Mutant noxy8 exposes functional specificities between the chloroplast chaperones CLPC1 and CLPC2 in the response to organelle stress and plant defence.

Chloroplast function is essential for growth, development, and plant adaptation to stress. Organelle stress and plant defence responses were examined here using noxy8 (nonresponding to oxylipins 8) from a series of Arabidopsis mutants. The noxy8 mutation was located at the CLPC2 gene, encoding a chloroplast chaperone of the protease complex CLP. Although its CLPC1 paralogue is considered to generate redundancy, our data reveal significant differences distinguishing CLPC2 and CLPC1 functions. As such, clpc1 mutants displayed a major defect in housekeeping chloroplast proteostasis, leading to a pronounced reduction in growth and pigment levels, enhanced accumulation of chloroplast and cytosol chaperones, and resistance to fosmidomycin. Conversely, clpc2 mutants showed severe susceptibility to lincomycin inhibition of chloroplast translation and resistance to Antimycin A inhibition of mitochondrial respiration. In the response to Pseudomonas syringae pv. tomato, clpc2 but not clpc1 mutants were resistant to bacterial infection, showing higher salicylic acid levels, defence gene expression and 9-LOX pathway activation. Our findings suggest CLPC2 and CLPC1 functional specificity, with a preferential involvement of CLPC1 in housekeeping processes and of CLPC2 in stress responses.

Influence of COVID-19 confinement on the size of malignant skin tumours surgically removed at a Spanish hospital.

The COVID-19 pandemic required people to confine themselves to their homes where possible, and disrupted normal hospital activities. We examine whether this lockdown generated changes in the size of the tumours. We compared the dimensions of the surgically removed malignant skin tumours from the first 150 patients treated after the confinement ended in Spain (22 May 2020) with those of the last 150 patients to receive such treatment before the confinement began (13 March 2020). Data on tumour surface area were collected from pathology reports. Overall, no significant difference was seen in the tumour sizes. However, among men, the tumours removed after confinement were significantly larger (P < 0.05). Controversy exists over how the reduction in the number of tumours diagnosed during lockdowns might have influenced the characteristics of tumours. In this study, no overall difference was seen in the size of the tumours removed, although those removed from men after confinement were larger.

Fear of cancer recurrence in patients with non-metastatic melanoma: Spanish validation and disease-related factors.

INTRODUCTION: It is essential for clinicians to understand the phenomenon of fear of cancer recurrence (FCR) in order to understand the psychological impact it has on patients with melanoma. OBJECTIVES: To validate an FCR questionnaire in Spanish for patients with non-metastatic melanoma and to describe the clinical and demographic variables associated with FCR in these patients. METHODS: Patients diagnosed with non-metastatic melanoma were selected. The questionnaire was translated and adapted to Spanish following international guidelines. The internal consistency, construct validity, and temporal stability of the questionnaire were analysed using Cronbach's alpha, confirmatory factor analysis, and test-retest reliability, respectively. Following this, the correlation between FCR scores and the study variables was evaluated. RESULTS: A total of 123 patients were included in the study. The translated and adapted questionnaire showed high reliability (overall Cronbach's alpha 0.834), temporal stability (intraclass correlation coefficient 0.8), and unidimensionality. The mean FCR score was 16.1 ± 6.7. The highest FCR scores were observed in women and young patients (p < 0.01). Patients with a personal history of cancer, facial melanoma, or skin graft reconstruction also obtained a high FCR score (p < 0.05). No differences were found between FCR and other tumour characteristics, such as the Breslow index or the time since diagnosis. CONCLUSIONS: This validated questionnaire is suitable for evaluating FCR. We also identified factors that tend to increase FCR scores, thus allowing clinicians to identify patients at risk and start preventive measures.

Development of a Prediction Model for Patients at Risk of Incidental Skin Cancer: A Multicentre Prospective Study.

In the absence of guidelines recommending routine total-body skin examination, patient concern remains the main factor in seeking consultation regarding suspicion of skin cancer. This study explores gaps in patients' understanding of malignant skin lesions, through the factors associated with incidental skin cancer. Included patients had a confirmed histological diagnosis of basal cell carci-noma, squamous cell carcinoma or melanoma. Tumour characteristics, patient demographics and other risk factors related to the development of skin cancer were obtained from each participant. The main measure was incidental skin cancer detection, using both binary logistic regression and Chi-squared Automatic Interaction Detection (CHAID) algorithm. Of the total tumours, 26.6% were detected incidentally. The following variables: male sex, living alone, long-axis diameter, tumour location, symptoms and time of disease evolution were independent predictors of incidental skin cancer. According to the CHAID algorithm, the most significant risk factor for incidental skin cancer was the absence of symptoms at diagnosis.

Factors associated with high Altmetric Attention Score in dermatology research.

BACKGROUND: Alternative metrics are emerging scores to assess the impact of research beyond the academic environment. OBJECTIVE: To analyse whether a correlation exists between manuscript characteristics and alternative citation metrics. MATERIALS AND METHODS: This bibliometric analysis included original articles published in the five journals with the highest impact factors during 2019. We extracted the following characteristics from each record: journal, publication month, title, number of authors, type of institution, type of publication, research topic, number of references, financial support, free/open access status and literature citations. The main measure was the identification of variables of higher social attention (measured by the Altmetric Attention Score ≥25) using binary logistic regression. Model performance was assessed by the change in the area under the curve (AUC). RESULTS: A total of 840 manuscripts were included. The Altmetric scores across all five journals ranged from 0 to 465 (mean 12.51 ± 33.7; median 3). The most prevalent topic was skin cancer, and the study design was clinical science. The scientific journal (P < 0.001), the presence of conflicts of interest (OR 2.2 [95%CI 1.3-3.7]; P = 0.002) and open access status OR 3.2 [95%CI 1.6-6.7]; P = 0.002) were found as independent predictors of high Altmetric scores. CONCLUSIONS: Our study suggests an article´s social recognition may be dependent on some manuscript characteristics, thus providing useful information on the dissemination of dermatology research to the general public.

Arabidopsis nonresponding to oxylipins locus NOXY7 encodes a yeast GCN1 homolog that mediates noncanonical translation regulation and stress adaptation.

Stress adaptation and translational regulation was studied using noxy7 (nonresponding to oxylipins7) from a series of Arabidopsis thaliana mutants. We identified the noxy7 mutation in At1g64790, which encodes a homolog of the yeast translational regulator General Control Nonderepressible1 (GCN1) that activates the GCN2 kinase; GCN2 in turn phosphorylates the α subunit of the translation initiation factor eIF2. This regulatory circuit is conserved in yeast and mammals, in which phosphorylated eIF2α (P-eIF2α) facilitates stress adaptation by inhibiting protein synthesis. In phenotypic and de novo protein synthesis studies with Arabidopsis mutants, we found that NOXY7/GCN1 and GCN2 mediate P-eIF2α formation and adaptation to amino acid deprivation; however, P-eIF2α formation is not linked to general protein synthesis arrest. Additional evidence suggested that NOXY7/GCN1 but not GCN2 regulates adaptation to mitochondrial dysfunction, high boron concentration, and activation of plant immunity to infection by Pseudomonas syringae pv tomato (Pst). In these responses, NOXY7/GCN1 acts with GCN20 to regulate translation in a noncanonical pathway independently of GCN2 and P-eIF2α. These results show the lesser functional relevance of GCN2 and P-eIF2α in plants relative to other eukaryotes and highlight the prominent role of NOXY7/GCN1 and GCN20 in regulation of translation and stress adaptation in plants.

Transgender adolescents and acne: A cases series.

We describe the difficulties of treating acne in a series of female-to-male transgender adolescents, including concerns about potential hepatotoxicity with concomitant use of testosterone with isotretinoin or tetracyclines. Acne is a foreseeable adverse effect of testosterone treatment in transgender adolescents, so monitoring for acne is advised. The treatment of acne in transgender adolescents is important given that severe acne and transgenderism are associated with higher rates of depression and suicide.

Effectiveness of omalizumab in a case of urticarial vasculitis.

Urticarial vasculitis (UV) is a mainly leucocytoclastic vasculitis with urticarial plaques. Treating these patients is challenging as the available treatments have poor efficacy. Oral corticosteroids are considered the first-line treatment, but H1 antihistamines, dapsone, colchicine, antimalarials, ciclosporin and antileucotrienes have all been tried also. However, because of their adverse effects and/or lack of efficacy, new agents are still needed. Omalizumab, an anti-IgE antibody, shows efficacy in chronic spontaneous urticaria, and might also be a good treatment for angio-oedema and urticarial vasculitis. To our knowledge, there have been only seven relevant case reports published in the English literature. We add a new case of severe chronic recurrent urticarial vasculitis refractory to all of the drugs mentioned above. We started the patient on subcutaneous omalizumab 300 mg every 4 weeks, which produced clinical improvement within the first month and total remission in the fifth month. The patient has remained stable for 23 months, and follow-up is ongoing.

Local skin reactions following the administration of topical ingenol mebutate for actinic keratosis.

Actinic keratoses are cutaneous lesions that appear as the result of the proliferation of atypical keratinocytes. These lesions are considered pre-malignant and they can progress to squamous cell carcinoma. Ingenol mebutate has been approved as an effective treatment for AK on the face and trunk. We studied the local skin reactions to this therapy. Data about local skin reactions were collected in a series of 5 patients with photographic documentation, a visual analog scale, and a ranking of satisfaction of the patient. Moderate to severe reactions were reported in most of patients, but only one stopped treatment early. The short duration of treatment contributes to high adherence to the therapy.

Refractory pyoderma gangrenosum treated with infliximab in an infant.

We report the case of an 11-month-old boy with severe recalcitrant pyoderma gangrenosum refractory to prednisone, dapsone and ciclosporin. Treatment with infliximab was well tolerated, and resulted in an excellent clinical response that has been sustained for 15 months. The characteristics of this condition in children and the use of infliximab in infants are both reviewed.