Mitochondria are dynamic organelles that supply energy required to drive key cellular processes, such as survival, proliferation, and migration. Critical to all of these processes are changes in ...mitochondrial architecture, a mechanical mechanism encompassing both fusion and fragmentation (fission) of the mitochondrial network. Changes to mitochondrial shape, size, and localization occur in a regulated manner to maintain energy and metabolic homeostasis, while deregulation of mitochondrial dynamics is associated with the onset of metabolic dysfunction and disease. In cancers, oncogenic signals that drive excessive proliferation, increase intracellular stress, and limit nutrient supply are all able to alter the bioenergetic and biosynthetic requirements of cancer cells. Consequently, mitochondrial function and shape rapidly adapt to these hostile conditions to support cancer cell proliferation and evade activation of cell death programs. In this review, we will discuss the molecular mechanisms governing mitochondrial dynamics and integrate recent insights into how changes in mitochondrial shape affect cellular migration, differentiation, apoptosis, and opportunities for the development of novel targeted cancer therapies.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To evaluate the 2013 American Heart Association (AHA)-American College of Cardiology (ACC)-Atherosclerotic Cardiovascular Disease (ASCVD) risk score among four different race/ethnic groups and to ...ascertain which factors are most associated with risk overestimation by the AHA-ACC-ASCVD score.
The Multi-Ethnic Study of Atherosclerosis (MESA), a prospective community-based cohort, was used to examine calibration and discrimination of the AHA-ACC-ASCVD risk score in 6441 White, Black, Chinese, and Hispanic Americans (aged 45-79 years and free of known ASCVD at baseline). Using univariable and multivariable absolute risk regression, we modelled the impact of individual risk factors on the discordance between observed and predicted 10-year ASCVD risk. Overestimation was observed in all race/ethnic groups in MESA and was highest among Chinese (252% for women and 314% for men) and lowest in White women (72%) and Hispanic men (67%). Higher age, Chinese race/ethnicity (when compared with White), systolic blood pressure (treated and untreated), diabetes, alcohol use, exercise, lipid-lowering medication, and aspirin use were all associated with more risk overestimation, whereas family history was associated with less risk overestimation in a multivariable model (all P < 0.05).
The AHA-ACC-ASCVD risk score overestimates ASCVD risk among men, women, and all four race/ethnic groups evaluated in a modern American primary prevention cohort. Clinicians treating patients similar to those in MESA, particularly older individuals and those with factors associated with more risk overestimation, may consider interpreting absolute ASCVD risk estimates with caution.
Summary
Background
The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function ...is diminished, increasing skin sensitivity to irritants and allergens.
Objectives
To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation.
Methods
A randomized observer‐blind intrapatient‐controlled study in 34 adults with dry, eczema‐prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier‐transform infrared spectroscopy using a novel interface.
Results
Skin barrier integrity was greater at sites treated with the test cream effect size for area under the transepidermal water loss curve −162, 95% confidence interval (CI) −206 to −118. Skin sensitivity to sodium lauryl sulfate was reduced (−0·5 points visual redness, 97·57% CI −1·00 to −0·25), as was transepidermal water loss (−15·3 g m−2 h−1, 95% CI −20·3 to −10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61–10·6) and decreased signs of dryness.
Conclusions
The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin.
Linked Comment: A.C. Kendall and A. Nicolaou. Br J Dermatol 2022; 186:764–765.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
There is a reasonably extensive body of literature recording mass loss of polyhydroxyalkanoates (PHAs) (a class of biodegradable plastics) in the natural marine environment. However, to date, this ...research has been very disparate. Thus, it remains unclear what the timeframe for the biodegradation of such marine biodegradable plastics actually is. The aim of this work was to determine the rate of biodegradation of PHA in the marine environment and apply this to the lifetime estimation of PHA products. This provides the clarification required as to what ‘marine biodegradation of PHA’ means in practicality and allows the risks and benefits of using PHA to be transparently discussed. It was determined that the mean rate of biodegradation of PHA in the marine environment is 0.04–0.09 mg·day−1·cm−2 (p = 0.05) and that, for example, a PHA water bottle could be expected to take between 1.5 and 3.5 years to completely biodegrade.
•All relevant literature relating to the marine biodegradation of PHA is collated.•The mean rate of biodegradation is 0.04–0.09 mg·day−1·cm−2 (p = 0.05).•Lifetimes of PHA products in the marine environment are estimated.•A PHA bottle has a mean lifetime of 1.5–3.5 yrs, a thin film lasts 0.1–0.2 yrs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ultrathin metal–organic framework (MOF) nanosheets show great potential in various separation applications. In this study, MOF nanosheets are incorporated as a gutter layer in high-performance, ...flexible thin-film composite membranes (TFCMs) for CO2 separation. Ultrathin MOF nanosheets (∼3–4 nm) were prepared via a surfactant-assisted method and subsequently coated onto a flexible porous support by vacuum filtration. This produced an ultrathin (∼25 nm), extremely flat MOF layer, which serves as a highly permeable gutter with reduced gas resistance when compared with conventional polydimethylsiloxane gutter layers. Subsequent spin-coating of the ultrathin MOF gutter layer with a polymeric selective layer (Polyactive) afforded a TFCM exhibiting the best CO2 separation performance yet reported for a flexible composite membrane (CO2 permeance of ∼2100 GPU with a CO2/N2 ideal selectivity of ∼30). Several unique MOF nanosheets were examined as gutter layers, each differing with regard to structure and thickness (∼10 and ∼80 nm), with results indicating that flexibility in the ultrathin MOF layer is critical for optimized membrane performance. The inclusion of ultrathin MOF nanosheets into next-generation TFCMs has the potential for major improvements in gas separation performance over current composite membrane designs.
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IJS, KILJ, NUK, PNG, UL, UM
Protein phase separation is implicated in formation of membraneless organelles, signaling puncta and the nuclear pore. Multivalent interactions of modular binding domains and their target motifs can ...drive phase separation. However, forces promoting the more common phase separation of intrinsically disordered regions are less understood, with suggested roles for multivalent cation-pi, pi-pi, and charge interactions and the hydrophobic effect. Known phase-separating proteins are enriched in pi-orbital containing residues and thus we analyzed pi-interactions in folded proteins. We found that pi-pi interactions involving non-aromatic groups are widespread, underestimated by force-fields used in structure calculations and correlated with solvation and lack of regular secondary structure, properties associated with disordered regions. We present a phase separation predictive algorithm based on pi interaction frequency, highlighting proteins involved in biomaterials and RNA processing.
Social vulnerability indices were created to measure resiliency to environmental disasters based on socioeconomic and population characteristics of discrete geographic regions. They are comprised of ...multiple validated constructs that can also potentially identify geographically vulnerable populations after injury. Our objective was to determine if these indices correlate with injury fatality rates in the US.
We evaluated three social vulnerability indices: The Hazards & Vulnerability Research Institute's Social Vulnerability Index (SoVI), the CDC Social Vulnerability Index (SVI) and the Economic Innovation Group's Distressed Community Index (DCI). We analyzed SVI sub-indices and common individual census variables as indicators of socioeconomic status. Outcomes included age-adjusted county-level overall, firearm, and motor vehicle collision (MVC) deaths per 100,000 population. Linear regression determined the association of injury fatality rates with the SoVI, SVI, and DCI. Bivariate choropleth mapping identified geographic variation and spatial autocorrelation of overall fatality, SoVI, and DCI.
3,137 US counties were included. Only 24.6% of counties fell into the same vulnerability quartile for all three indices. Despite this, all indices were associated with increasing fatality rates for overall, firearm, and MVC fatality. The DCI performed best by model fit, explanation of variance, and diagnostic performance on overall injury fatality. There is significant geographic variation in SoVI, DCI, and injury fatality rates at the county-level across the US, with moderate spatial autocorrelation of SoVI (Moran's I 0.35, p<0.01) and high autocorrelation of injury fatality rates (Moran's I 0.77, p<0.01) and DCI (Moran's I 0.53, p<0.01).
While the indices contribute unique information, higher social vulnerability is associated with higher injury fatality across all indices. These indices may be useful in the epidemiologic and geographic assessment of injury-related fatality rates. Further study is warranted to determine if these indices outperform traditional measures of socioeconomic status and related constructs used in trauma research.
Epidemiological, IV.
Trauma field triage matches injured patients to the appropriate level of care. Prior work suggests the Glasgow Coma Scale motor (GCSm) is as accurate as the total GCS (GCSt) and easier to use. ...However, older patients present with higher GCS for a given injury, and as such, it is unclear if this substitution is advisable. Our objective was to compare the GCS deficit patterns between geriatric and adult patients presenting with severe traumatic brain injury (TBI), as well as the diagnostic performance of the GCSm versus GCSt within the field triage criteria in these populations.
We conducted a retrospective, observational cohort study of patients ≥16 y in the National Trauma Data Bank 2007–2015. GCS deficit patterns were compared between adults (16-65) and geriatric patients (>65). Measures of diagnostic performance of GCSt≤13 versus GCSm≤5 criteria to predict trauma center need (TCN) were compared.
In total, 4,480,185 patients were analyzed (28% geriatric). Geriatric patients more frequently presented with non–motor–only deficits than adults (16.4% versus 12.4%, P < 0.001), and these patients demonstrated higher severe TBI (40.3% versus 36.7%, P < 0.001) and craniotomy (5.8% versus 5.1%, P < 0.001) rates. GCSt was more sensitive and accurate in predicting TCN for geriatric patients and had lower rates of undertriage as compared to GCSm.
Geriatric patients more frequently present with non–motor–only deficits after injury, and this is associated with severe head injury. Substitution of GCSm for GCSt would exacerbate undertriage in geriatric patients and, thus, the total GCS should be maintained for field triage in geriatric patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Intestinal peristalsis is a dynamic physiologic process influenced by dietary and microbial changes. It is tightly regulated by complex cellular interactions; however, our understanding of these ...controls is incomplete. A distinct population of macrophages is distributed in the intestinal muscularis externa. We demonstrate that, in the steady state, muscularis macrophages regulate peristaltic activity of the colon. They change the pattern of smooth muscle contractions by secreting bone morphogenetic protein 2 (BMP2), which activates BMP receptor (BMPR) expressed by enteric neurons. Enteric neurons, in turn, secrete colony stimulatory factor 1 (CSF1), a growth factor required for macrophage development. Finally, stimuli from microbial commensals regulate BMP2 expression by macrophages and CSF1 expression by enteric neurons. Our findings identify a plastic, microbiota-driven crosstalk between muscularis macrophages and enteric neurons that controls gastrointestinal motility.
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•Muscularis macrophages produce BMP2 that activates BMPR on enteric neurons•Enteric neurons produce CSF1 that promotes homeostasis of muscularis macrophages•Macrophage-neuronal crosstalk regulates constitutive gastrointestinal motility•Macrophage-neuronal crosstalk is driven by gut microbiota
A unique population of macrophages residing in the smooth muscle of the gut regulates gastrointestinal motility by communicating with enteric neurons. This macrophage-neuronal dialog is plastic and is affected by intestinal microbiota, a discovery that offers mechanistic insights into gastrointestinal motility disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT Anomaly detection is used to explore the link between data-driven anomalous storms and their socio-economic impact on countries within the North-West Pacific. Three anomaly detection models ...are trialled using three distinct algorithms on the storm tracks and temperature profiles of storms. A feature-based comparison of the top 5% of anomalous storms from each model is used to reveal variations in anomalous storm activity. Further to this, the socio-economic impact of the anomalous storms is assessed, revealing a link between the anomalous behaviour of storms and the impact experienced by countries on their path. A final cross-comparison shows that the k-Nearest Neighbour and Isolation Forest algorithms succeeded at identifying high-impacting storms. However, the agglomerative clustering model found many unique storms that had low impact. This highlights the importance of considering both trajectory and temperature in determining the severity and impact of erroneous storms.
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