Tapinarof validates the aryl hydrocarbon receptor as a therapeutic target: A clinical review.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that has wide-ranging roles, including regulation of inflammation and homeostasis. AhR is not a cell surface receptor; rather, it exists in a cytoplasmic complex that responds to a wide variety of structurally dissimilar endogenous, microbial, and environmental ligands. The ubiquitous expression of AhR, its ability to be activated by a wide range of ligands, and its capacity to act as a master regulator for gene expression and homeostasis make it a promising new therapeutic target. Clinical trials of tapinarof cream have now validated AhR agonism as a therapeutic approach that can deliver significant efficacy for treating inflammatory skin diseases, including psoriasis and atopic dermatitis. Tapinarof 1% cream is a first-in-class, nonsteroidal, topical, AhR agonist with a pharmacokinetic profile that results in localized exposure at sites of disease, avoiding systemic safety concerns, drug interactions, or off-target effects. Psoriasis and atopic dermatitis both involve epidermal inflammation, cellular immune responses, dysregulation of skin barrier protein expression, and oxidative stress. On the basis of the clinical effectiveness of tapinarof cream for treating inflammatory skin diseases, we review how targeting AhR may offer a significant opportunity in other conditions that share key aspects of pathogenesis, including asthma, inflammatory bowel disease, eosinophilic esophagitis, ophthalmic, and nervous system diseases.

Curcumin does not significantly affect immediate skin tests.

Background: Curcumin has been shown to decrease allergic symptoms and biomarkers in some animal and human studies. Objective: Our study aimed to determine if curcumin affects immediate skin-prick testing. Methods: We enrolled 34 participants sensitized to select antigens. The participants were randomized to treatment with curcumin or placebo in a double-blind fashion. The participants underwent titrated skin-prick testing before and after 1 week of treatment, and the pre- and posttreatment skin test wheals and flares were compared. Results: Curcumin did not have a statistically significant effect on immediate skin-prick test wheal or flare size. Conclusion: Although curcumin may attenuate allergic symptoms and biomarkers, it does not have a significant effect on immediate skin-prick test results and does not need to be discontinued before testing.

Resource use by individual Drosophila suzukii reveals a flexible preference for oviposition into healthy fruits.

The invasive pest fruit fly Drosophila suzukii is thought to be a specialist on healthy, i.e. unwounded, non-fermenting fruits. Morphological (sharp ovipositor) and neurophysiological/behavioural adaptations have been suggested to contribute to distinct adult feeding (wounded/microbe-laden fruits) and reproductive (healthy fruits) sites. We tested whether (1) variation in the overall availability of fruits, (2) variation in fruit type (healthy, wounded, fermenting), and (3) the relative abundance of different fruit types are ecological determinants of D. suzukii egg-laying decisions. Even though individual flies reduced their reproductive output when resource availability (blueberries) was low, a significantly higher proportion of eggs was allocated to healthy fruits, relative to wounded and fermenting fruits. However, the preference for healthy over wounded fruits declined continuously with a decrease in the relative abundance of healthy fruits and the overall reproductive output did not change. Under laboratory conditions, D. suzukii larvae achieved a higher developmental success on wounded than on healthy blueberries, but suffered less from density-dependent competition in healthy fruits. These data suggest that D. suzukii, despite showing an egg-laying preference for healthy fruits, also uses wounded/fermenting fruits as egg-laying sites, and that it may thrive well in windfall fruits.

The impact of weather and climate on pollen concentrations in Denver, Colorado, 2010-2018.

BACKGROUND: Increasing evidence indicates that climate change is affecting the timing of pollen season and concentrations of allergenic pollens. To date, pollen trends and their associations with meteorological variables have not been studied in most of the United States. OBJECTIVE: The purpose of this study was to investigate the effects of weather and climate on pollen concentrations and pollen season timing in Denver, Colorado. METHODS: We retrospectively analyzed tree, grass, and weed pollen counts and meteorological variables from 2010-2018 using linear and Poisson regression models. RESULTS: Pollen season timing did not demonstrate uniform trends from 2010 to 2018. Certain species demonstrated earlier season start dates (linden, oak) or end dates (birch, maple), and others had later end dates (oak, grass). Only a few species demonstrated changes in season duration (linden, oak, maple, birch) and peak date (maple, birch). Pollen concentrations either remained stable or increased over the years. Temperature and carbon dioxide levels increased over the study period, with the exception of decreased temperature in August. Wind speed remained stable or decreased over the study period. CONCLUSION: This study illustrates the complex interactions between pollens and meteorology. Meteorological variables associated with climate change do appear to affect allergenic pollens, though the relationship is variable both amongst pollens and from year to year.

Exhaled Nitric Oxide: An Update.

Fractional concentration of exhaled nitric oxide (FENO) is a biomarker used to identify allergic airway inflammation. Because it is noninvasive and easy to obtain, its utility has been studied in the diagnosis and management of several respiratory diseases. Much of the research has been done in asthma, and many studies support the use of FENO in aiding diagnosing asthma, predicting steroid responsiveness, and preventing exacerbations by guiding medication dosage and assessing adherence.

Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies.

BACKGROUND: Primary cardiac angiosarcomas are rare, but they are the most aggressive type of primary cardiac neoplasms. When patients do present, it is with advanced pulmonary and/or cardiac symptoms. Therefore, many times the correct diagnosis is not made at the time of initial presentation. These patients have metastatic disease and the vast majority of these patients die within a few months after diagnosis. Currently the treatment choices are limited and there are no targeted therapies available. CASE PRESENTATION: A 56-year-old male presented with shortness of breath, night sweats, and productive cough for a month. Workup revealed pericardial effusion and multiple bilateral pulmonary nodules suspicious for metastatic disease. Transthoracic echocardiogram showed a large pericardial effusion and a large mass in the base of the right atrium. Results of biopsy of bilateral lung nodules established a diagnosis of primary cardiac angiosarcoma. Aggressive pulmonary disease caused rapid deterioration; the patient went on hospice and subsequently died. Whole exome sequencing of the patient's postmortem tumor revealed a novel KDR (G681R) mutation, and focal high-level amplification at chromosome 1q encompassing MDM4, a negative regulator of TP53. CONCLUSION: Mutations in KDR have been reported previously in angiosarcomas. Previous studies also demonstrated that KDR mutants with constitutive KDR activation could be inhibited with specific KDR inhibitors in vitro. Thus, patients harboring activating KDR mutations could be candidates for treatment with KDR-specific inhibitors.

Superior sagittal sinus thrombosis as the initial presentation of renal cell carcinoma.

We describe a 68-year-old man who presented with headaches, nausea, and dizziness and was found to have a superior sagittal sinus venous thrombosis on magnetic resonance imaging. His initial hypercoagulable workup was negative. Computed tomography of the abdomen revealed a large mass originating from the kidney. A radical nephrectomy was performed at an outside hospital, and histological study of the excised mass disclosed clear cell renal carcinoma.

Predictors, clinical characteristics, and outcome of conduct disorder in girls with attention-deficit/hyperactivity disorder: a longitudinal study.

BACKGROUND: Research on the overlap between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) in males has provided useful information on the etiology, correlates, course, and nosology of this co-morbid condition. However, it is unclear how these results extend to females. Our aim was to examine the predictors, clinical characteristics, and functional outcome of CD in a sample of female youth with and without ADHD. METHOD: We conducted a blind, 5-year prospective longitudinal study of girls with (n=140) and without (n=122) ADHD, aged 6-18 years at baseline. At the 5-year follow-up, 123 (88%) and 112 (92%) of the ADHD and control children respectively were reassessed at a mean age of 16.7 years. Psychiatric disorders were assessed using blind structured diagnostic interviews. RESULTS: Baseline ADHD was a significant risk factor for lifetime CD throughout childhood and adolescence [hazard ratio (HR) 5.8, 95% confidence interval (CI) 2.9-11.5, p<0.001]. Among ADHD girls, childhood-onset (<12 years) CD was predicted by paternal antisocial personality disorder (ASPD), while adolescent-onset CD (12 years) was predicted by family conflict. In addition, lifetime CD significantly predicted academic, psychiatric and sexual behavior problems in girls with ADHD at follow-up. CONCLUSIONS: ADHD is a significant risk factor for CD in girls. CD is associated with increased risk for academic, psychiatric and sexual behavior problems compared to ADHD girls without CD. Given that the therapeutic approaches indicated by ADHD and CD differ, these findings highlight the importance of improved efforts aimed at early identification and treatment of CD in girls with ADHD.