Unaffected Sites Research Articles

Primary Hyperhidrosis and Sensitive Skin: Exploring the Link with Predictive Machine Learning-Based Classification Models.

Primary hyperhidrosis (PHH) is a disorder of excessive sweating caused by aberrant cholinergic signaling. Sensitive skin (SS) is a condition of subjective cutaneous hyperreactivity to innocuous stimuli, impacting 40% to 70% of the population. SS is exacerbated by sweat, stress, and heat, suggesting that cholinergic stimulation may contribute to SS flares. To survey PHH sufferers to assess hyperhidrosis (HH) and SS symptom burden. An International Review Board (IRB)-exempt survey was disseminated by the International Hyperhidrosis Society. A predictive classification model for SS was built using random forest machine learning algorithms. Of the 637 respondents with PHH, 89% reported SS; and there was a significant association between HH and SS severity scores. Importantly, SS occurred on body sites affected and unaffected by HH. Predictive modeling designated Sensitive Scale-10 (SS-10), a validated questionnaire to gauge SS severity, to be the most helpful in predicting SS in this cohort. Self-reported data. These data are the first to propose and support a relationship between SS and HH. SS occurred with greatest frequency at HH-afflicted body sites, but also occurred on unaffected sites, suggesting that sweat is not the sole causative link. Future work can explore cholinergic signaling as a potential link between these conditions. Screening HH patients for SS may be warranted. J Drugs Dermatol. 2024;23(10):882-888. doi:10.36849/JDD.8461.

Epidermal Barrier Parameters in Psoriasis: Implications in Assessing Disease Severity.

Psoriasis is characterized by an aberrant immune response due to myeloid dendritic cells and T helper cells intertwining with keratinocyte hyperproliferation. Skin integrity alterations may predispose patients to physiological imbalances, such as xerosis, reduced elasticity, and increased friability. This study aims to assess the epidermal barrier dysfunction in chronic plaque psoriasis and gain a comprehensive view of the dynamic changes in the epidermal barrier during various topical therapies. Adult patients with chronic plaque psoriasis were enrolled in this observational study. For each patient, skin barrier parameters, stratum corneum hydration (SCH), transepidermal water loss (TEWL), elasticity, erythema, and melanin levels were measured in lesional and non-lesional skin. Two extensions of the initial study design, with subsequent epidermal barrier determinations, were made as follows: one in which patients with moderate psoriasis were treated with clobetasol propionate 0.5% and the second one in which mild psoriasis was treated with either clobetasol propionate 0.5% or clobetasol propionate 0.5% with 10% urea. TEWL and erythema were found to be higher in the sites affected by psoriatic lesions than the unaffected sites, while SCH and elasticity were decreased. Severe psoriasis presented with higher TEWL (p = 0.032), erythema (p = 0.002), and lower SCH (p < 0.001) compared with the mild and moderate forms. SCH significantly improved during clobetasol propionate 0.5% treatment (p = 0.015). Clobetasol propionate 0.5% with 10% urea was found to be superior to clobetasol propionate 0.5% in improving TEWL and SCH in psoriasis.

Seven years of microbial community metagenomes from temperate soils affected by an ongoing coal seam fire.

We examined the dynamics of soil microbiomes under heat press disturbance from an underground coal mine fire in Centralia, PA. Here, we present metagenomic sequencing and assembly data from soil microbiomes across seven consecutive years at repeatedly sampled fire-affected sites along with unaffected reference sites.

Novel multispectral imaging to predict disease progression in pediatric morphea.

Morphea, or localized scleroderma, is an inflammatory, fibrosing skin disorder that can be progressive and debilitating. Infrared thermography frequently has false positive results. The aim of this study was to assess the ability of multispectral imaging to predict disease progression in children with morphea. Children with morphea were recruited between 2016 and 2022. Multispectral images of affected and matched contralateral unaffected sites were obtained using the Antera™ 3D camera. Clinical assessment was performed using the Localized Scleroderma Assessment Tool (LoSCAT). Children were followed up every 3 months for imaging and clinical review. The main outcome measurement was correlation of hemoglobin gradient between affected and matched contralateral unaffected tissue and progression. Of 17 children, the average age was 12 years (range 6-18 years); most were female (76.5%) and white (94.1%). Nearly two-thirds (64.7%) had linear morphea, 35.2% had plaque morphea; 58.8% had been treated with systemic agents. The average LoSCAT score was 20.6 (range 5-73). The average hemoglobin gradient between affected and matched contralateral unaffected skin was four times higher in those who had progression (average differential 0.3, range 0.1-0.4) compared to those who did not (average differential 0.08, range 0.02-0.15). Using a cut off of a 0.18 hemoglobin gradient between affected and unaffected skin, the sensitivity of multispectral imaging for detecting progression in pediatric morphea is 90% with specificity of 100%. Multispectral imaging is a novel assessment tool with promising accuracy in predicting progression as an adjunct to clinical assessment in pediatric morphea. Further research should examine its performance against thermography.

Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems.

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies and integration with public single-cell transcriptomics data revealed marked differences in immune microniches between healthy and inflamed skin. Tissue-scale cartography further identified core disease features across all active lesions, including the emergence of an inflamed suprabasal epidermal state and the presence of B lymphocytes in lesional skin. Both lesional and distal nonlesional samples were stratified by skin disease severity and not by the presence of systemic disease. This segregation was driven by macrophage-, fibroblast-, and lymphatic-enriched spatial regions with gene signatures associated with metabolic dysfunction. Together, these findings suggest that mild and severe forms of PsO have distinct molecular features and that severe PsO may profoundly alter the cellular and metabolic composition of distal unaffected skin sites. In addition, our study provides a valuable resource for the research community to study spatial gene organization of healthy and inflamed human skin.

Total and arbuscular mycorrhizal fungal communities in the first 3 years after the collapse of the Fundão Dam: are we on the ecosystem recovery pathway?

After the collapse of Fundão Dam in Mariana‐MG, Brazil, the discharge of iron ore mining waste into the Doce River watershed negatively impacted the landscape. Monitoring the composition and species richness of soil microbiota may be useful bioindicators of ecosystem recovery. This study aimed to compare soil chemical properties, total fungal species, and arbuscular mycorrhizal fungi (AMF) in sites unaffected and affected by mining tailings in the first 3 years after the collapse of Fundão Dam. Soil and root samples were collected in dry and rainy seasons over 3 years in unaffected (adjacent forest and pasture) and affected areas (REC1, REC2, and PASTrec) by mine tailings. Changes in soil chemical properties over the sampling period were measured by routine chemical analyses. Total fungi in the soil was determined by high‐throughput sequencing. AMF community was evaluated using spore number, root colonization, and denaturing gradient gel electrophoresis. Affected sites had higher ranges of pH and lower soil organic matter than unaffected sites. Revegetation had a positive effect on soil fungal community. Increased similarity in AMF DGGE analysis was observed in the two sampling sites over time. A high similarity of total fungi and AMF was observed between REC and pasture areas, suggesting that revegetation strategy employed may be heading towards a pasture condition. Thus, post‐disturbance analysis of this study was important to evaluate of ecosystem recovery affected by the rupture of iron ore mining dam and demonstrated that the soil microbiota was a sensitive bioindicator in this long path of ecosystem recovery.

STUDY OF PATHOLOGICAL CHANGES IN THE CONJUNCTIVA AND CORNEA USING IMPRESSION CYTOLOGY IN CASES OF PTERYGIUM: A CROSSSECTIONAL STUDY CONDUCTED AT ONE OF THE TERTIARY CARE CENTERS OF NORTHERN INDIA

Background: Pterygium is a benign, proliferative, degenerative condition of conjunctiva and sub conjunctival tissue that has the potential to impair vision. Impression cytology is the process of removing the outermost layers of ocular surface epithelium using cellulose acetate filter paper. There are various methods to investigate Pterygium, we carried out this study through impression cytology. This was a cross-sectional study carried out in Materials and Methodology: Career Institute of Medical Sciences, Lucknow including 100 patients with pterygium. From each eye, 4 impressions were collected through impression cytology, which included 2 conjunctival and 2 corneal impressions to study thecytological changes occurring throughout inter-palpebral ocular surface in the eye with pterygium. The cytology Results: of the surface cells overlying the pterygium exhibits squamous metaplasia, goblet cell hyperplasia, and keratinization of the epithelial cells. These cytological changes are not only seen over pterygium conjunctiva and cornea around the pterygium but they are also seen over the unaffected sites of the interpalpebral conjunctiva and cornea in the same eye. Conclusion: Pterygium is a graded series of the ocular surface variations occurring through out the inter-palpebral bulbar conjunctiva and cornea, with most advanced variation shappening directly over pterygium surface, confirming that pterygium is certainly anocular surface disorder. This study suggests that impression cytology represents a fast,cost-effective,and non-invasive tool for understanding the pathology of pterygium.

A scuticociliate causes mass mortality of Diadema antillarum in the Caribbean Sea

Echinoderm mass mortality events shape marine ecosystems by altering the dynamics among major benthic groups. The sea urchin Diadema antillarum, virtually extirpated in the Caribbean in the early 1980s by an unknown cause, recently experienced another mass mortality beginning in January 2022. We investigated the cause of this mass mortality event through combined molecular biological and veterinary pathologic approaches comparing grossly normal and abnormal animals collected from 23 sites, representing locations that were either affected or unaffected at the time of sampling. Here, we report that a scuticociliate most similar to Philaster apodigitiformis was consistently associated with abnormal urchins at affected sites but was absent from unaffected sites. Experimentally challenging naïve urchins with a Philaster culture isolated from an abnormal, field-collected specimen resulted in gross signs consistent with those of the mortality event. The same ciliate was recovered from treated specimens postmortem, thus fulfilling Koch's postulates for this microorganism. We term this condition D. antillarum scuticociliatosis.

Genome- and Transcriptome-Wide Association Studies Identify Susceptibility Genes and Pathways for Periodontitis.

Several genes associated with periodontitis have been identified through genome-wide association studies (GWAS); however, known genes only explain a minority of the estimated heritability. We aimed to explore more susceptibility genes and the underlying mechanisms of periodontitis. Firstly, a genome-wide meta-analysis of 38,532 patients and 316,185 healthy controls was performed. Then, cross- and single-tissue transcriptome-wide association studies (TWAS) were conducted based on GWAS summary statistics and the Genotype-Tissue Expression (GTEx) project. Risk genes were evaluated to determine if they were differentially expressed in periodontitis sites compared with unaffected sites using public datasets. Finally, gene co-expression network analysis was conducted to identify the functional biology of the susceptible genes. A total of eight single nucleotide polymorphisms (SNPs) within the introns of lncRNA LINC02141 approached genome-wide significance after meta-analysis. EZH1 was identified as a novel susceptibility gene for periodontitis by TWAS and was significantly upregulated in periodontitis-affected gingival tissues. EZH1 co-expression genes were greatly enriched in the cell-substrate junction, focal adhesion and other important pathways. Our findings may offer a fundamental clue for comprehending the genetic mechanisms of periodontitis.

Exploratory analyses of biomarkers in blood and stratum corneum in patients with atopic dermatitis.

Background:The pathogenesis of atopic dermatitis (AD) involves various mediators, including cytokines and chemokines, which are produced by immune cells, such as dendritic cells and lymphocytes, and non-immune cells, such as epidermal cells. Several mediators, including thymus and activation-regulated chemokine (TARC), are used as biomarkers for AD severity and activity. However, additional local and systemic biomarkers of AD are required.Methods:This study will include 10 male patients with AD and 5 healthy adult males (age range: 20–80 years). The Eczema Area and Severity Index will be used to objectively evaluate the clinical findings. In addition, the severity of eruptions will be assessed on a 5-point scale by scoring symptoms (erythema, edema/papules, oozing/crusting, excoriation, lichenification, and xerosis), and the total intensity will be calculated by adding the symptom scores together. Subjective symptoms will be assessed using a peak pruritus numerical rating scale. Laboratory tests, including measurements of peripheral eosinophil count and serum total immunoglobulin E, TARC, and lactate dehydrogenase levels, will be performed. Using blood samples and extracts of stratum corneum samples obtained by tape stripping, we will conduct an exploratory analysis of protein expression using an antibody array to identify mediators whose levels are significantly altered in patients with AD. After 4 to 8 weeks, blood samples and stratum corneum samples will be collected again from AD patients. Moreover, we will examine whether the candidate proteins can be quantified using enzyme-linked immunosorbent assays.Discussion:This is an important study exploring potential local and systemic biomarkers of AD. The results of this study will be clinically meaningful for the discovery of new biomarkers for diagnosing and assessing the severity of AD.

Azoles May Target Underlying Mechanism(s) of Localized Provoked Vulvodynia

ABSTRACT Introduction Vulvodynia is a crippling disease that drastically reduces the quality of life in women. Chronic, otherwise unexplained pain localized to the vulvar vestibule is the identifying symptom associated with this disease, in which pain lasts greater than three months, often significantly longer, on the order of years. Vulvodynia is difficult to diagnose and assess, let alone deliver adequate treatment due to the disease being poorly understood. We have evidence that suggests the cytochrome P450 (CYP450) family of enzymes is involved in the vulvodynia mechanism and may represent a new therapeutic target. Objective Our goal is to identify underlying mechanisms of disease in vulvodynia to develop improved therapeutic strategies. For this investigation, we focused on CYP450 and specifically aimed to narrow down the list of possible enzymes within this nearly 50 member family that might relieve vulvar pain if targeted. Methods We used a validated primary human fibroblast culture system where each woman serves as her own control. In this model, fibroblasts are cultured from affected and unaffected sites in patients. In addition, fibroblasts are cultured from the same sites in women without the disease. Pro-inflammatory mediator production, specifically prostaglandin E2 (PGE2) and interleukin-6 (IL-6) are surrogate measures of pain, which we measured via ELISA assays. We evaluated the role of CYP450 in vulvar pain by antagonizing specific family members to (1) determine if CYP450 is a reasonable target for therapeutic intervention, (2) pinpoint family members of interest, and (3) evaluate if azoles used to treat vulvovaginal yeast infection, which are known to target CYP450, would have therapeutic effect for vulvodynia. Results We found that azoles commonly used to treat vulvovaginal yeast infection (e.g. miconazole and terconazole) reduced pro-inflammatory mediator production in fibroblasts. Miconazole and terconazole target a similar group of CYPs, suggesting that CYP2C9, CYP2C19, CYP3A4, and CYP3A7 may be involved in the vulvodynia mechanism. Global inhibition of the CYP family with 1-aminobenzotriazole also reduced pro-inflammatory mediator production, which may mean that targeting any one CYP or group of CYPs could be effective. This is potentially promising information as it could mean that any azole approved for vulvovaginal use would address vulvodynia symptoms. We are currently investigating this possibility. Conclusions As we uncover additional pieces of the vulvodynia mechanism, we identify new avenues for improved patient care. Based on published clinical data and our in vitro findings, azoles may have a role in treating vulvodynia. Disclosure No

Invertebrate metal accumulation and toxicity from sediments affected by the Mount Polley mine disaster.

On August 4, 2014, a tailings dam failed at the Mount Polley copper and gold mine near Likely, British Columbia, Canada, releasing approximately 25 M m[Formula: see text] of contaminated water and solid tailings material into Polley and Quesnel lakes. Water, sediment, freshwater scuds (Hyalella azteca), and mayfly larvae (Ephemeroptera) were collected during the summer of 2018 from Polley Lake, affected and unaffected sites in Quesnel Lake, and both mine-contaminated and clean far-field sites as references. Analytical results indicated that invertebrates from sites affected by the tailings breach had elevated metal concentrations relative to those from non-affected or reference sites. We conducted a controlled laboratory exposure to determine if laboratory-reared Hyalella azteca metal concentrations were related to field-collected water or sediments from the same sites as the field study. Half of the replicates prevented amphipods from directly contacting sediments (water-only exposure), while the other half allowed them direct access (sediment and water exposure). Whole-body Cu concentration was highest in Hyalella exposed to substrate from the most contaminated sites as well as in treatments where they were allowed direct access to sediments. Hyalella having direct access to metal-contaminated sediments showed reduced survival and growth relative to those in reference or control treatments. These results suggest that metals from the fine sediments associated with the Mount Polley mine disaster are bioavailable and potentially toxic to epibenthic invertebrates, even several years after the initial breach.

Effects of Trace Metals and Municipal Wastewater on the Ephemeroptera, Plecoptera, and Trichoptera of a Stream Community.

Simple SummaryMayflies (Ephemeroptera), stoneflies (Plecoptera), and caddisflies (Trichoptera) (EPT) are aquatic insects that are well known to the general public and are commonly used as indicators of environmental quality in water management. Knowledge of how EPT communities react to human-induced gradients in real environments can be important, for example, during the assessment of the implications of newly planned or currently active human disturbances for natural or cultural landscapes. We sampled a stream ecosystem affected by mining and smelting industries and communal wastewaters with pronounced concentrations of cadmium, lead, and zinc, as well as high levels of pesticides, pharmaceuticals, illegal drugs, and sewage-derived organic matter. Changes in other environmental factors such as increases in temperature were also studied at the affected sites. The abundance and species richness of stoneflies fell rapidly at the study sites. The richness of mayfly families also declined, from four to one, even though overall mayfly abundance was not affected. Conversely, the abundances of caddisflies were higher at the affected sites, and their richness did not decrease. This study will provide feedback for ecotoxicologists who perform better controlled and manipulated tests in laboratories, although any such test results are limited by simple artificial environments.Abundances of EPT larvae sampled in a Central European locality affected by mining and smelting, as well as by the continual inflow of treated communal wastewaters (WWs), were recorded. High concentrations of trace metals in water (maximum 1200 µg·L–1 for zinc) and sediments (maximum 140,000 mg·kg–1 in dry weight for lead) were found at the most contaminated sites. The highest loads of pesticides, pharmaceuticals, and illegal drugs were found under the WW effluent. Other associated factors such as the physicochemical parameters of the water and alterations to microhabitats were also evaluated and taken into account. Although EPT richness was lower at affected sites, abundances did not fall. Stoneflies were dominant at unaffected sites, while caddisflies dominated at affected sites. Only baetid mayflies were detected at the sites contaminated by trace metals and WWs; ephemerellid, heptageniid, and leptophlebiid mayflies were absent from these sites. The site contaminated by trace metals was also inhabited by numerous limnephilid caddisflies, in which limb malformations were detected in up to 11.8% of all specimens of a single taxon. Downstream from the entrance of the WWs, the locality was dominated by hydropsychid caddisflies. The increasing prevalence of predator or passive filter-feeding strategies in these EPT communities was significantly related to increasing water conductivity and acute ecosystemic exposure to ‘poorly treated’ WWs.

The proper choice of proxies for relevant strontium isotope baselines used for provenance and mobility studies in glaciated terranes – Important messages from Denmark

Strontium (Sr) isotope based provenance and mobility studies of ancient humans and animals necessitate representative isoscapes/baselines. However, regions/terranes that were shaped and affected by glaciers during the last Ice Ages and are covered by glaciogenic sediments present a challenge with regards to the choice of suitable surface proxy archives. Recent studies proposed that only 87Sr/86Sr signatures from pristine areas are relevant for this purpose.To test this theory, 160 new Sr concentrations [Sr] and 87Sr/86Sr signatures composed from ~960 subsamples of soil leachates and plants, complemented with 55 surface waters from agriculturally unaffected pristine forest sites from all over Denmark (island of Bornholm excluded) were analyzed. The results reveal that average 87Sr/86Sr signatures of all three proxies (plants: 0.7115 ± 0.0025; 2σ, n = 162; soil leachates: 0.7118 ± 0.0037; 2σ; n = 161, surface waters: 0.7104 ± 0.0030; 2σ, n = 55) are elevated compared to larger water bodies (creeks, rivers, lakes). In mixing diagrams, the data converge in a shared high [Sr] low 87Sr/86Sr endmember, which points to either remnant natural carbonates and/or organic components retaining carbonate Sr in the studied Podzols/Luvisols. The indications for more abundant carbonates in the past, compared to today's acid leached soils, implies that 87Sr/86Sr values measured from pristine forest locations and heathlands do not adequately reflect the biosphere compositions that prevailed ~12,000–2000 thousand years ago. Consequently, pristine forests in Denmark seem to be unsuitable proxy archive environments for constructing Sr isotope baselines for determining the provenance and mobility of ancient humans and animals. Hence, 87Sr/86Sr values measured in these pristine areas are non-representative and inadequate, and their use will lead to wrong interpretations.Finally, our study sheds light on the complexity of defining relevant and representative isoscapes/baselines in significantly changing environments and areas where the surface biosphere conditions do not necessary reflect the underlying geology.

Tree-ring stable isotopes indicate mass wasting processes at Radicofani in the upper Orcia Valley (Tuscany, Italy)

Tree-ring carbon (C) and oxygen (O) stable isotope (SI) chronologies spanning the period 1983–2012 were analysed at three Pinus nigra Arn. sites located in the upper Orcia Valley (Tuscany, Italy) in a badlands landscape. The goal of the study was to determine the extent to which tree-ring stable isotopes (SI) can serve as a proxy for mass wasting processes. To this end, we applied an established dual-isotope model to detect physiological changes between trees growing at three sites, one along the upper border of a well-studied shallow landslide, one on the landslide, and one in a stable area, as control. We further analysed whether trees at the three sites showed different δ18O responses to climate and to precipitation δ18O. Tree-ring δ13C and δ18O variations and trends revealed impairments of the photosynthetic process at the landslide site. We found that trees growing on the landslide show signs of reduced photosynthetic capacity since the onset of the landslide in 1993, whereas since 2000, while producing compression wood during periods of landslide activity, the trees show trends of higher average maximum net photosynthesis. The correlation analysis performed between the SI chronologies and the climatic variables revealed that the climatic signals at the site located on the landslide are masked by growth stress induced by the mass wasting processes. The most distinct differences in climate responses between sites were found in tree-ring δ13C in response to mean temperature and to mean temperature range, and in tree-ring δ18O in response to precipitation δ18O. Our research confirms that it is possible to reconstruct mass-wasting processes on forested slopes and to date geomorphological events by considering the trees' physiological conditions as recorded by stable C and O isotopes in tree rings, and by comparing affected with unaffected sites.

Ecological assessment of high sediment loads based on macroinvertebrate communities in the Bohemian Massif in Austria – A sensitivity analysis

Sediment dynamics and composition in streams are key factors influencing the habitat quality of aquatic organisms, consequently playing an important role in terms of river restoration. The superposition of the river-bed with fine sediments is an increasing global stressor affecting local habitat diversity and leading to changes of benthic communities. We analysed benthic macroinvertebrates in five streams of the Bohemian Massif from morphologically unaffected reference sites, and impacted sites influenced by fine sediment deposition (D = 1 mm – 10 mm) of different intensity. Siltation resulted in a gradually decline in biodiversity, abundance and biomass of macroinvertebrates linked with increasing fine sediment deposition. While for reference sites, dominated by coarse substrates, a specific community was allocated, no characteristic fauna was identified for the impacted sites. However, the results of the EU Water Framework Directive compliant Austrian national method for assessing the ecological status did not react accordingly. Solely streams highly impacted by fine sediment deposition in combination with low river-bed heterogeneity and non-natural riparian conditions indicated status shifts. Based on positive faunal responses to micro-habitats such as woody debris we recommend to support the introduction of small-scaled river restorations and anthropogenic initiated river-type specific stable structural elements (e.g. large stones) serving as refugial habitats, which can result in a significant improvement of macroinvertebrate diversity and composition.

Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel–Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study

ABSTRACTPurposePIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients.MethodsPatients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day). The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of (1) tissue volume at affected and unaffected sites, both clinically and on imaging; (2) cutaneous vascular outcomes when relevant; (3) biologic parameters; (4) quality of life; and (5) patient-reported outcomes.ResultsAmong 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1 mg cohort (n = 6). No significant reduction in affected tissue volume was observed (mean −4.2%; p = 0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement).ConclusionDespite functional improvement, the safety profile of low-dose taselisib precludes its long-term use.

Catchment water quality in the year preceding and immediately following restoration of a drained afforested blanket bog

The restoration of drained afforested peatlands, through drain blocking and tree removal, is increasing in response to peatland restoration targets and policy incentives. In the short term, these intensive restoration operations may affect receiving watercourses and the biota that depend upon them. This study assessed the immediate effect of ‘forest-to-bog’ restoration by measuring stream and river water quality for a 15 month period pre- and post-restoration, in the Flow Country peatlands of northern Scotland. We found that the chemistry of streams draining restoration areas differed from that of control streams following restoration, with phosphate concentrations significantly higher (1.7–6.2 fold, mean 4.4) in restoration streams compared to the pre-restoration period. This led to a decrease in the pass rate (from 100 to 75%) for the target “good” quality threshold (based on EU Water Framework Directive guidelines) in rivers in this immediate post-restoration period, when compared to unaffected river baseline sites (which fell from 100 to 90% post-restoration). While overall increases in turbidity, dissolved organic carbon, iron, potassium and manganese were not significant post-restoration, they exhibited an exaggerated seasonal cycle, peaking in summer months in restoration streams. We attribute these relatively limited, minor short-term impacts to the fact that relatively small percentages of the catchment area (3–23%), in our study catchments were felled, and that drain blocking and silt traps, put in place as part of restoration management, were likely effective in mitigating negative effects. Looking ahead, we suggest that future research should investigate longer term water quality effects and compare different ways of potentially controlling nutrient release.

Single-cell immunopathology of systemic contact allergy associated with corticosteroids

Rationale Allergic contact dermatitis (ACD) is a classic delayed hypersensitivity reaction commonly associated with corticosteroids that can rarely manifest as a delayed rash following systemic administration. Methods A 50-year old woman developed local edema and delayed spreading rash following interarticular injection with dexamethasone and methylprednisolone acetate (MA). 6-months following this intradermal skin testing (IDST) was positive to MA and methylprednisolone sodium succinate, and IDST and patch test negative to other corticosteroids. She tolerated dexamethasone challenge. Cells were isolated from 4-mm punch biopsies from 48-hour positive IDST and unaffected skin with liberase digestion and sorted on CD3. scTCR and scRNA-seq were performed using plate-based assays (Smart-seq-2). Data was filtered using Seurat and analysed with Visual Genomics Analysis Studio (VGAS) software. Results Histopathology showed a superficial perivascular dermatitis with epidermal spongiosis in keeping with ACD. T-cells were 18x more prevalent in affected skin and those from both affected and unaffected sites were predominantly CD8+ T-cells that expressed CD45RO and polyclonal TCR alpha beta. Differentially expressed genes (DEG) in T-cells from affected skin reflected homing (CCR7,S1PR1), T-cell activation and proliferation (TNFRS9, GRAP2, ZYG11A, ZHX1), T-cell effector differentiation (IL-21R), and stress survival (EEF1A1, IFI6) without representation of markers of T-cell residency (ITGAE) or regulation. Conclusions We demonstrate insights into the immunopathogenesis of drug-induced ACD by showing that IDST+ methylprednisolone associated ACD is corticosteroid-specific and associated with a polyclonal population of primarily CD45RO+ memory CD8+ T-cells showing upregulation of markers of homing, T-cell activation, proliferation and differentiation but lacking markers of T-cell residency and regulation.

Twitter, disasters and cultural heritage: A case study of the 2015 Nepal earthquake

AbstractThe purpose of this paper was to understand how Twitter users responded to the cultural heritage damaged during the 2015 Nepal earthquake. This paper utilizes 201,457 tweets (including retweets) from three different data sets. The analysis shows that approximately 4% of tweets were regarding cultural heritage. Moreover, asymmetrical information was available on Twitter regarding cultural heritage during the Nepal earthquake, that is not every site received equal attention from the public. Damaged sites received more attention than unaffected sites. The content of tweets can be divided into five categories: information, sentiment, memory, action and noise. Most people (89.1%) used Twitter during the disaster to disseminate information regarding damaged cultural heritage sites.