Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73

Transcriptional disturbance is implicated in the pathology of polyglutamine diseases, including Huntington's disease (HD). However, it is unknown whether transcriptional repression leads to neuronal death or what forms that death might take. We found transcriptional repression-induced atypical death (TRIAD) of neurons to be distinct from apoptosis, necrosis, or autophagy. The progression of TRIAD was extremely slow in comparison with other types of cell death. Gene expression profiling revealed the reduction of full-length yes-associated protein (YAP), a p73 cofactor to promote apoptosis, as specific to TRIAD. Furthermore, novel neuron-specific YAP isoforms (YAPΔCs) were sustained during TRIAD to suppress neuronal death in a dominant-negative fashion. YAPΔCs and activated p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin (htt) transgenic mice. YAPΔCs also markedly attenuated Htt-induced neuronal death in primary neuron and Drosophila melanogaster models. Collectively, transcriptional repression induces a novel prototype of neuronal death associated with the changes of YAP isoforms and p73, which might be relevant to the HD pathology

Long-term safety and efficacy of trifarotene 50μg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne

Treatment for both facial and truncal acne has not sufficiently been studied.To evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne.In a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne, received trifarotene 50 μg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26, and 52/ET.Of 453 patients enrolled 342(75.5%) completed the study. Trifarotene-related treatment emergent adverse events (TEAEs) were reported in 12.6% of patients, none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to week 2 to 4 on the trunk with both decreasing thereafter. At week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e., no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit CONCLUSION: In this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne. This article is protected by copyright. All rights reserved. Background Treatment for both facial and truncal acne has not sufficiently been studied. Objectives To evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne. Methods In a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne received trifarotene 50 mu g/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET. Results Of 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene-related treatment-emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter. At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit. Conclusion In this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne

A slowly enlarging mass on the finger

An otherwise healthy 71-year-old woman presented with an asymptomatic mass on her right 4th finger that had been slowly enlarging over the past 2 years. On physical examination, there was a tan-pink, freely mobile, rubbery, 9-mm papule with a central keratotic plug located over the extensor aspect of the proximal interphalangeal joint of the right 4th finger. A 3-mm punch biopsy of the lesion was performed. Histopathologic findings were consistent with a diagnosis of aggressive digital papillary adenocarcinoma (ADPAca), an adnexal tumor with high metastatic potential that is unfortunately initially misdiagnosed secondary to its rarity and nondescript appearance. Aggressive surgical treatment including radical excision or digital amputation with or without sentinel lymph node biopsy is advocated in the treatment of ADPAca

A slowly enlarging mass on the finger

An otherwise healthy 71-year-old woman presented with an asymptomatic mass on her right 4th finger that had been slowly enlarging over the past 2 years. On physical examination, there was a tan-pink, freely mobile, rubbery, 9-mm papule with a central keratotic plug located over the extensor aspect of the proximal interphalangeal joint of the right 4th finger. A 3-mm punch biopsy of the lesion was performed. Histopathologic findings were consistent with a diagnosis of aggressive digital papillary adenocarcinoma (ADPAca), an adnexal tumor with high metastatic potential that is unfortunately initially misdiagnosed secondary to its rarity and nondescript appearance. Aggressive surgical treatment including radical excision or digital amputation with or without sentinel lymph node biopsy is advocated in the treatment of ADPAca

Coral contact dermatitis

Corals can elicit both toxic and allergic reactions upon contact with the skin. Clinical presentations vary depending on whether the reaction is acute, delayed, or chronic. Literature concerning cutaneous reactions to corals and other Cnidarians is scarce. Herein we report a case of delayed contact hypersensitivity reaction to coral and review the clinical and histopathological features of coral contact dermatitis

Coral contact dermatitis

Corals can elicit both toxic and allergic reactions upon contact with the skin. Clinical presentations vary depending on whether the reaction is acute, delayed, or chronic. Literature concerning cutaneous reactions to corals and other Cnidarians is scarce. Herein we report a case of delayed contact hypersensitivity reaction to coral and review the clinical and histopathological features of coral contact dermatitis

Coexisting with cannabis: wildlife response to marijuana cultivation in the Klamath-Siskiyou Ecoregion

The recent expansion of cannabis agriculture in rural areas of the western United States provides an ideal opportunity to study the outcomes of policy change for land use and wildlife. Small scale (<1 acre), private-land cannabis cultivation has the ability to coexist with or alter surrounding wildlife communities. To date, there has been little to no formal research on wildlife response to this form of cannabis cultivation. This study examines local wildlife community dynamics on and nearby active private-land cannabis farms. Using camera data collected between 2018–2019, we summarized the frequency of occurrence of 11 wildlife species and 3 domestic animals on and adjacent to (within 500 m) eight cannabis farms within the Klamath-Siskiyou Ecoregion in southern Oregon. We also assessed how cannabis production influenced the occupancy (defined here as space use) of black-tailed deer (Odocoileus hemionus columbianus), lagomorphs, and gray fox (Urocyon cinereoargenteus) in our study area. We found that cannabis farms were generally occupied by smaller-bodied wildlife species, and had a higher proportion of domestic dog (Canis familiaris), cat (Felis catus), and human activity compared to nearby comparison sites. The presence of a cannabis farm helped explain detection probabilities of deer and gray fox, but did not affect lagomorphs. Farms also helped predict gray fox occupancy, but were not selected in lagomorph or deer models. These results suggest species-specific responses to cannabis cultivation, and highlight the need for further research on site-level production practices and their influence on surrounding ecological communities