bluuebunny/crossref_metadata_2025 huggingface dataset:
Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis
Authors: Mendonça Lígia Pelosi , Costa Natalia de Souza Xavier , do Nascimento Ellen Caroline Toledo , de Oliveira Martina Rodrigues , de Carvalho Carlos Roberto Ribeiro , Baldi Bruno Guedes , Dolhnikoff Marisa
Published: January 2024

Background

Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS).

Methods

Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-β expression, and infiltration of LAM cells and inflammatory cells within the small airway walls.

Results

The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content.

Conclusion

LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).
Enhancing knowledge, attitudes, and practices related to dental caries in mothers and caregivers of children through a neuroeducational strategy
Authors: Angarita-Díaz María del Pilar , Durán-Arismendy Elsa , Cabrera-Arango Claudia , Vásquez-Aldana Daniel , Bautista-Parra Valentina , Laguna-Moreno Jessica , Mondragón-López Winnifer
Published: January 2024

Background

Knowledge, attitudes, and practices related to oral health among parents play a crucial role in shaping oral hygiene and preventing early childhood caries. This study was intended to determine the effect of a neuroeducational strategy in improving knowledge, attitudes, and practices related to early childhood caries among mothers or caregivers of children.

Methods

A quasi-experimental study was conducted, implementing an educational strategy involving 33 mothers or female caregivers of children who met specific selection criteria. The strategy consisted of three key elements derived from neuroeducation: (1) experiment, (2) surprise and play, and (3) learn. Based on the participants’ attendance at the sessions, they were categorized into two groups: those who underwent in-person intervention (G1) and those who received a combined in-person and virtual intervention (G2). The impact of the strategy was evaluated by comparing the participants’ knowledge and attitudes, as well as their children’s plaque index, before and after the intervention (immediate and 6-month impact).

Results

The participants exhibited a favorable and statistically significant effect on the median number of correct answers related to knowledge (G1 immediate effect (IE): p = 0.03, 6-month effect (ME): p = 0.002; G2 IE p = 0.002, ME: p = 0.001), and in the children’s plaque index (G1 IE: p = 0.003, ME: p = 0.003; G2 IE: p = 0.033, ME: p = 0.003). Furthermore, there was an increase in the number of participants with a high level of knowledge (G1 IE: 41.5%; ME: 75%; G2 IE: 45.5%, ME: 42.9%), and of children with a good level of oral hygiene (G1 IE: 50%; ME: 73.0%; G2 IE: 27.3%, ME: 84.6%). Finally, qualitative interviews revealed a lasting clarity in concepts and sustained knowledge and attitudes at the six-month mark. However, a slightly diminished understanding of the relationship between bacteria, sugar, and caries was observed in G2 group, and some loss of association in the G1 group, at six months.

Conclusion

The implementation of this strategy resulted in significant and lasting impacts on knowledge, attitudes, and practices, especially in the G1 group. Nevertheless, there is a need for further reinforcement of the association between bacteria, sugar, and caries.
Properties of a novel composite elastomeric polymer vinyl polyether siloxane in comparison to its parent materials: a systemic review and meta-analysis
Authors: Saini Ravinder S. , Alshadidi Abdulkhaliq Ali F. , Hassan Saeed Awod Bin , Aldosari Lujain Ibrahim N. , Mosaddad Seyed Ali , Heboyan Artak
Published: January 2024

Background

The effectiveness of newly developed elastomeric polymer hybrid siloxane (PVES), which combines the properties of polyethylene (PE) and polyvinyl siloxane (PVS) elastomers, has been a subject of interest in recent studies. This study aimed to assess the physical properties of hybrid PVES materials by analyzing existing data from recent studies on this topic.

Methods

A systematic literature search was conducted to retrieve peer-reviewed articles published up to February 5, 2023. The population, intervention, comparison, and pertinent outcomes were specified under the PICO framework. The primary data analysis was performed in Microsoft Excel, while statistical analysis used Meta-Essentials.

Results

Of the 1152 articles assessed, 14 met the inclusion criteria. The meta-analysis of the selected studies indicated that polyether (PE) and polyvinyl siloxane (PVS) were highly correlated (two-tailed p-values of 0.000 and 0.001, respectively) with the improved tensile strength of vinyl polyether siloxane (PVES) with a significantly positive effect size. Similarly, the hydrophilic characteristics of PVES were significantly improved compared to those of PE and PVS. PE was a significant contributor to the hydrophilic characteristics of PVES, with a two-tailed p-value of 0.000. The effect size was highly positive for hydrophilicity but showed high heterogeneity. It was also observed that the dimensional accuracy of PVES was comparable to those of PE and PVS, with no statistically significant differences among the three materials.

Conclusions

PVES showed promising features, with improved tensile strength and hydrophilic characteristics compared to those of PE and PVS.
Exploring the knowledge, attitudes, and performance of dentists in providing care to elderly patients
Authors: Nouri Fateme Najmi , Afshar Mehrnaz Karimi , Afshar Marzieh Karimi , Hooshmand Hamze , Nia Rahil Ghorbani
Published: January 2024

Background

Supportive care and dental treatment for older adults are crucial in addressing the global emergency of population aging, requiring specialized healthcare services and knowledge-based practices.

Methods

This cross-sectional content analysis study was conducted on 150 general dentists in Kerman in 2021. The participants were selected using cluster sampling. The data were collected using a questionnaire with four sections assessing the participants’ demographic characteristics, knowledge, attitudes, and performance. The data were analyzed with SPSS-26 software using the t-test, ANOVA, and linear regression analysis.

Results

The dentists’ mean age was 36.10 ± 7.60 years. The mean knowledge score of the participants was 5.29 ± 1.49 (out of 9). The mean attitude score was 59.42 ± 11.6 (out of 85), and the mean performance score was 24.13 ± 4.96 (out of a maximum of 35). The data showed a positive relationship between the dentists’ knowledge, attitudes, and performance. However, the participants’ gender had no significant correlation with their knowledge, attitudes, or performance. It was also shown that 50% of dentists had adequate experience treating elderly patients with complex medical problems.

Conclusions

The participants had an adequate level of knowledge and performance and a positive attitude toward dental care for older adults. Health officials and administrators need to organize and hold effective training and refresher courses on geriatric dentistry to promote dentists’ knowledge and performance.

Trial registration

Ethics code IR.KMU.REC.1401.007.
Comparison of Easydo Activator, ultrasonic and needle irrigation techniques on sealer penetration and smear layer removal in vitro
Authors: Zhang Shao-Hui , Gao Zheng-Rong , Zhou Ying-Hui , Tan Li , Feng Yao , Ye Qin , Zhao Jie , Zhao Ya-Qiong , Hu Jing , Chen Yun , Liu Qiong , Aimee Dusenge Marie , Guo Yue , Feng Yun-Zhi
Published: January 2024

The effects of Easydo Activator (EA), a new sonic irrigation system, on sealer penetration at the root apex were compared to needle irrigation (NI) and passive ultrasonic irrigation (PUI) in this study. Forty-two single-rooted teeth were prepared and randomly divided into three groups (n = 14): group 1: NI; group 2: PUI; and group 3: EA. A solution of 3% sodium hypochlorite (NaOCl) was used for irrigation. Nine teeth in each group were filled with AH Plus sealer mixed with CY5 fluorescent dye and a single gutta-percha cone. The sealer penetration area, maximum penetration depth and percentage of sealer penetration at 5 mm and 1 mm from the apex were analyzed by confocal laser scanning microscopy (CLSM). The remaining 5 teeth in each group were subjected to test smear layer scores by scanning electron microscopy (SEM). The CLSM evaluation showed that increases in the area, depth and percentage of sealer penetration were detected at 1 and 5 mm from the root apex in the PUI group compared with the NI group, and greater increases were observed in the EA group (P < 0.05). The SEM experiment showed that the lowest scores for the smear layer and debris removal were achieved by the EA group when compared with the PUI and NI groups (P < 0.05). In conclusion, EA was superior to PUI and NI regarding sealer penetration at the root apex during endodontic treatment, and it could provide a new technical idea for clinical root canal therapy.
Indigofera suffruticosa aerial parts extract induce G2/M arrest and ATR/CHK1 pathway in Jurkat cells
Authors: Tran Hong-Loan , Lai Kuei-Hung , Chang Hsun-Shuo , Chen Yi-Siao , Wang Hui-Chun , Yang Shuen-Shin , Chang Hsueh-Wei , Hsu Chin-Mu , Yen Chia-Hung , Hsiao Hui-Hua
Published: January 2024

Background

Indigofera suffruticosa Mill. is used as a folk medicine for treating patients with leukemia, however very little is known regarding the molecular mechanism of its anti-leukemic activity and the chemical profile of the active extract. The present study aimed to reveal the molecular effect of I. suffruticosa aerial parts extract (ISAE) on leukemia cells and its chemical constituents.

Methods

Cytotoxicity of ISAE were determined by resazurin viability assay, multitox – Glo multiplex cytotoxicity assay, and Annexin V staining assay. Cell cycle profiles were revealed by propidium iodide staining assay. The effects of ISAE on G2/M arrest signaling and DNA damage were evaluated by Western blot assay and phospho-H2A.X staining assay. The chemical profile of ISAE were determined by tandem mass spectroscopy and molecular networking approach.

Results

We showed that the acute lymphoblastic leukemia cell line Jurkat cell was more responsive to ISAE treatment than other leukemia cell lines. In contrast, ISAE did not induce cytotoxic effects in normal fibroblast cells. Cell cycle analysis revealed that ISAE triggered G2/M arrest in Jurkat cells in dose- and time-dependent manners. Elevation of annexin V-stained cells and caspase 3/7 activity suggested ISAE-induced apoptosis. Furthermore, ISAE alone could increase the phosphorylation of CDK1 at Y15 and activate the ATR/CHK1/Wee1/CDC25C signaling pathway. However, the addition of caffeine, a widely used ATR inhibitor to ISAE, reduced the phosphorylation of ATR, CHK1, and CDK1, as well as G2/M arrest in Jurkat cells. Moreover, increased phospho-H2A.X stained cells indicated the involvement of DNA damage in the anti-leukemic effect of ISAE. Finally, qualitative analysis using UPLC-tandem mass spectroscopy and molecular networking revealed that tryptanthrin was the most abundant organoheterocyclic metabolite in ISAE. At equivalent concentrations to ISAE, tryptanthrin induced G2/M arrest of Jurkat cells, which can be prevented by caffeine.

Conclusions

ISAE causes G2/M arrest via activating ATR/CHK1/CDK1 pathway and tryptanthrin is one of the active components of ISAE. Our findings provide subtle support to the traditional use of I. suffruitcosa in leukemia management in folk medicine.
Predictors of hospital nursing staff’s adherence to safe injection guidelines: application of the protection motivation theory in Fars province, Iran
Authors: Karimi Masoud , Khoramaki Zakieh , faradonbeh Maryam Rabiey , Ghaedi Maryam , Ashoori Fatemeh , Asadollahi Abdolrahim
Published: January 2024

Background

Needle stick injuries (NSI) can lead to dangerous infectious diseases for health care workers. This study aimed to determine the predictors of observance of safe injection guidelines in hospital nursing staff, based on protection motivation theory.

Methods

This cross-sectional study was conducted on the nursing staff of five randomly selected teaching and general hospitals of Shiraz University of Medical Sciences, Fars province, Iran, in 2021. Data were collected using a researcher-made questionnaire which was developed based on protection motivation theory. Data were processed and analyzed using SPSS 22 and Amos 24 at a significance level of  < 0.05. Pearson’s correlation coefficient, Multiple linear regression, and Structural Equation Modeling were used.

Results

The mean age of the participants (No = 280) was 32.5 ± 8.09 years. Most of the participants [80%] had encountered NSI, patients’ blood, or body fluids at least once. Protection motivation was the only predictor of protective behaviors (β = 0.573), while perceived efficacy (β = 0.142) and perceived rewards (β = -0.229) were the strongest predictors of motivation. The structural equation modeling analysis showed that standardized total effects of protection motivation, perceived response costs, rewards, and efficacy on the protective behaviors were 0.573, -0.159, -.104, and 0.81, respectively. While standardized total effects of perceived rewards, efficacy, and response cost on protection motivation were -0.229, 0.142, and -0.033, respectively. The model fit indices indicated the acceptable final model fit.

Conclusion

The results suggest that perceived efficacy, perceived effectiveness, and perceived rewards were the most important predictors of adherence to Safe Injection Guidelines in nursing staff.
Indian Model of Integrated Healthcare (IMIH): a conceptual framework for a coordinated referral system in resource-constrained settings
Authors: Mirza Moonis , Verma Madhur , Aggarwal Arun , Satpathy Sidhartha , Sahoo Soumya Swaroop , Kakkar Rakesh
Published: January 2024

Introduction

With the escalating burden of chronic disease and multimorbidity in India, owing to its ageing population and overwhelming health needs, the Indian Health care delivery System (HDS) is under constant pressure due to rising public expectations and ambitious new health goals. The three tired HDS should work in coherence to ensure continuity of care, which needs a coordinated referral system. This calls for optimising health care through Integrated care (IC). The existing IC models have been primarily developed and adopted in High-Income Countries. The present study attempts to review the applicability of existing IC models and frame a customised model for resource-constrained settings.

Methods

A two-stage methodology was used. Firstly, a narrative literature review was done to identify gaps in existing IC models, as per the World Health Organization framework approach. The literature search was done from electronic journal article databases, and relevant literature that reported conceptual and theoretical concepts of IC. Secondly, we conceptualised an IC concept according to India's existing HDS, validated by multiple rounds of brainstorming among co-authors. Further senior co-authors independently reviewed the conceptualised IC model as per national relevance.

Results

Existing IC models were categorised as individual, group and disease-specific, and population-based models. The limitations of having prolonged delivery time, focusing only on chronic diseases and being economically expensive to implement, along with requirement of completely restructuring and reorganising the existing HDS makes the adoption of existing IC models not feasible for India. The Indian Model of Integrated Healthcare (IMIH) model proposes three levels of integration: Macro, Meso, and Micro levels, using the existing HDS. The core components include a Central Gateway Control Room, using existing digital platforms at macro levels, a bucket overflow model at the meso level, a Triple-layered Concentric Circle outpatient department (OPD) design, and a three-door OPD concept at the micro level.

Conclusion

IMIH offers features that consider resource constraints and local context of LMICs while being economically viable. It envisages a step toward UHC by optimising existing resources and ensuring a continuum of care. However, health being a state subject, various socio-political and legal/administrative issues warrant further discussion before implementation.
Randomized controlled trial demonstrates novel tools to assess patient outcomes of Indigenous cultural safety training
Authors: Smylie Janet , Rotondi Michael A. , Filipenko Sam , Cox William T. L. , Smylie Diane , Ward Cheryl , Klopfer Kristina , Lofters Aisha K. , O’Neill Braden , Graham Melissa , Weber Linda , Damji Ali N. , Devine Patricia G. , Collins Jane , Hardy Billie-Jo
Published: January 2024

Background

Health care routinely fails Indigenous peoples and anti-Indigenous racism is common in clinical encounters. Clinical training programs aimed to enhance Indigenous cultural safety (ICS) rely on learner reported impact assessment even though clinician self-assessment is poorly correlated with observational or patient outcome reporting. We aimed to compare the clinical impacts of intensive and brief ICS training to control, and to assess the feasibility of ICS training evaluation tools, including unannounced Indigenous standardized patient (UISP) visits.

Method

Using a prospective parallel group three-arm randomized controlled trial design and masked standardized patients, we compared the clinical impacts of the intensive interactive, professionally facilitated, 8- to10-h Sanyas ICS training; a brief 1-h anti-bias training adapted to address anti-Indigenous bias; and control continuing medical education time-attention matched to the intensive training. Participants included 58 non-Indigenous staff physicians, resident physicians and nurse practitioners from family practice clinics, and one emergency department across four teaching hospitals in Toronto, Canada. Main outcome measures were the quality of care provided during UISP visits including adjusted odds that clinician would be recommended by the UISP to a friend or family member; mean item scores on patient experience of care measure; and clinical practice guideline adherence for NSAID renewal and pain assessment.

Results

Clinicians in the intensive or brief ICS groups had higher adjusted odds of being highly recommended to friends and family by standardized patients (OR 6.88, 95% CI 1.17 to 40.45 and OR 7.78, 95% CI 1.05 to 58.03, respectively). Adjusted mean item patient experience scores were 46% (95% CI 12% to 80%) and 40% (95% CI 2% to 78%) higher for clinicians enrolled in the intensive and brief training programs, respectively, compared to control. Small sample size precluded detection of training impacts on clinical practice guideline adherence; 100% of UISP visits were undetected by participating clinicians.

Conclusions

Patient-oriented evaluation design and tools including UISPs were demonstrated as feasible and effective. Results show potential impact of cultural safety training on patient recommendation of clinician and improved patient experience. A larger trial to further ascertain impact on clinical practice is needed.

Trial registration

Clinicaltrials.org NCT05890144. Retrospectively registered on June 5, 2023.
Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age
Authors: Seaton Gillian , Smith Hannah , Brancale Andrea , Westwell Andrew D. , Clarkson Richard
Published: January 2024

In the early 1990’s a group of unrelated genes were identified from the sites of recurring translocations in B-cell lymphomas. Despite sharing the nomenclature ‘Bcl’, and an association with blood-borne cancer, these genes have unrelated functions. Of these genes, BCL2 is best known as a key cancer target involved in the regulation of caspases and other cell viability mechanisms. BCL3 on the other hand was originally identified as a non-canonical regulator of NF-kB transcription factor pathways – a signaling mechanism associated with important cell outcomes including many of the hallmarks of cancer. Most of the early investigations into BCL3 function have since focused on its role in NF-kB mediated cell proliferation, inflammation/immunity and cancer. However, recent evidence is coming to light that this protein directly interacts with and modulates a number of other signaling pathways including DNA damage repair, WNT/β-catenin, AKT, TGFβ/SMAD3 and STAT3 – all of which have key roles in cancer development, metastatic progression and treatment of solid tumours. Here we review the direct evidence demonstrating BCL3’s central role in a transcriptional network of signaling pathways that modulate cancer biology and treatment response in a range of solid tumour types and propose common mechanisms of action of BCL3 which may be exploited in the future to target its oncogenic effects for patient benefit.
Mitigating role of financial inclusion on the perceived difficulties, concerns, and borrowing for medical expenses in Saudi Arabia
Authors: Al-Hanawi Mohammed Khaled , Al Rahahleh Naseem
Published: January 2024

Access to convenient quality healthcare at all times is considered a basic human right; however, many countries are still striving to achieve this goal for their populations. The persistent rise in healthcare expenditure remains a significant obstacle in achieving universal health coverage on a global scale. The aim of this study was to investigate the role of financial inclusion in addressing the financial hardship related to health and medical expense concerns in the Kingdom of Saudi Arabia. Probit models were applied to analyse nationally representative data from the Global Financial Inclusion (Global Findex) database. The results showed that financial inclusion had a significant impact on reducing the hardship associated with obtaining money for emergency expenses within 30 days as indicated by a significant coefficient of -0.262. Additionally, Financial inclusion substantially increases the likelihood of borrowing money for health or medical purposes in the past 12 months, with a coefficient of 0.585. Moreover, correlations were identified between low income levels and decreased likelihood of borrowing for health/medical purposes, increased difficulty in obtaining money for emergency expenses, and heightened concern regarding the ability to afford medical costs in the event of serious illness or accidents. These findings highlight the need for policy makers and health providers to prioritize financial inclusion and support programs for low-income individuals to achieve equity in health treatment for all in Saudi Arabia.
Extracellular vesicle therapy for obesity-induced NAFLD: a comprehensive review of current evidence
Authors: Zhang Jiali , Ma Baochen , Wang Zixu , Chen Yaoxing , Li Chengzhong , Dong Yulan
Published: January 2024

Non-alcoholic fatty liver disease (NAFLD) as a chronic disease especially in Western countries, is still a tough question in the clinical therapy. With the rising prevalence of various chronic diseases, liver transplantation is expected to be the most common therapy after the next 10 years. However, there is still no approved drug for NAFLD, and targeted therapy for NAFLD is urgent. Exosomes as a kind of extracellular vesicle are cell-derived nanovesicles, which play an essential role in intercellular communication. Due to complex cell–cell interactions in the liver, exosomes as therapeutic drugs or drug delivery vesicles may be involved in physiological or pathological processes in NAFLD. Compared with other nanomaterials, exosomes as a cell-free therapy, are not dependent on cell number limitation, which means can be administered safely in high doses. Apart from this, exosomes with the advantages of being low-toxic, high stability, and low-immunological are chosen for targeted therapy for many diseases. In this review, firstly we introduced the extracellular vesicles, including the biogenesis, composition, isolation and characterization, and fundamental function of extracellular vesicles. And then we discussed the modification of extracellular vesicles, cargo packing, and artificial exosomes. Finally, the extracellular vesicles for the therapies of NAFLD are summarized. Moreover, we highlight therapeutic approaches using exosomes in the clinical treatment of NAFLD, which provide valuable insights into targeting NAFLD in the clinical setting.

Graphical Abstract
The cell cycle, autophagy, and cell wall integrity pathway jointly governed by MoSwe1 in Magnaporthe oryzae
Authors: Li Lin , Zhu Xue-Ming , Bao Jian-Dong , Wang Jiao-Yu , Liu Xiao-Hong , Lin Fu-Cheng
Published: January 2024

The cell cycle is pivotal to cellular differentiation in plant pathogenic fungi. Cell wall integrity (CWI) signaling plays an essential role in coping with cell wall stress. Autophagy is a degradation process in which cells decompose their components to recover macromolecules and provide energy under stress conditions. However, the specific association between cell cycle, autophagy and CWI pathway remains unclear in model pathogenic fungi Magnaporthe oryzae. Here, we have identified MoSwe1 as the conserved component of the cell cycle in the rice blast fungus. We have found that MoSwe1 targets MoMps1, a conserved critical MAP kinase of the CWI pathway, through protein phosphorylation that positively regulates CWI signaling. The CWI pathway is abnormal in the ΔMoswe1 mutant with cell cycle arrest. In addition, we provided evidence that MoSwe1 positively regulates autophagy by interacting with MoAtg17 and MoAtg18, the core autophagy proteins. Moreover, the S phase initiation was earlier, the morphology of conidia and appressoria was abnormal, and septum formation and glycogen degradation were impaired in the ΔMoswe1 mutant. Our research defines that MoSWE1 regulation of G1/S transition, CWI pathway, and autophagy supports its specific requirement for appressorium development and virulence in plant pathogenic fungi.
cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation
Authors: Liu Jingwen , Zhou Jing , Luan Yuling , Li Xiaoying , Meng Xiangrui , Liao Wenhao , Tang Jianyuan , Wang Zheilei
Published: January 2024

Background

Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression and organ degeneration, but the mechanism and regulation of the crosstalk network remain unclear.

Main body of the abstract

Cellular stress disrupts mitochondrial homeostasis, facilitates the opening of mitochondrial permeability transition pore and the leakage of mitochondrial DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, and subsequently induces inflammasomes activation and the onset of pyroptosis. Meanwhile, the inflammasome-associated protein caspase-1, Gasdermin D, the CARD domain of ASC and the potassium channel are involved in regulating cGAS-STING pathway. Importantly, this crosstalk network has a cascade amplification effect that exacerbates the immuno-inflammatory response, worsening the pathological process of inflammatory and autoimmune diseases. Given the importance of this crosstalk network of cGAS-STING, inflammasomes and pyroptosis in the regulation of innate immunity, it is emerging as a new avenue to explore the mechanisms of multiple disease pathogenesis. Therefore, efforts to define strategies to selectively modulate cGAS-STING, inflammasomes and pyroptosis in different disease settings have been or are ongoing. In this review, we will describe how this mechanistic understanding is driving possible therapeutics targeting this crosstalk network, focusing on the interacting or regulatory proteins, pathways, and a regulatory mitochondrial hub between cGAS-STING, inflammasomes, and pyroptosis.

Short conclusion

This review aims to provide insight into the critical roles and regulatory mechanisms of the crosstalk network of cGAS-STING, inflammasomes and pyroptosis, and to highlight some promising directions for future research and intervention.
Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial
Authors: Olsen Thomas , Stolt Emma , Øvrebø Bente , Elshorbagy Amany , Tore Elena C. , Lee-Ødegård Sindre , Troensegaard Hannibal , Johannessen Hanna , Doeland Beate , Vo Anna A. D. , Dahl Anja F. , Svendsen Karianne , Thoresen Magne , Refsum Helga , Rising Russell , Barvíková Kristýna , van Greevenbroek Marleen , Kožich Viktor , Retterstøl Kjetil , Vinknes Kathrine J.
Published: January 2024

Background

Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity.

Methods

N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex.

Results

SAAR led to a ~ 20% greater weight loss compared to controls (β 95% CI − 1.14 (− 2.04, − 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated.

Conclusion

Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans.

Trial registration: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021,https://www.clinicaltrials.gov/study/NCT04701346
Autosomal dominant polycystic kidney disease with ectopic unilateral multicystic kidney: a case report
Authors: Amoah Yaw , Kyei Mathew Yamoah , Mensah James Edward , Palm Bridget , Adrah Henry Kwasi , Asiedu Isaac
Published: January 2024

Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder and the fourth cause of death of end-stage renal disease. The disease has a prevalence of 1:400–1:1000 accounting for 10% of patients on dialysis. In most ADPKD patients, bilateral kidneys are similarly affected, with numerous fluid-filled cysts arising from different nephron segments. Only a few cases of ADPKD with ectopic unilateral multicystic kidney have been reported. It has been observed that the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings especially when the ectopic kidney is dysplastic.

Case presentation

We report a case of a 46-year-old Ghanaian male patient who presented with left flank pain and hematuria with high BP and deranged renal function. Abdominal ultrasonography showed both kidneys to be larger than normal and had multiple cysts of varying sizes with the right kidney located in the right iliac fossa. Follow up Abdominopelvic computer tomographic scan (CT–Scan) without contrast showed enlarged kidneys with the renal parenchyma replaced by innumerable cyst of varying sizes. The right kidney was ectopically located in the right aspect of the pelvis. A diagnosis of ADPKD with right pelvic ectopic multicystic kidney was made. He was put on antihypertensives, analgesia for the left flank pain and to have follow up at the urology and nephrology departments.

Conclusion

In most ADPKD patients, bilateral kidneys are similarly affected. Only a few cases of ADPKD with ectopic unilateral multicystic kidney have been reported. It has been observed that the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings especially when the ectopic kidney is dysplastic.
Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes
Authors: Mooshage Christoph M. , Schimpfle Lukas , Tsilingiris Dimitrios , Kender Zoltan , Aziz-Safaie Taraneh , Hohmann Anja , Szendroedi Julia , Nawroth Peter , Sturm Volker , Heiland Sabine , Bendszus Martin , Kopf Stefan , Jende Johann M. E. , Kurz Felix T.
Published: January 2024

Background

Previous studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC).

Methods

3-T MRN of the right sciatic nerve at thigh level was performed in 14 HC, 10 patients with T1D (3 with diabetic neuropathy), and 28 patients with T2D (10 with diabetic neuropathy). Results were subsequently correlated with clinical and electrophysiological data.

Results

The sciatic nerve’s MTR was lower in patients with T2D (0.211 ± 0.07, mean ± standard deviation) compared to patients with T1D (T1D 0.285 ± 0.03; p = 0.015) and HC (0.269 ± 0.05; p = 0.039). In patients with T1D, sciatic MTR correlated positively with tibial nerve conduction velocity (NCV; r = 0.71; p = 0.021) and negatively with hemoglobin A1c (r =  − 0.63; p < 0.050). In patients with T2D, we found negative correlations of sciatic nerve’s MTR peroneal NCV (r =  − 0.44; p = 0.031) which remained significant after partial correlation analysis controlled for age and body mass index (r = 0.51; p = 0.016).

Conclusions

Lower MTR values of the sciatic nerve in T2D compared to T1D and HC and diametrical correlations of MTR values with NCV in T1D and T2D indicate that there are different macromolecular changes and pathophysiological pathways underlying the development of neuropathic nerve damage in T1D and T2D.

Trial registration

https://classic.clinicaltrials.gov/ct2/show/NCT03022721. 16 January 2017.

Relevance statement

Magnetization transfer ratio imaging may serve as a non-invasive imaging method to monitor the diseases progress and to encode the pathophysiology of nerve damage in patients with type 1 and type 2 diabetes.

Key points

• Magnetization transfer imaging detects distinct macromolecular nerve lesion patterns in diabetes patients.

• Magnetization transfer ratio was lower in type 2 diabetes compared to type 1 diabetes.

• Different pathophysiological mechanisms drive nerve damage in type 1 and 2 diabetes.

Graphical Abstract
Patient, health professional and psychiatrist satisfaction with emergency department telepsychiatry during the COVID-19 pandemic: a pilot study
Authors: Dugas Erika N. , Bouhamdani Nadia , Poirier Martine , Lang Rino , Robichaud Martin , Aube-Pinet Julie , Godin Stéphane
Published: January 2024

Background

Emergency department telepsychiatry (EDTP) can improve healthcare delivery. However, no studies document implementation and overall satisfaction within the Canadian pandemic context. The objectives of this study were to (i) describe barriers associated with EDTP; and (ii) assess patients’, ED health professionals’, and psychiatrists’ perceived satisfaction with EDTP during the COVID-19 pandemic. Data were collected in three New Brunswick hospitals over 8-weeks in 2021. Psychiatrists (n = 6) completed a self-report questionnaire following each EDTP consultation, patients (n = 58) completed a telephone-administered questionnaire 1-week post EDTP consultation, and ED health professionals (n = 31) completed a single self-report questionnaire at the end of the study period.

Results

One-third of psychiatrists and two-thirds of ED health professionals encountered a barrier, respectively. The most common barriers related to problems linked to sound/video/connection, lack of experience and guidelines, or increased workload. Despite these barriers, high levels of satisfaction were reported by patients and psychiatrists (mean satisfaction score (sd): 4.2 (0.6) and 4.8 (0.4), respectively). ED health professionals reported lower satisfaction scores; however, most believed that EDTP was associated with healthcare delivery advantages.

Conclusions

These findings indicate moderate to high EDTP satisfaction. Additional training, guidelines, and change management strategies may be necessary to insure harmonious EDTP implementation for all health professionals.
Exploring the support needs of young adult caregivers, their issues, and preferences towards a web-based tool: a mixed-method study
Authors: Dang Srishti , Looijmans Anne , Sharma Nikita , Jansen Annemarie Braakman , Hagedoorn Mariët
Published: January 2024

Background

Young adult caregivers (YACs, aged 18–25) who take care of a loved one may juggle between caregiving responsibilities and other life areas such as education and social life, leading to an imbalance in their lives. The web-based tool ‘MantelzorgBalans’ aims to support informal caregivers (ICGs) in balancing caregiving tasks and activities in other life areas. However, this tool was designed to support ICGs of loved ones receiving palliative care and is not yet tailored to the needs of YACs. In order to do so, in this study we aim to explore (i) challenges and support needs of YACs in caregiving, (ii) their needs towards the content of the ‘MantelzorgBalans’ tool, and (iii) issues they encountered in using the tool and their preferences for adaptation of the tool.

Method

We conducted semi-structured interviews and usability testing with 13 student YACs in the Netherlands. Within usability testing, we used three approaches: (i) a thinking-aloud approach (verbalizing thoughts while using the tool), (ii) a task-based performance approach (scoring task completion rate), and (iii) questionnaires. We used thematic analysis to synthesize the qualitative data. For the quantitative data, we calculated frequencies and mean scores.

Results

Our findings suggest that the majority of YACs faced challenges in balancing caregiving with life areas such as education and social life. They needed support from healthcare professionals who could listen to them without judging them. With respect to the MantelzorgBalans tool, YACs needed more information on how to provide emotional support to their loved one and the emotional support that is available for them. In regards to the aesthetics, they preferred bright colours and more visuals in the tool. Overall, they were satisfied with the information presented in the tool, but they were neutral in their willingness to use it in the future.

Conclusion

From this study, we learn that YACs may experience specific challenges and needs in general, and towards a web-based tool in specific. In the near future, it will be important to develop digital tools to support YACs that match their specific needs. This may enable healthcare professionals to offer targeted and personalized digital support to YACs in future.
From Klinefelter Syndrome to High Grade Aneuploidies: Expanding the Gene-dosage Effect of Supernumerary X Chromosomes
Authors: Spaziani Matteo , Carlomagno Francesco , Tarantino Chiara , Angelini Francesco , Paparella Roberto , Tarani Luigi , Putotto Carolina , Badagliacca Roberto , Pozza Carlotta , Isidori Andrea M , Gianfrilli Daniele
Published: January 2024

Objective

High-grade aneuploidies of X and Y sex chromosomes (HGAs) are exceedingly rare and complex conditions. We aimed to investigate the effect of supernumerary X chromosomes (extra-Xs) on the clinical, hormonal, metabolic, and echocardiographic features of patients with HGAs.

Design and Methods

In a cross-sectional study, we compared 23 subjects with HGAs and 46 age-matched subjects with 47,XXY Klinefelter syndrome (KS), according to the number of extra-Xs: two (47,XXY and 48,XXYY), three (48,XXXY and 49,XXXYY), or four supernumerary Xs (49,XXXXY). A second cohort consisting of 46 pubertal stage-matched KS subjects was employed for validation. Clinical, hormonal, metabolic and ultrasonographic parameters were collected and analyzed.

Results

The increase in the number of extra-Xs was associated with a progressive adverse effect on height, pubertal development, testicular volume and function, adrenal steroidogenesis, and thyroid function. A progressive linear increase in ACTH and a decrease in cortisol/ACTH ratios were found. Weight and body mass index, Sertoli cell function, lipid profile, and glucose tolerance post-oral glucose tolerance test were all worse in the HGA cohort compared to KS. Cardiac evaluation revealed a linear association with reduced left and right end-diastolic diameters and reduced ejection fraction.

Conclusion

The increase in the number of extra-Xs is associated with a “dose-dependent” progressive impairment in steroid producing glands, thyroid function, cardiac structure, and performance.
Seismic soil structure interaction of navigation locks
Authors: Μαλτίδης Γεώργιος
Published: January 2024

Αντικείμενο αυτής της εργασίας είναι η διερεύνηση της σεισμικής συμπεριφοράς υδραυλικών κατασκευών σκυροδέματος λαμβάνοντας υπόψη την αλληλεπίδραση εδάφους-κατασκευής και ρευστού-κατασκευής με έμφαση στις κλεισιάδες πλοήγησης. Το αντικείμενο αυτής της διατριβής είναι να επαληθεύσει μέσω αναλύσεων πεπερασμένων στοιχείων και να επεκτείνει περαιτέρω τις υπάρχουσες θεωρίες που αναφέρονται στις δυναμικές πιέσεις εδάφους και ρευστού και να δώσει περαιτέρω χρήσιμες πληροφορίες για τον σωστό σχεδιασμό ενσωματωμένων στο έδαφος κατασκευών σε σχέση με την αντισεισμική ασφάλεια. Το πρώτο κεφάλαιο περιγράφει το προς επίλυση πρόβλημα, εισάγει το πεδίο της έρευνας στον αναγνώστη και θέτει τους στόχους αυτής της εργασίας. Το δεύτερο και το τρίτο κεφάλαιο αποτελούν τη βιβλιογραφική έρευνα για αυτό το θέμα. Στα κεφάλαια αυτά συλλέγονται πληροφορίες σχετικά με τη δυναμική συμπεριφορά των υδραυλικών κατασκευών από σκυρόδεμα, επικεντρώνοντας: 1. Στις υδροδυναμικές πιέσεις σε κατασκευές 2. Στις δυναμικές πιέσεις εδάφους στις κατασκευές 3. Στη δυναμική συμπεριφορά κατασκευών με αλληλεπίδραση εδάφους-κατασκευής. Το τέταρτο και το πέμπτο κεφάλαιο περιγράφουν τα μοντέλα πεπερασμένων στοιχείων που χρησιμοποιήθηκαν για την αναφερόμενη έρευνα. Εδώ, συζητούνται οι έννοιες και οι υποθέσεις μοντελοποίησης και γίνονται παραμετρικές μελέτες. Αυτά τα κεφάλαια στοχεύουν στην επαλήθευση της ορθότητας του θεωρητικού υποβάθρου και στην επέκταση του για περιπτώσεις όπου μια αναλυτική λύση είναι δύσκολο να βρεθεί. Το τέταρτο κεφάλαιο πραγματεύεται την υδροδυναμικές πίέσεις συστημάτων εδάφους-νερού-κατασκευής και το πέμπτο κεφάλαιο με δυναμικές πιέσεις εδάφους συστημάτων εδαφους-κατασκευής. Το έκτο κεφάλαιο διαφέρει από τα δύο προηγούμενα κεφάλαια και διερευνά ένα άλλο θέμα της αριθμητικής ανάλυσης για την αλληλεπίδραση εδάφους-κατασκευής, αυτό των συνοριακών συνθηκών του αριθμητικού μοντέλου. Για ενσωματωμένες στο έδαφος κατασκευές ή για γενικά προβλήματα αλληλεπίδρασης εδάφους-κατασκευής, όπου το αριθμητικό μοντέλο πρέπει να περιλαμβάνει το έδαφος, οι συνοριακές συνθήκες, που δίνονται στο μοντέλο μπορούν να επηρεάσουν δραματικά τη διάδοση των (σεισμικών) κυμάτων και επομένως εφαρμόζεται εσφαλμένη χονοϊστορία επιτάχυνσης στην κατασκευή. Αυτό το κεφάλαιο συγκρίνει τις αποκρίσεις των μοντέλων χρησιμοποιώντας τις πιο κοινές συνοριακές συνθήκες μετην προβλεπόμενη απόκριση της μονοδιάστατης διάδοσης κύματος.Το έβδομο κεφάλαιο παρουσιάζει δύο παραδείγματα σεισμικής ανάλυσης κλεισιάδων πλοήγησης. Η πρώτη κλεισιάδα πλοήγησης έχει ως τοιχώματα του θαλάμου τοίχους αντιστήριξης βαρύτητας και η δεύτερη έχει θάλαμο σε διατομή πλαισίου σχήματος U. Αυτό το κεφάλαιο στοχεύει στην επικύρωση των ευρημάτων του τρίτου και τέταρτου κεφαλαίου. Το όγδοο και τελευταίο κεφάλαιο συνοψίζει τα συμπεράσματα που εξάγονται από αυτήν την αριθμητική έρευνα και υποδεικνύει ορισμένα θέματα για περαιτέρω διερεύνηση.
Το αρχαίο δράμα ως θεραπευτικό μέσο: Οι θεατρικές παραστάσεις από νοσηλευόμενους του Δρομοκαΐτειου Θεραπευτηρίου τη δεκαετία του 1960
Authors: Μποσταντζής Τριαντάφυλλος
Published: January 2024

Τη δεκαετία του 1960 εφαρμόστηκε στο Δρομοκαΐτειο Ψυχιατρικό Νοσοκομείο από τον ψυχίατρο Γιώργο Λυκέτσο μια πρωτοποριακή μέθοδος ομαδικής ψυχοθεραπείας βασισμένη στο αρχαίο δράμα. Κατά τη διάρκεια της θεραπευτικής αυτής διαδικασίας, οι τρόφιμοι του ιδρύματος που συμμετείχαν διδάσκονταν έργα αρχαίου δράματος και λάμβαναν ενεργά μέρος σε πρόβες που αποσκοπούσαν στην παρουσίαση παραστάσεων αρχαίων τραγωδιών (και όχι μόνο). Στο παρόν άρθρο επιχειρείται η σκιαγράφηση της ψυχοθεραπευτικής μεθόδου που ακολουθήθηκε από τον Λυκέτσο από το 1960 έως το 1965, με ιδιαίτερη αναφορά στην παράσταση των Ευμενίδων του Αισχύλου το 1965, που δόθηκε στο αρχαιοπρεπές θεατράκι του θεραπευτηρίου και στην οποία συμμετείχαν ως ηθοποιοί μακροχρόνια νοσηλευόμενοι του Δρομοκαΐτειου. Επιπλέον, στο άρθρο γίνεται προσπάθεια προσδιορισμού της «μεθόδου Λυκέτσου» σε σχέση με το ευρύτερο πεδίο της δραματοθεραπείας, αλλά και ιχνηλάτηση τυχόν εκλεκτικών συγγενειών της με το «ψυχόδραμα» του Jacob Moreno.