What is the evidence-base for atopic eczema treatments? A summary of published randomised controlled trials

Atopic eczema (AE) is a common chronic inflammatory skin condition. Whilst many AE treatment options are available, the evidence to support their efficacy varies in depth and quality. In 2000, an NIHR HTA systematic review identified and evaluated existing randomised controlled trials (RCTs) of AE treatments. To ensure continuing utility, the NIHR commissioned an update to the review. Here, we present an overview of the updated report and key findings. Systematic reviews and RCTs of AE treatments that included participants with AE (criteria based or diagnosed) were identified using: MEDLINE, EMBASE, CENTRAL, LILACS, AMED, CINAHL and Cochrane Skin Group Specialised Register (searched to August 31st 2013 (RCTs) and 31st December 2015 (systematic reviews)). Outcome measures included: symptoms, AE severity, quality-of-life, and adverse effects. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Of the 287 new RCTs identified, only 22 (8%) were judged to be low risk of bias. When combined with RCTs from the previous review (n= 254), we found ‘reasonable evidence of benefit’ for corticosteroids, calcineurin inhibitors, Atopiclair™, ciclosporin, azathioprine, ultraviolet light and education programmes. Interventions with reasonable evidence of ‘no benefit’ included some dietary interventions, ion exchange water softeners, multiple daily applications of topical corticosteroids and antibiotic-containing corticosteroids for non-infected AE. Many common treatments lack evidence of efficacy and warrant further evaluation. The evidence base for AE is still hampered by poor trial design and reporting. The trials included in this review were used to establish the Global Resource of Eczema Trials (GREAT) Database

Multi-omic approaches to investigate molecular mechanisms in peach post-harvest ripening

Peach post-harvest ripening is a complex developmental process controlled by a plethora of genetic and epigenetic factors. Specifically, it leads to protein, lipid and nucleic acid degradation, all resulting in cell death. Substantial research has been directed at investigating peach regulatory mechanisms underlying genomic, metabolomic and transcriptomic modifications occurring during this stage, and much progress has been made thanks to the advent of Next Generation Sequencing technologies. This review is focused on the latest multi-omics studies, with the aim of highlighting the most significant results and further investigating the regulation of the key genes involved in peach post-harvest processes and related physiology. By offering an exhaustive overview of peach omics profiles, it provides a comprehensive description of gene expression changes and their correlation with ripening stages, including some post-harvest treatments, as well as with volatile organic compound modifications. However, the present work highlights that, due to the complexity of the process, recent investigations do not elucidate all underlying molecular mechanisms, making further studies still necessary. For this reason, some key points for future research activities and innovative peach breeding programs are discussed, relying on trusted multi-omic approaches

Dementia assessment and management in primary care settings: a survey of current provider practices in the United States.

BACKGROUND:Primary care providers (PCPs) are typically the first to screen and evaluate patients for neurocognitive disorders (NCDs), including mild cognitive impairment and dementia. However, data on PCP attitudes and evaluation and management practices are sparse. Our objective was to quantify perspectives and behaviors of PCPs and neurologists with respect to NCD evaluation and management. METHODS:A cross-sectional survey with 150 PCPs and 50 neurologists in the United States who evaluated more than 10 patients over age 55 per month. The 51-item survey assessed clinical practice characteristics, and confidence, perceived barriers, and typical practices when diagnosing and managing patients with NCDs. RESULTS:PCPs and neurologists reported similar confidence and approaches to general medical care and laboratory testing. Though over half of PCPs performed cognitive screening or referred patients for cognitive testing in over 50% of their patients, only 20% reported high confidence in interpreting results of cognitive tests. PCPs were more likely to order CT scans than MRIs, and only 14% of PCPs reported high confidence interpreting brain imaging findings, compared to 70% of specialists. Only 21% of PCPs were highly confident that they correctly recognized when a patient had an NCD, and only 13% were highly confident in making a specific NCD diagnosis (compared to 72 and 44% for neurologists, both p < 0.001). A quarter of all providers identified lack of familiarity with diagnostic criteria for NCD syndromes as a barrier to clinical practice. CONCLUSIONS:This study demonstrates how PCPs approach diagnosis and management of patients with NCDs, and identified areas for improvement in regards to cognitive testing and neuroimaging. This study also identified all providers' lack of familiarity with published diagnostic criteria for NCD syndromes. These findings may inform the development of new policies and interventions to help providers improve the efficacy of their decision processes and deliver better quality care to patients with NCDs

Gender Equity in Transplantation: A Report From the Women in Transplantation Workshop of The Transplantation Society of Australia and New Zealand

The exponential growth of young talented women choosing science and medicine as their professional career over the past decade is substantial. Currently, more than half of the Australian medical doctoral graduates and early career researchers are comprised of women, but less than 20% of all academic professorial staff are women. The loss of female talent in the hierarchical ladder of Australian academia is a considerable waste of government investment, productivity, and scientific innovation. Gender disparity in the professional workforce composition is even more striking within the field of transplantation. Women are grossly underrepresented in leadership roles, with currently no female heads of unit in any of the Australian and New Zealand transplanting centers. At the same time, there is also gender segregation with a greater concentration of women in lower-status academic position compared with their male counterparts. Given the extent and magnitude of the disparity, the Women in Transplantation Committee, a subcommittee of The Transplantation Society of Australia and New Zealand established a workshop comprising 8 female clinicians/scientists in transplantation. The key objectives were to (i) identify potential gender equity issues within the transplantation workforce; (ii) devise and implement potential strategies and interventions to address some of these challenges at a societal level; (iii) set realistic and achievable goals to enhance and facility gender equality, equity, and diversity in transplantation

Tolerogenic dendritic cells protect against acute kidney injury

Ischemia reperfusion injury is a common precipitant of acute kidney injury that occurs following disrupted perfusion to the kidney. This includes blood loss and hemodynamic shock, as well as during retrieval for deceased donor kidney transplantation. Acute kidney injury is associated with adverse long-term clinical outcomes and requires effective interventions that can modify the disease process. Immunomodulatory cell therapies such as tolerogenic dendritic cells remain a promising tool, and here we tested the hypothesis that adoptively transferred tolerogenic dendritic cells can limit kidney injury. The phenotypic and genomic signatures of bone marrow–derived syngeneic or allogeneic, Vitamin-D3/IL-10–conditioned tolerogenic dendritic cells were assessed. These cells were characterized by high PD-L1:CD86, elevated IL-10, restricted IL-12p70 secretion and a suppressed transcriptomic inflammatory profile. When infused systemically, these cells successfully abrogated kidney injury without modifying infiltrating inflammatory cell populations. They also provided protection against ischemia reperfusion injury in mice pre-treated with liposomal clodronate, suggesting the process was regulated by live, rather than reprocessed cells. Co-culture experiments and spatial transcriptomic analysis confirmed reduced kidney tubular epithelial cell injury. Thus, our data provide strong evidence that peri-operatively administered tolerogenic dendritic cells have the ability to protect against acute kidney injury and warrants further exploration as a therapeutic option. This technology may provide a clinical advantage for bench-to-bedside translation to affect patient outcomes

Physiological, metabolite and volatile analysis of cut size in melon during postharvest storage

Melons are an important component of fresh fruit salads, however, they suffer from limited shelf life. Processing of melon fruit for use in fruit salads induces a number of changes including alterations in colour and texture. In addition, respiration rate and ethylene production are affected. Processing also elicits changes in flavour (sweetness) and aroma (production of volatile organic compounds – VOCs), of critical importance to the consumer. Several parameters govern shelf life; temperature is a critical factor. In this study we tested whether cut size is another parameter that can affect quality indicators. Melon (Cucumis melo ‘Arapaho’) cubes of three sizes were stored at 4°C and assessed for quality at five time-points over a 15-day period. We assessed a number of parameters including firmness, loss of fresh weight, respiration rate, antioxidant capacity, phenolic compounds and carotenoid content. In addition we measured VOC profiles to assess whether there were any qualitative changes associated with storage period and/or cut size. Fresh weight (FW) loss and respiration rate increased significantly with storage time and FW loss was affected by cut size. Total carotenoid levels remained stable during the storage time as did antioxidant capacity in all cut sizes. However, cinnamic acid levels tended to decrease in the last stage of the storage period and changes in β-carotene content correlated with cut size (though not significantly). We were also able to separate the VOC profiles from the different cut sizes indicating that VOCs may be useful markers as indicators of the effects of cut size and storage time on quality

Scoping systematic review of treatments for eczema

Background: Eczema is a very common chronic inflammatory skin condition.Objectives: To update the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) systematic review of treatments for atopic eczema, published in 2000, and to inform health-care professionals, commissioners and patients about key treatment developments and research gaps.Data sources: Electronic databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Skin Group Specialised Register, Latin American and Caribbean Health Sciences Literature (LILACS), Allied and Complementary Medicine Database (AMED) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from the end of 2000 to 31 August 2013. Retrieved articles were used to identify further randomised controlled trials (RCTs).Review methods: Studies were filtered according to inclusion criteria and agreed by consensus in cases of uncertainty. Abstracts were excluded and non-English language papers were screened by international colleagues and data were extracted. Only RCTs of treatments for eczema were included, as other forms of evidence are associated with higher risks of bias. Inclusion criteria for studies included availability of data relevant to the therapeutic management of eczema; mention of randomisation; comparison of two or more treatments; and prospective data collection. Participants of all ages were included. Eczema diagnosis was determined by a clinician or according to published diagnostic criteria. The risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. We used a standardised approach to summarising the data and the assessment of risk of bias and we made a clear distinction between what the studies found and our own interpretation of study findings.Results: Of 7198 references screened, 287 new trials were identified spanning 92 treatments. Trial reporting was generally poor (randomisation method: 2% high, 36% low, 62% unclear risk of bias; allocation concealment: 3% high, 15% low, 82% unclear risk of bias; blinding of the intervention: 15% high, 28% low, 57% unclear risk of bias). Only 22 (8%) trials were considered to be at low risk of bias for all three criteria. There was reasonable evidence of benefit for the topical medications tacrolimus, pimecrolimus and various corticosteroids (with tacrolimus superior to pimecrolimus and corticosteroids) for both treatment and flare prevention; oral ciclosporin; oral azathioprine; narrow band ultraviolet B (UVB) light; Atopiclair™ and education. There was reasonable evidence to suggest no clinically useful benefit for twice-daily compared with once-daily topical corticosteroids; corticosteroids containing antibiotics for non-infected eczema; probiotics; evening primrose and borage oil; ion-exchange water softeners; protease inhibitor SRD441 (Serentis Ltd); furfuryl palmitate in emollient; cipamfylline cream; and Mycobacterium vaccae vaccine. Additional research evidence is needed for emollients, bath additives, antibacterials, specialist clothing and complementary and alternative therapies. There was no RCT evidence for topical corticosteroid dilution, impregnated bandages, soap avoidance, bathing frequency or allergy testing

Effect of temperature and cut size on the volatile organic compound profile, and expression of Chorismate synthase in fresh-cut melon

The postharvest quality of fresh-cut melon is strongly affected by storage conditions to which it is subjected. During postharvest, fruit undergoes several stresses and its physiology is similar to that in senescent tissues. This affects both its biochemistry and the expression of genes involved in secondary metabolite biosynthesis. Volatile organic compounds (VOCs) have been used previously to assess quality of fresh cut melon as they reflect changes in flavor and also changes in overall metabolism. Chorismate synthase (CS) is a key enzyme in the shikimate pathway and catalyzes the formation of chorismate, which is the precursor of numerous aromatic compounds in plants. In this work the effects of different storage temperatures and cut-sizes were studied, with the aim of identifying effects on flavor through changes in VOCs, and molecular responses of the CmCS gene to different postharvest conditions. Melon (Cucumis melo L. 'Macigno') fruits were harvested at a fully ripened commercial stage, were washed in a chlorine water solution, and the mesocarp (pulp) was cut in cube-shaped portions; two sizes were chosen, 1×1 and 3×2 cm. Melon cubes were then stored at 20 or 4°C. VOCs were assessed in the 3×2 cut size at both temperatures and showed clear changes during storage. A subset of VOCs were shown to correlate negatively with storage time and temperature and from these, specific compounds can be identified that act as markers for an overall change in VOC profiles. CmCS was more affected by temperature, showing decreased levels of expression during storage at 20°C with respect to harvest and to cold storage. On the other hand, cut-size did not result in changes in its expression in 3×2 cut size

St. Louis Area Earthquake Hazards Mapping Project: Seismic and Liquefaction Hazard Maps

We present probabilistic and deterministic seismic and liquefaction hazard maps for the densely populated St. Louis metropolitan area that account for the expected effects of surficial geology on earthquake ground shaking. Hazard calculations were based on a map grid of 0.005°, or about every 500 m, and are thus higher in resolution than any earlier studies. To estimate ground motions at the surface of the model (e.g., site amplification), we used a new detailed near-surface shear-wave velocity model in a 1D equivalent- linear response analysis. When compared with the 2014 U.S. Geological Survey (USGS) National Seismic Hazard Model, which uses a uniform firm-rock-site condition, the new probabilistic seismic-hazard estimates document much more variability. Hazard levels for upland sites (consisting of bedrock and weathered bedrock overlain by loess-covered till and drift deposits), show up to twice the ground-motion values for peak ground acceleration (PGA), and similar ground-motion values for 1.0 s spectral acceleration (SA). Probabilistic ground-motion levels for lowland alluvial floodplain sites (generally the 20-40-m-thick modern Mississippi and Missouri River floodplain deposits overlying bedrock) exhibit up to twice the ground-motion levels for PGA, and up to three times the ground-motion levels for 1.0 s SA. Liquefaction probability curves were developed from available standard penetration test data assuming typical lowland and upland water table levels. A simplified liquefaction hazard map was created from the 5%-in-50-year probabilistic ground-shaking model. The liquefaction hazard ranges from low (\u3c40% of area expected to liquefy) in the uplands to severe (\u3e60% of area expected to liquefy) in the lowlands. Because many transportation routes, power and gas transmission lines, and population centers exist in or on the highly susceptible lowland alluvium, these areas in the St. Louis region are at significant potential risk from seismically induced liquefaction and associated ground deformation

Identifying volatile and non‐volatile organic compounds to discriminate cultivar, growth location, and stage of ripening in olive fruits and oils

BACKGROUND: There is increasing consumer demand for olive oil to be traceable. However, genotype, environmental factors, and stage of maturity, all affect the flavor and composition of both the olives and olive oil. Few studies have included all three variables. Key metabolites include lipids, phenolics, and a wide range of volatile organic compounds (VOCs), which provide the olives and oil with their characteristic flavor. Here we aim to identify markers that are able to discriminate between cultivars, that can identify growth location, and can discriminate stages of fruit maturity. ‘Nocellara messinese’ and ‘Carolea’ olive fruits were grown at three locations differing in altitude in Calabria, Italy, and harvested at three stages of maturity. Oil was analyzed from the two most mature stages. RESULTS: Nine and 20 characters discriminated all fruit and oil samples respectively, and relative abundance of two fatty acids distinguished all oils. Whole VOC profiles discriminated among the least mature olives, and oil VOC profiles discriminated location and cultivar at both stages. Three VOCs putatively identified as hexanal, methyl acetate, and 3-hexen-1-ol differentiated all samples of oils from the most mature fruit stage. CONCLUSION: The results confirm that interactions of location, cultivar and fruit maturity stage are critical for the overall pattern of aroma compounds, and identify potential markers of commercial relevance. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry