Background/Objectives: As musculoskeletal injuries in gastroenterologists related to the performance of endoscopic procedures are on the rise, solutions and new approaches are needed to prevent these undesired outcomes. In our study, we evaluated an approach to ergonomic challenges in the form of a belt-like endoscope holder designed to redistribute the weight of the endoscope across the whole body of the practitioner. The aim of the study was to determine how the use of this holder affected the body posture of practitioners during endoscopy. Methods: We designed a special endoscopic model that emulates basic endoscopic movement and maneuvers. With the use of the MoCap camera system, we recorded experienced endoscopists exercising a standardized set of tasks with and without the holder. Results: Following video and statistical analyses, the most significant differences were observed in the position of the left arm which pointed to a more relaxed arm position. Conclusions: The ergonomic benefits of the belt holder in this model merit testing in the clinical setting to evaluate its effectiveness and prevention of musculoskeletal injuries in GI endoscopy.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: There is no consensus regarding the indication for postoperative radiotherapy (PORT) for T1- and T2-classified squamous cell carcinoma (SCC) of the external auditory canal (EAC) even with negative surgical margins. This study aimed to evaluate whether PORT provides additional benefits for these cases. METHODS: We collected retrospective data from fourteen international hospitals, including resected pT1- and pT2-classified EAC SCC with negative surgical margins. RESULTS: A total of 112 early-stage radically resected EAC SCC were included, with 48 patients receiving PORT. The 5-year DFS of T1- and T2-classified EAC SCC treated with PORT was not statistically significantly different (92.9% and 76.9%, respectively) compared to the group treated without PORT (100% and 90.9%, respectively; p-values of 0.999 and 0.526, respectively). EAC SCC treated with PORT more frequently exhibited perineural and angioinvasive growth. Eighteen patients experienced side effects related to radiotherapy, of which one patient developed osteoradionecrosis. CONCLUSIONS: Our study suggests that PORT for early-stage radically resected EAC SCC should only be considered in selected cases with perineural, infiltrative growth or angioinvasive growth, and with a close margin. This approach helps mitigate the negative impact on quality of life and the risk of side effects associated with radiotherapy.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Loneliness, a major public health concern, could be alleviated through social interventions with nature contact as a primary component. "Friends in Nature" is a complex nature-based social intervention designed to be implemented as part of "Reimagining Environments for Connection and Engagement: Testing Actions for Social Prescribing in Natural Spaces" (RECETAS). This project aims to alleviate loneliness and promote health-related quality of life in six different geographic areas worldwide. Feasibility studies are crucial to assess the viability of complex interventions and study procedures before conducting definitive studies. This paper aims to describe the design, implementation, and evaluation of the six-related feasibility studies on the "Friends in Nature" intervention. These studies specifically evaluate feasibility of recruitment and study procedures, intervention implementation, and data collection and distribution. METHODS: We defined a comprehensive set of indicators to assess the feasibility of "Friends in Nature." For the first domain, recruitment procedures were assessed to determine their adequacy, while attrition rates were examined to assess participant retention. For the second domain, the implementation of interventions was evaluated, along with the study design's ability to adapt to unexpected situations and participant adherence to the intervention. Finally, for the third domain, completion rates and the acceptability of the study activities were also analyzed. The feasibility of using specific scales to assess loneliness and well-being was also explored. RESULTS: The feasibility indicators defined for this study were useful to assess the feasibility of "Friends in Nature." Recruitment procedures were generally found to be adequate, and the number of dropouts was low. Interventions were implemented with minor adjustments, and facilitators played a vital role in the well-functioning of the interventions. Although some unexpected situations occurred during the study, adaptations were made, and participants were generally satisfied with the activities proposed. Scales used to assess loneliness and quality of life showed potential for measuring the effects of nature-based social prescribing in the full trial. CONCLUSION: This paper offers valuable insights into the design and execution of feasibility studies for complex interventions like "Friends in Nature." Findings from these assessments explore the feasibility of "Friends in Nature" and will inform the main RECETAS studies, which are designed to strengthen the evidence base to support the use of nature-based social prescribing to reduce loneliness and promote quality of life. TRIAL REGISTRATION: Barcelona trial: NCT05488496, Prague trial: NCT05522140, and Helsinki trial: NCT05507684.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Among inherited cardiomyopathies involving the left ventricle, whether dilated or not, certain genotypes carry a well-established arrhythmic risk, notably manifested as sustained monomorphic ventricular tachycardia (SMVT). Nonetheless, the precise localization and electrophysiological profile of this substrate remain undisclosed across different genotypes. METHODS: Patients diagnosed with cardiomyopathy and left ventricle involvement due to high-risk genetic variants and SMVT treated by electrophysiological study were recruited from 18 European/US centers. Electrophysiological study, imaging, and outcomes data after ablation were assessed in relation to genotype. RESULTS: Seventy-one patients were included (49.6 Q1-Q3 [40-60] years, 76% men). They were divided into 4 groups according to the affected protein: desmosomal (DSP, PKP2, DSG2, and DSC2), nuclear membrane (LMNA and TMEM43), cytoskeleton (FLNC and DES), and sarcoplasmic reticulum (PLN). Desmosomal genes, TMEM43, and PLN were associated with biventricular disease, while variants in LMNA and cytoskeleton genes had predominant left ventricle involvement (P=0.001). The location of the clinical-SMVT substrate was significantly different based on genotype (P=0.005). DSP and cytoskeleton genes presented SMVTs with right bundle branch block morphology, which origin was identified in the inferolateral segments of the left ventricle. The other desmosomal genes (PKP2 and DSG2), along with TMEM43, showed SMVTs with left bundle branch block morphology and predominantly right ventricular substrate. In contrast, LMNA substrate was mainly observed in the interventricular septum. During a median of 26 Q1-Q3 (10.6-65) months, 27% of patients experienced recurrences of clinical SMVT with differences between genotypes (log-rank 0.016). Nuclear membrane genes demonstrated the highest recurrence rate compared with desmosomal genes (hazard ratio, 4.56 [95% CI, 1.5-13.8]). CONCLUSIONS: The anatomic substrate of SMVTs shows a strong correlation with the underlying genotype, electrocardiographic morphology, and recurrence rate. Particularly, patients with nuclear membrane gene variants have a significantly higher recurrence rate compared with those with desmosomal gene variants.
- MeSH
- akční potenciály MeSH
- dospělí MeSH
- elektrofyziologické techniky kardiologické MeSH
- fenotyp * MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie MeSH
- genotyp MeSH
- hodnocení rizik MeSH
- kardiomyopatie genetika patofyziologie diagnóza MeSH
- katetrizační ablace MeSH
- komorová tachykardie * genetika patofyziologie diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- rizikové faktory MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Geografické názvy
- Evropa MeSH
Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy.
- MeSH
- autoimunita * MeSH
- hojení ran * imunologie MeSH
- interleukin-6 * metabolismus imunologie MeSH
- lidé MeSH
- nádorové mikroprostředí * imunologie MeSH
- nádory * imunologie metabolismus patologie MeSH
- stárnutí * imunologie MeSH
- zánět * imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Understanding environmental correlates of sedentary behaviour (SB) among young people is important as such data can identify approaches to limit sedentary time. This paper estimates associations of parent-reported neighbourhood and adolescent-reported home environments with SB among adolescents aged 11-19 years from 14 countries. METHODS: In the International Physical activity and the Environment Network (IPEN) Adolescent Study (an observational, cross-sectional multi-country study), adolescents wore a triaxial accelerometer for seven days that assessed sedentary time (ST). Adolescents completed survey measures of sedentary behaviour (SB) related to recreational screen time and sitting time in motor vehicles. Parents and adolescents completed surveys assessing neighbourhood and home environments. Accelerometer based ST was available in 3,982 adolescents while survey data were available for 6,302 dyads. We estimated the total and direct effects of each environmental attribute on ST and SB. Sex of the adolescent and city/country were examined as moderators. RESULTS: The average ST in adolescents from 14 countries ranged from 7.8 to 10.5 h/day. Personal social media was the only significant correlate of total ST across both sexes. With respect to self-reported SB, adolescents accumulated an average of 3.8 h of non-school screen time per day and nearly 40 min of transport-related sitting time. Screen time was associated with all home environment variables, including social media account, as well as land use mix-diversity, traffic safety, and crime safety. Transport-related sitting time was related to land use mix-diversity, recreation facilities, walking facilities, and pedestrian infrastructure, but no home environment variables. City/country and sex were significant moderators of several associations. CONCLUSIONS: Both home and neighbourhood environment features were related to ST and SB. Having social media accounts emerged as a major contributor towards sedentarism in adolescents.
- MeSH
- akcelerometrie MeSH
- čas strávený před obrazovkou MeSH
- charakteristiky bydlení * MeSH
- chování mladistvých MeSH
- cvičení MeSH
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- rodiče MeSH
- sedavý životní styl * MeSH
- sociální média MeSH
- životní prostředí - projekt MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
Achondroplasia is the most common form of human dwarfism caused by mutations in the FGFR3 receptor tyrosine kinase. Current therapy begins at 2 years of age and improves longitudinal growth but does not address the cranial malformations including midface hypoplasia and foramen magnum stenosis, which lead to significant otolaryngeal and neurologic compromise. A recent clinical trial found partial restoration of cranial defects with therapy starting at 3 months of age, but results are still inconclusive. The benefits of achondroplasia therapy are therefore controversial, increasing skepticism among the medical community and patients. We used a mouse model of achondroplasia to test treatment protocols aligned with human studies. Early postnatal treatment (from day 1) was compared with late postnatal treatment (from day 4, equivalent to ~5 months in humans). Animals were treated with the FGFR3 inhibitor infigratinib and the effect on skeleton was thoroughly examined. We show that premature fusion of the skull base synchondroses occurs immediately after birth and leads to defective cranial development and foramen magnum stenosis in the mouse model to achondroplasia. This phenotype appears significantly restored by early infigratinib administration when compared with late treatment, which provides weak to no rescue. In contrast, the long bone growth is similarly improved by both early and late protocols. We provide clear evidence that immediate postnatal therapy is critical for normalization of skeletal growth in both the cranial base and long bones and the prevention of sequelae associated with achondroplasia. We also describe the limitations of early postnatal therapy, providing a paradigm-shifting argument for the development of prenatal therapy for achondroplasia.
- MeSH
- achondroplazie * patologie farmakoterapie MeSH
- lebka patologie účinky léků MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- myši MeSH
- receptor fibroblastových růstových faktorů, typ 3 * genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Penile squamous cell carcinoma (pSCC) is a rare tumour with a variable prognosis. More prognostic markers linked to mutational signatures and the tumour immune microenvironment are needed. A cohort made up of 165 invasive pSCC was retrospectively analysed using formalin-fixed, paraffin-embedded tumour tissue, focusing on tumour mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the number of tumour infiltrating lymphocytes (TILs) expressing cytotoxic T-lymphocyte-associated protein 4 (CTLA4), HPV status determined by p16 immunohistochemistry, and several traditional histopathological variables. High TMB (>10 mut/Mb) was associated with high PD-L1 expression (TPS 50-100%), and HPV-negative status. High PD-L1 expression was linked to HPV negativity, a high number of intratumoural CTLA4+ cells, and brisk lymphocytic infiltrate. High TMB was a significant predictor of shorter overall survival (OS) in both univariate and multivariate analysis when using a median cut-off value of 4.3 mut/Mb, but not when using an arbitrary cut-off of 10 mut/Mb. Low CTLA4+ cell infiltration at the tumour invasion front was a marker of shorter OS and cancer-specific survival in both univariate and multivariate analysis. PD-L1 expression had no significant impact on prognosis. Only two cases were MSI high. The results support the hypothesis of two aetiological pathways in pSCC cancerogenesis: (1) SCC linked to HPV infection characterised by low TMB, less common PD-L1 expression, and a lower number of TILs; and (2) SCC linked to chronic inflammation leading to a high number of acquired mutations (high TMB), HPV negativity, increased neoantigen production (i.e., PD-L1), and high immune cell infiltration.
- MeSH
- antigen CTLA-4 MeSH
- antigeny CD274 metabolismus MeSH
- infekce papilomavirem * komplikace MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory penisu * genetika MeSH
- retrospektivní studie MeSH
- spinocelulární karcinom * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Eryptosis is a regulated cell death (RCD) of mature erythrocytes initially described as a counterpart of apoptosis for enucleated cells. However, over the recent years, a growing number of studies have emphasized certain differences between both cell death modalities. In this review paper, we underline the hallmarks of eryptosis and apoptosis and highlight resemblances and dissimilarities between both RCDs. We summarize and critically discuss differences in the impact of caspase-3, Ca2+ signaling, ROS signaling pathways, opposing roles of casein kinase 1α, protein kinase C, Janus kinase 3, cyclin-dependent kinase 4, and AMP-activated protein kinase to highlight a certain degree of divergence between apoptosis and eryptosis. This review emphasizes the crucial importance of further studies that focus on deepening our knowledge of cell death machinery and identifying novel differences between cell death of nucleated and enucleated cells. This might provide evidence that erythrocytes can be defined as viable entities capable of programmed cell destruction. Additionally, the revealed cell type-specific patterns in cell death can facilitate the development of cell death-modulating therapeutic agents.
