Strategies to Overcome Barriers to Physical Activity Participation in Children and Adults Living With Congenital Heart Disease: A Narrative Review.

Physical activity participation is critical for optimal physical, psychological, and cognitive health in children and adults living with congenital heart disease (CHD). Majority of the general population are not sufficiently active, and with the added psychological, physical, and socioeconomic barriers faced by individuals with CHD, it is unsurprising that many people living with CHD do not meet the recommendations for physical activity either. The aim of this review is to outline lifelong physical activity barriers faced by individuals living with CHD and provide age-appropriate strategies that can be used to ensure the development of long-term positive physical activity behaviours. Barriers to physical activity include safety fears, lack of encouragement, low exercise self-efficacy, body image concerns, limited education, socioeconomic status, reduced access to resources, and cardiac diagnosis and severity. These barriers are multifaceted and often begin in early childhood and continue to develop well into adulthood. Therefore, it is important for children to participate in physical activity from early stages of life as it has been shown to improve cardiorespiratory fitness, muscular endurance, and quality of life. Current literature demonstrates that participation in physical activity and higher intensity exercise after appropriate screening is safe and should be encouraged rather than dissuaded in people born with a congenital heart condition.

L'activité physique est essentielle à une santé cognitive, psychologique et physique optimale chez les enfants et les adultes atteints d'une cardiopathie congénitale (CC). La majorité de la population générale n'est pas suffisamment active et compte tenu des obstacles socio-économiques, physiques et psychologiques auxquels sont également confrontées les personnes atteintes d'une CC, il n'est pas surprenant que celles-ci soient nombreuses à ne pas respecter non plus les recommandations en matière d'activité physique. L'objet de cette analyse est de décrire les obstacles à l'activité physique que rencontrent tout au long de leur vie les personnes atteintes d'une CC et de proposer des stratégies adaptées à l'âge qui peuvent être utilisées pour promouvoir l'adoption durable de saines habitudes en matière d'activité physique. Les obstacles en question comprennent la peur du danger, l'absence d'encouragement, un faible sentiment d'auto-efficacité, une mauvaise image de soi, un faible niveau d'études, le statut socio-économique, l'accès limité aux ressources et le diagnostic de cardiopathie ou la gravité de la cardiopathie. Ces obstacles, qui comportent de multiples facettes, trouvent souvent leur origine dans la petite enfance et se perpétuent jusqu'à l'âge adulte. Il est donc important pour les enfants de s'adonner très tôt à l'activité physique. Il a en effet été montré que l'activité physique améliore la capacité cardiorespiratoire, l'endurance musculaire et la qualité de vie. Les données publiées indiquent par ailleurs que l'activité physique en général et les exercices à haute intensité ­ après une évaluation adéquate ­ sont sûrs et doivent être encouragés plutôt que découragés chez les personnes nées avec une cardiopathie congénitale.

Realtime physical simulator for virtual reality sailing by patients with spinal cord injury: an innovative voyage.

Background: The aim of this study was to explore whether sail training using a VSail® simulator would allow people with spinal cord injuries (SCI) to learn to sail in a safe controlled environment and then sail competently on the water in wind of moderate strength (12 knots). A battery of physical tests and questionnaires was used to evaluate possible improvements in health and well-being as a consequence of participation in the trial. Methods: Twenty participants were recruited with the assistance of their physicians from The International Center for Spinal Cord Injury, Kennedy Krieger Institute. Inclusion criteria were SCI >6 months previously, medically stable, with no recent (1 month or less) inpatient admission for acute medical or surgical issues. All neurological SCI levels (C1-S1) were eligible. All subjects followed a programme of instruction leading to mastery of basic sailing techniques (steering predetermined courses, sail trimming, tacking, gybing and mark rounding). Results: Not all participants completed the study for various reasons. Those that did were seven males and six females, six with tetraplegia and seven with paraplegia. The mean age was 45 years (23 to 63) and the average time since injury was 14.7 years (2 to 38 years). At the end of the course subjects were able to perform the sailing maneuvers and navigate a triangular racecourse on the simulator's display in 12 knots of wind within a pre-set time. At 6 weeks post completion of training most subjects showed a decrease in depression, physical and social limitations, and an improvement in physical tests. These improvements were maintained or increased in most participants by 12 weeks, but not others. Conclusions: The primary objective of the trial was achieved as all participants who completed the VSail® training were able to sail on the water at the Downtown Sailing Center in Baltimore.

Comparing the Physiological Responses to the 6-Minute Walk Test, Timed Up and Go Test, and Treadmill Cardiopulmonary Exercise Test.

Purpose: To compare physiological responses during a treadmill cardiopulmonary exercise test (CPX), 6-minute walk test (6MWT), and timed up and go test (TUGT) in individuals referred for unexplained breathlessness and symptom limited treadmill exercise testing. Methods: Heart rate (HR), oxygen consumption (V̇O2), carbon dioxide production (V̇CO2), respiratory exchange ratio (RER), minute ventilation (V̇E), systolic blood pressure (SBP), and rating of perceived exertion (RPE) were recorded throughout each test. Results: Each test demonstrated a significant increase (p < 0.01) in the cardiopulmonary (V̇O2, V̇CO2 and V̇E, RPE, SBP, and HR) and perceptual (RPE) responses from rest to end exercise. The increase in cardiopulmonary and perceptual responses was greatest for the CPX with significantly smaller responses demonstrated during the 6MWT (p < 0.01) and even smaller responses for the TUGT (p < 0.01 vs CPX and 6MWT). Conclusion: Not surprisingly, the treadmill CPX results is the greatest physiological response in our group. Despite being of short duration, the TUGT results in an increased physiological response.

APOBR Is Downregulated in EBV+ Tonsils of Children with Obstructive Sleep-Disordered Breathing.

Background: Obstructive sleep-disordered breathing (oSDB) is a heterogeneous phenotype that is increasing in prevalence worldwide and has many potential comorbidities that could severely affect quality of life. There is a need to identify biomarkers for oSDB and its comorbidities to improve clinical management, particularly in children. Methods: We performed bulk mRNA-sequencing, differential expression analysis, and qPCR replication of selected differentially expressed genes (DEGs) using RNA samples extracted from tonsils of children with oSDB. Two variables were used as classifier, namely, detection of Epstein-Barr virus (EBV) in tonsils and need for continuous positive airway pressure (CPAP) treatment. Standard statistical tests were used to determine associations across clinical, EBV, and DEG variables. Results: Nineteen genes were dysregulated in tonsils that are EBV+ or from children needing CPAP. Of these genes, APOBR was downregulated in both EBV+ and CPAP+ tonsils, and this downregulation was replicated by qPCR in an independent set of pediatric samples. In the tonsils of adult patients with oSDB, APOBR was positively correlated with age, and potentially with diastolic blood pressure. Conclusions: Taken together, APOBR and DEGs in tonsillar tissues may be useful as potential biomarkers of oSDB severity and comorbidity across the lifespan, with APOBR levels being dependent on latent EBV infection.

Impact of Natural Disasters on Mental Health: Evidence and Implications.

Natural disasters are large-scale catastrophic events, and they are increasing in frequency and severity. Converging evidence indicates that the mental health consequences of disasters are extensive and are often associated with trauma and the disruption of personal and socioeconomic factors in people's lives. Although most individuals experiencing disaster-related traumatic events do not develop mental illnesses, some experience adverse psychological effects of disasters. These mental health effects begin immediately following a disaster and may persist for extended periods. In this article, we summarize the literature findings to provide a narrative review that focuses on the mental health consequences of natural disasters. An overview of the disaster mental health research field is provided, and the findings are ordered into theoretical frameworks. Then, the development and course of psychopathology regarding disaster aftermath are described in a methodological context. Next, understanding a disaster as an event of transition is highlighted, and the impact of this disaster-specific transition is discussed. Lastly, a potential relationship between the transitional impact of a disaster and mental health consequences is speculated on, and the implications are discussed. The impact of disasters on mental health can be direct or indirect, short-term or long-term, and to some extent depends on the recovery process of the affected community. Also, we propose the possible merits of using the Transitional Impact Scale in the context of disaster mental health research by assessing the features of disaster-related transition and its effects on mental health. We conclude by suggesting a direction for future research in terms of measuring the disaster mental health effects in community settings (affected vs. non-affected) and also considering cross-cultural and cross-regional differences. In recent decades, a large amount of knowledge has been gathered from disaster mental health research, but, still, more research is needed to resolve some irregular findings through refining the methodological variations.

Mechanisms of retinal photoreceptor loss in spontaneously hypertensive rats.

Retinal neurodegenerative diseases, including hypertensive retinopathy, involve progressive damage to retinal neurons, leading to visual impairment. In this study, we investigated the pathological mechanisms underlying retinal neurodegeneration in spontaneously hypertensive rats (SHR), using Wistar Kyoto (WKY) rats as normotensive controls. We observed that SHR exhibited significantly higher blood pressure and decreased retinal thickness, indicating retinal neurodegeneration. Molecular tests including quantitative real-time polymerase chain reaction, immunoblot, and immunofluorescent staining showed elevated levels of the pro-inflammatory cytokine tumor necrosis factor-α, apoptotic markers (Fas, FasL, caspase-8, active caspase-3, and cleaved poly (ADP-ribose) polymerase), and necroptotic markers (receptor-interacting protein kinase-1 and -3) in SHR retinas. Additionally, we found elevated transforming growth factor-ß (TGF-ß) levels in the retinal pigment epithelium (RPE) of SHR, with a decrease in lecithin retinol acyltransferase (LRAT), which regulates retinoid metabolism and photoreceptor health. In human RPE cells (ARPE-19), TGF-ß administration suppressed mRNA and protein levels of LRAT; and vactosertib, a selective inhibitor of TGF-ß receptor kinase type 1, reversed the effect of TGF-ß. These findings suggest that hypertension-induced retinal neurodegeneration involves inflammation, apoptosis, necroptosis, and disrupted retinoid metabolism, providing potential therapeutic targets for hypertensive retinopathy.

The Arabidopsis KASH protein SINE3 is involved in male and female gametogenesis.

KEY MESSAGE: The Arabidopsis KASH protein SINE3 is involved in male and female gametophyte development, likely affecting the first post-meiotic mitosis in both cases, and is required for full seed set. Linker of nucleoskeleton and cytoskeleton (LINC) complexes are protein complexes spanning the inner and outer membranes of the nuclear envelope (NE) and are key players in nuclear movement and positioning. Through their roles in nuclear movement and cytoskeletal reorganization, plant LINC complexes affect processes as diverse as pollen tube rupture and stomatal development and function. KASH proteins are the outer nuclear membrane component of the LINC complex, with conserved C-termini but divergent N-terminal cytoplasmic domains. Of the known Arabidopsis KASH proteins, SUN-INTERACTING NUCLEAR ENVELOPE PROTEIN 3 (SINE3) has not been functionally characterized. Here, we show that SINE3 is expressed at all stages of male and female gametophyte development. It is located at the NE in male and female gametophytes. Loss of SINE3 results in a female-derived seed set defect, with sine3 mutant ovules arresting at stage FG1. Pollen viability is also significantly reduced, with microspores arresting prior to pollen mitosis I. In addition, sine3 mutants have a minor male meiosis defect, with some tetrads containing more than four spores. Together, these results demonstrate that the KASH protein SINE3 plays a crucial role in male and female gametophyte development, likely affecting the first post-meiotic nuclear division in both cases.

Identification of a serum proteomic biomarker panel using diagnosis specific ensemble learning and symptoms for early pancreatic cancer detection.

BACKGROUND: The grim (<10% 5-year) survival rates for pancreatic ductal adenocarcinoma (PDAC) are attributed to its complex intrinsic biology and most often late-stage detection. The overlap of symptoms with benign gastrointestinal conditions in early stage further complicates timely detection. The suboptimal diagnostic performance of carbohydrate antigen (CA) 19-9 and elevation in benign hyperbilirubinaemia undermine its reliability, leaving a notable absence of accurate diagnostic biomarkers. Using a selected patient cohort with benign pancreatic and biliary tract conditions we aimed to develop a data analysis protocol leading to a biomarker signature capable of distinguishing patients with non-specific yet concerning clinical presentations, from those with PDAC. METHODS: 539 patient serum samples collected under the Accelerated Diagnosis of neuro Endocrine and Pancreatic TumourS (ADEPTS) study (benign disease controls and PDACs) and the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS, healthy controls) were screened using the Olink Oncology II panel, supplemented with five in-house markers. 16 specialized base-learner classifiers were stacked to select and enhance biomarker performances and robustness in blinded samples. Each base-learner was constructed through cross-validation and recursive feature elimination in a discovery set comprising approximately two thirds of the ADEPTS and UKCTOCS samples and contrasted specific diagnosis with PDAC. RESULTS: The signature which was developed using diagnosis-specific ensemble learning demonstrated predictive capabilities outperforming CA19-9, the only biomarker currently accepted by the FDA and the National Comprehensive Cancer Network guidelines for pancreatic cancer, and other individual biomarkers and combinations in both discovery and held-out validation sets. An AUC of 0.98 (95% CI 0.98-0.99) and sensitivity of 0.99 (95% CI 0.98-1) at 90% specificity was achieved with the ensemble method, which was significantly larger than the AUC of 0.79 (95% CI 0.66-0.91) and sensitivity 0.67 (95% CI 0.50-0.83), also at 90% specificity, for CA19-9, in the discovery set (p = 0.0016 and p = 0.00050, respectively). During ensemble signature validation in the held-out set, an AUC of 0.95 (95% CI 0.91-0.99), sensitivity 0.86 (95% CI 0.68-1), was attained compared to an AUC of 0.80 (95% CI 0.66-0.93), sensitivity 0.65 (95% CI 0.48-0.56) at 90% specificity for CA19-9 alone (p = 0.0082 and p = 0.024, respectively). When validated only on the benign disease controls and PDACs collected from ADEPTS, the diagnostic-specific signature achieved an AUC of 0.96 (95% CI 0.92-0.99), sensitivity 0.82 (95% CI 0.64-0.95) at 90% specificity, which was still significantly higher than the performance for CA19-9 taken as a single predictor, AUC of 0.79 (95% CI 0.64-0.93) and sensitivity of 0.18 (95% CI 0.03-0.69) (p = 0.013 and p = 0.0055, respectively). CONCLUSION: Our ensemble modelling technique outperformed CA19-9, individual biomarkers and indices developed with prevailing algorithms in distinguishing patients with non-specific but concerning symptoms from those with PDAC, with implications for improving its early detection in individuals at risk.

GIS-ODE: linking dynamic population models with GIS to predict pathogen vector abundance across a country under climate change scenarios.

Mechanistic mathematical models such as ordinary differential equations (ODEs) have a long history for their use in describing population dynamics and determining estimates of key parameters that summarize the potential growth or decline of a population over time. More recently, geographic information systems (GIS) have become important tools to provide a visual representation of statistically determined parameters and environmental features over space. Here, we combine these tools to form a 'GIS-ODE' approach to generate spatiotemporal maps predicting how projected changes in thermal climate may affect population densities and, uniquely, population dynamics of Ixodes ricinus, an important tick vector of several human pathogens. Assuming habitat and host densities are not greatly affected by climate warming, the GIS-ODE model predicted that, even under the lowest projected temperature increase, I. ricinus nymph densities could increase by 26-99% in Scotland, depending on the habitat and climate of the location. Our GIS-ODE model provides the vector-borne disease research community with a framework option to produce predictive, spatially explicit risk maps based on a mechanistic understanding of vector and vector-borne disease transmission dynamics.

Pilot study assessing gut microbial diversity among sexual and gender minority young adults.

Evidence supports that people identifying as a sexual or gender minority (SGMs) experience minority-related stress resulting from discrimination or expectations of prejudice, and that this is associated with increased mental and physical health problems compared to cisgender heterosexuals. However, the biological mechanisms driving minority-related stress impacts remain unknown, including the role of the gut microbiome. Thus, the aim of this study was to determine the relationship between SGM status and gut microbiome health among young adults attending a 4-year university. To this end, a prospective pilot study was completed in the fall and spring semesters of 2021-22. Self-identified SGMs (N = 22) and cisgender-heterosexuals (CIS-HET, N = 43) completed in-person interviews to provide mental health data and demographic information. Nail and saliva samples were collected at the time of interview to quantify chronic and acute cortisol. Stool samples were collected within 48 hours of interview for microbiome analysis. Assessment of the gut microbiota identified a significant reduction in alpha diversity among the SGM group, even when adjusting for mental health outcome. SGM group showed trends for higher abundance of microbes in phylum Bacteroidetes and lower abundance of microbes in phyla Firmicutes, Actinobacteria, and Proteobacteria compared to the CIS-HET group. These findings support that the gut microbiome could be contributing to negative health effects among the SGM community.

Overnight Monitoring Criteria for Children with Obstructive Sleep-Disordered Breathing After Tonsillectomy: Revisited.

OBJECTIVES: Previous studies indicate children who pass an Asleep Room Air Challenge (AsRAC) do not have significant postoperative adverse respiratory events after adenotonsillectomy (T&A). Subsequently, we revised our overnight monitoring (OM) criteria, allowing patients with an obstructive apnea/hypopnea index (OAHI) ≤20 or nonsevere obesity (Class I) to be considered for same-day surgery (SDS) if they passed an AsRAC. Our hypothesis is that our modified OM criteria would not increase the return visits or readmission rates for patients undergoing SDS within 48 h or 15 days of T&A. METHODS: A retrospective review of all children aged ≥3 and <21 years who underwent T&A at a tertiary children's hospital and its satellite locations was performed from January 2017 to September 2022. Descriptive statistics and outcome measures were compared using a 3% margin noninferiority test before and after the new criteria implementation. RESULTS: Before intervention, 3,266 (58%) T&As were performed as SDS. Afterward, 74% of T&As were performed as SDS (p-value <0.05). There was no difference in the ED revisit rate for SDS within the 3% noninferiority margin. Following intervention, 29% more children with Class I obesity (62% vs. 33%) underwent SDS (p-value <0.001). Afterward, 19% more children with polysomnography underwent SDS (39% vs. 20%), p-value <0.001. After intervention, within 48 h of SDS, six (0.9%) children had revisits for bleeding and seven (1.2%) for vomiting. There were no perioperative respiratory events. CONCLUSION: Our revised monitoring criteria did not demonstrate an increase in ED visit or readmissions rates within 48 h or 15 days of T&A. Additionally, we found a 29% increase in Class I obese children undergoing SDS T&A. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Longitudinal Success of Tonsillectomy for Obstructive Sleep Apnea in Children with Down Syndrome.

OBJECTIVE: Obstructive sleep apnea is common in children with Down syndrome (DS). Tonsillectomy is recommended as the first-line approach in treating children with obstructive sleep apnea (OSA), however, there is limited data on the long-term outcomes in children with DS who undergo tonsillectomy. In this retrospective study, we examined the long-term polysomnographic and symptomatic outcomes in children with DS who underwent tonsillectomy with or without an adenoidectomy (T&A). We hypothesize that the success of T&A to treat OSA in children with DS will diminish with time. STUDY DESIGN: A retrospective chart review of children with DS who underwent T&A between 2009 and 2015 was conducted. Inclusion criteria were children with at least 1 postoperative polysomnogram (PSG) within 6 months of T&A with an obstructive apnea/hypopnea index (OAHI) < 5. Outcomes were determined by subsequent clinic visits and postoperative polysomnograms: OAHI ≥ 5, snoring reported during clinic visit and time to reoccurrence. SETTING: Childrens Hospital Colorado. RESULTS: Of the 57 children with mild OSA at 1st (initial) PSG, 13/40 (33%) children had OAHI ≥ 5 at the 2nd postoperative PSG. Of the 18 patients who underwent a 3rd PSG, 4 (22%) progressed to moderate/severe OSA. A total of 17 patients out of the original 57 (30%) progressed to moderate/severe OSA with the median time for the additional post-op PSG's being 2.3 years. CONCLUSION: Children with DS who have at most mild OSA (OAHI < 5) following a T&A are at risk for progressing to at least moderate OSA within 2 years after their T&A. A surveillance PSG 2 years following surgery will identify these children.

ABC Efflux Transporters and Solute Carriers in the Early Developing Brain of a Marsupial Monodelphis domestica (South American Gray Short-Tailed Opossum).

This study used a marsupial Monodelphis domestica, which is born very immature and most of its development is postnatal without placental protection. RNA-sequencing (RNA-Seq) was used to identify the expression of influx and efflux transporters (ATP-binding cassettes [ABCs] and solute carriers [SLCs]) and metabolizing enzymes in brains of newborn to juvenile Monodelphis. Results were compared to published data in the developing eutherian rat. To test the functionality of these transporters at similar ages, the entry of paracetamol (acetaminophen) into the brain and cerebrospinal fluid (CSF) was measured using liquid scintillation counting following a single administration of the drug along with its radiolabelled tracer [3H]. Drug permeability studies found that in Monodelphis, brain entry of paracetamol was already restricted at P5; it decreased further in the first week of life and then remained stable until the oldest age group tested (P110). Transcriptomic analysis of Monodelphis brain showed that expression of transporters and their metabolizing enzymes in early postnatal (P) pups (P0, P5, and P8) was relatively similar, but by P109, many more transcripts were identified. When transcriptomes of newborn Monodelphis brain and E19 rat brain and placenta were compared, several transporters present in the rat placenta were also found in the newborn Monodelphis brain. These were absent from E19 rat brain but were present in the adult rat brain. These data indicate that despite its extreme immaturity, the newborn Monodelphis brain may compensate for the lack of placental protection during early brain development by upregulating protective mechanisms, which in eutherian animals are instead present in the placenta.

Effects of co-administration of lamotrigine on valproate transfer across the placenta and its brain entry in developing Genetic Absence Epilepsy Rats from Strasbourg (GAERS).

During development, embryos and foetuses may be exposed to maternally ingested antiseizure medications (ASM), valproate and lamotrigine, essential in some patients to control their epilepsy symptoms. Often, the two drugs are co-administered to reduce required doses of valproate, a known potential teratogen. This study used Genetic Absence Epilepsy Rat from Strasbourg to evaluate transfer of valproate and lamotrigine across late gestation placenta and their entry into cerebrospinal fluid (CSF) and brain of developing rats, in mono- and combination therapies. Animals at embryonic day (E) 19, postnatal day (P) 0, 4 and 21, and adults were administered valproate (30 mg/kg) or lamotrigine (6 mg/kg) with their respective [3H]-tracers, either alone or in combination. In chronic experiments, females consumed valproate-containing diet from 2 weeks prior to mating until offspring were used at E19 and P0. Drugs were injected 30 min before blood, CSF and brain samples were collected from terminally anaesthetised animals. Radioactivity in samples was measured. In acute monotherapy brain entry of valproate was higher in foetal than postnatal animals, correlating with its plasma protein binding. Brain entry of lamotrigine was not age-dependent. Combination therapy enhanced entry of lamotrigine into the adult brain but had no effects on brain and CSF entry of valproate. Following chronic valproate exposure, placental transfer of valproate decreased in combination therapy; however, foetal brain entry increased. Results suggest that during pregnancy, the use of combination therapy of valproate and lamotrigine may mitigate overall foetal exposure to valproate but potential risks to foetal brain development are less clear.

Do Surgical Smoke Evacuators Increase the Risk of Hearing Loss for Operative Personnel During Routine Adenotonsillectomy Surgery?

INTRODUCTION: Aerosol mitigation equipment implemented due to COVID-19 has increased noise levels in the operating room (OR) during otolaryngological procedures. Intraoperative sound levels may potentially place personnel at risk for occupational hearing loss. This study hypothesized that cumulative intraoperative noise exposures with aerosol mitigation equipment exceed recommended occupational noise exposure levels. METHODS: Sound levels generated by the surgical smoke evacuator (SSE) during adenotonsillectomy were measured using a sound level meter and compared to surgery without SSE. RESULTS: Thirteen adenotonsillectomy surgeries were recorded. Mean sound levels with the SSE were greater than the control (72 ± 3 A-weighted decibels (dBA) vs. 68 ± 2 dBA; p=0.015). Maximum noise levels during surgery with SSE reached 82 ± 3 dBA. CONCLUSION: Surgeons performing adenotonsillectomy with aerosol mitigation equipment are exposed to significant noise levels. Intraoperative sound levels exceeded international standards for work requiring concentration. Innovation is needed to reduce cumulative OR noise exposures.

Encapsulated Ferritin-like Proteins: A Structural Perspective.

Encapsulins are self-assembling nano-compartments that naturally occur in bacteria and archaea. These nano-compartments encapsulate cargo proteins that bind to the shell's interior through specific recognition sequences and perform various metabolic processes. Encapsulation enables organisms to perform chemical reactions without exposing the rest of the cell to potentially harmful substances while shielding cargo molecules from degradation and other adverse effects of the surrounding environment. One particular type of cargo protein, the ferritin-like protein (FLP), is the focus of this review. Encapsulated FLPs are members of the ferritin-like protein superfamily, and they play a crucial role in converting ferrous iron (Fe+2) to ferric iron (Fe+3), which is then stored inside the encapsulin in mineralized form. As such, FLPs regulate iron homeostasis and protect organisms against oxidative stress. Recent studies have demonstrated that FLPs have tremendous potential as biosensors and bioreactors because of their ability to catalyze the oxidation of ferrous iron with high specificity and efficiency. Moreover, they have been investigated as potential targets for therapeutic intervention in cancer drug development and bacterial pathogenesis. Further research will likely lead to new insights and applications for these remarkable proteins in biomedicine and biotechnology.

Wildfire Ashes from the Wildland-Urban Interface Alter Vibrio vulnificus Growth and Gene Expression.

Climate change-induced stressors are contributing to the emergence of infectious diseases, including those caused by marine bacterial pathogens such as Vibrio spp. These stressors alter Vibrio temporal and geographical distribution, resulting in increased spread, exposure, and infection rates, thus facilitating greater Vibrio-human interactions. Concurrently, wildfires are increasing in size, severity, frequency, and spread in the built environment due to climate change, resulting in the emission of contaminants of emerging concern. This study aimed to understand the potential effects of urban interface wildfire ashes on Vibrio vulnificus (V. vulnificus) growth and gene expression using transcriptomic approaches. V. vulnificus was exposed to structural and vegetation ashes and analyzed to identify differentially expressed genes using the HTSeq-DESeq2 strategy. Exposure to wildfire ash altered V. vulnificus growth and gene expression, depending on the trace metal composition of the ash. The high Fe content of the vegetation ash enhanced bacterial growth, while the high Cu, As, and Cr content of the structural ash suppressed growth. Additionally, the overall pattern of upregulated genes and pathways suggests increased virulence potential due to the selection of metal- and antibiotic-resistant strains. Therefore, mixed fire ashes transported and deposited into coastal zones may lead to the selection of environmental reservoirs of Vibrio strains with enhanced antibiotic resistance profiles, increasing public health risk.

Japanese value set for the EORTC QLU-C10D: A multi-attribute utility instrument based on the EORTC QLQ-C30 cancer-specific quality-of-life questionnaire.

PURPOSE: This study aimed to develop a Japanese value set for the EORTC QLU-C10D, a multi-attribute utility measure derived from the cancer-specific health-related quality-of-life (HRQL) questionnaire, the EORTC QLQ-C30. The QLU-C10D contains ten HRQL dimensions: physical, role, social and emotional functioning, pain, fatigue, sleep, appetite, nausea, and bowel problems. METHODS: Quota sampling of a Japanese online panel was used to achieve representativeness of the Japanese general population by sex and age (≥ 18 years). The valuation method was an online discrete choice experiment. Each participant considered 16 choice pairs, randomly assigned from 960 choice pairs. Each pair included two QLU-C10D health states and life expectancy. Data were analyzed using conditional logistic regression, parameterized to fit the quality-adjusted life-year framework. Preference weights were calculated as the ratio of each dimension-level coefficient to the coefficient for life expectancy. RESULTS: A total of 2809 eligible panel members consented, 2662/2809 (95%) completed at least one choice pair, and 2435/2662 (91%) completed all choice pairs. Within dimensions, preference weights were generally monotonic. Physical functioning, role functioning, and pain were associated with the largest utility weights. Intermediate utility weights were associated with social functioning and nausea; the remaining symptoms and emotional functioning were associated with smaller utility decrements. The value of the worst health state was - 0.221, lower than that seen in most other existing QLU-C10D country-specific value sets. CONCLUSIONS: The Japan-specific QLU-C10D value set is suitable for evaluating the cost and utility of oncology treatments for Japanese health technology assessment and decision-making.