 4 (CBX4) in a mouse system was demonstrated to alleviate post-traumatic osteoarthritis (PTOA) by reducing cellular senescence. Additionally, replicative cellular senescence of WI-38 fibroblasts can be attenuated by CBX4. However, the mechanisms underlying this senomorphic function of CBX4 are not fully understood. In this study, we aimed to investigate the role of CBX4 in cellular senescence in human primary osteoarthritic chondrocytes and to identify the functional domains of CBX4 necessary for its function in modulating senescence.

Methods

Chondrocytes, isolated from 6 individuals undergoing total knee replacement for OA, were transduced with wild-type CBX4, mutant CBX4, and control lentiviral constructs. Senescence-related phenotypic outcomes included the following: multiple flow cytometry-measured markers (p16INK4A, senescence-associated β-galactosidase [SA-β-gal] activity and dipeptidyl peptidase-4 [DPP4], and proliferation marker EdU), multiplex ELISA-measured markers in chondrocyte culture media (senescence-associated secretory phenotypes [SASPs], including IL-1β, IL-6, IL-8, TNF-α, MMP-1, MMP-3, and MMP-9), and PCR array-evaluated senescence-related genes.

Results

Compared with control, CBX4 overexpression in OA chondrocytes decreased DPP4 expression and SASP secretion and increased chondrocyte proliferation confirming CBX4 senomorphic effects on primary human chondrocytes. Point mutations of the chromodomain domain (CDM, involved in chromatin modification) alone were sufficient to partially block the senomorphic activity of CBX4 (p16INK4A and DPP4 increased, and EdU decreased) but had minimal effect on SASP secretion. Although having no effect on p16INK4A, DPP4, and EdU, deletion of two small-ubiquitin-like-modifier-interaction motifs (CBX4 ΔSIMs) led to increased SASP secretion (IL-1β, TNF-α, IL-8). The combination CBX4 CDMΔSIMs altered all these measures adversely and to a greater degree than the single domain mutants. Deletion of the C-terminal (CBX4 ΔC-box) involved with transcriptional silencing of polycomb group proteins increased IL-1β slightly but significantly but altered none of the other senescence outcome measures.

Conclusions

CBX4 has a senomorphic effect on human osteoarthritic chondrocytes. CDM is critical for CBX4-mediated regulation of senescence. The SIMs are supportive but not indispensable for CBX4 senomorphic function while the C-box is dispensable.