125 research outputs found

    Identifying Epidermolysis Bullosa Patient Needs and Perceived Treatment Benefits:An Explorative Study Using the Patient Benefit Index

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    Epidermolysis bullosa (EB) is a genetic blistering skin condition for which no cure exists. Symptom alleviation and quality of life are therefore central to EB care. This study aimed to gain insight into EB patient needs and benefits from current clinical care. Two questionnaires were administered cross-sectionally to adult EB patients at the Dutch expertise centre for blistering diseases. Patient needs and benefits were analyzed using the patient benefit index survey (PBI-S). Ancillary data were compiled pertaining to self-reported EB severity, pain and pruritus, as well as current and previous treatments. In total, 104 participants were included (response rate 69.8%). Sixty-eight participants comprised the analyzed cohort (n = 36 omitted from analysis). The needs given the highest importance were to get better skin quickly (64.7%) and to be healed of all skin alterations (61.8%). A positive correlation between pain and EB severity and the importance of most needs was observed. Minimal clinically important differences within the PBI-S, relating to reported benefits from clinical care, were reported by 60.3% of the cohort. This study highlights a discrepancy between patient needs and feasible treatment outcomes. Utilizing the PBI-S in conjunction with well-established multidisciplinary care may catalyze the process of tailoring treatments to the needs of individual patients

    Reef state and performance as indicators of cumulative impacts on coral reefs

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    Coral bleaching, cyclones, outbreaks of crown-of-thorns seastar, and reduced water quality (WQ) threaten the health and resilience of coral reefs. The cumulative impacts from multiple acute and chronic stressors on “reef State” (i.e., total coral cover) and “reef Performance” (i.e., the deviation from expected rate of total coral cover increase) have rarely been assessed simultaneously, despite their management relevance. We evaluated the dynamics of coral cover (total and per morphological groups) in the Central and Southern Great Barrier Reef over 25 years, and identified and compared the main environmental drivers of State and Performance at the reef level (i.e. based on total coral cover) and per coral group. Using a combination of 25 environmental metrics that consider both the frequency and magnitude of impacts and their lagged effects, we find that the stressors that correlate with State differed from those correlating with Performance. Importantly, we demonstrate that WQ metrics better predict Performance than State. Further, inter-annual dynamics in WQ (here available for a subset of the data) improved the explanatory power of WQ metrics on Performance over long-term WQ averages. The lagged effects of cumulative acute stressors, and to a lesser extent poor water quality, correlated negatively with the Performance of some but not all coral groups. Tabular Acropora and branching non-Acropora were the most affected by water quality demonstrating that group-specific approaches aid in the interpretation of monitoring data and can be crucial for the detection of the impact of chronic pressures. We highlight the complexity of coral reef dynamics and the need of evaluating Performance metrics in order to prioritise local management interventions

    Cannabinoid use and effects in patients with epidermolysis bullosa:an international cross-sectional survey study

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    Abstract Background Epidermolysis bullosa (EB) patient anecdotes and case reports indicate that cannabinoid-based medicines (CBMs) may alleviate pain and pruritus and improve wound healing. CBM use has not been characterized in the EB patient population. Objectives To evaluate CBM use among EB patients, including CBM types, effects on symptoms (e.g., pain and pruritus), disease process (e.g., blistering, wounds, and inflammation), well-being (e.g., sleep, appetite) and concomitant medications. Methods English-speaking EB patients or caregivers completed an online international, anonymous, cross-sectional survey regarding CBM use. Respondents reported the types of CBMs, subsequent effects including perceived EB symptom alteration, changes in medication use, and side effects. Results Seventy-one EB patients from five continents reported using or having used CBMs to treat their EB. Missing question responses ranged between 0 (0%) and 33 (46%). Most used more than one CBM preparation (mean: 2.4 ± 1.5) and route of administration (mean: 2.1 ± 1.1). Topical and ingested were the most common routes. Pain and pruritus were reported retrospectively to decrease by 3 points (scale: 0–10; p < 0.001 for both) after CBM use. Most reported that CBM use improved their overall EB symptoms (95%), pain (94%), pruritus (91%) and wound healing (81%). Most participants (79%) reported decreased use of pain medications. The most common side-effect was dry mouth (44%). Conclusions CBMs improve the perception of pain, pruritus, wound healing, and well-being in EB patients and reduced concomitant medication use. Nevertheless, a direct relation between the use of CBMs and reduction of the above-mentioned symptoms cannot be proven by these data. Therefore, future controlled studies using pharmaceutically standardised CBM preparations in EB are warranted to delineate the risks and benefits of CBMs

    Savanna fire management can generate enough carbon revenue to help restore Africa's rangelands and fill protected area funding gaps

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    Many savanna-dependent species in Africa including large herbivores and apex predators are at increasing risk of extinction. Achieving effective management of protected areas (PAs) in Africa where lions live will cost an estimated US>12billion/yearinnewfunding.Weexplorethepotentialforfiremanagementbasedcarbonfinancingprogramstofillthisfundinggapandbenefitdegradingsavannaecosystems.Wedemonstratehowintroducingearlydryseasonfiremanagementprogramscouldproducepotentialcarbonrevenues(PCRs)fromeitherasinglecarbonfinancingmethod(avoidedemissions)orfrommultiplesequestrationmethodsrangingfromUS >1–2 billion/year in new funding. We explore the potential for fire-management-based carbon financing programs to fill this funding gap and benefit degrading savanna ecosystems. We demonstrate how introducing early dry season fire management programs could produce potential carbon revenues (PCRs) from either a single carbon financing method (avoided emissions) or from multiple sequestration methods ranging from US 59.6–655.9 million/year (at US5/ton)orUS 5/ton) or US 155.0 million/year to US1.7billion/year(atUS 1.7 billion/year (at US 13/ton). We highlight variable but significant PCRs for savanna PAs from US$ 1.5–44.4 million/year per PA. We suggest investing in fire management programs to jump-start the United Nations Decade of Ecological Restoration to help restore degraded African savannas and conserve imperiled keystone herbivores and apex predators.https://www.cell.com/one-earth/homeam2022Zoology and Entomolog

    Machine-learning guided Venom Induced Dermonecrosis Analysis tooL: VIDAL

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    Snakebite envenoming is a global public health issue that causes significant morbidity and mortality, particularly in low-income regions of the world. The clinical manifestations of envenomings vary depending on the snake's venom, with paralysis, haemorrhage, and necrosis being the most common and medically relevant effects. To assess the efficacy of antivenoms against dermonecrosis, a preclinical testing approach involves in vivo mouse models that mimic local tissue effects of cytotoxic snakebites in humans. However, current methods for assessing necrosis severity are time-consuming and susceptible to human error. To address this, we present the Venom Induced Dermonecrosis Analysis tooL (VIDAL), a machine-learning-guided image-based solution that can automatically identify dermonecrotic lesions in mice, adjust for lighting biases, scale the image, extract lesion area and discolouration, and calculate the severity of dermonecrosis. We also introduce a new unit, the dermonecrotic unit (DnU), to better capture the complexity of dermonecrosis severity. Our tool is comparable to the performance of state-of-the-art histopathological analysis, making it an accessible, accurate, and reproducible method for assessing dermonecrosis in mice. Given the urgent need to address the neglected tropical disease that is snakebite, high-throughput technologies such as VIDAL are crucial in developing and validating new and existing therapeutics for this debilitating disease

    Immunohistochemical assessment of intrinsic and extrinsic markers of hypoxia in reproductive tissue: differential expression of HIF1α and HIF2α in rat oviduct and endometrium

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    Hypoxia is thought to be critical in regulating physiological processes within the female reproductive system, including ovulation, composition of the fluid in the oviductal/uterine lumens and ovarian follicle development. This study examined the localisation of exogenous (pimonidazole) and endogenous [hypoxia inducible factor 1α and 2α (HIF1α, -2α), glucose transporter type 1 (GLUT1) and carbonic anhydrase 9 (CAIX)] hypoxia-related antigens within the oviduct and uterus of the rat reproductive tract. The extent to which each endogenous antigen co-compartmentalised with pimonidazole was also assessed. Female Wistar Furth rats (n = 10) were injected intraperitoneally with pimonidazole (60 mg/kg) 1 h prior to death. Reproductive tissues were removed immediately following death and fixed in 4% paraformaldehyde before being embedded in paraffin. Serial sections were cut (6–7 μm thick) and antigens of interest identified using standard immunohistochemical procedures. The mucosal epithelia of the ampulla, isthmus and uterus were immunopositive for pimonidazole in most sections. Co-compartmentalisation of pimonidazole with HIF1α was only expressed in the mucosa of the uterus whilst co-compartmentalisation with HIF2α was observed in the mucosa of the ampulla, isthmus and uterus. Both GLUT1 and CAIX were co-compartmentalised with pimonidazole in mucosa of the isthmus and uterus. This study confirms that mucosal regions of the rat oviduct and uterus frequently experience severe hypoxia and there are compartment specific variations in expression of endogenous hypoxia-related antigens, including the HIF isoforms. The latter observation may relate to target gene specificity of HIF isoforms or perhaps HIF2α’s responsiveness to non-hypoxic stimuli such as hypoglycaemia independently of HIF1α

    Methylation of HOXA9 and ISL1 predicts patient outcome in high-grade non-invasive bladder cancer

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    Introduction Inappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in low/intermediate grade non-muscle invasive bladder cancer (NMIBC) have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG) NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin), novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis. Methods Promoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correlated with tumour behaviour, including tumour recurrence and progression to muscle invasive bladder cancer or metastases. Results The ISL1 genes’ promoter-associated island was more frequently methylated in recurrent and progressive high-grade tumours than their non-recurrent counterparts (60.0% vs. 18.2%, p = 0.008). ISL1 and HOXA9 showed significantly higher mean methylation in recurrent and progressive tumours compared to non-recurrent tumours (43.3% vs. 20.9%, p = 0.016 and 34.5% vs 17.6%, p = 0.017, respectively). Concurrent ISL1/HOXA9 methylation in HG-NMIBC reliably predicted tumour recurrence and progression within one year (Positive Predictive Value 91.7%), and was associated with disease-specific mortality (DSM). Conclusions In this study we report methylation differences and similarities between clinical sub-types of high-grade NMIBC. We report the potential ability of methylation biomarkers, at initial diagnosis, to predict tumour recurrence and progression within one year of diagnosis. We found that specific biomarkers reliably predict disease outcome and therefore may help guide patient treatment despite the unpredictable clinical course and heterogeneity of high-grade NMIBC. Further investigation is required, including validation in a larger patient cohort, to confirm the clinical utility of methylation biomarkers in high-grade NMIBC
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