This study confirms that endometriosis is a condition that often has considerable impact on a woman's life. However, the study also found that endometriosis does not always cause pain, that treatment in many cases is effective, that infertility may be overcome, and that almost all postmenopausal women were free from endometriosis-associated pain.
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ImportanceTopical vitamin D analogues are routine treatment for psoriasis, but the effect of oral supplementation has not been established.ObjectiveTo examine the effect of vitamin D supplementation on psoriasis severity throughout the winter.Design, Setting, and ParticipantsThis randomized, double-blind placebo-controlled clinical trial with 2 parallel groups was performed through 2 winter seasons (2017 to 2018 and 2018 to 2019). Randomization was computer generated. All participants, health care clinicians, and outcome assessors were masked to group assignment. Each participant was followed for 4 months. The presented analyses were conducted in May 2022. The trial was conducted at the clinical research unit of the University Hospital of North Norway (Tromsø; Norway). Adults from the general population in Tromsø with active plaque psoriasis and 25-hydroxyvitamin D (25[OH]D) levels of less than 24 ng/mL (to convert to nmol/L, multiply by 2.496) were included.InterventionVitamin D (cholecalciferol, 100 000 IU, loading dose, followed by 20 000 IU/week) or placebo for 4 months.Main outcomes and MeasuresPsoriasis Area Severity Index (PASI) (primary outcome), Physician Global Assessment, self-administered PASI, and Dermatology Life Quality Index scores (secondary outcomes).ResultsA total of 122 participants (46 women [37.7%]; mean [SD] age, 53.6 [10.0] years; mean [SD] PASI score, 3.1 [2.0]; mean [SD] serum 25(OH)D, 14.9 [3.9] ng/mL) were included. Of these, 60 (49.2%) were randomized to the vitamin D group and 62 (50.8%) to the placebo group. A total of 120 participants (59 vitamin D [49.2%]/61 placebo [51.8%]) completed the study. By completion, mean (SD) 25(OH)D levels were 29.7 (5.2) ng/mL (vitamin D) and 12.0 (3.8) ng/mL (placebo). There was no significant difference in change in PASI score between the groups (adjusted difference, 0.11; 95% CI, −0.23 to 0.45). There was no significant difference in change in Physician Global Assessment score (adjusted odds ratio, 0.66; 95% CI, 0.27-1.63), self-administered PASI (adjusted difference, −0.60; 95% CI, −1.76 to 0.55) or Dermatology Life Quality Index (adjusted difference, −0.86; 95% CI, −1.9 to 0.19) between the groups. No adverse effects of the intervention were registered.Conclusion and RelevanceThe results of this randomized clinical trial showed that vitamin D supplementation did not affect psoriasis severity. Low baseline severity scores may explain the lack of measurable effect. Levels of 25(OH)D in the intervention group increased to a less-than-expected degree based on previous experimental data from the same source population, and this may have affected the results.Trial RegistrationClinicalTrials.gov Identifier: NCT03334136
BackgroundMicroRNAs are small regulatory molecules that are dysregulated in psoriasis. Despite previous efforts, much is unknown about the regulatory mechanisms of psoriasis genetics and their contributions to disease development and activity.ObjectivesTo globally characterize the miRNAome of psoriatic skin in a large sample of psoriatic cases and controls for increased understanding of psoriasis pathophysiology.MethodsSkin biopsies from psoriatic cases (n=75) and non-psoriatic controls (n=57) were RNA sequenced. Count data was meta-analyzed with a previously published dataset (cases, n=24, controls, n=20), increasing the number of psoriatic cases four-fold from previously published studies. Differential expression analyses were performed comparing lesional psoriatic (PP), non-lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell specific analyses were performed.ResultsWe identified 439 significantly differentially expressed miRNAs (DEMs), of which 131 were novel and 11 were related to disease severity. Meta-analyses identified 20 DEMs between PN and NN, suggesting an inherent change in all psoriatic skin. By integrating the miRNA transcriptome with mRNA target interactions, we identified several functionally enriched terms, including ‘thyroid hormone signaling’, ‘insulin resistance’ and various infectious diseases. Cell specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells.ConclusionsWe have provided the most comprehensive overview of the miRNome in psoriatic skin to date and identified a miRNA signature related to psoriasis severity. Our results may represent molecular links between psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify biomarkers and treatment targets.
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