Genetic insights into biological mechanisms governing human ovarian ageing.

Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

ATRX, a guardian of chromatin.

ATRX (alpha-thalassemia mental retardation X-linked) is one of the most frequently mutated tumor suppressor genes in human cancers, especially in glioma, and recent findings indicate roles for ATRX in key molecular pathways, such as the regulation of chromatin state, gene expression, and DNA damage repair, placing ATRX as a central player in the maintenance of genome stability and function. This has led to new perspectives about the functional role of ATRX and its relationship with cancer. Here, we provide an overview of ATRX interactions and molecular functions and discuss the consequences of its impairment, including alternative lengthening of telomeres and therapeutic vulnerabilities that may be exploited in cancer cells.

Telomeric C-circles localize at nuclear pore complexes in Saccharomyces cerevisiae.

As in human cells, yeast telomeres can be maintained in cells lacking telomerase activity by recombination-based mechanisms known as ALT (Alternative Lengthening of Telomeres). A hallmark of ALT human cancer cells are extrachromosomal telomeric DNA elements called C-circles, whose origin and function have remained unclear. Here, we show that extrachromosomal telomeric C-circles in yeast can be detected shortly after senescence crisis and concomitantly with the production of survivors arising from "type II" recombination events. We uncover that C-circles bind to the nuclear pore complex (NPC) and to the SAGA-TREX2 complex, similar to other non-centromeric episomal DNA. Disrupting the integrity of the SAGA/TREX2 complex affects both C-circle binding to NPCs and type II telomere recombination, suggesting that NPC tethering of C-circles facilitates formation and/or propagation of the long telomere repeats characteristic of type II survivors. Furthermore, we find that disruption of the nuclear diffusion barrier impairs type II recombination. These results support a model in which concentration of C-circles at NPCs benefits type II telomere recombination, highlighting the importance of spatial coordination in ALT-type mechanisms of telomere maintenance.

Yra1-bound RNA-DNA hybrids cause orientation-independent transcription-replication collisions and telomere instability.

R loops are an important source of genome instability, largely due to their negative impact on replication progression. Yra1/ALY is an abundant RNA-binding factor conserved from yeast to humans and required for mRNA export, but its excess causes lethality and genome instability. Here, we show that, in addition to ssDNA and ssRNA, Yra1 binds RNA-DNA hybrids in vitro and, when artificially overexpressed, can be recruited to chromatin in an RNA-DNA hybrid-dependent manner, stabilizing R loops and converting them into replication obstacles in vivo. Importantly, an excess of Yra1 increases R-loop-mediated genome instability caused by transcription-replication collisions regardless of whether they are codirectional or head-on. It also induces telomere shortening in telomerase-negative cells and accelerates senescence, consistent with a defect in telomere replication. Our results indicate that RNA-DNA hybrids form transiently in cells regardless of replication and, after stabilization by excess Yra1, compromise genome integrity, in agreement with a two-step model of R-loop-mediated genome instability. This work opens new perspectives to understand transcription-associated genome instability in repair-deficient cells, including tumoral cells.

Congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disease due to the deficient, but not absent, activity of uroporphyrinogen III synthase (UROS), the fourth enzyme in the heme biosynthesis pathway. Biallelic variants in the UROS gene result in decreased UROS enzymatic activity and the accumulation of non-physiologic Type I porphyrins in cells and fluids. Overproduced uroporphyrins in haematopoietic cells are released into the circulation and distributed to tissues, inducing primarily hematologic and dermatologic symptoms. The clinical manifestations vary in severity ranging from non-immune hydrops fetalis in utero to mild dermatologic manifestations in adults. Here, the biochemical, molecular and clinical features of CEP as well as current and new treatment options, including the rescue of UROS enzyme activity by chaperones, are presented.

The MC1R r allele does not increase melanoma risk in MITF E318K carriers.

BACKGROUND: Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored. OBJECTIVES: To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K- individuals. MATERIALS AND METHODS: Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/- cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank). RESULTS: The cohort comprised 1165 MITF E318K- and 322 E318K+ individuals. In E318K- cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P < 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P < 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67-2.49); P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54-1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20-1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P < 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ individuals. CONCLUSIONS: RHC alleles/genotypes modify melanoma risk differently in MITF E318K- and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K- individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ individuals.

Evaluation of Metabolic Changes in Acute Intermittent Porphyria Patients by Targeted Metabolomics.

Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. The goal of this research was to explore the metabolome of symptomatic AIP patients by state-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS). A case versus control study including 18 symptomatic AIP patients and 33 healthy controls was performed. Plasmatic levels of 51 metabolites and 16 ratios belonging to four metabolic pathways were determined. The results showed that the AIP patients presented significant changes in the two main areas of the metabolome under study: (a) the tryptophan/kynurenine pathway with an increase of tryptophan in plasma together with increase of the kynurenine/tryptophan ratio; and (b) changes in the tricarboxylic acid cycle (TCA) including increase of succinic acid and decrease of the fumaric acid/succinic acid ratio. We performed a complementary in vitro study adding ALA to hepatocytes media that showed some of the effects on the TCA cycle were parallel to those observed in vivo. Our study confirms in plasma previous results obtained in urine showing that AIP patients present a moderate increase of the kynurenine/tryptophan ratio possibly associated with inflammation. In addition, it also reports changes in the mitochondrial TCA cycle that, despite requiring further research, could be associated with an energy misbalance due to sustained overproduction of heme-precursors in the liver.

Arbuscular mycorrhizal fungi from acidic soils favors production of tomatoes and lycopene concentration.

BACKGROUND: Tomato is widely consumed throughout the world for its flavor and nutritional value. This functional food largely depends on the implementation of new strategies to maintain the nutraceutical value, e.g. lycopene concentration, and overcome the challenges of sustainable production and food security. The use of arbuscular mycorrhizal fungi (AMF)-based biostimulants represents one of the most promising tools for sustainable management of agricultural soils, being fundamental for organic food production, reducing fertilizers and pesticides use, and decreasing environmental damage. This study aimed at elucidating whether native arbuscular mycorrhizal fungi (AMF) could positively affect tomato yield and lycopene concentration. RESULTS: Native AMF inoculum consisted of two inoculum types: the single species Claroideoglomus claroideum, and a mix of Scutellospora calospora, Acaulospora laevis, Claroideoglomus claroideum, and Claroideoglomus etunicatum. At the end of the study up to 78% of the root system was colonized by single inoculum. Tomato diameters in single and mix mycorrhizal plants showed increases of 80% and 35% respectively. Fresh weights were 84% and 38% higher with single and mix inocula compared with the controls, respectively. The lycopene concentration in tomato fruits of plants with single and mix inoculum was higher than controls. The lycopene concentration was 124.5% and 113.9% greater in single and mix than non-inoculated plants. CONCLUSION: Tomato diameters, fresh weight and lycopene concentration was significantly higher in plants colonized by AMF compared with uninoculated plants. Results suggest that the role of single species Claroideoglomus claroideum could generate better plant performance due to its high production of extraradical mycelium. © 2021 Society of Chemical Industry.

Inherited duplications of PPP2R3B predispose to nevi and melanoma via a C21orf91-driven proliferative phenotype.

PURPOSE: Much of the heredity of melanoma remains unexplained. We sought predisposing germline copy-number variants using a rare disease approach. METHODS: Whole-genome copy-number findings in patients with melanoma predisposition syndrome congenital melanocytic nevus were extrapolated to a sporadic melanoma cohort. Functional effects of duplications in PPP2R3B were investigated using immunohistochemistry, transcriptomics, and stable inducible cellular models, themselves characterized using RNAseq, quantitative real-time polymerase chain reaction (qRT-PCR), reverse phase protein arrays, immunoblotting, RNA interference, immunocytochemistry, proliferation, and migration assays. RESULTS: We identify here a previously unreported genetic susceptibility to melanoma and melanocytic nevi, familial duplications of gene PPP2R3B. This encodes PR70, a regulatory unit of critical phosphatase PP2A. Duplications increase expression of PR70 in human nevus, and increased expression in melanoma tissue correlates with survival via a nonimmunological mechanism. PPP2R3B overexpression induces pigment cell switching toward proliferation and away from migration. Importantly, this is independent of the known microphthalmia-associated transcription factor (MITF)-controlled switch, instead driven by C21orf91. Finally, C21orf91 is demonstrated to be downstream of MITF as well as PR70. CONCLUSION: This work confirms the power of a rare disease approach, identifying a previously unreported copy-number change predisposing to melanocytic neoplasia, and discovers C21orf91 as a potentially targetable hub in the control of phenotype switching.

Dysregulation of homocysteine homeostasis in acute intermittent porphyria patients receiving heme arginate or givosiran.

Acute intermittent porphyria (AIP) is a rare metabolic disease caused by mutations within the hydroxymethylbilane synthase gene. Previous studies have reported increased levels of plasma total homocysteine (tHcy) in symptomatic AIP patients. In this study, we present long-term data for tHcy and related parameters for an AIP patient cohort (n = 37) in different clinical disease-states. In total, 25 patients (68%) presented with hyperhomocysteinemia (HHcy; tHcy > 15 µmol/L) during the observation period. HHcy was more frequent in AIP patients with recurrent disease receiving heme arginate, than in nonrecurrent (median tHcy: 21.6 µmol/L; range: 10-129 vs median tHcy: 14.5 µmol/L; range 6-77). Long-term serial analyses showed a high within-person tHcy variation, especially among the recurrent patients (coefficient of variation: 16.4%-78.8%). HHcy was frequently associated with low blood concentrations of pyridoxal-5'-phosphate and folate, while cobalamin concentration and the allele distribution of the methylene-tetrahydrofolate-reductase gene were normal. Strikingly, 6 out of the 9 recurrent patients who were later included in a regime of givosiran, a small-interfering RNA that effectively reduced recurrent attacks, showed further increased tHcy (median tHcy in 9 patients: 105 µmol/L; range 16-212). Screening of amino acids in plasma by liquid-chromatography showed co-increased levels of methionine (median 71 µmol/L; range 23-616; normal <40), suggestive of acquired deficiency of cystathionine-ß-synthase. The kynunerine/tryptophan ratio in plasma was, however, normal, indicating a regular metabolism of tryptophan by heme-dependent enzymes. In conclusion, even if HHcy was observed in AIP patients receiving heme arginate, givosiran induced an aggravation of the dysregulation, causing a co-increase of tHcy and methionine resembling classic homocystinuria.

Histologic features of melanoma associated with germline mutations of CDKN2A, CDK4, and POT1 in melanoma-prone families from the United States, Italy, and Spain.

BACKGROUND: CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes. OBJECTIVE: We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1. METHODS: We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and noncarriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family. RESULTS: Histologic slides were evaluated for 290 melanomas (139 from 132 noncarriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, and 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in 10 of 15 invasive melanomas (67%) from POT1 carriers (P < .0001 vs noncarriers). This finding was independently confirmed by 3 expert melanoma dermatopathologists in 9 of 15 invasive melanomas (60%). In situ and invasive melanomas from CDKN2A and CDK4 carriers were histologically similar to melanomas from noncarriers. LIMITATIONS: Limited sample sizes for rare melanoma-susceptibility syndromes (CDK4, POT1). CONCLUSION: Spitzoid morphology was associated with POT1 mutations suggesting that telomere dysfunction (POT1 mutations) may contribute to spitzoid differentiation in melanocytic tumors.

Sutton Naevi as Melanoma Simulators: Can Confocal Microscopy Help in the Diagnosis?

Sutton naevi can sometimes present a challenging appearance with atypical presentation, also by dermoscopy. Reflectance confocal microscopy could help in making a diagnosis. This study prospectively collected two groups of Sutton nevi: the first one was composed by typical white halo naevi monitored for one year (13, 23%) and the second one was made up of atypical lesions excised in order to rule out melanoma, which were histologically diagnosed as Sutton naevi (21, 37%). These two groups of Sutton naevi were compared to a retrospectively collected cohort of thin melanomas with histologic regression features (23, 40%). On dermoscopy, atypical Sutton naevi and melanomas were indistinguishable. Reflectance confocal microscopy demonstrated significant differences at the dermo-epidermal junction: marked dermo-epidermal junction thickening and non-edged papilla were associated with melanoma, while the presence of nests was associated with Sutton naevi. However, reflectance confocal microscopy also detected marked intraepidermal pagetoid cells in Sutton naevi that were a combination of MelanA+ and CD1a+ cells. Sutton naevi can simulate melanoma, under both dermoscopy and reflectance confocal microscopy. Nevertheless, relevant confocal dermo-epidermal junction features and the clinical scenario can be helpful to make a final diagnosis, especially in those situations where melanoma must be ruled out.

Showing their mettle: extraradical mycelia of arbuscular mycorrhizae form a metal filter to improve host Al tolerance and P nutrition.

BACKGROUND: New evidence has shown that arbuscular mycorrhizal (AM) fungi can contribute to the aluminum (Al3+ ) tolerance of host plants growing in acidic soils with phytotoxic levels of Al3+ . The aim of this study was to investigate the role of AM fungi isolated from naturally occurring Al3+ acidic soils in conferring host tolerance to Al3+ toxicity in three wheat cultivars differing in Al3+ sensitivity. The experiment was conducted in a soilless substrate (vermiculite/perlite, 2:1 v/v) using two Al3+ -tolerant wheat genotypes and one Al3+ -sensitive wheat genotype. The wheat was colonized with a consortium of AM fungi isolated from an Andisol, with or without Al3+ at a concentration of 200 µmol L-1 . RESULTS: The response of wheat to Al3+ in the medium was dependent on both the plant genotype and AM colonization. The benefits of the AM fungi to the wheat cultivars included an increased P concentration and relatively low Al3+ accumulation in the plants. This was achieved through two mechanisms. First, the metal-chelating capacity of the AM fungi was clear in two of the cultivars ('Tukan' and 'Porfiado'), in which the enhanced extraradical mycelium development was able to retain Al3+ in the glomalin and hyphae. Second, the increased AM-induced acid phosphatase activity in the rhizosphere of the other cultivar ('Atlas 66') increased host nutrition possibly by hyphae-mediated nutrient uptake and glomalin-related soil protein. CONCLUSION: The results suggest that the role of AM fungi in cultivar-specific Al3+ detoxification can be achieved by increased extraradical mycelial filters and enhanced bioavailability of P in the host rhizosphere. © 2019 Society of Chemical Industry.

An epidemiological and molecular study regarding the spread of vancomycin-resistant Enterococcus faecium in a teaching hospital in Bogotá, Colombia 2016.

BACKGROUND: Enterococcus faecium is ranked worldwide as one of the top ten pathogens identified in healthcare-associated infections (HAI) and is classified as one of the high priority pathogens for research and development of new antibiotics worldwide. Due to molecular biology techniques' higher costs, the approach for identifying and controlling infectious diseases in developing countries has been based on clinical and epidemiological perspectives. Nevertheless, after an abrupt vancomycin-resistant Enterococcus faecium dissemination in the Méderi teaching hospital, ending up in an outbreak, further measures needed to be taken into consideration. The present study describes the vancomycin-resistant Enterococcus faecium pattern within Colombian's largest installed-bed capacity hospital in 2016. METHODS: Thirty-three vancomycin-resistant Enterococcus faecium isolates were recovered during a 5-month period in 2016. Multilocus variable-number tandem-repeat analysis was used for molecular typing to determine clonality amongst strains. A modified time-place-sequence algorithm was used to trace VREfm spread patterns during the outbreak period and estimate transmission routes. RESULTS: Four clonal profiles were identified. Chronological clonal profile follow-up suggested a transitional spread from profile "A" to profile "B", returning to a higher prevalence of "A" by the end of the study. Antibiotic susceptibility indicated high-level vancomycin-resistance in most isolates frequently matching vanA gene identification. DISCUSSION: Transmission analysis suggested cross-contamination via healthcare workers. Despite epidemiological control of the outbreak, post-outbreak isolates were still being identified as having outbreak-related clonal profile (A), indicating reduction but not eradication of this clonality. This study supports the use of combined molecular and epidemiological strategies in an approach to controlling infectious diseases. It contributes towards a more accurate evaluation of the effectiveness of the epidemiological measures taken regarding outbreak control and estimates the main cause related to the spread of this microorganism.

Clinical and photobiological response in eight patients with solar urticaria under treatment with omalizumab, and review of the literature.

BACKGROUND: Solar urticaria (SU) is a rare photodermatosis. Treatment is challenging, and outcomes are often disappointing. Omalizumab is an anti-IgE, currently approved for treatment of chronic spontaneous urticaria. We sought to evaluate therapy with omalizumab in refractory SU and describe predictive factors for response. MATERIALS/METHODS: Patients with refractory SU under treatment with omalizumab were included in this study. Clinical outcome was evaluated using the Urticaria Activity Score 7 (UAS7), Dermatology Life Quality Index (DLQI) and Pruritus Visual Analogue Scale (VAS). Complete clinical response (CCR) was defined as having an UAS7 = 0, DLQI <6 and VAS = 0. Phototesting was performed and compared to baseline. We performed a PubMed search to identify reported cases of SU in adults treated with omalizumab, analysing their characteristics in order to predict response to omalizumab. RESULTS: Eight patients were included. Median age was 45.5 years (range, 23-64). Light spectrum most commonly implicated was UV-A. Clinical outcomes: 89% (7/8) achieved CCR with omalizumab. Phototesting was normal in 42.8% (3/7) of them. In our review, we identified 38 patients (including the current case series), and 68.4% showed favourable outcomes with omalizumab. Median time since onset of SU was lower in responders. CONCLUSIONS: Omalizumab can be an effective treatment in refractory SU.

Patterns of distribution of giant congenital melanocytic nevi (GCMN): The 6B rule.

BACKGROUND: Garment-related terms have been used to describe the pattern of distribution of giant congenital melanocytic nevi (GCMN). OBJECTIVE: We sought to describe patterns of distribution of GCMN and propose a classification scheme. METHODS: Photographic records of patients with GCMN from the Hospital Clinic of Barcelona were analyzed and a classification based on observed GCMN distribution patterns was created. The classification was independently applied by 8 observers to cases found in the literature. The interobserver agreement was assessed. RESULTS: Among 22 patients we observed 6 repeatable patterns of distribution of GCMN, which we termed the "6B": bolero (involving the upper aspect of the back, including the neck), back (on the back, without involvement of the buttocks or shoulders), bathing trunk (involving the genital region and buttocks), breast/belly (isolated to the chest or abdomen without involvement of bolero or bathing trunk distributions), body extremity (isolated to extremity), and body (both bolero and bathing trunk involvement). Our literature search found 113 cases of GCMN, which we were able to classify into 1 of the 6B patterns with an overall kappa of 0.89. LIMITATIONS: Some patterns occur infrequently with a dearth of images available for analysis. CONCLUSIONS: The anatomic distribution of GCMN occurs in 6 recognizable and repeatable patterns.

Dermoscopy Improves the Diagnostic Accuracy of Melanomas Clinically Resembling Seborrheic Keratosis: Cross-Sectional Study of the Ability to Detect Seborrheic Keratosis-Like Melanomas by a Group of Dermatologists with Varying Degrees of Experience.

BACKGROUND: Malignant melanomas mimicking seborrheic keratosis (SK-like MMs) carry the risk of delayed diagnosis and inadequate treatment. The value of dermoscopy to improve the correct detection of these mimickers has not been previously studied. OBJECTIVE: To evaluate the diagnostic accuracy of clinically SK-like MMs with and without dermoscopy. METHODS: Clinical and dermoscopic images of histopathologically proven SK-like MMs (n = 134) intermingled with other melanomas and benign tumors were randomly presented to clinicians with different levels of experience, blinded to the diagnosis and goal of the study. Each participant classified each lesion as melanoma or benign tumor. The clinical and clinical-dermoscopic diagnostic accuracies were measured separately. RESULTS: Overall, 54 participants with a mean clinical experience of 15.8 years (SD 11.8) evaluated 231 tumors. Almost 40% of SK-like melanomas were clinically misclassified as benign tumor. Dermoscopy improved diagnostic accuracy for all participants, independently of experience, from 60.9 to 68.1% (p < 0.001), mostly due to a significant increase in the sensitivity (clinical 61.9% vs. dermoscopic 74.5%) (p < 0.001). Dermoscopy did not significantly affect specificity among the experienced participants (≥6 years of experience) compared to clinical examination (61.1 vs. 59.6%, respectively); in contrast, dermoscopy was associated with a decrease in specificity compared to clinical diagnosis among novice participants (< 6 years) (45.6 vs. 61.1%, respectively; p = 0.02). CONCLUSION: Melanomas can be clinically indistinguishable from SKs despite being evaluated by expert dermatologists. Dermoscopy, even in nonexpert hands, significantly improves their recognition.

Efficacy of a Daily Protective Moisturizer with High UVB and UVA Photoprotection in Decreasing Ultraviolet Damage: Evaluation by Reflectance Confocal Microscopy.

Patients with photodermatoses or actinic keratosis benefit from very high ultraviolet B-ultraviolet A (UVB-UVA) photoprotection. However, poor compliance is an issue that jeopardizes adequate protection, leading to disease recurrence. This study evaluated the efficacy of a daily protective moisturizer with high UVB and UVA photoprotection applied 8 h before irradiation. A monocentric, open-label, prospective, control pilot study was performed including 10 patients. Patients were irradiated with UVB and UVA before and 8 h after topical application of the product. Reflectance confocal microscopy (RCM) assessment was performed 24 h later. Clinical assessment showed a statistically significant increase in minimal erythema dose (MED) after application of the product (p <0.001). Signs of UV damage according to RCM were not observed on photoprotected skin (p <0.05). Skin irradiated 8 h after applying a daily protective moisturizer presented an increase in MED and RCM findings that equal the findings for non-irradiated skin.

Porokeratosis ptychotropica responding to photodynamic therapy: An alternative treatment for a refractory disease.

BACKGROUND: Porokeratosis ptychotropica (PP) is a rare variant of porokeratosis with a special predisposition to affect body folds, particularly the intergluteal cleft. This disease is resistant to most topical and systemic treatments, as shown in the review of the literature we provide here. Itching and discomfort are often a difficult problem to solve. PATIENTS AND METHODS: Two patients with PP that had not responded to multiple topical treatments were treated with photodynamic therapy (PDT). Changes in plaque size, thickness and symptoms were assessed after treatment. RESULTS: Pruritus disappearance was observed in both patients after treatment with PDT. Partial clearance of the plaques was observed in one case. In the other case, a moderate clearance of hyperkeratosis was observed, although the size of the lesions persisted unchanged. CONCLUSIONS: PDT seems to be a good therapeutic alternative in the treatment of PP, as it can provide symptomatic relief and clinical improvement of the lesions. However, it does not appear to be a curative treatment. Moreover, long-term response is still unknown.