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Background and Objectives: Alopecia areata (AA) impairs quality of life. However, there is no evidence on the impact of this disease in terms of sexual dysfunction (SD). The aim of the present study was to assess the prevalence of SD and possible associated factors in a cohort of patients with AA., Patients and Methods: A cross-sectional study was conducted in a cohort of AA patients matched with healthy controls. Sexual function was assessed using a numerical scale and gender-specific questionnaires., Results: A total of 60 patients with AA and 60 healthy controls were included. The prevalence of SD was higher in women with AA than in healthy controls and in men with AA (p < 0.05). Female SD was associated with younger age, shorter duration of illness and higher rates of anxiety and depression (p < 0.05). Male SD was associated with older age and greater severity of AA (p < 0.05)., Conclusions: Women with AA appear to have higher rates of SD than healthy controls and men with AA. Similarly, the factors associated with SD differ between men and women, with mood disturbance being of greater relevance in women, whereas disease severity seems to play a key role in men., (© 2024 Deutsche Dermatologische Gesellschaft (DDG).)

Introduction: A clinical dermatological research was conducted in Spain from 2005 through 2014 as part of the MaIND project with the provinces or centers with the highest number of published articles. However, a low level of evidence in scientific production was confirmed as the overall result. The aim of this study is to update the Spanish clinical dermatological research in bibliometric terms from 2015 through 2021 with comparisons between both periods of time., Material and Methods: We conducted a bibliometric study to replicate the methodology used in the article to be updated. We included articles whose corresponding authors' affiliation was a Spanish dermatological center, which met the criteria for clinical research in dermatology, including a level of evidence ≤4., Results: A total of 1,674 out of the 10,199 articles met the inclusion criteria. An interactive map representing quantitative and qualitative indicators calculated for the 2005-2021 is presented here. In the study period, we found an increasing trend both in the number of published articles (P<.002) and in the mean number of citation-years per article (P<.01). A total of 22 of the articles had a level of evidence >4, with a positive trend towards more articles having a higher level of evidence (P<.03). ACTAS DERMOSIFILOGRÁFICAS still maintains its position as the journal with the highest number of articles received (18%, a total of 302 articles)., Conclusions: The results of this study show that, in Spain, the scientific production of dermatology represents an upward trend in quantity, impact, and level of evidence., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: A clinical dermatological research was conducted in Spain from 2005 through 2014 as part of the MaIND project with the provinces or centers with the highest number of published articles. However, a low level of evidence in scientific production was confirmed as the overall result. The aim of this study is to update the Spanish clinical dermatological research in bibliometric terms from 2015 through 2021 with comparisons between both periods of time., Material and Methods: We conducted a bibliometric study to replicate the methodology used in the article to be updated. We included articles whose corresponding authors' affiliation was a Spanish dermatological center, which met the criteria for clinical research in dermatology, including a level of evidence ≤4., Results: A total of 1,674 out of the 10,199 articles met the inclusion criteria. An interactive map representing quantitative and qualitative indicators calculated for the 2005-2021 is presented here. In the study period, we found an increasing trend both in the number of published articles (P<.002) and in the mean number of citation-years per article (P<.01). A total of 22 of the articles had a level of evidence >4, with a positive trend towards more articles having a higher level of evidence (P<.03). ACTAS DERMOSIFILOGRÁFICAS still maintains its position as the journal with the highest number of articles received (18%, a total of 302 articles)., Conclusions: The results of this study show that, in Spain, the scientific production of dermatology represents an upward trend in quantity, impact, and level of evidence., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Spanish Autonomous Communities (ACs) are entitled to decide on the prescription requirements of their own territories, which can create inequalities in access to new drugs in the management of psoriasis. The objective of this study was to assess whether the level of restrictions in the access to new drugs for the management psoriasis was associated with the probability of achieving disease control measured using the Minimum Disease Activity (MDA) criteria. Therefore, we combined the results of 2 previous independent, cross-sectional studies: one that described the MDA in psoriasis by AC, and another that evaluated the level of restrictions to drug access by AC. We found that the higher the number of restrictions the lower the chances of achieving the MDA criteria (P=.013). Our results suggest that, in Spain, geographical differences in the access to new drugs may be creating health inequalities across the country., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Spanish Autonomous Communities (ACs) are entitled to decide on the prescription requirements of their own territories, which can create inequalities in access to new drugs in the management of psoriasis. The objective of this study was to assess whether the level of restrictions in the access to new drugs for the management psoriasis was associated with the probability of achieving disease control measured using the Minimum Disease Activity (MDA) criteria. Therefore, we combined the results of 2 previous independent, cross-sectional studies: one that described the MDA in psoriasis by AC, and another that evaluated the level of restrictions to drug access by AC. We found that the higher the number of restrictions the lower the chances of achieving the MDA criteria (P=.013). Our results suggest that, in Spain, geographical differences in the access to new drugs may be creating health inequalities across the country., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background : Bullous pemphigoid (BP) is an autoimmune disease characterized by the appearance of very pruritic subepidermal blisters. It appears mostly in the elderly and is associated with multiple comorbidities, which makes its management and treatment difficult. The purpose of this systematic review is to compile current information on published cases of BP treated with omalizumab (omalizumab) and dupilumab (dupilumab) in order to obtain information on clinical efficacy and safety data available. Methods : A literature search of all cases of BP treated with omalizumab/dupilumab published in the literature up to January 2024 was performed using the Pubmed database. After an exhaustive search, a total of 61 studies encompassing 886 patients met the inclusion criteria and were included in the review. Results : The majority of patients with BP treated with omalizumab/dupilumab presented a significant improvement in symptomatology, being very safe drugs with minimal side effects. The main limitation of the presented review is the quality of the included studies, most of them being case series or individual cases. The development of studies with a higher level of scientific evidence in the near future would be of great interest. Conclusions : Both omalizumab and dupilumab appear to be effective options for treating BP in patients refractory to other pharmacological therapies. They are drugs with a good safety profile and the adverse reactions associated with their use are infrequent and generally mild.

Pseudomonas aeruginosa ( P. aeruginosa ) is a common nosocomial pathogen that can cause severe infections in critically ill patients. Due to its resistance to multiple drugs, it is challenging to treat, which can result in serious illness and death. Conventional treatments for infected wounds often involve the topical or systemic application of antibiotics, which can lead to systemic toxicity and the development of drug resistance. The combination of wound dressings that promote wound healing with nanoparticles (NPs) represents a revolutionary strategy for optimizing the safety and efficacy of antibiotics. This review assesses a systematic search to identify the latest approaches where the evaluation of wound dressings loaded with antibiotic NPs is conducted. The properties of NPs, the features of wound dressings, the antimicrobial activity and biocompatibility of the different strategies are analyzed. The results indicate that most research in this field is focused on dressings loaded with silver NPs (57.1%) or other inorganic materials (22.4%). Wound dressings loaded with polymeric NPs and carbon-based NPs represent 14.3% and 6.1% of the evaluated studies, respectively. Nevertheless, there are no clinical trials that have evaluated the efficacy of NPs-loaded wound dressings in patients. Further research is required to ensure the safety of these treatments and to translate the findings from the bench to the bedside., Competing Interests: The authors declare that there are no conflicts of interest in this work., (© 2024 Quiñones-Vico et al.)

Burnout syndrome is a mental health condition related to chronic occupational stress; its prevalence, as well as its relationship with other mental health disorders in physicians, has become a topic of growing interest. However, no studies with large sample sizes evaluate this association in dermatologists. With this background, a cross-sectional study was designed, which included 420 Spanish dermatologists; the mean age was 44.5 years (12.39), and 62% (260/420) were women. Eleven percent (45/420) of the participants presented a moderate risk of burnout, more than half of the sample had at least one of the burnout symptoms, 47% (198/420) had some degree of anxiety, and 20.3% (85/420) presented some degree of depression. Less than 1% (4/420) demonstrated a high risk of alcohol use disorder. Being female was associated with a higher risk of depression and anxiety. Meanwhile, men and residents showed an increasedrisk of alcohol use disorder. Burnout and its domains showed a significative association with depression and anxiety, while no relationship with alcohol abuse was observed., (© 2024 the International Society of Dermatology.)

Introduction: Hidradenitis suppurativa (HS) is a chronic skin disease whose impact on skin homeostasis has not been adequately studied at present. Knowledge about how skin function changes in these patients, and could be of interest not only to improve the topical management of the disease, but also as an objective measure of disease activity. The aim of this study was to compare skin homeostasis and the epidermal barrier function in lesional and healthy skin areas of patients with HS., Methods: We conducted a cross-sectional study. Skin homeostasis and the epidermal barrier function of lesions were assessed in HS patients using validated tools. A healthy perilesional skin control was assigned to each lesion to compare skin homeostasis parameters., Results: A total of 43 patients were included: 22 nodules, 10 abscesses and 25 draining tunnels were measured. The male-to-female ratio was 20:23, and the mean age, 35.95 years (SD, 14.82). Increased transepidermal water loss (TEWL) and erythema were found in nodules, abscesses and draining tunnel vs healthy skin. A direct association was observed between inflammatory nodules TEWL and IHS4 stage. In draining tunnels, a direct association was observed between TEWL and smoking. A trend of increasing TEWL values was observed as a function of Hurley stage., Conclusion: HS lesions exhibit epidermal barrier dysfunction that depends on the severity of inflammatory activity. These results could be useful to develop objective classification systems for the severity and degree of involvement of HS or help in the development of vehicles for specific drugs, antiseptics and dressings for the management of this disease., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Background: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer., Objective: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic., Material & Methods: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected., Results: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases., Conclusions: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer., Objective: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic., Material & Methods: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected., Results: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases., Conclusions: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities., Material and Methods: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022., Results: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community)., Conclusions: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objective: Quality of professional life (QPL) is defined as a sense of well-being derived from a balance between the challenges of work and the resources available to deal with them. Impaired QPL can contribute to burnout. The aim of this study was to evaluate QPL in Spanish dermatologists using a validated questionnaire., Material and Methods: We designed a cross-sectional study in which Spanish dermatologists were invited to complete an online questionnaire sent out by messaging applications. The dermatologists were asked to provide sociodemographic information, answer 3 open questions, and complete the 35-item Spanish QPL questionnaire (Spanish abbreviation, CVP-35)., Results: We analyzed the information submitted by 106 dermatologists (62 women, 58%) with a mean age of 41 years (95% CI, 43.3-38.8 years). Women and department heads scored significantly higher in the workload domain of the questionnaire (P=.02 and P=.005, respectively). A heavy caseload was mentioned as the main factor contributing to impaired QPL and the main change in the wake of the COVID-19 pandemic., Conclusions: Female dermatologists reported heavier workloads. Heavy caseloads and more remote work were the main changes identified after the COVID-19 pandemic. Heavy caseloads have a significant impact on the QPL of dermatologists in Spain. Reducing caseloads would improve general job satisfaction and quality of care provision., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities., Material and Methods: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022., Results: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community)., Conclusions: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy., Methods: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed., Results: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them., Conclusions: Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies., (© 2024 S. Karger AG, Basel.)

Bladder cancer is a highly prevalent tumor, requiring the urgent development of novel therapies, especially for locally advanced and metastatic disease. Nintedanib is a potent antifibrotic angio-kinase inhibitor, which has shown clinical efficacy in combination with chemotherapy in patients with locally advanced muscle-invasive bladder cancer. Nintedanib inhibits fibroblast growth factor receptors (FGFRs), validated targets in patients with bladder cancer harboring FGFR3/2 genetic alterations. Here, we aimed at studying its mechanisms of action to understand therapy resistance, identify markers predictive of response, and improve the design of future clinical trials. We have used a panel of genetically well-characterized human bladder cancer cells to identify the molecular and transcriptomic changes induced upon treatment with nintedanib, in vitro and in vivo, at the tumor and stroma cell levels. We showed that bladder cancer cells display an intrinsic resistance to nintedanib treatment in vitro, independently of their FGFR3 status. However, nintedanib has higher antitumor activity on mouse xenografts. We have identified PI3K activation as a resistance mechanism against nintedanib in bladder cancer and evidenced that the combination of nintedanib with the PI3K inhibitor alpelisib has synergistic antitumor activity. Treatment with this combination is associated with cell-cycle inhibition at the tumoral and stromal levels and potent nontumor cell autonomous effects on α-smooth muscle actin-positive tumor infiltrating cells and tumor vasculature. The combination of nintedanib with PI3K inhibitors not only reversed bladder cancer resistance to nintedanib but also enhanced its antiangiogenic effects., (©2023 American Association for Cancer Research.)

Introduction: Distressed personality (or Type D personality, TDp) is a personality trait that has been associated with poor quality of life in patients suffering from a variety of skin diseases such as psoriasis or urticaria. To date the potential association between Alopecia areata (AA) and TDp has not been studied. The aim of this study was to compare the prevalence of TDp between patients with AA and controls, and to analyse the impact of TDp on patients with AA regarding mood status disturbances, quality of life and sexuality., Methods: Cross-sectional study includes patients suffering from mild-to-severe AA and sex- and age-matched healthy controls. Socio-demographic and clinical variables, quality of life, sexual disfunction, anxiety, depression and TDp were collected using validated questionnaires., Results: A total of 120 participants (60 patients and 60 controls) were included. Patients with AA showed higher prevalence of TDp than controls (35% vs. 15% p = 0.01), as well as higher rates of anxiety, depression and sexual dysfunction (p < 0.05). TDp was found to be linked to disease severity (p = 0.04), anxiety and depression scores (p < 0.001) and worse quality of life (p = 0.001). No relationship was found between TDp and sexual dysfunction., Discussion: Type D personality prevalence is higher in patients with AA than in controls. It is associated with higher rates of anxiety, depression and worse quality of life. Screening for this type of personality could be useful to detect patients who could benefit from additional psychological support as a complement to their medical treatment., (© 2022 European Academy of Dermatology and Venereology.)

Introduction: Hidradenitis suppurativa (HS) has been linked to higher cardiovascular risk (CVR) due to its inflammatory burden. There is little evidence on how biologic treatment could modify the cardiovascular risk of patients with HS. The aims of the present study were to explore the modification of CVR in patients under adalimumab treatment and to explore the potential factors associated with CVR improvement., Methods: A prospective longitudinal study was performed. A cohort of patients with HS treated with adalimumab was followed up. Carotid intima-media thickness (IMT) and other clinical and biochemical CVR factors were collected at baseline and 32 weeks after starting the treatment., Results: Twenty-seven patients with severe HS were included. Overall, there were no differences in IMT between baseline (633 μm) and 32 weeks follow-up (634 μm). However, 40.7% (11/27) of the patients presented an improvement in IMT. This group (IMT responders) had a higher prevalence of dyslipidemia, diabetes mellitus, higher HbA1c levels, consumed more tobacco, and had higher BMI at baseline. Moreover, these patients had lower IHS4 scores at baseline and tended to have a greater IMT basal value, indicating a higher burden of subclinical atherosclerosis., Conclusions: Adalimumab treatment might benefit a subset of patients with HS in terms of cardiovascular risk reduction. In light of the results of the present study patients with classical cardiovascular risk factors, and those with higher burden of subclinical atherosclerosis and with less inflammatory load, may be more likely to improve their IMT during adalimumab treatment., (© 2023. The Author(s).)

Chronic Spontaneous Urticaria (CSU) leads to a decreased quality of life in patients because of pruritus and skin lesions. However, there is still little evidence on the impact that a worse sleep quality could have on the quality of life and emotional disorders in these patients. The aims of the present study are to analyze the potential impact of sleep quality on the quality-of-life and emotional status of patients with CSU. A cross-sectional study of 75 CSU patients was performed. Socio-demographic variables and disease activity, quality of life, sleep, sexual disfunction, anxiety, depression and personality traits were collected. A majority of 59 of the patients suffered from poor sleep quality. Sleep quality impairment was associated with worse disease control, greater pruritus and swelling and poorer general and urticaria-related quality-of-life ( p < 0.05). Patients with poor sleep quality showed an increased prevalence of anxiety (1.62-fold) and depression risk (3.93-fold). Female sexual dysfunction, but not male, was found to be linked to poorer sleep quality ( p = 0.04). To conclude, sleep quality impairment in patients with CSU is related to poor quality-of-life, worse disease control and higher rates of anxiety and depression. Global management of the disease should take sleep quality into account to improve the care of CSU patients.

Type D personality is characterized by social inhibition and negative affectivity. Poorer outcomes and worse quality of life have been linked to type D personality in patients with a variety of non-dermatological diseases. Despite increasing evidence of the importance of type D personality in skin diseases, there are no reviews on this subject. The aim of this review is to summarize the current evidence regarding type D personality and skin diseases. A systematic search was performed using Medline and Web of Science databases from inception to 11 October 2022. Studies addressing the presence of type D personality, its associated factors, its impact on the outcomes of the disease or the quality of life of the patients were included in the systematic review. A total of 20 studies, including 3,124 participants, met the eligibility criteria and were included in the review. Acne, hidradenitis suppurativa, psoriasis, melanoma, atopic dermatitis, chronic spontaneous urticaria and pruritic disorders were the main diseases assessed. Type D personality was more frequent among patients with skin diseases than among controls. Type D personality was found to be associated with poorer quality of life and higher rates of psychological comorbidities in patients with skin diseases. In conclusion, type D personality appears to be a marker of patients with increased risk of poorer quality of life and higher rates of psychological comorbidities. Screening for type D personality in specialized dermatology units might be beneficial to identify patients who are more psychologically vulnerable to the consequences of chronic skin diseases.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle which presents with painful nodules, abscesses, and fistulae in apocrine gland-bearing areas of the skin. Approved treatments include antibiotics and biologic drugs such as adalimumab. Despite these treatments, HS management is challenging. Acitretin is an oral retinoid used for its management as 3rd or 4th line therapy. There is little evidence regarding the effectiveness and safety of acitretin treatment for HS, and no reports have previously explored the potential clinical predictors associated with the response to the treatment., Methods: Retrospective cohort study to assess the effectiveness and safety of acitretin treatment in HS patients who failed to respond to topical therapies., Results: Sixty-two patients with moderate to severe HS were included. A significant decrease in the International HS Severity Scoring System (IHS4) score was found over time. Higher basal IHS4 score, family history of HS, follicular phenotype, and history of follicular plugging conditions were potential predictors of response. Most patients did not suffer any adverse events, and no severe side effects were observed. The main cause of discontinuation was lack of efficacy., Conclusion: Acitretin can be considered as a therapeutic option for patients with HS. The presence of follicular phenotype or a history of components of follicular occlusion syndrome is associated with better outcomes., (© 2022 S. Karger AG, Basel.)

Background: Chronic spontaneous urticaria (CSU) has been associated with poor quality of life and mood disturbances. However, factors associated with these dimensions have not been properly assessed. Moreover, there is a lack of studies regarding sexual dysfunction (SxD) and CSU. Therefore, the aims of this study were to assess quality of life associated factors and to evaluate the prevalence and potential impact of SxD in patients with CSU., Method: Cross-sectional study of patients suffering from CSU. Sociodemographic and disease activity variables, quality of life, sleep, SxD, anxiety, and depression were collected using validated questionnaires., Results: Seventy-five patients were included, with a female-to-male ratio of 2.40. Female sex, worse disease control, and sexual dysfunction were associated with poor quality-of-life indexes (p &lt; 0.001). SxD was detected in 52% of female and 63% of male patients. SxD was associated with poor disease control (p &lt; 0.001). Female SxD, but not male, was associated with poorer quality of life (p = 0.02) and an increased risk for anxiety 85% and depression 90% (p &lt; 0.05)., Conclusions: Female patients and those with an inadequate control of CSU are in higher risk of having poorer quality of life. SxD seems to be frequent in patients with CSU. Moreover, female SxD seems to have a more profound impact on quality of life and mood disturbances when compared to males. Assessment of SxD in Urticaria Clinic might be of benefit to identify patients at a higher risk of poor quality of life., (© 2023 S. Karger AG, Basel.)

A poor quality of life has been described in patients suffering from Alopecia Areata (AA). However, there is little evidence on how AA can impact on those living with patients. The aim of this study is to analyze the impact of AA on a cohabitant’s quality-of-life, mood status disturbances and sexual satisfaction. This is a cross-sectional study of AA patients and their cohabitants. Socio-demographic variables and disease severity, the quality of life, mood status disturbances and sexual dysfunction were collected using validated questionnaires. Eighty-four subjects were included in the study: 42 AA patients and 42 cohabitants. A poor quality of life and worse disease control in the patients were associated with a poorer quality of life of the family, higher scores of anxiety and depression, and the lower sexual satisfaction of cohabitants (p < 0.05). Anxiety and depression in patients were associated with worse family quality of life, higher rates of anxiety and less sexual satisfaction in cohabitants (p < 0.05). To conclude, AA seems to have an impact on the quality of life of cohabitants, leading to increased rates of anxiety, depression, a poorer quality of life, and reduced sexual satisfaction. In light of the results, a global approach for AA patients, including the care of the people who live with them, should be implemented.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle that has previously been associated with a higher cardiovascular risk (CVR). Although different methods have been described for CVR stratification in HS, there is little evidence about the role of hemogram indexes in CVR in HS. Given its potential convenience, the aim of this study was to assess the role of the hemogram indexes systemic immune-inflammation index (SII) and neutrophil-lymphocyte ratio (NLR) in CVR stratification for patients with HS. A cross-sectional study was performed to assess the role of SII and NLR in CVR stratification in patients with moderate to severe HS who were candidates for biologic therapy. SII, NLR, carotid intima-media thickness, and other clinical and biochemical CVR factors were assessed before the start of the treatment. Fifty patients were included. The male:female ratio was 3:2, and the mean International Hidradenitis Suppurativa Severity Score System score was 21.6. After multivariate analysis, SII correlated with higher values of systolic blood pressure, metabolic syndrome, and higher risk of insulin resistance (p < 0.05). NLR was associated with insulin resistance (p < 0.05). These associations were independent of age, sex, body mass index, severity of the disease, and tobacco consumption. The implementation of SII and NLR in daily practice may be of benefit for identifying patients with HS at higher risk of high blood pressure, insulin resistance, or metabolic syndrome. Since these indexes are simple to calculate, they could be used as a screening tool in HS-specific units., (© 2022 Japanese Dermatological Association.)

Alopecia Areata (AA) is a chronic condition which has been associated with poor quality of life and mood status disturbances. The aim of this study is to compare the sleep quality between AA patients and controls, and to analyze the impact of poor sleep quality on patients with AA regarding mood status disturbances, quality of life and sexuality. A cross-sectional study including patients suffering from mild-to-severe AA and sex- and age-matched healthy controls was performed. Socio-demographic and clinical variables, sleep quality, quality of life, sexual disfunction, anxiety, depression and personality were collected using validated questionnaires. A total of 120 participants (60 patients and 60 controls) were included. Patients with AA showed worse sleep scores than controls ( p = 0.003), as well as higher rates of anxiety and depression ( p < 0.05). After a multivariate analysis, a worse sleep quality was found to be linked to anxiety, depression, a poorer quality of life and a type D personality score independently of the disease severity. In light of the results, patients with AA have a worse sleep quality than healthy controls. A poor sleep quality is associated with anxiety, depression and a worse quality of life, therefore being a general marker of a poor quality of life. Screening for sleep disturbances in specialized units could be useful to detect patients who could benefit from additional psychological support.

Previous studies have shown that polyphenol consumption enhances recovery of the muscle after exercise-induced muscle damage (EIMD). However, EIMD markers have not been studied by sport type. The main aim of this research was to perform a systematic review to determine the efficacy of polyphenolic consumption in increasing muscle recovery for performing team sport skills. Eligible studies included, following PICOS structure, presented at least one of the following outcomes: maximal isometric voluntary contraction (MVIC); countermovement jump (CMJ); delayed onset muscle soreness (DOMS); 20 m sprint test; creatine kinase (CK); and C-reactive protein (hsCRP). A structured search was carried out following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The risk of bias was assessed using the PEDro scale tool. The review showed a possibly positive impact of polyphenol consumption on recovery after EIMD in team sports athletes. No differences were found between sexes. Considering the limitations, there is moderate to very low certainty of polyphenol supplementation effects on recovery of team sport females and males. A dose of 60 mL/day, divided into two times per day, ingested for >7 days may present positive effects on muscle function and muscle soreness in team sport athletes. However, further investigation is required, specifically in females.

Type D personality (TDp) is a stable personality type that has been associated with poor quality of life in the general population and in patients with a variety of diseases, such as cancer, cardiac diseases, and dermatological diseases (e.g. psoriasis). To date, the potential association between chronic spontaneous urticaria and TDp has not been studied. The aim of this study is to analyse the impact of TDp on patients with chronic spontaneous urticaria, regarding mood disturbances, quality of life, sexuality, and sleep disturbances. A cross-sectional study including 75 patients with chronic spontaneous urticaria was performed. Data on socio- demographic variables and disease activity, quality of life, sleep, sexual dysfunction, anxiety, depression and TDp were collected using validated questionnaires. TDp was present in 28% (21/75) of the patients. Although TDp was not related to worse disease control, the presence of anxiety and depression was higher in patients with TDp. Regarding quality of life, TDp was associated with poorer quality of life and higher frequency of sleep disturbances. Prevalence of TDp in patients with chronic spontaneous urticaria is similar to that in the general population. It is associated with mood status disturbances and worse quality of life regardless of disease severity, especially in the emotional and psychological domains. This group of patients could benefit from additional psychological support as a complement to their medical treatment.

Chronic Spontaneous Urticaria (CSU) has been associated with patients’ poor quality of life. Despite being a chronic disease that could alter the quality of life of the people who live with patients, the potential burden on their cohabitants has not been studied to date. The aim of this study is to analyze the relationship between the patient’s quality of life, disease control, disease duration and family quality of life and the cohabitant’s mood disturbances, sexual dysfunction, type D personality and sleep quality. A cross-sectional study including patients suffering from CSU and their cohabitants was performed. Sociodemographic variables and disease activity, quality of life, sleep, sexual disfunction, anxiety, depression and type D personality were collected using validated questionnaires. Sixty-two subjects, 31 CSU patients and 31 cohabitants, were included in the study. Worse disease control and poorer quality of life in patients were associated with poorer family quality of life and higher rates of anxiety among the cohabitants (p < 0.05). Patients’ poor quality of life was associated with reduced sexual satisfaction among the cohabitants (p < 0.05). Long disease duration (>10 years) was associated with an increased prevalence of type D personality among the cohabitants (prevalence ratio: 2.59, CI 95% 1.03−7.21). CSU seems to have an impact on the quality of life of cohabitants, especially in terms of increased rates of anxiety, poorer quality of life and reduced sexual satisfaction. The prolonged course of the disease could be associated with the increased presence of non-adaptative personality traits.

Recent findings have demonstrated that mitochondria can be transferred between cells to control metabolic homeostasis. Although the mitochondria of brown adipocytes comprise a large component of the cell volume and undergo reorganization to sustain thermogenesis, it remains unclear whether an intercellular mitochondrial transfer occurs in brown adipose tissue (BAT) and regulates adaptive thermogenesis. Herein, we demonstrated that thermogenically stressed brown adipocytes release extracellular vesicles (EVs) that contain oxidatively damaged mitochondrial parts to avoid failure of the thermogenic program. When re-uptaken by parental brown adipocytes, mitochondria-derived EVs reduced peroxisome proliferator-activated receptor-γ signaling and the levels of mitochondrial proteins, including UCP1. Their removal via the phagocytic activity of BAT-resident macrophages is instrumental in preserving BAT physiology. Depletion of macrophages in vivo causes the abnormal accumulation of extracellular mitochondrial vesicles in BAT, impairing the thermogenic response to cold exposure. These findings reveal a homeostatic role of tissue-resident macrophages in the mitochondrial quality control of BAT., Competing Interests: Declaration of interests J.R.B. has a pending patent application related to mitochondria transfer. The other authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The mini-pulse oral corticosteroids treatment for alopecia areata (AA) is an accessible treatment whose efficacy and adverse effects have not yet been properly described. The objective of the study was to assess the effectiveness and safety of the mini-pulse oral corticosteroids treatment in patients with AA, and to explore potential factors associated to the response in a real-world setting. An observational study of a prospective cohort to assess the effectiveness and safety of a mini-pulse dexamethasone treatment in patients with AA, who failed to improve with topical therapies, was performed. A SALT II score and other clinical and safety variables were recorded at baseline, 3, 6, 9, and 12 months. An overall significant and progressive decrease of the SALT score was found during treatment: SALT-50 response was achieved after 9 months in 51.8% of the patients. Hypothyroidism and early age of onset were predictors of the lack of response to treatment. The treatment combination with oral minoxidil showed no effect on the SALT score reduction. Dexamethasone daily and cumulative dose were associated with a higher percentage of side effects. To conclude, the mini-pulse oral corticosteroids treatment is an effective treatment for AA, although patients with an early onset of the disease and hypothyroidism may not benefit.

Hidradenitis suppurativa (HS) is an inflammatory chronic disease with difficult management. In some scenarios, intralesional (IL) treatments could be useful. However, the scientific evidence available is limited and heterogeneous. We aimed to synthesize the available scientific evidence on IL treatments in HS. We conducted a systematic review in July 2021. The clinical databases reviewed included MEDLINE and Embase. All types of epidemiological studies and case series with at least 10 patients were included; reviews, guidelines, protocols, conference abstracts, case series with less than 10 patients, and case reports were excluded. Fifteen articles representing 599 patients and 1,032 lesions were included for review. Corticosteroid injections were the most reported treatment. They showed effectiveness for the treatment of acute inflammatory lesions and fistulas in terms of reduction of lesion counts, symptoms, and signs of inflammation and were safe in general terms. Light-based therapies were the other main treatment group, including photodynamic therapy and 1,064-nm diode laser. They were also effective, but more local and systemic adverse events were reported. Other treatments included botulinum toxin type B and punch-trocar-assisted cryoinsufflation (cryopunch). They were effective and safe, although were reported anecdotally. The main limitation of the systematic review was the general quality of the articles included. In conclusion, IL treatments such as corticosteroid injections and light-based therapies seem to be effective and safe for both acute inflammatory lesions and fistulas, although more prospective studies, with higher sample sizes and with standardized outcomes are needed to provide more scientific evidence on the subject., (© 2022 S. Karger AG, Basel.)

Psoriasis and hidradenitis suppurativa (HS) are chronic inflammatory skin diseases that frequently develop in young women. The aim of this study is to evaluate how hidradenitis suppurativa and psoriasis impact women desiring to conceive, and their influence on fertility and gestation. A systematic review of articles dating from January 2015 to April 2021 was performed using the Scopus (Elsevier) database. The search terms were (psoriasis and (birth or pregnancy or fertility)) and ((hidradenitis suppurativa or acne inversa) and (birth or pregnancy or fertility)). The search was limited to human data. Systematic reviews, case reports, clinical practice guidelines, expert consensus and conference papers were excluded. The impact of HS on pregnancy includes an impaired desire for pregnancy, a decrease in fertility, the worsening of the disease during pregnancy and potential adverse events during pregnancy. Moreover, the pregnancy might imply a change on the treatment of HS. The impact of psoriasis on pregnancy includes a decrease in fertility, potential adverse events during pregnancy and an unpredictable evolution of the disease. Moreover, the pregnancy might imply a change on the treatment of psoriasis, although biologic therapies do not appear to increase the risk of adverse events. In conclusion, both HS and psoriasis have an impact on pregnancy. A decrease of fertility has been reported. Moreover, both diseases have an unpredictable evolution during pregnancy. Pregnant women who are under biologic therapy do not seem to have a higher rate of adverse events. Treatment of both conditions is usually halted during pregnancy since scientific evidence about their safety is not conclusive, or teratogenic risk has been proven.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that has been associated with a greater risk of metabolic and cardiovascular comorbidities. The aim of this study is to assess cardiovascular risk by means of intima-media thickness (IMT), metabolic syndrome, and other potential biomarkers in patients with severe hidradenitis suppurativa who are candidates for biologic therapy and to explore potentially associated factors. A cross-sectional study was performed. Body mass index (BMI), carotid intima-media thickness (IMT), and blood tests, including glycemic and lipid profile, insulin, vitamin D, and inflammation markers were performed. Fifty patients were included in the study; the male/female ratio was 3:2. The mean age was 38 years, and the mean disease duration was 21.8 years. The mean carotid IMT was 651.39 μm. A positive association of IMT with disease duration, tobacco consumption, and HbA1c levels was observed. HbA1c correlated with the age of onset, hypertension, metabolic syndrome, and glucose levels. Vitamin D levels inversely correlated with the number of areas affected. In conclusion, patients with severe HS present a higher cardiovascular risk, but it is not distributed equally within the patients: Tobacco consumption, inadequate glycemic control, and disease duration could be useful clinical and biochemical markers to identify patients at higher risk.

Genetic variants that result in truncation in desmoplakin ( DSP ) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 °C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram.

Oral minoxidil is an approved treatment for high blood pressure which is also used as an off-label drug for alopecia. Knowledge about the effects of systemic minoxidil in the paediatric population is limited. A retrospective case series study of paediatric patients with history of systemic minoxidil intake due to contaminated sets of omeprazole was performed to describe side effects of high dose oral minoxidil intake in children. Twenty patients aged between 2 months and 13 years joined the study. They had received high doses of oral minoxidil (mean dose 0.90 mg/kg/day) during a mean time of 38.3 days. Hypertrichosis appeared in 65%, with a mean latency time of 24.31 days. Treatment time was associated with the appearance of hypertrichosis ( p < 0.05). Most common initial zone of hypertrichosis was the face. Systemic effects developed in 15%, with no cases of severe disorders. The present study shows a novel insight into the side effects of high doses of oral minoxidil in children.

The well-known immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) are the reason why they are being used for the treatment of many diseases. Because they are considered hypoimmunogenic, MSCs treatments are performed without considering histocompatibility barriers and without anticipating possible immune rejections. However, recent preclinical studies describe the generation of alloantibodies and the immune rejection of MSCs. This has led to an increasing number of clinical trials evaluating the immunological profile of patients after treatment with MSCs. The objective of this systematic review was to evaluate the generation of donor specific antibodies (DSA) after allogeneic MSC (allo-MSC) therapy and the impact on safety or tolerability. Data from 555 patients were included in the systematic review, 356 were treated with allo-MSC and the rest were treated with placebo or control drugs. A mean of 11.51% of allo-MSC-treated patients developed DSA. Specifically, 14.95% of these patients developed DSA and 6.33% of them developed cPRA. Neither the production of DSA after treatment nor the presence of DSA at baseline (presensitization) were correlated with safety and/or tolerability of the treatment. The number of doses administrated and human leucocyte antigen (HLA) mismatches between donor and recipient did not affect the production of DSA. The safety of allo-MSC therapy has been proved in all the studies and the generation of alloantibodies might not have clinical relevance. However, there are very few studies in the area. More studies with adequate designs are needed to confirm these results.

Anxiolytics (N05B) are one of the most widely used pharmacological groups. This study aimed to analyze the progression of the consumption of anxiolytics (ATC classification: N05B) dispensed in pharmacies in Castile and Leon, Spain, from 2015 to 2020, with a special focus on the possible impact of COVID-19 on the use of these drugs. A quantitative-qualitative analysis of usage was carried out using the total number of packs and the packs per 1000 inhabitants. Overall, the use of anxiolytics grew by 14.41% during 2015-2020. The most commonly used drugs were the short-acting benzodiazepine derivatives lorazepam (whose use increased by 15.18%) and alprazolam (whose use increased by 21.40%), and the dispensing of the long-acting derivative diazepam increased the most, by 31.83%. Anxiolytics consumption increased significantly in 2020 and peaked in March. The pattern of use remained the same in 2020. The consumption of anxiolytics has continued to increase in Castile and Leon over the last six years. The COVID-19 pandemic situation affected the dispensing of these drugs, causing a sharp increase in prescriptions, especially during March, when the confinement of the population was initiated.

The term clinically amyopathic dermatomyositis (CADM) is used to represent a subgroup of patients with the typical cutaneous features of dermatomyositis (DM) in the absence of muscle involvement. Similar to classic DM, CADM can be associated with other connective tissue disorders and systemic manifestations such as interstitial lung disease and malignancy. Owing to the frequent discordance between muscle response and skin disease, the therapeutic approach to CADM represents a challenge. The current literature suggests that CADM treatment should follow a specific protocol, influenced by visceral involvement and the expression of certain myositis-specific antibodies, and different from the recommendation in the presence of myositis. Here, we present five new cases of CADM. We describe the available therapeutic options for skin manifestations in this type of DM, and we propose a step-by-step therapeutic scheme, using the cutaneous dermatomyositis disease area and severity index to assess response. Our literature review establishes mycophenolate mofetil and intravenous immunoglobulin as the most frequently successful therapies in refractory skin disease., (© 2021 Wiley Periodicals LLC.)

The skin is the largest organ of the human body and its main functions include providing protection from external harmful agents, regulating body temperature, and homeostatic maintenance. Skin injuries can damage this important barrier and its functions so research focuses on approaches to accelerate wound healing and treat inflammatory skin diseases. Due to their regenerative and immunomodulatory properties, mesenchymal stromal cells (MSCs) have been reported to play a significant role in skin repair and regeneration. However, it seems that the secretome of these cells and exosomes in particular may be responsible for their functions in skin regeneration and the immunomodulation field. The present review aims to gather the available information about the role of MSC-derived exosomes for both in vitro and in vivo models of different skin conditions and to highlight the need for further research in order to overcome any limitations for clinical translation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Quiñones-Vico, Sanabria-de la Torre, Sánchez-Díaz, Sierra-Sánchez, Montero-Vílchez, Fernández-González and Arias-Santiago.)

Background: New integrative hidradenitis suppurativa (HS) lesion pattern phenotypes have been proposed, an inflammatory phenotype (IP) and a follicular phenotype (FP). They are characterized by different lesion patterns, symptoms, and risks of disease progression., Objectives: To evaluate whether lesion pattern phenotypes (1) have a different cardiovascular risk factor profile, and (2) are associated with a different therapeutic approach in the setting of an HS clinic., Methods: A retrospective cohort study was conducted on 233 patients with HS. They were classified according to lesion pattern phenotype criteria. Data regarding cardiovascular risk factors and treatment decisions were gathered., Results: One hundred and seventeen HS patients (50.21%) were classified as FP and 112 (48.07%) as IP. IP was associated with more severe disease and greater impairment of quality of life. Regardless of disease severity, patients with IP may have a higher cardiovascular risk, assessed according to higher C-reactive protein (CRP) levels (12.75 vs. 5.89, p = 0.059). The lesion pattern phenotype also influenced treatment decisions regardless of disease severity. Patients with IP were more likely to be treated with systemic corticosteroids and adalimumab, showing that lesion pattern phenotypes are associated with different therapeutic approaches., Conclusions: IP is associated with higher CRP values, suggesting a greater cardiovascular risk in these patients and also a different therapeutic approach. This information could help guide dermatologists in the management of HS patients and help to determine future treatment recommendations., (© 2021 S. Karger AG, Basel.)

Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte's autophagy machinery that was enhanced during cardiac stress. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function. VIDEO ABSTRACT., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The heart pumps blood throughout the whole life of an organism, without rest periods during which to replenish energy or detoxify. Hence, cardiomyocytes, the working units of the heart, have mechanisms to ensure constitutive production of energy and detoxification to preserve fitness and function for decades. Even more challenging, the heart must adapt to the varying conditions of the organism from fetal life to adulthood, old age, and pathological stress. Mitochondria are at the nexus of these processes by producing not only energy but also metabolites and oxidative byproducts that can activate alarm signals and be toxic to the cell. We review basic concepts about cardiac mitochondria with a focus on their remarkable adaptations, including elimination, throughout the mammalian lifetime., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Foreseen climate change is expected to impact on grape composition, both sugar and pigment content. We tested the hypothesis that interactions between main factors associated with climate change (elevated CO 2 , elevated temperature, and water deficit) decouple sugars and anthocyanins, and explored the possible involvement of vegetative area, photosynthesis, and grape C uploading on the decoupling. Tempranillo grapevine fruit-bearing cuttings were exposed to CO 2 (700 vs. 400 ppm), temperature (ambient vs. + 4 °C), and irrigation levels (partial vs. full) in temperature-gradient greenhouses. In a search for mechanistic insights into the underlying processes, experiments 1 and 2 were designed to maximize photosynthesis and enlarge leaf area range among treatments, whereas plant growth was manipulated in order to deliberately down-regulate photosynthesis and control vegetative area in experiments 3 and 4. Towards this aim, treatments were applied either from fruit set to maturity with free vegetation and fully irrigated or at 5-8% of pot capacity (experiments 1 and 2), or from veraison to maturity with controlled vegetation and fully irrigated or at 40% of pot capacity (experiments 3 and 4). Modification of air 13 C isotopic composition under elevated CO 2 enabled the further characterization of whole C fixation period and C partitioning to grapes. Increases of the grape sugars-to-anthocyanins ratio were highly and positively correlated with photosynthesis and grape 13 C labeling, but not with vegetative area. Evidence is presented for photosynthesis, from fruit set to veraison, and grape C uploading, from veraison to maturity, as key processes involved in the establishment and development, respectively, of the grape sugars to anthocyanins decoupling.

Hematopoietic-specific transcription factors require coactivators to communicate with the general transcription machinery and establish transcriptional programs that maintain hematopoietic stem cell (HSC) self-renewal, promote differentiation, and prevent malignant transformation. Mediator is a large coactivator complex that bridges enhancer-localized transcription factors with promoters, but little is known about Mediator function in adult stem cell self-renewal and differentiation. We show that MED12, a member of the Mediator kinase module, is an essential regulator of HSC homeostasis, as in vivo deletion of Med12 causes rapid bone marrow aplasia leading to acute lethality. Deleting other members of the Mediator kinase module does not affect HSC function, suggesting kinase-independent roles of MED12. MED12 deletion destabilizes P300 binding at lineage-specific enhancers, resulting in H3K27Ac depletion, enhancer de-activation, and consequent loss of HSC stemness signatures. As MED12 mutations have been described recently in blood malignancies, alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis., (Copyright © 2016 Elsevier Inc. All rights reserved.)