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Outdoor programs involving recreational physical challenges are becoming increasingly popular for training and development purposes among adults, but rigorous studies investigating their effectiveness remain scarce. A randomized controlled trial was conducted to evaluate the effects of an outdoor adventure-based program on measures of self-efficacy, resilience, risk-taking propensity, and perceived stress. Participants were randomly assigned either to an intervention condition (half-day high ropes course) or a wait-list control group. Measures were taken at baseline and four days post-intervention and on the day to measure intervention perceptions. Significant increases in self-efficacy and risk-taking propensity were observed for the intervention arm compared to the control arm. Greater intervention engagement and affective valence ratings were associated with self-efficacy change. These findings highlight the practical relevance of adventure-based experiences for organizations and educational institutions seeking to enhance young adults' self-confidence. Additionally, they emphasize the importance of tailoring interventions to individual needs and ensuring positive participant experiences to achieve desired outcomes.
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Recreación , Asunción de Riesgos , Autoeficacia , Humanos , Masculino , Femenino , Adulto Joven , Recreación/psicología , Adulto , Estrés Psicológico/psicología , Resiliencia Psicológica , AdolescenteRESUMEN
Although greater lifetime stressor exposure has been associated with physical and mental health issues in the general population, relatively little is known about how lifetime stressors impact the physical and mental health of elite athletes or the factors moderating this association. Given that many elite athletes show signs of perfectionism, and that this trait has been linked with ill-health, it is possible that perfectionism may moderate the lifetime stressor-health relationship. To test this possibility, we examined how cumulative lifetime stressor exposure was associated with general mental and physical health complaints in elite athletes, and the extent to which these associations were moderated by perfectionism. Participants were 110 elite athletes (64 female; M age = 29.98 years, SD = 10.54) who completed assessments of lifetime stressor exposure, physical health, psychological distress, and perfectionism. As hypothesised, hierarchical regression analyses revealed that experiencing more severe lifetime stressors was related to poorer physical and mental health. Furthermore, self-oriented perfectionism moderated the association between lifetime stressor count and severity and physical health, but not mental health. Overall, these data demonstrate stressor-specific effects among elite athletes and highlight the potential importance of assessing lifetime stressor exposure and perfectionistic tendencies in order to improve athlete health and well-being.
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Food digestion is important for human health. Advances have been made using in vitro models to study food digestion, but there is considerable potential for numerical approaches in stomach modeling, as they can provide a comprehensive understanding of the complex flow and chemistry in the stomach. The focus of this study is to provide a concise review of the developed numerical stomach models over the past two decades. The gastric physiological parameters that are required for a computational model to represent the human gastric digestion process are discussed, including the stomach geometry, gastric motility, gastric emptying, and gastric secretions. Computational methods used to model gastric digestion are introduced and compared, including different computational fluid dynamics as well as solid mechanics methods. The challenges and limitations of current studies are discussed, as well as the areas for future research that need to be addressed. There has been progress in simulating gastric fluid flow with stomach wall motion, but much work remains to be done. The complex food breakdown mechanisms and a comprehensive chemical digestion process have not been implemented in any developed models. Numerical method that was once computationally expensive will be revolutionized as computing power continues to improve. Ultimately, the advancement of modeling of gastric food digestion will allow for additional hypothesis testing to streamline the development of food products that are beneficial to human health.
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Digestión , Vaciamiento Gástrico , Modelos Biológicos , Estómago , Digestión/fisiología , Humanos , Estómago/fisiología , Vaciamiento Gástrico/fisiología , Simulación por Computador , HidrodinámicaRESUMEN
Biological invasions are of special conservation concern in the Iberian Peninsula and other regions with high levels of endemism. Environmental variability, such as the seasonal fluctuations of Mediterranean streams, is a key factor that affects the spread of aquatic species in novel habitats. Fish parasites have a great potential to reflect such changes in the habitat features of freshwater ecosystems. The aim of this study consisted of seasonally analysing the health status and parasitological traits of non-native fish in Iberian waters. In particular, a strongly invasive population of Languedoc minnow Phoxinus septimaniae (leuciscid species native to south-east France) was assessed in Tordera Stream (north-eastern Iberian Peninsula, Mediterranean conditions). Fish were sampled in April, July, and October 2023 by electrofishing. Health status (external/internal organs) was significantly better in autumn (HAI = 28.8) than spring (HAI = 35.6). Life-cycle complexity was higher in spring (LCI = 1.98), whereas parasite abundance and Shannon diversity were significantly lower in autumn (TA = 19.6 and H' = 2.15, respectively). In October (more 'benign' environmental conditions in Iberian streams), minnows could display elevated foraging activity, with fish increasing their health condition and level of parasite resistance/tolerance. Overall results showed a particular seasonal profile of health and parasite infra-communities that allow this minnow species to thrive under highly fluctuating habitat conditions. This information could help environmental managers to control non-native fish in Mediterranean streams.
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Loss-of-function (LoF) variants in the filaggrin (FLG) gene are the strongest known genetic risk factor for atopic dermatitis (AD), but the impact of these variants on AD outcomes is poorly understood. We comprehensively identified genetic variants through targeted region sequencing of FLG in children participating in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort. Twenty FLG LoF variants were identified, including 1 novel variant and 9 variants not previously associated with AD. FLG LoF variants were found in the cohort. Among these children, the presence of 1 or more FLG LoF variants was associated with moderate/severe AD compared with those with mild AD. Children with FLG LoF variants had a higher SCORing for Atopic Dermatitis (SCORAD) and higher likelihood of food allergy within the first 2.5 years of life. LoF variants were associated with higher transepidermal water loss (TEWL) in both lesional and nonlesional skin. Collectively, our study identifies established and potentially novel AD-associated FLG LoF variants and associates FLG LoF variants with higher TEWL in lesional and nonlesional skin.
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Dermatitis Atópica , Proteínas Filagrina , Proteínas de Filamentos Intermediarios , Mutación con Pérdida de Función , Fenotipo , Dermatitis Atópica/genética , Dermatitis Atópica/patología , Humanos , Masculino , Femenino , Preescolar , Estudios Prospectivos , Lactante , Proteínas de Filamentos Intermediarios/genética , Predisposición Genética a la Enfermedad , Niño , Hipersensibilidad a los Alimentos/genéticaRESUMEN
Background Perforated peptic ulcer disease has a high mortality rate, and there is consensus regarding the use of antifungals in the management of immunocompromised patients; however, there is variability in the utilization of antifungals in the non-immunocompromised cohort. This study aims to describe the current practice related to the use of antifungals in perforated peptic ulcer disease in Western Australia and to determine the peri-operative morbidity and mortality in the immunocompromised and non-immunocompromised cohort receiving antifungals. Methods Medical records of patients who underwent surgical repair of perforated peptic ulcer in all Western Australian tertiary hospitals between January 1, 2010, and December 31, 2017, were reviewed retrospectively. Data regarding pre-operative patient factors such as age, gender, and comorbidities, post-operative outcomes such as intra-abdominal sepsis/bleeding, peri-operative antifungal prescription, and abundance of fungal growth on intra-operative samples were collected. Results The study included 359 patients. The antifungal prescription was variable. An American Society of Anesthesiologists (ASA) score of 3 or more, presence of pre-operative shock and acidosis, and level of abundance of fungal growth on intra-operative samples were associated with antifungal prescription. Amongst the non-immunocompromised cohort, receiving antifungals was associated with higher morbidity. Conclusion The use of antifungals for patients with perforated peptic ulcer disease was variable. An ASA score of 3 or greater and pre-operative shock and acidosis are pre-operative factors predisposing patients to receiving antifungals. There was no difference in morbidity or mortality amongst immunocompromised patients regardless of antifungal prescription or non-prescription. However, in the non-immunocompromised cohort, those who received antifungals had a higher morbidity compared to those who did not.
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Forecasting large earthquakes along active faults is of critical importance for seismic hazard assessment. Statistical models of recurrence intervals based on compilations of paleoseismic data provide a forecasting tool. Here we compare five models and use Bayesian model-averaging to produce time-dependent, probabilistic forecasts of large earthquakes along 93 fault segments worldwide. This approach allows better use of the measurement errors associated with paleoseismic records and accounts for the uncertainty around model choice. Our results indicate that although the majority of fault segments (65/93) in the catalogue favour a single best model, 28 benefit from a model-averaging approach. We provide earthquake rupture probabilities for the next 50 years and forecast the occurrence times of the next rupture for all the fault segments. Our findings suggest that there is no universal model for large earthquake recurrence, and an ensemble forecasting approach is desirable when dealing with paleoseismic records with few data points and large measurement errors.
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The combination of urbanization and global warming leads to urban overheating and compounds the frequency and intensity of extreme heat events due to climate change. Yet, the risk of urban overheating can be mitigated by urban green-blue-grey infrastructure (GBGI), such as parks, wetlands, and engineered greening, which have the potential to effectively reduce summer air temperatures. Despite many reviews, the evidence bases on quantified GBGI cooling benefits remains partial and the practical recommendations for implementation are unclear. This systematic literature review synthesizes the evidence base for heat mitigation and related co-benefits, identifies knowledge gaps, and proposes recommendations for their implementation to maximize their benefits. After screening 27,486 papers, 202 were reviewed, based on 51 GBGI types categorized under 10 main divisions. Certain GBGI (green walls, parks, street trees) have been well researched for their urban cooling capabilities. However, several other GBGI have received negligible (zoological garden, golf course, estuary) or minimal (private garden, allotment) attention. The most efficient air cooling was observed in botanical gardens (5.0 ± 3.5°C), wetlands (4.9 ± 3.2°C), green walls (4.1 ± 4.2°C), street trees (3.8 ± 3.1°C), and vegetated balconies (3.8 ± 2.7°C). Under changing climate conditions (2070-2100) with consideration of RCP8.5, there is a shift in climate subtypes, either within the same climate zone (e.g., Dfa to Dfb and Cfb to Cfa) or across other climate zones (e.g., Dfb [continental warm-summer humid] to BSk [dry, cold semi-arid] and Cwa [temperate] to Am [tropical]). These shifts may result in lower efficiency for the current GBGI in the future. Given the importance of multiple services, it is crucial to balance their functionality, cooling performance, and other related co-benefits when planning for the future GBGI. This global GBGI heat mitigation inventory can assist policymakers and urban planners in prioritizing effective interventions to reduce the risk of urban overheating, filling research gaps, and promoting community resilience.
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PROBLEM: Despite advances in Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO), a significant mortality rate persists due to complications. The non-physiological blood flow dynamics of VA-ECMO may lead to neurological complications and organ ischemia. Continuous retrograde high-flow oxygenated blood enters through a return cannula placed in the femoral artery which opposes the pulsatile deoxygenated blood ejected by the left ventricle (LV), which impacts upper body oxygenation and subsequent hyperoxemia. The complications underscore the critical need to comprehend the impact of VA-ECMO support level and return cannula size, as mortality remains a significant concern. AIM: The aim of this study is to predict and provide insights into the complications associated with VA-ECMO using computational fluid dynamics (CFD) simulations. These complications will be assessed by characterising blood flow and emboli transport patterns through a comprehensive analysis of the influence of VA-ECMO support levels and arterial return cannula sizes. METHODS: Patient-specific 3D aortic and major branch models, derived from a male patient's CT scan during VA-ECMO undergoing respiratory dysfunction, were analyzed using CFD. The investigation employed species transport and discrete particle tracking models to study ECMO blood (oxygenated) mixing with LV blood (deoxygenated) and to trace emboli transport patterns from potential sources (circuit, LV, and aorta wall). Two cannula sizes (15 Fr and 19 Fr) were tested alongside varying ECMO pump flow rates (50%, 70%, and 90% of the total cardiac output). RESULTS: Cannula size did not significantly affect oxygen transport. At 90% VA-ECMO support, all arteries distal to the aortic arch achieved 100% oxygen saturation. As support level decreased, oxygen transport to the upper body also decreased to a minimum saturation of 73%. Emboli transport varied substantially between emboli origin and VAECMO support level, with the highest risk of cerebral emboli coming from the LV with a 15 Fr cannula at 90% support. CONCLUSION: Arterial return cannula sizing minimally impacted blood oxygen distribution; however, it did influence the distribution of emboli released from the circuit and aortic wall. Notably, it was the support level alone that significantly affected the mixing zone of VA-ECMO and cardiac blood, subsequently influencing the risk of embolization of the cardiogenic source and oxygenation levels across various arterial branches.
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Oxigenación por Membrana Extracorpórea , Masculino , Humanos , Hidrodinámica , Hemodinámica/fisiología , Cateterismo , OxígenoRESUMEN
Outdoor adventure challenges are commonly used to enhance self-efficacy, but the physiological mechanisms involved remain unexplored. Additionally, while studies have documented the influence of self-efficacy on stress management, general self-efficacy has yet to be fully understood in the context of cardiovascular stress reactivity (CVR). This study investigated the influence of self-efficacy beliefs on CVR during acute psychological stress tasks. Additionally, it explored whether CVR serves as a novel mechanism underlying the outcomes of outdoor adventure challenges. As part of a wider randomized controlled trial, participants (n = 55) were invited to complete a laboratory session to assess CVR to an active (paced auditory serial addition test (PASAT)) and a passive (cold pressor test (CPT)) stress task. Randomized participants (n = 33) to the experimental condition also engaged in a high ropes challenge course after the laboratory session. It was found that greater self-reported self-efficacy was associated with larger CVR during the CPT and positively associated with perceived engagement and performance during the PASAT. Secondly, participants reporting positive change in self-efficacy post-intervention were associated with greater CVR and greater CVR was associated with higher ratings of intervention engagement and perceived challenge. This study provides preliminary evidence suggesting that greater efficacy beliefs may heighten CVR to passive acute psychological stressors. Habitual stress reactivity may represent a novel mechanism involved in outdoor and adventure-based interventions. Future research should continue to explore the impact of psychological variables on stress physiology and examine CVR as a potential mechanism in adventure experiences.
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Frecuencia Cardíaca , Autoeficacia , Estrés Psicológico , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Estrés Psicológico/fisiopatologíaRESUMEN
BACKGROUND AND OBJECTIVE: The movement of the respiratory walls has a significant impact on airflow through the respiratory tract. The majority of computational fluid dynamics (CFD) studies assume a static geometry which may not provide a realistic flow field. Furthermore, many studies use Reynolds Averaged Navier-Stokes (RANS) turbulence models that do not resolve turbulence structure. Combining the application of advanced scale-resolving turbulence models with moving respiratory walls using CFD will provide detailed insights into respiratory flow structures. METHODS: This study simulated a complete breathing cycle involving inhalation and exhalation in a nasal cavity to trachea geometry that incorporated moving glottis walls. A second breathing cycle was simulated with static glottis walls for comparison. A recently developed hybrid RANS-LES turbulence model, the Stress-Blended Eddy Simulation (SBES), was incorporated to resolve turbulent flow structures in fine detail for both transient simulations. Transient results were compared with steady-state RANS simulations for the same respiratory geometry. RESULTS: Glottis motion caused substantial effects on flow structure through the complete breathing cycle. Significant flow structure and velocity variations were observed due to glottal motion, primarily in the larynx and trachea. Resolved turbulence structures using SBES showed an intense mixing section in the glottis region during inhalation and in the nasopharynx during expiration, which was not present in the RANS simulations. CONCLUSION: Transient simulations of a realistic breathing cycle uncovered flow structures absent in simulations with a constant flow rate. Furthermore, the incorporation of glottis motion impacted airflow characteristics that suggest rigid respiratory walls do not accurately describe respiratory flow. Future research in respiratory airflow should be conducted using transient scale-resolving models in conjunction with moving respiratory walls to capture flow structures in detail.
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BACKGROUND: The omental patch repair is the gold standard for the repair of perforated peptic ulcers. This can be performed open or laparoscopically. However, in the event of non-viable or inadequate omentum available at the time of surgery the falciform ligament has been reportedly used to as an alternative. Nonetheless, evidence for its safety is scant. This study aims to determine differences in patient outcomes when comparing the two repair techniques. METHODS: Following ethics approval, patients who underwent surgical repair of perforated peptic ulcers using omental or falciform patch repair, between 1 January 2010 and 31 December 2017, across all three Western Australian tertiary hospital services and at least 18 years of age were included. Data were collected by reviewing medical records of included patients. RESULTS: Three hundred twenty-nine patients who underwent either open or laparoscopic repairs were included. Thirty-seven patients had falciform repairs and were mostly ASA of 2 compared to 292 patients receiving omental patch repair who were mostly ASA 3. Falciform patch repairs were more commonly used in duodenal ulcer perforations. There were no statistically significant differences in patient outcomes between the omental patch and falciform ligament groups. This included post-operative intra-abdominal sepsis, return to theatre, post-operative ICU admission, inpatient mortality, 30-day readmission and ulcer healing on follow-up gastroscopy. CONCLUSIONS: This study demonstrates safety, efficacy and similar outcomes for patients receiving the falciform ligament patch repair compared with omental patch repair.
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Úlcera Duodenal , Laparoscopía , Úlcera Péptica Perforada , Humanos , Estudios Retrospectivos , Epiplón , Australia , Laparoscopía/métodos , Úlcera Duodenal/cirugía , Complicaciones Posoperatorias/cirugía , Úlcera Péptica Perforada/cirugía , Resultado del TratamientoRESUMEN
A swirling airflow is incorporated in several dry powder inhalers (DPIs) for effective powder de-agglomeration. This commonly requires the use of a flow-straightening grid in the DPI to reduce drug deposition loss caused by large lateral spreading of the emerging aerosol. Here, we propose a novel grid-free DPI design concept that improves the aerosol flow characteristics and reduces the aforementioned drug loss. The basis of this design is the implementation of a secondary airflow that swirls in the opposite direction (counter-swirl) to that of a primary swirling airflow. In-vitro deposition, computational fluid dynamics simulations and particle image velocimetry measurements are used to evaluate the counter-swirl DPI aerosol performance and flow characteristics. In comparison with a baseline-DPI that has only a primary swirling airflow, the counter-swirl DPI has 20% less deposition of the emitted drug dose in the induction port and pre-separator of a next generation impactor (NGI). This occurs as a result of the lower flow-swirl generated from the counter-swirl DPI which eliminates the axial reverse flow outside of the mouthpiece and substantially reduces lateral spreading in the exiting aerosol. Modifications to the counter-swirl DPI design were made to prevent drug loss from the secondary airflow tangential inlets, which involved the addition of wall perforations in the tangential inlets and the separation of the primary and secondary swirling airflows by an annular channel. These modified DPI devices were successful in that aspect but had higher flow-swirl than that in the counter-swirl DPI and thus had higher drug mass retained in the device and deposited in the induction port and pre-separator of the NGI. The fine particle fraction in the aerosols generated from all the counter-swirl-based DPIs and the baseline-DPI are found to be statistically similar to each other.
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Inhaladores de Polvo Seco , Pulmón , Inhaladores de Polvo Seco/métodos , Tamaño de la Partícula , Aerosoles , Administración por Inhalación , Diseño de Equipo , PolvosRESUMEN
BACKGROUND AND OBJECTIVES: Recent research has shown that lifetime stressor exposure can negatively impact sport performers. However, this work has predominantly relied on quantitative methods, which has provided limited information regarding how stressors occurring over the life course affect health, well-being, and performance. This study aimed to explore how relatively high levels of lifetime (non-sport and sport-specific) stressor exposure influenced sport performers' health, well-being, and performance. METHODS AND DESIGN: To identify participants who had experienced high lifetime (non-sport and sport-specific) stressors, we used criterion-based purposeful sampling from a prior study. Subsequently, semi-structured interviews, complemented by timelining, were conducted with 22 sport performers (17 female; Mage = 25.89, SD = 10.20). RESULTS: We used reflexive thematic analysis to develop three overarching themes that illustrate how high lifetime (non-sport and sport-specific) stressor exposure influences sport performers' health, well-being, and performance. These were: psychological (e.g., maladaptive coping strategies), social (e.g., difficulties in building relationships), and behavioral (e.g., risky behaviors) factors. CONCLUSIONS: These findings can help practitioners identify sport performers at risk of developing stress-related health, well-being, and performance problems, and may aid the development of effective interventions.
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Deportes , Estrés Psicológico , Humanos , Femenino , Adulto , Deportes/psicología , Asunción de Riesgos , Habilidades de Afrontamiento , Acontecimientos que Cambian la VidaRESUMEN
Background: Polymeric heart valves (PHVs) may address the limitations of mechanical and tissue valves in the treatment of valvular heart disease. In this study, a bioinspired valve was designed, assessed in silico, and validated by an in vitro model to develop a valve with optimum function for pediatric applications. Methods: A bioinspired heart valve was created computationally with leaflet curvature derived from native valve anatomies. A valve diameter of 18 mm was chosen to approach sizes suitable for younger patients. Valves of different thicknesses were fabricated via dip-coating with siloxane-based polyurethane and tested in a pulse duplicator for their hydrodynamic function. The same valves were tested computationally using an arbitrary Lagrangian-Eulerian plus immersed solid approach, in which the fluid-structure interaction between the valves and fluid passing through them was studied and compared with experimental data. Results: Computational analysis showed that valves of 110 to 200 µm thickness had effective orifice areas (EOAs) of 1.20 to 1.30 cm2, with thinner valves exhibiting larger openings. In vitro tests demonstrated that PHVs of similar thickness had EOAs of 1.05 to 1.35 cm2 and regurgitant fractions (RFs) <7%. Valves with thinner leaflets exhibited optimal systolic performance, whereas thicker valves had lower RFs. Conclusions: Bioinspired PHVs demonstrated good hydrodynamic performance that exceeded ISO 5840-2 standards. Both methods of analysis showed similar correlations between leaflet thickness and valve systolic function. Further development of this PHV may lead to enhanced durability and thus a more reliable heart valve replacement than contemporary options.
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Introduction: We have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism underlying downregulation of PGC1α expression and activity during IBD is not yet clear. Methods: Mice (male; C57Bl/6, Villincre/+;Pgc1afl/fl mice, and Pgc1afl/fl) were subjected to experimental colitis and treated with nicotinamide riboside. Western blot, high-resolution respirometry, nicotinamide adenine dinucleotide (NAD+) quantification, and immunoprecipitation were used to in this study. Results: We demonstrate a significant depletion in the NAD+ levels within the intestinal epithelium of mice undergoing experimental colitis, as well as humans with ulcerative colitis. While we found no decrease in the levels of NAD+-synthesizing enzymes within the intestinal epithelium of mice undergoing experimental colitis, we did find an increase in the mRNA level, as well as the enzymatic activity, of the NAD+-consuming enzyme poly(ADP-ribose) polymerase-1 (PARP1). Treatment of mice undergoing experimental colitis with an NAD+ precursor reduced the severity of colitis, restored mitochondrial function, and increased active PGC1α levels; however, NAD+ repletion did not benefit transgenic mice that lack PGC1α within the intestinal epithelium, suggesting that the therapeutic effects require an intact PGC1α axis. Discussion: Our results emphasize the importance of PGC1α expression to both mitochondrial health and homeostasis within the intestinal epithelium and suggest a novel therapeutic approach for disease management. These findings also provide a mechanistic basis for clinical trials of nicotinamide riboside in IBD patients.
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Colitis , Enfermedades Inflamatorias del Intestino , Humanos , Masculino , Animales , Ratones , NAD , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Ratones Transgénicos , Mitocondrias , InflamaciónAsunto(s)
Cambio Climático , Cirujanos , Humanos , Nueva Zelanda , Australia , Actitud del Personal de Salud , Encuestas y CuestionariosRESUMEN
Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as sustained potency through orchestrating the host immunity to optimize the resolution of infection and tissue damage. Cystic fibrosis (CF) patients suffer from a lung disease characterized by excessive inflammation and chronic infection as well as a variety of other systemic anomalies associated with the consequences of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function. The application of hMSC immunotherapy to the CF clinical armamentarium is important even in the era of modulators when patients with an established disease still need anti-inflammatory and anti-microbial therapies. Additionally, people with CF mutations not addressed by current modulator resources need anti-inflammation and anti-infection management. Furthermore, hMSCs possess dynamic therapeutic properties, but the potency of their products is highly variable with respect to their anti-inflammatory and anti-microbial effects. Due to the variability of hMSC products, we utilized standardized in vitro and in vivo models to select hMSC donor preparations with the greatest potential for clinical efficacy. The models that were used recapitulate many of the pathophysiologic outcomes associated with CF. We applied this strategy in pursuit of identifying the optimal donor to utilize for the "First in CF" Phase I clinical trial of hMSCs as an immunotherapy and anti-microbial therapy for people with cystic fibrosis. The hMSCs screened in this study demonstrated significant diversity in antimicrobial and anti-inflammatory function using models which mimic some aspects of CF infection and inflammation. However, the variability in activity between in vitro potency and in vivo effectiveness continues to be refined. Future studies require and in-depth pursuit of hMSC molecular signatures that ultimately predict the capacity of hMSCs to function in the clinical setting.
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Background Sacrococcygeal pilonidal sinus disease (SPD) is a common general surgical condition encountered in practice and predominantly affects young males. Surgical practice parameters for the management of SPD are variable. This study aimed to review current surgical practice parameters for SPD management in Western Australia. Methodology This study conducted a de-identified 30-item multiple-response ranking, dichotomous, quantitative, and qualitative survey of self-reported surgeon practice preferences and outcomes. The survey was sent to 115 Royal Australian College of Surgeons - Western Australia general/colorectal surgical fellows. Data were analyzed using SPSS version 27 (IBM Corp., Armonk, NY, USA). Results The survey response rate was 66% (N = 77). The cohort comprised mostly senior collegiate (n = 50, 74.6%), and most were low-volume practitioners (n = 49, 73.1%). For local disease control, most surgeons perform a complete wide local excision (n = 63, 94%). The preferred wound closure method was an off-midline primary closure (n = 47, 70.1%). Self-reported SPD recurrence, wound infection, and wound dehiscence rates were 10%, 10%, and 15%, respectively. The three high-ranked closure techniques were the Karydakis flap, Limberg's flap (LF), and Z-Plasty flap. Each surgeon's median annual SPD procedures were 10 (interquartile range = 15). The surgeons could utilize their preferred SPD closure technique (mean = 83.5%, standard deviation = ±15.6). Univariate analysis showed significant associations between years of experience and SPD flap techniques utilized, with senior surgeons significantly less likely to use either the LF (p = 0.009) or the Bascom procedure (BP) (p = 0.034). Instead, there was a preference for using healing by secondary-intention technique (SIT) compared to younger fellows (p = 0.017). A significant negative correlation existed between practice volume and SPD flap technique utilization, with low-volume surgeons less likely to prefer the gluteal fascia-cutaneous rotational flap (p = 0.049) or the BP (p = 0.010). However, low-volume practice surgeons were significantly more likely to use SITs (p = 0.023). The three most important patient factors in choosing SPD techniques were comorbidities, likely patient compliance, and attitude toward the disease. Meanwhile, factors influencing local conditions included the proximity of the disease to the anus, the number and location of pits and sinuses, and previous definitive SPD surgery. Key informants for technique preference were perceived low recurrence rate, familiarity, and overall good patient outcomes. Conclusions Surgical practice parameters for managing SPD remain highly variable. Most surgeons perform midline excision with off-midline primary closure as the gold standard. There is a clear and present need for clear, concise, and yet comprehensive guidelines on managing this chronic and often disabling condition to ensure the delivery of consistent, evidence-based care.