Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.

Introduction: Psychological consequences of the COVID-19 pandemic include pandemic triggered feelings of fear, uncertainty, and anxiety added to the effects of restricting the population's activities in lockdown. Aim: We aimed to study the effect of COVID-19 pandemic on sexual satisfaction of females and males in Egypt and to evaluate possible predictive factors. Methods: Married men and females in Egypt were invited to respond to an online questionnaire. The questionnaire addressed medical history, socioeconomic status, sexual performance satisfaction before and during the lockdown in addition to validated Arabic questionnaires for depression, sexual function in males and females, and sexual satisfaction (Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Female Sexual Function Index, International Index of Erectile Function-5, Index of Sexual Satisfaction, respectively). Main outcome measure: The main outcome measures were frequency of depression, anxiety, sexual dysfunction, and sexual satisfaction in males and females during COVID-19 lockdown. Results: A total of 479 females and 217 males completed the questionnaire. Sexual satisfaction was significantly higher before (91.2%, 73.5%) than during lockdown (70.5%, 56.2%) in both males and females, respectively. During lockdown, significantly more males (70.5%) reported being satisfied with their sexual performance than females (56.2%) (P < .001). More than half of the male subjects (68.2%) had no erectile dysfunction while 97.3% females scored 26.5 on the Female Sexual Function Index scale suggestive of sexual difficulties. Sexual stress was significantly greater in females (70.8%) than males (63.1%). Educational level, occupation, anxiety, and erectile dysfunction were independently associated with sexual stress in males. Being a housewife or unemployed, husband's age >35 years, marriage duration of 5-10 years, anxiety, and female sexual dysfunction were predictors of sexual relation stress in females. Conclusion: COVID-19 pandemic was associated with lower sexual satisfaction in both genders. Females however suffered more anxiety and depression and thereby greater risk of sexual function difficulties and sexual dissatisfaction. Intervention strategies in order to lessen the suffering of affected individuals particularly after the pandemic are recommended.

The Breast Size Satisfaction Survey (BSSS) was established to assess women's breast size dissatisfaction and breasted experiences from a cross-national perspective. A total of 18,541 women were recruited from 61 research sites across 40 nations and completed measures of current-ideal breast size discrepancy, as well as measures of theorised antecedents (personality, Western and local media exposure, and proxies of socioeconomic status) and outcomes (weight and appearance dissatisfaction, breast awareness, and

This combination therapy was effective for treatment of auricular keloids, with a low recurrence rate and a favorable cosmetic outcome. Therapy was well tolerated and without significant side effects.

This is the first report on the prevalence of eye comorbidities in Egyptian psoriatic patients. Dry eyes were more common with psoriasis, particularly the erythrodermic type. Other ocular findings were not statistically significantly different except for conjunctival injection and pinguecula.