Housing typologies and asthma: a scoping review.

Asthma is related to triggers within the home. Although it is recognised that triggers likely occur due to characteristics of housing, these characteristics have not been comprehensively reviewed, and there is a paucity of housing-focused interventions to reduce asthma and asthma symptoms. Following five steps identified by Arksey and O'Malley, we conducted a scoping review of published evidence on the associations between asthma and housing characteristics. We searched three electronic databases (PubMed, Scopus, Web of Science), identifying 33 studies that met our inclusion criteria. Through an iterative approach, we identified nine housing characteristics relevant to asthma onset or exacerbation, categorised as relating to the surrounding environment (location), the house itself (dwelling), or to conditions inside the home (occupancy). We conceptualise these three levels through a housing typologies framework. This facilitates the mapping of housing characteristics, and visualises how they can cluster and overlap to exacerbate asthma or asthma symptoms. Of the three levels in our framework, associations between asthma and locational features were evidenced most clearly in the literature reviewed. Within this category, environmental pollutants (and particularly air pollutants) were identified as a potentially important risk factor for asthma. Studies concerning associations between dwelling features and occupancy features and asthma reported inconsistent results, highlighting the need for greater research in these areas. Interpreting housing-related asthma triggers through this framework paves the way for the identification and targeting of typologies of housing that might adversely affect asthma, thus addressing multiple characteristics in tandem rather than as isolated elements.

Mental illness and increased vulnerability to negative health effects from extreme heat events: a systematic review.

RATIONALE: Across countries, extreme heat events are projected to increase in frequency and intensity because of climate change. Exposure to extreme heat events can have a substantial negative impact on human health, and extant research suggests that individuals with mental illness are particularly vulnerable. To date, there has been no review of evidence regarding this vulnerability to inform response strategies and future research. OBJECTIVE: A systematic review was undertaken to investigate mental illness as an effect modifier of the relationship between heat exposure and morbidity or mortality. METHODS: Six databases (Medline, Embase, Global Health, PsychInfo, CINAHL and Scopus) were searched for studies published between the years 2000 to 2022. Twenty-two observational studies that met the inclusion criteria were investigated through narrative synthesis. The RoBANS tool, ROBIS and GRADE were used to assess the certainty of evidence including the risk of bias. RESULTS: Individuals with mental illness experience worse morbidity and mortality outcomes compared to their counterparts without mental illness in all studies investigating high temperature over a single day. This did not hold for studies examining heatwaves, which reported mixed findings. CONCLUSIONS AND IMPLICATIONS: People with diagnosed mental illness should be targeted for policy and service attention during high temperature days. Further research should investigate specific mental illness and adjust for a wider range of confounding factors.

Cell wounding activates phospholipase D in primary mouse keratinocytes.

Plasma membrane disruptions occur in mechanically active tissues such as the epidermis and can lead to cell death if the damage remains unrepaired. Repair occurs through fusion of vesicle patches to the damaged membrane region. The enzyme phospholipase D (PLD) is involved in membrane traffickiing; therefore, the role of PLD in membrane repair was investigated. Generation of membrane disruptions by lifting epidermal keratinocytes from the substratum induced PLD activation, whereas removal of cells from the substratum via trypsinization had no effect. Pretreatment with 1,25-dihydroxyvitamin D3, previously shown to increase PLD1 expression and activity, had no effect on, and a PLD2-selective (but not a PLD1-selective) inhibitor decreased, cell lifting-induced PLD activation, suggesting PLD2 as the isoform activated. PLD2 interacts functionally with the glycerol channel aquaporin-3 (AQP3) to produce phosphatidylglycerol (PG); however, wounding resulted in decreased PG production, suggesting a potential PG deficiency in wounded cells. Cell lifting-induced PLD activation was transient, consistent with a possible role in membrane repair, and PLD inhibitors inhibited membrane resealing upon laser injury. In an in vivo full-thickness mouse skin wound model, PG accelerated wound healing. These results suggest that PLD and the PLD2/AQP3 signaling module may be involved in membrane repair and wound healing.

Parental co-residence and young adults' mental health.

The growing trend towards young adults staying in the parental home has garnered much recent scholarly interest. However, less is known about which young adults are living at home, and the impacts this has over young adults' lives. Using The Household, Income and Labour Dynamics in Australia (HILDA) dataset, this study examines the profiles of co-residing young adults and how these have changed over the first two decades of the 21st century. It then analyses the associations between co-residence and young adults' mental health, applying a propensity score modelling approach to determine differences in mental health between young adults living at home and their counterparts living independently. Results indicate that rates of co-residence have increased over the 2000s, most steeply amongst those residing outside of major cities (by 46%), older adults (by 36%), females (by 28%), and low-income groups (by 10%). Findings show a significant negative association between co-residence and mental health (a 4-point difference on the 100-point scale, 95% CI -5.93, -2.14). However, the greatest differential in mental health between co-resident and independent young adults is observed amongst those for whom rates of co-residence have increased most dramatically, i.e., females and older adults (a 6-point difference in mental health) and residents of regional and rural areas (a 5-point difference in mental health). We situate this discussion in the context of intensifying housing market constraints, considering how the transformation of the Australian housing system into a vehicle for wealth accumulation has generated barriers to residential independence.

Receptor for advanced glycation end products (RAGE) prevents endothelial cell membrane resealing and regulates F-actin remodeling in a beta-catenin-dependent manner.

Receptor for advanced glycation end products (RAGE), an immunoglobin superfamily cell surface receptor, contributes to the vascular pathology associated with multiple disorders, including Alzheimer disease (AD), diabetic complications, and inflammatory conditions. However, the underlying mechanisms remain largely unclear. Here, using the human umbilical vein endothelial cell line (ECV-304) expressing human RAGE, we report that RAGE expression leads to an altered F-actin organization and impaired membrane resealing. To investigate the underlying mechanisms, we showed that RAGE expression increases ß-catenin level, which decreases F-actin stress fibers and attenuates plasma membrane resealing. These results thus suggest a negative function for RAGE in endothelial cell membrane repair and reveal a new mechanism underlying RAGE regulation of F-actin remodeling and membrane resealing.

Anabolic Function Downstream of TOR Controls Trade-offs Between Longevity and Reproduction at the Level of Specific Tissues in C. elegans.

As the most energetically expensive cellular process, translation must be finely tuned to environmental conditions. Dietary restriction attenuates signaling through the nutrient sensing mTOR pathway, which reduces translation and redirects resources to preserve the soma. These responses are associated with increased lifespan but also anabolic impairment, phenotypes also observed when translation is genetically suppressed. Here, we restricted translation downstream of mTOR separately in major tissues in C. elegans to better understand their roles in systemic adaptation and whether consequences to anabolic impairment were separable from positive effects on lifespan. Lowering translation in neurons, hypodermis, or germline tissue led to increased lifespan under well-fed conditions and improved survival upon withdrawal of food, indicating that these are key tissues coordinating enhanced survival when protein synthesis is reduced. Surprisingly, lowering translation in body muscle during development shortened lifespan while accelerating and increasing reproduction, a reversal of phenotypic trade-offs associated with systemic translation suppression. Suppressing mTORC1 selectively in body muscle also increased reproduction while slowing motility during development. In nature, this may be indicative of reduced energy expenditure related to foraging, acting as a "GO!" signal for reproduction. Together, results indicate that low translation in different tissues helps direct distinct systemic adaptations and suggest that unknown endocrine signals mediate these responses. Furthermore, mTOR or translation inhibitory therapeutics that target specific tissues may achieve desired interventions to aging without loss of whole-body anabolism.

Virtual reality for management of pain in hospitalized patients: A randomized comparative effectiveness trial.

OBJECTIVES: Therapeutic virtual reality (VR) has emerged as an effective, drug-free tool for pain management, but there is a lack of randomized, controlled data evaluating its effectiveness in hospitalized patients. We sought to measure the impact of on-demand VR versus "health and wellness" television programming for pain in hospitalized patients. METHODS: We performed a prospective, randomized, comparative effectiveness trial in hospitalized patients with an average pain score of ≥3 out of 10 points. Patients in the experimental group received a library of 21 VR experiences administered using the Samsung Gear Oculus headset; control patients viewed specialized television programming to promote health and wellness. Clinical staff followed usual care; study interventions were not protocolized. The primary outcome was patient-reported pain using a numeric rating scale, as recorded by nursing staff during usual care. Pre- and post-intervention pain scores were compared immediately after initial treatment and after 48- and 72-hours. RESULTS: There were 120 subjects (61 VR; 59 control). The mean within-subject difference in immediate pre- and post-intervention pain scores was larger in the VR group (-1.72 points; SD 3.56) than in the control group (-0.46 points; SD 3.01); this difference was significant in favor of VR (P < .04). When limited to the subgroup of patients with severe baseline pain (≥7 points), the effect of VR was more pronounced vs. control (-3.04, SD 3.75 vs. -0.93, SD 2.16 points; P = .02). In regression analyses adjusting for pre-intervention pain, time, age, gender, and type of pain, VR yielded a .59 (P = .03) and .56 (P = .04) point incremental reduction in pain versus control during the 48- and 72-hour post-intervention periods, respectively. CONCLUSIONS: VR significantly reduces pain versus an active control condition in hospitalized patients. VR is most effective for severe pain. Future trials should evaluate standardized order sets that interpose VR as an early non-drug option for analgesia.

Understanding the Relationship Between the Neurologic Pupil Index and Constriction Velocity Values.

The pupillary light reflex (PLR) describes the response when light hits the retina and sends a signal (cranial nerve II) to the Edinger-Westphal Nucleus which via cranial nerve III results in pupillary constriction. The Neurological Pupil indexTM (NPi) and pupil constriction velocity (CV) are two distinct variables that can be observed and measured using a pupillometer. We examine NPi and CV in 27,462 pupil readings (1,617 subjects). NPi values <3.0 and a CV < 0.8 mm/sec were considered abnormal. Regression was used to clarify the effect of pupil size and repeated measures. An odds ratio of abnormal CV given normal NPi (and vice versa) was computed using the glimmixed (SAS) regression. Of 27,462 readings, 49.2% revealed bilaterally normal NPi wtih brisk CV, and 10.8% revealed bilaterally abnormal NPi and slow CV; 9.1% with unilaterally normal NPi and brisk CV where the opposite pupil had an abnormal NPi and slow CV. The remaining 30.9% revealed that one or both PLR had either a normal NPi with slow CV, or abnormal NPi with brisk CV. Brisk CV does not rule out an abnormal PLR; slow CV does not rule in abnormal PLR. Practitioners should consider these implications when interpreting pupillometry readings.

Assessing Health Span in Caenorhabditis elegans: Lessons From Short-Lived Mutants.

Genetic changes resulting in increased life span are often positively associated with enhanced stress resistance and somatic maintenance. A recent study found that certain long-lived Caenorhabditis elegans mutants spent a decreased proportion of total life in a healthy state compared with controls, raising concerns about how the relationship between health and longevity is assessed. We evaluated seven markers of health and two health-span models for their suitability in assessing age-associated health in invertebrates using C elegans strains not expected to outperform wild-type animals. Additionally, we used an empirical method to determine the transition point into failing health based on the greatest rate of change with age for each marker. As expected, animals with mutations causing sickness or accelerated aging had reduced health span when compared chronologically to wild-type animals. Physiological health span, the proportion of total life spent healthy, was reduced for locomotion markers in chronically ill mutants, but, surprisingly, was extended for thermotolerance. In contrast, all short-lived mutants had reduced "quality-of-life" in another model recently employed for assessing invertebrate health. Results suggest that the interpretation of physiological health span is not straightforward, possibly because it factors out time and thus does not account for the added cost of extrinsic forces on longer-lived strains.

Virtual Reality for Management of Pain in Hospitalized Patients: Results of a Controlled Trial.

BACKGROUND: Improvements in software and design and reduction in cost have made virtual reality (VR) a practical tool for immersive, three-dimensional (3D), multisensory experiences that distract patients from painful stimuli. OBJECTIVE: The objective of the study was to measure the impact of a onetime 3D VR intervention versus a two-dimensional (2D) distraction video for pain in hospitalized patients. METHODS: We conducted a comparative cohort study in a large, urban teaching hospital in medical inpatients with an average pain score of ≥3/10 from any cause. Patients with nausea, vomiting, dementia, motion sickness, stroke, seizure, and epilepsy and those placed in isolation were excluded. Patients in the intervention cohort viewed a 3D VR experience designed to reduce pain using the Samsung Gear Oculus VR headset; control patients viewed a high-definition, 2D nature video on a 14-inch bedside screen. Pre- and postintervention pain scores were recorded. Difference-in-difference scores and the proportion achieving a half standard deviation pain response were compared between groups. RESULTS: There were 50 subjects per cohort (N=100). The mean pain reduction in the VR cohort was greater than in controls (-1.3 vs -0.6 points, respectively; P=.008). A total of 35 (65%) patients in the VR cohort achieved a pain response versus 40% of controls (P=.01; number needed to treat=4). No adverse events were reported from VR. CONCLUSIONS: Use of VR in hospitalized patients significantly reduces pain versus a control distraction condition. These results indicate that VR is an effective and safe adjunctive therapy for pain management in the acute inpatient setting; future randomized trials should confirm benefit with different visualizations and exposure periods. TRIAL REGISTRATION: Clinicaltrials.gov NCT02456987; https://clinicaltrials.gov/ct2/show/NCT02456987 (Archived by WebCite at http://www.webcitation.org/6pJ1P644S).

Reducing translation through eIF4G/IFG-1 improves survival under ER stress that depends on heat shock factor HSF-1 in Caenorhabditis elegans.

Although certain methods of lowering and/or altering mRNA translation are associated with increased lifespan, the mechanisms underlying this effect remain largely unknown. We previously showed that the increased lifespan conferred by reducing expression of eukaryotic translation initiation factor 4G (eIF4G/IFG-1) enhances survival under starvation conditions while shifting protein expression toward factors involved with maintaining ER-dependent protein and lipid balance. In this study, we investigated changes in ER homeostasis and found that lower eIF4G/IFG-1 increased survival under conditions of ER stress. Enhanced survival required the ER stress sensor gene ire-1 and the ER calcium ATPase gene sca-1 and corresponded with increased translation of chaperones that mediate the ER unfolded protein response (UPRER ). Surprisingly, the heat-shock transcription factor gene hsf-1 was also required for enhanced survival, despite having little or no influence on the ability of wild-type animals to survive ER stress. The requirement for hsf-1 led us to re-evaluate the role of eIF4G/IFG-1 on thermotolerance. Results show that lowering expression of this translation factor enhanced thermotolerance, but only after prolonged attenuation, the timing of which corresponded to increased transcription of heat-shock factor transcriptional targets. Results indicate that restricting overall translation through eIF4G/IFG-1 enhances ER and cytoplasmic proteostasis through a mechanism that relies heavily on hsf-1.

Role of translation initiation factor 4G in lifespan regulation and age-related health.

Inhibiting expression of eukaryotic translation initiation factor 4G (eIF4G) arrests normal development but extends lifespan when suppressed during adulthood. In addition to reducing overall translation, inhibition alters the stoichiometry of mRNA translation in favor of genes important for responding to stress and against those associated with growth and reproduction in C. elegans. In humans, aberrant expression of eIF4G is associated with certain forms of cancer and neurodegeneration. Here we review what is known about the roles of eIF4G in molecular, cellular, and organismal contexts. Also discussed are the gaps in understanding of this factor, particularly with regard to the roles of specific forms of expression in individual tissues and the importance of understanding eIF4G for development of potential therapeutic applications.

Promotion of plasma membrane repair by vitamin E.

Severe vitamin E deficiency results in lethal myopathy in animal models. Membrane repair is an important myocyte response to plasma membrane disruption injury as when repair fails, myocytes die and muscular dystrophy ensues. Here we show that supplementation of cultured cells with α-tocopherol, the most common form of vitamin E, promotes plasma membrane repair. Conversely, in the absence of α-tocopherol supplementation, exposure of cultured cells to an oxidant challenge strikingly inhibits repair. Comparative measurements reveal that, to promote repair, an anti-oxidant must associate with membranes, as α-tocopherol does, or be capable of α-tocopherol regeneration. Finally, we show that myocytes in intact muscle cannot repair membranes when exposed to an oxidant challenge, but show enhanced repair when supplemented with vitamin E. Our work suggests a novel biological function for vitamin E in promoting myocyte plasma membrane repair. We propose that this function is essential for maintenance of skeletal muscle homeostasis.

A novel cellular defect in diabetes: membrane repair failure.

OBJECTIVE: Skeletal muscle myopathy is a common diabetes complication. One possible cause of myopathy is myocyte failure to repair contraction-generated plasma membrane injuries. Here, we test the hypothesis that diabetes induces a repair defect in skeletal muscle myocytes. RESEARCH DESIGN AND METHODS: Myocytes in intact muscle from type 1 (INS2(Akita+/-)) and type 2 (db/db) diabetic mice were injured with a laser and dye uptake imaged confocally to test repair efficiency. Membrane repair defects were also assessed in diabetic mice after downhill running, which induces myocyte plasma membrane disruption injuries in vivo. A cell culture model was used to investigate the role of advanced glycation end products (AGEs) and the receptor for AGE (RAGE) in development of this repair defect. RESULTS: Diabetic myocytes displayed significantly more dye influx after laser injury than controls, indicating a repair deficiency. Downhill running also resulted in a higher level of repair failure in diabetic mice. This repair defect was mimicked in cultured cells by prolonged exposure to high glucose. Inhibition of the formation of AGE eliminated this glucose-induced repair defect. However, a repair defect could be induced, in the absence of high glucose, by enhancing AGE binding to RAGE, or simply by increasing cell exposure to AGE. CONCLUSIONS: Because one consequence of repair failure is rapid cell death (via necrosis), our demonstration that repair fails in diabetes suggests a new mechanism by which myopathy develops in diabetes.

ADHD is associated with a "Western" dietary pattern in adolescents.

OBJECTIVE: To examine the relationship between dietary patterns and ADHD in a population-based cohort of adolescents. METHOD: The Raine Study is a prospective study following 2,868 live births. At the 14-year follow-up, the authors collected detailed adolescent dietary data, allowing for the determination of major dietary patterns using factor analysis. ADHD diagnoses were recorded according to International Classification of Deiseases, 9th Revision coding conventions. Logistic regression was used to assess the relationship between scores for major dietary pattern and ADHD diagnoses. RESULTS: Data were available for 1,799 adolescents, and a total of 115 adolescents had an ADHD diagnosis. Two major dietary patterns were identified: "Western" and "Healthy." A higher score for the Western dietary pattern was associated with ADHD diagnosis (odds ratio=2.21, 95% confidence interval=1.18, 4.13) after adjusting for known confounding factors from pregnancy to 14 years. ADHD diagnosis was not associated with the "Healthy" dietary pattern. CONCLUSION: A Western-style diet may be associated with ADHD.