The usefulness of a dermocosmetic containing Myrtus communis extract and azelaic acid for maintenance phase of adult female acne: Results from a randomized exploratory investigator-blinded comparative study.

BACKGROUND: Acne is a very common condition. Currently, there are relatively few studies available to help guidance-based decisions for its long-term management, especially studies with cosmetic care products. We have developed a skin care product dedicated to adult female acne. OBJECTIVES: Evaluate the efficacy and tolerance of the test product containing Myrtus communis extract and azelaic acid compared with a light moisturizing cream (LCM) in adult females in the acne maintenance phase. METHODS: A clinical study was conducted as a Brazilian, multicentre, randomized, investigator-blinded trial in adult females with clear or almost clear facial acne after anti-acne treatment. The test group (26 subjects) applied the test product and the comparative product group (27 subjects) applied LCM. Both groups applied the products twice daily on the whole face. Subjects were evaluated every 4 weeks over 16 weeks. Efficacy was evaluated according to acne relapse; Investigator's Global Assessment (IGA); acne lesions counting; AcneQoL questionnaire; Subject Global change Assessment (SGA) of acne severity; and the number of Post-Inflammatory Hyperpigmentation (PIH) and Post-Inflammatory Erythema (PIE) lesions. Tolerance was assessed according to a 5-point scale. RESULTS: Over 16 weeks, the number of acne relapse was more than double in the comparator compared to the test product group (eight subjects vs. three subjects respectively). There was no statistical difference in the evolution of the mean IGA from baseline between the two groups; however, 85% of subjects were assessed as clear or almost clear in the test product group and 67% in the comparative group. CONCLUSIONS: This study demonstrated the effectiveness topical application of the test product compared to LCM on acne severity in the maintenance phase of adult female acne. Efficacy results after 16 weeks suggested a trend to limit acne relapses and a benefit of the test product in maintaining long-term remission.

Prevalence of and risk factors for post-COVID: Results from a survey of 6,958 patients from Brazil.

A plethora of prolonged COVID-19 symptoms, or late manifestations has been reported after acute disease and labeled "post-COVID". The aim of this study was to identify the prevalence of and risk factors for post-COVID up to 12 weeks after the onset of acute COVID-19. An electronic survey was conducted to evaluate post-COVID-19 symptoms, disease severity, demographics, and pre-existing diseases. The participants were recruited through 88,648 SMS messages, and post on social media. The associations between variables were explored through multivariate models. From 6,958 respondents with confirmed COVID-19, 753 (10.8%) required hospitalization, and 5,791 (83.2%) exhibited at least one post-COVID manifestation. Hair loss (49.4%), memory loss (40.7%), low attention (37.0%), fatigue (34.2%), anxiety (31.2%), and headache (29.6%) were the most reported post-COVID manifestations. Female sex, myalgia, anosmia, and severe disease were associated with most post-COVID manifestations. Pre-existing depression was associated with the development of neuropsychiatric manifestations. Post-COVID manifestations were identified in most patients following COVID-19 infection, placing a supplementary burden on the healthcare system. Hair loss, fatigue, and neuropsychiatric symptoms were the most prevalent post-COVID manifestations. Female sex, myalgia, anosmia, and more severe disease are risk factors for multiple post-COVID manifestations.

Testicular alterations in cryptorchid/orchiopexic rats chronically exposed to acrylamide or di-butyl-phthalate.

Exposure of Sprague-Dawley (SD) rats to acrylamide (AA) or di-butyl-phthalate (DBP) from the 12th gestational day to the 16th postnatal week (PNW) has been shown to reduce the effectiveness of orchiopexy in recovering the testicular alterations associated with experimental cryptorchidism established at weaning. Herein, we provide information about the long-term effects of AA or DBP on the testes of cryptorchid/orchiopexic rats. Male offspring exposed in utero to 10 mg/kg/day AA or 500 mg/kg/day DBP underwent bilateral surgical cryptorchidism at the 3rd PNW and orchiopexy at the 6th week, with continuous exposure to the chemicals through diet until the 58th week. Regardless of the test chemical, there were severe qualitative/quantitative alterations in the seminiferous tubules and increased numbers of Leydig cells. There was an increase and decrease in the number of tubules with c-Kit- and placental alkaline phosphatase-labeled germ cells, respectively, as compared to those in the control group, suggesting an imbalance between apoptosis and cell proliferation processes. The histological scores of the testicular lesions at the end of this one-year study were higher than those in the previous 16-week study, indicating that exposure of rats to the toxicants AA or DBP enhanced the testicular alterations induced by the chemicals beginning at the intra-uterine life, and impaired the effectiveness of orchiopexy in restoring the testes to normal morphology. Although the present experimental protocol does not completely replicate the natural human undescended testes, our findings may contribute to understanding the alterations occurring in cryptorchid/orchiopexic testes potentially exposed to exogenous chemicals for extended periods.

Characterization of the Activity of Croton tiglium Oil in Hetter's Very Heavy Phenol-Croton Oil Chemical Peels.

BACKGROUND: Croton oil (CO) is used by dermatologists and plastic surgeons in deep chemical peels. It is mixed with phenol, water, and a soap in Baker-Gordon's or Hetter's formulas. There is controversy as to whether CO or phenol is the active agent in the dermal effect of deep chemical peels. OBJECTIVE: To better clarify the role of CO in deep peels, by identification of active compounds in commercially available CO in the United States and biological effects in vivo. MATERIALS AND METHODS: Liquid chromatography-tandem mass spectrometry on CO and a domestic pig model experiment using 3 different formulas: G1: 5% Septisol (SEP), G2: 1.6% croton oil in 35% phenol with 5% SEP, and G3: 35% phenol with 5% SEP. RESULTS: Liquid chromatography-tandem mass spectrometry indicated the presence of phorbol esters. G1 was null overall. Extent of the coagulative necrosis: G2 > G3. Vascular ectasia: G2 > G3. Inflammation pattern: intense neutrophilic inflammatory band in G2 versus mild, sparse, perivascular mononuclear cell infiltrate in G3. Neocollagenesis: pronounced in G2, negligible in G3. CONCLUSION: Coagulative necrosis of the epidermis, superficial fibroblasts, and vasculature can be attributed to the action of phenol. Phorbol esters on CO could be responsible for the dense deep acute inflammation and the distinctive neocollagenesis.

Dimensionality and psychometric analysis of DLQI in a Brazilian population.

BACKGROUND: The Dermatology Life Quality Index (DLQI) is the most commonly used instrument for clinical evaluation of the impact on health-related quality of life (HRQOL) in dermatological research protocols. The DLQI's classical psychometric properties have been considered adequate in validation studies from several countries. However, the structure of the DLQI is a matter of discussion, especially concerning the dimensionality and informative properties of its questions according to the item response theory (IRT). METHODS: Pooled data from studies in Brazil that utilized the DLQI to assess HRQOL in 14 dermatoses were reanalyzed. Classical psychometrical analysis, dimensionality assessment through parallel analysis and IRT (Samejima's ordinal model) analysis were performed. RESULTS: The sample consisted of 1286 patients with a mean age of 47 years (SD = 16), and the proportion of women was 59% (765). The DLQI scores ranged from 0 to 29, with a median (p25-p75) of 5 (2-11). All items indicated significant correlations with the total DLQI score (rho > 0.54). The Cronbach's alpha result was 0.90 (CI 95% 0.89-0.91). Parallel analysis indicated a unidimensional factor structure. According to IRT analysis, items q6 (sports) and q7 (work/study) exhibited insufficient fit to the model (p < 0.01), while the items that indicated the best discrimination and information functions were q2 (embarrassment), q3 (shopping/gardening), q4 (clothing) and q5 (social/leisure). The ordination of the scores was confirmed for all items. Most items revealed non-uniform behavior according to sex, age and type of disease. CONCLUSIONS: The DLQI exhibits adequate psychometric reliability and a unidimensional structure for assessing HRQOL in Brazilian dermatological patients. The DLQI's performance varies in the assessment of HRQOL in heterogeneous samples.

Efficacy and Safety of 2 Injection Techniques for Hand Biostimulatory Treatment With Diluted Calcium Hydroxylapatite.

BACKGROUND: Calcium hydroxylapatite (CaHA) is effective for dorsal hand rejuvenation. Higher dilutions are used for biostimulation with fewer side effects. OBJECTIVE: To evaluate the efficacy and safety of 2 techniques of diluted CaHA injection for dorsal hand treatment. METHODS: A prospective, evaluator-blinded study was performed to compare (side-to-side) techniques for treating the dorsum of the hands with diluted CaHA: deep fat lamina or subdermal injection. Fifteen women with aging grades between 1 and 3 on the MHGS (Merz hand grading scale) were enrolled and followed up for 24 weeks. The outcomes were a histological analysis of collagen, skin viscoelasticity, high-frequency ultrasound parameters, MHGS score, and the global aesthetic improvement scale (GAIS) score. RESULTS: Improvement in the MHGS and GAIS scores (p < .01) was observed, with no difference between techniques (p > .05). Skin viscoelasticity measures and ultrasonography for dermal parameters improved for both treatments (p < .01). The mean total collagen density increased from the baseline for both techniques (p < .01). Pain during the procedure as well as adverse effects within the follow-up did not differ between treatments (p > .4). The overall satisfaction was 12% greater for the subdermal technique (p < .05). CONCLUSION: Diluted CaHA improves the skin quality of aging hands with a safe profile, without substantial differences between the techniques.

Isolation and molecular characterization of spermatogonia from male Sprague-Dawley rats exposed in utero and postnatally to dibutyl phthalate or acrylamide.

The increased incidence of testicular disorders in young men and the possible influence of environmental chemicals, such as dibutyl phthalate (DBP) and acrylamide (AA), requires experimental models for identifying modes of action. Most published reproductive toxicologic studies use RNA samples from the total testis to evaluate testicular gene expression; however, analyses of isolated cell types could provide a more specific tool. Among testicular germ cells, spermatogonia are critical since they represent the onset of spermatogenesis. This study aimed, (1) to establish a technique for spermatogonia isolation; (2) to apply this isolation technique to verify possible gene expression alterations (Pou5f1, Kitlg, Mki-67, Bak1 and Spry4) in prepubertal post-natal day, (PND24) and pubertal (PND45) testes after in utero and postnatal exposure to DBP or AA. The technique was efficient for isolation of a majority of spermatogonia. In utero DBP exposure led to reduced litter body weight at birth, reduced anogenital distance of male pups on PND4, and increased frequency of male nipple retention on PND14 compared to controls. DBP-exposed relative testes weights were reduced only at PND24 compared to control but they did not differ at PND45. DBP-exposed animals showed reduced expression levels of Pou5f1 and Mki67 on PND24, and reduced expression of Pou5f1 and Spry4 on PND45. AA exposure reduced expression of Pou5f1, Mki67, and Spry4 at PND45 although not significantly. Our results suggest that DBP acts by reducing cell proliferation and impairing differentiation in prepubertal and pubertal testes.

Five percent 5-fluorouracil in a cream or for superficial peels in the treatment of advanced photoaging of the forearms: a randomized comparative study.

BACKGROUND: The antimetabolite 5-fluorouracil (5-FU) is used for topical treatment of actinic keratosis. Overall improvement in the skin is also observed. Additionally, 5-FU was reported to be used for superficial peels. OBJECTIVES: To evaluate the efficacy and safety of 5% 5-FU cream compared with peels for photodamaged forearms. METHODS: This interventional, randomized, comparative, evaluator-blind study included 32 patients with severe photoaging of forearms. The regimens comprised either application of 5% 5-FU cream everyday for 4 weeks on 1 forearm and 4 weekly peels on the other. Efficacy assessment included: clinical photodamage scores, opinion of patients and investigators, and blind photographic evaluation by independent observers. Skin biopsies were performed for histologic and immunohistochemical analysis. Safety evaluation comprised observation of adverse events. RESULTS: Clinical and histologic findings confirmed the benefits of topical 5% 5-FU, in cream or peels, which improved skin appearance and decreased the dermal elastotic material. Immunohistochemistry showed reduced levels of epidermal p53 and increase in the level of procollagen I. Results were maintained after 6 months. Predictable adverse events occurred, with no differences between treatments. Patients reported better tolerability to peels. CONCLUSION: Five percent 5-FU cream or peels was safe and effective for the treatment of photodamaged forearms. Decreased epidermal p53 levels and new dermal collagen were confirmed.

Clinical and microbiologic evaluation of chronic leg ulcers: a cross-sectional study.

OBJECTIVE: This study aimed at evaluating the flora and bacterial load of chronic leg ulcers (CLUs) according to the clinical judgment of colonization or infection. DESIGN: This was an analytical and cross-sectional study. SETTING: This study was conducted in an outpatient wound care unit in the Dermatology Department of the Botucatu School of Medicine-UNESP, Brazil. PARTICIPANTS: The participants were patients with CLUs who did not use systemic antibiotics. METHODS: The ulcers were clinically divided into 3 groups: ulcers with good granulation tissue (GGT), critical colonization (CC), and infection. Secretion was collected from a 1-cm area using a swab and seeded by the semiquantitative method. OUTCOME MEASURES: The main outcome measures were genus and species of the bacteria found in the cultures and result of the semiquantitative culture correlating with the clinical diagnosis of GGT, CC, and infection. MAIN RESULTS: Seventy-seven ulcers were evaluated: 27 with GGT, 29 with CC, and 21 with infection. Gram-negative bacteria were most often found in all groups (81%): Pseudomonas aeruginosa, in granulation and colonized ulcers, and Proteus mirabilis, in infected ulcers. Ulcers from the infected group showed higher bacterial load. CONCLUSIONS: The flora of CLUs was predominantly constituted by gram-negative bacteria, and P aeruginosa was the most prevalent. The bacterial load of infected ulcers was higher as compared with the others, although some ulcers with GGT also presented a high load. The interpretation of microbiologic tests based on the swab techniques and even on semiquantitative analysis requires close clinical correlation.

Sequential therapy with topical clobetasol for 14 days followed by hydroquinone versus hydroquinone alone in facial melasma treatment: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Clobetasol has demonstrated remarkable results in treating melasma within a short time frame; however, its use is limited because of the risk of local side effects. To date, there is no controlled trial on sequential clobetasol/hydroquinone for melasma. This study aimed to investigate the tolerability and efficacy of 0.05% clobetasol followed by 4% hydroquinone (CLOB-HQ) in comparison to the isolated use of 4% hydroquinone (HQ). METHODS: A double-blinded, randomized clinical trial involving 50 women with facial melasma was performed. They were directed to apply 0.05% clobetasol every night for 14 days, followed by 4% hydroquinone for 46 days (CLOB-HQ group), or the use of hydroquinone for 60 days (HQ group). Evaluations were carried out at inclusion, and after 14 and 60 days of treatment, measuring modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life scale (MELASQoL), and colorimetry. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator. RESULTS: There was no difference in the main outcomes at D14 and D60 (P > 0.1). For CLOB-HQ, the mean (CI 95%) reduction in mMASI was 13.2% (5.1-21.3%) and 43.1% (32.2-54.0%) at D14 and D60, and for HQ, they were 10.6% (5.9-27.5%) and 44.8% (33.2-52.3%). The MELASQoL, colorimetric luminosity, and GAIS showed a progressive improvement for both groups despite no difference between them. No severe side effects were identified. No cases of telangiectasias, atrophy, or perioral dermatitis were associated with the use of CLOB. CONCLUSION: The sequential CLOB-HQ regimen was safe and well tolerated, even though its efficacy was not different from HQ after 14 or 60 days of treatment. Based on these findings, the use of clobetasol 14 days before hydroquinone is not advisable for the treatment of melasma.

Efficacy and Safety of Topical or Oral Hydrolyzed Collagen in Women with Dermatoporosis: A Randomized, Double-Blind, Factorial Design Study.

BACKGROUND: Dermatoporosis defines the progressive chronic cutaneous insufficiency syndrome. Stage I is characterized by cutaneous atrophy, senile purpura, and stellate pseudoscars. OBJECTIVE: To assess clinical, histologic, quality of life, and biophysical effects of oral and/or topical hydrolyzed collagen (HC) on forearm skin of postmenopausal women with Dermatoporosis stage I. METHODS: Double-blind randomized placebo-controlled factorial design study. Two groups of menopausal women with stage I dermatoporosis on forearms were randomized to oral HC 5 g/day or matching placebo, and also to topical serum 2.5% HC or matching placebo once a day, for 6 months. RESULTS: A total of 56 women, age range 60-93 years (mean 69.5 ± 7.3 years) were included. Comparing data from baseline and after 6 months, no significant difference was observed for each intervention nor their comparison, for all efficacy parameters: clinical and quality of life scores, dermal elasticity, thickness and echogenicity, and histologic and immunohistochemical markers (p > 0.1). LIMITATIONS: Larger studies to confirm our findings are warranted. CONCLUSIONS: In menopausal women with stage I dermatoporosis, oral or topical collagen peptides used alone or in combination do not have benefits on forearm skin after 6 months of intervention, and therefore should not be used routinely in this population. CONSORT flow chart.

Association between calcium channel blockers and the severity of actinic keratosis on face and scalp: a cross-sectional study.

BACKGROUND: Actinic keratosis (AK) is a skin condition associated with age, sun exposure, and immunosuppression. Certain drugs, such as photosensitizing medications and calcium channel blockers (CCBs), have been linked to AK. This study explores the impact of individual, behavioral, and exposure factors on the severity of AKs on the face and scalp. METHODS: A multicenter cross-sectional study was conducted on immunocompetent individuals with at least one AK on their face or scalp and assessed demographic factors, sun exposure and protection, history of skin cancer, and medication use within the last 6 months. The primary outcome was the Actinic Keratosis Area and Severity Index (AKASI) score, and a hierarchical generalized linear model was used to evaluate the variation in AKASI scores, adjusting for gender, age, and skin phototype. RESULTS: Two hundred seventy subjects between 39 and 92 years were evaluated. The majority had phototype I or II (77%), male gender (51%), personal history of skin cancer (55%), and low adherence to sunscreen use (29%). The use of photosensitizing medications was reported by 61%. Through multivariate analysis, older age (ßSE = 0.14; P < 0.01), lighter skin phototype (ßSE = 0.15; P = 0.01), history of skin cancer (ßSE = 0.12; P < 0.01), sunburning (ßSE = 0.12; P < 0.01), and use of CCBs (ßSE = 0.11; P = 0.02) were identified as independent risk factors for AK severity. Photosensitizing drugs were not identified as risk factors. CONCLUSION: Older age, lower skin phototype classifications, and a personal history of skin cancer were confirmed as severity risk factors for AK, while the use of CCBs was associated with more severe AK.

Histopathologic changes induced by intense pulsed light in the treatment of poikiloderma of Civatte.

BACKGROUND: The clinical efficacy of intense pulsed light (IPL) in the treatment of poikiloderma of Civatte (PC) is well documented, but little is known about microscopic changes. OBJECTIVE: To analyze histopathologic findings on the necks of individuals with PC after IPL therapy. MATERIALS AND METHODS: Fourteen patients with PC on the neck underwent three monthly sessions of IPL. Biopsies and clinical photographs were taken before and 60 days after treatment. A dermatopathologist analyzed histopathologic slides stained with hematoxylin and eosin, Masson's trichrome, Verhoeff-van Gieson and Fontana-Masson or processed for CD-34 immunohistochemistry. The slides also underwent digital image analysis. Clinical results were based on the analysis of the pictures by three dermatologists and on patient satisfaction. RESULTS: Intense pulsed light treatment resulted in more-homogeneous melanin distribution; a greater number of fibroblasts and nonfragmented elastic fibers; and greater density (p = .01), color intensity (p = .02), number and thickness of the collagen bundles. No significant changes in vessels' number or diameters were observed. Clinical results were positive in 92.9% of the cases. CONCLUSION: IPL treatment of PC induced a more-homogeneous distribution of melanin and increased nonfragmented elastic fibers, collagen density, and intensity. These changes were related to clinical improvement.

Update on Melasma-Part II: Treatment.

Melasma is a prevalent chronic relapsing pigmentary disorder that affects photoexposed areas, especially in women of childbearing age. Although there is currently no curative treatment available for melasma, this manuscript critically reviews the knowledge regarding photoprotection, topical and oral therapies, and procedures such as peelings, laser, and microneedling that represent the main strategies for control and prevention of this disease. As the pathogenesis of melasma is not entirely understood, there are prospects for the development of new therapeutic strategies that might act on the pathways that promote sustained pigmentation rather than merely decreasing melanin synthesis and removing melanin from the epidermis.

Indeterminate thyroid cytology: detecting malignancy using analysis of nuclear images.

BACKGROUND: Thyroid nodules diagnosed as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS) or 'follicular neoplasm/suspected follicular neoplasm' (FN/SFN), according to Bethesda's classification, represent a challenge in clinical practice. Computerized analysis of nuclear images (CANI) could be a useful tool for these cases. Our aim was to evaluate the ability of CANI to correctly classify AUS/FLUS and FN/SFN thyroid nodules for malignancy. METHODS: We studied 101 nodules cytologically classified as AUS/FLUS (n = 68) or FN/SFN (n = 33) from 97 thyroidectomy patients. Slides with cytological material were submitted for manual selection and analysis of the follicular cell nuclei for morphometric and texture parameters using ImageJ software. The histologically benign and malignant lesions were compared for such parameters which were then evaluated for the capacity to predict malignancy using the classification and regression trees gini model. The intraclass coefficient of correlation was used to evaluate method reproducibility. RESULTS: In AUS/FLUS nodule analysis, the benign and malignant nodules differed for entropy (P < 0.05), while the FN/SFN nodules differed for fractal analysis, coefficient of variation (CV) of roughness, and CV-entropy (P < 0.05). Considering the AUS/FLUS and FN/SFN nodules separately, it correctly classified 90.0 and 100.0% malignant nodules, with a correct global classification of 94.1 and 97%, respectively. We observed that reproducibility was substantially or nearly complete (0.61-0.93) in 10 of the 12 nuclear parameters evaluated. CONCLUSION: CANI demonstrated a high capacity for correctly classifying AUS/FLUS and FN/SFN thyroid nodules for malignancy. This could be a useful method to help increase diagnostic accuracy in the indeterminate thyroid cytology.

Morphologic changes and the expression of alpha-melanocyte stimulating hormone and melanocortin-1 receptor in melasma lesions: a comparative study.

Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light- to dark-brown macules on sun-exposed skin areas. The literature shows few studies on its physiopathogeny. However, changes in α-melanocyte stimulating hormone (α-MSH) secretion and melanocortin-1 receptor (MC1-R) expression may play a role to trigger this condition. Biopsies were taken from both melasma skin and adjacent perilesional normal skin of 44 patients. The biopsies were submitted for hematoxylin and eosin and Fontana-Masson staining and immunohistochemistry with Melan-A, α-MSH, and MC1-R, and processed for transmission electron microscopy. In some cases, they were submitted to MC1-R gene expression analysis by real-time polymerase chain reaction. Increased lymphohistiocytic infiltrate and solar elastosis, higher epidermal melanin were observed in melasma skin. Electron microscopy revealed a greater number of mature melanosomes in keratinocytes and melanocytes, and more prominent cytoplasmic organelles in melasma skin. There was no difference in melanocyte number between areas. However, melanocytes were larger and more dendritic in melasma skin. Immunohistochemistry with α-MSH and MC1-R showed significant labeling in melasmic epidermis but MC1-R messenger ribonucleic acid (RNAm) did not show significant quantitative difference between melasma and normal skin.