Clinical and preclinical approach in AGA treatment: a review of current and new therapies in the regenerative field.

Androgenetic alopecia (AGA) is the most prevalent type of hair loss. Its morbility is mainly psychological although an increased incidence in melanoma has also been observed in affected subjects. Current drug based therapies and physical treatments are either unsuccessful in the long term or have relevant side effects that limit their application. Therefore, a new therapeutic approach is needed to promote regenerative enhancement alternatives. These treatment options, focused on the cellular niche restoration, could be the solution to the impact of dihydrotestosterone in the hair follicle microenvironment. In this context emerging regenerative therapies such as Platelet-rich plasma or Platelet-rich fibrine as well as hair follicle stem cells and mesenchymal stem cell based therapies and their derivatives (conditioned medium CM or exoxomes) are highlighting in the evolving landscape of hair restoration. Nanotechnology is also leading the way in AGA treatment through the design of bioinks and nanobiomaterials whose structures are being configuring in a huge range of cases by means of 3D bioprinting. Due to the increasing number and the rapid creation of new advanced therapies alternatives in the AGA field, an extended review of the current state of art is needed. In addition this review provides a general insight in current and emerging AGA therapies which is intented to be a guidance for researchers highlighting the cutting edge treatments which are recently gaining ground.

Delayed Type Hypersensitivity Reaction Induced By Liraglutide With Tolerance to Semaglutide.

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the management of type 2 diabetes and obesity. It was the first GLP-1 receptor agonist to be approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of obesity. To date, numerous skin adverse reactions to liraglutide have been reported, but data regarding hypersensitivity reactions are scarce, raising concerns about its safety and clinical management. We present the case of a 56-year-old female patient with class 3 obesity who was started on subcutaneous liraglutide (Saxenda) by her endocrinologist. One month after starting the aforementioned treatment, the patient presented well-defined, round, erythematous pruriginous plaques surrounding the injection site, around 24 hours after the drug administration. A liraglutide-induced, delayed-type hypersensitivity reaction was suspected, which could be subsequently confirmed by allergy testing and histopathological study. This paper explores the clinical use of liraglutide, the occurrence of hypersensitivity reactions, diagnosis, management, and implications for future research. Understanding and managing liraglutide hypersensitivity is crucial to ensuring the safety and efficacy of this medication.

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.

Estudio de la calidad de vida en Dermatología Pediátrica: un ejemplo de la población española / Quality of life in children with skin disease: A Spanish sample

Introducción: Las enfermedades cutáneas pueden afectar a la calidad de vida de forma muy variable; el impacto de algunas dermatosis puede ser similar al del asma o la fibrosis quística. Material y métodos: Realizamos un estudio observacional, descriptivo y transversal con el objetivo de describir el grado de afectación de la calidad de vida de los niños que acudieron a la consulta monográfica de Dermatología Pediátrica, mediante el Children's Dermatology Life Quality Index (CDLQI). Resultados: En este estudio la dermatosis con mayor impacto en la calidad de vida fue la dermatitis atópica, debido principalmente a síntomas como el prurito y el insomnio. El segundo grupo diagnóstico con mayor afectación fue el acné, debido principalmente a los sentimientos negativos (vergüenza, tristeza, etc.) asociados al mismo. Los pacientes con verrugas víricas y moluscos contagiosos tuvieron impacto en la calidad de vida debido principalmente al tratamiento de los mismos, que se realizó principalmente con crioterapia. La mayor parte de los pacientes con nevus o manchas café con leche no tuvieron afectación en la calidad de vida, si bien hasta un tercio de ellos tuvieron sentimientos negativos secundarios a su dermatosis. Discusión: La dermatitis atópica fue la enfermedad dermatológica común que más impactó en la calidad de vida en nuestra muestra de pacientes, aunque otros procesos también afectaron a la calidad de vida en distintos aspectos de la misma. Cabe destacar la recomendación de emplear en verrugas víricas y moluscos contagiosos tratamientos más indoloros que la crioterapia, ya que es el tratamiento lo que más impacta en la calidad de vida de los pacientes pediátricos. (AU)

Introduction: The impact of skin diseases on quality of life varies widely, and some can have an impact similar to that of asthma or cystic fibrosis. Material and methods: We conducted a cross-sectional, observational and descriptive study with the aim of describing the degree to which quality of life was affected in paediatric patients managed in a dermatology clinic by means of the Children's Dermatology Life Quality Index (CDLQI). Results: In our study, the skin disease with the greatest impact on quality of life was atopic dermatitis, chiefly on account of symptoms like pruritus and insomnia. It was followed by acne, mainly due to the associated negative feelings (shame, sadness, etc.). Quality of life in patients with viral warts and molluscum contagiosum was mostly affected by the treatment, chiefly based on cryotherapy. Most patients with nevi or café-au-lait spots did not have a decreased quality of life, although up to one third of them had negative feelings in relation to their skin disease. Discussion: Atopic dermatitis was the common skin disease that caused the greatest impairment in quality of life in our sample, although other diseases also had an impact on different dimensions of quality of life. We ought to underscore the recommendation to use less painful treatments than cryotherapy for viral warts and molluscum contagiosum, as the impairment in quality of life in paediatric patients with these conditions was mainly due to the treatment. (AU)

Quality of life in children with skin disease: A Spanish sample.

INTRODUCTION: The impact of skin diseases on quality of life varies widely, and some can have an impact similar to that of asthma or cystic fibrosis. MATERIAL AND METHODS: We conducted a cross-sectional, observational and descriptive study with the aim of describing the degree to which quality of life was affected in paediatric patients managed in a dermatology clinic by means of the Children's Dermatology Life Quality Index (CDLQI). RESULTS: In our study, the skin disease with the greatest impact on quality of life was atopic dermatitis, chiefly on account of symptoms like pruritus and insomnia. It was followed by acne, mainly due to the associated negative feelings (shame, sadness, etc.). Quality of life in patients with viral warts and molluscum contagiosum was mostly affected by the treatment, chiefly based on cryotherapy. Most patients with nevi or café-au-lait spots did not have a decreased quality of life, although up to one third of them had negative feelings in relation to their skin disease. DISCUSSION: Atopic dermatitis was the common skin disease that caused the greatest impairment in quality of life in our sample, although other diseases also had an impact on different dimensions of quality of life. We ought to underscore the recommendation to use less painful treatments than cryotherapy for viral warts and molluscum contagiosum, as the impairment in quality of life in paediatric patients with these conditions was mainly due to the treatment.

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.

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.

Mitochondrial Stress Induces Plant Resistance Through Chromatin Changes.

Plants respond more efficiently when confronted with previous similar stress. In the case of pathogens, this memory of a previous infection confers resistance to future ones, which possesses a high potential for agricultural purposes. Some of the defense elements involved in this resistance phenotype, as well as epigenetic mechanisms participating in the maintenance of the memory, are currently known. However, the intracellular cascade from pathogen perception until the establishment of the epigenetic memory is still unexplored. Here, through the induction of mitochondrial stress by exogenous applications of Antimycin A in Arabidopsis thaliana plants, we discovered and characterized a role of mitochondrial stress in plant-induced resistance. Mitochondrial stress-induced resistance (MS-IR) is effective locally, systemically, within generation and transgenerationally. Mechanistically, MS-IR seems to be mediated by priming of defense gene transcription caused by epigenetic changes. On one hand, we observed an increment in the deposition of H3K4me3 (a positive epigenetic mark) at the promoter region of the primed genes, and, on the other hand, the DNA (de)methylation machinery seems to be required for the transmission of MS-IR to the following generations. Finally, we observed that MS-IR is broad spectrum, restricting the colonization by pathogens from different kingdoms and lifestyles. Altogether, this evidence positions mitochondria as a prominent organelle in environment sensing, acting as an integrating platform to process external and internal signals, triggering the appropriate response, and inducing the epigenetic memory of the stress to better react against future stressful conditions.