Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae.

Importance: Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission. Objective: To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing. Design, Setting, and Participants: This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers. Main Outcome and Measure: Improvement or resolution at the last follow-up assessment. Results: Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 µg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates. Conclusion and Relevance: The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.

A Case of Amoxicillin-Induced Drug Reaction With Eosinophilia and Systemic Symptoms (Dress) Syndrome Associated With Significant Reactive Hypereosinophilia (HE): A Case Report.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe cutaneous drug reaction characterized by a skin rash, eosinophilia, atypical lymphocytosis, and involvement of multiple organs. The mortality rate of DRESS syndrome is moderate, and prompt diagnosis and treatment are essential. When DRESS syndrome is presented with significant hypereosinophilia (HE), it should be differentiated from other conditions that can cause HE through a comprehensive approach to diagnostic evaluation. Amoxicillin has been well-documented as a potential cause of DRESS syndrome. It is important to note that amoxicillin can trigger DRESS syndrome in patients who already have a known allergy to sulfasalazine, as well as when it is administered with a beta-lactamase inhibitor such as clavulanic acid. Here, we describe a case of amoxicillin alone-induced DRESS syndrome associated with significant reactive HE. A 39-year-old female presented with three days of shortness of breath, fatigue, facial swelling, and a generalized maculopapular skin rash. The patient endorsed taking amoxicillin two to three weeks prior to the presentation. Diagnostic tests revealed HE, significant generalized lymphadenopathy on computed tomography (CT) scans of the neck and abdomen, and bilateral interstitial infiltration on a CT scan of the chest suggestive of eosinophilic infiltration. Based on the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system, the case was categorized as "probable" DRESS syndrome related to amoxicillin. High-dose steroids were initiated as the treatment of choice for suspected DRESS syndrome. Other potential causes of HE were investigated and ruled out. The patient showed significant clinical improvement, with the normalization of absolute eosinophil count (AEC) and complete resolution of lung infiltrates on a repeat CT scan of the chest. The case highlights the importance of conducting a comprehensive diagnostic evaluation to differentiate DRESS syndrome from other causes of HE when significant HE is present. Prompt treatment with high-dose steroids is essential in managing patients with severe symptoms associated with DRESS syndrome. It is crucial to consider amoxicillin as a potential trigger for DRESS syndrome, even when there is no history of sulfasalazine allergy or concurrent administration of a beta-lactamase inhibitor.

Toxicity of Varronia curassavica Jacq. Essential Oil to Two Arthropod Pests and Their Natural Enemy.

This study aimed to evaluate the toxicity of the Varronia curassavica Jacq. essential oil to two cosmopolitan and polyphagous pest species, the two-spotted spider mite (Tetranychus urticae Koch) and the green aphid (Myzus persicae Sulzer). Additionally, we tested the essential oil toxicity to a generalist predatory insect, the green lacewing Ceraeochrysa cubana Hagen. The treatments consisted of four essential oil concentrations (0.25, 0.5, 0.75 and 1.0%) and one control (Tween® 80 + water). At 0.75% concentration, the V. curassavica essential oil caused the highest mortalities for both pests. The concentration of 1.0% of the essential oil interfered mainly in the rates of oviposition and egg hatching and caused a decrease in the instantaneous population growth rate (ri) of T. urticae. Survival of the C. cubana was not affected by the highest tested concentration of the essential oil (1%). Tested concentrations V. curassavica essential oil were toxic to T. urticae and M. persicae, but not to the predator C. cubana.

Reference values for skin microanatomy: A systematic review and meta-analysis of ex vivo studies.

BACKGROUND: Few studies have characterized reference values of normal human skin microanatomy parameters. OBJECTIVE: To quantify histologic measurements of epidermal thickness, melanocyte density, hair follicle density, and eccrine gland density as a function of age and anatomic site. METHOD: We searched the PubMed, Embase, Web of Science, and Cochrane databases for articles published through May 25, 2017. Two reviewers independently screened 2016 articles; 327 relevant articles and 151 additional articles found via forward or reference citations underwent full-text review by 1 of 4 reviewers for relevance, data extraction, and critical appraisal. Weighted averages, meta-analysis, and meta-regression were used in statistical analysis. RESULTS: A total of 56 articles were included; when all anatomic locations were used, the overall estimates for epidermal thickness, melanocyte density, hair follicle density, and eccrine gland density were 99.75 µm (95% confidence interval [CI], 83.25-116.25), 955.05 cells/mm2 (95% CI. 880.89-1029.21), 1.40 hairs/mm2 (95% CI. 0.91-1.89), and 1.28 glands/mm2 (95% CI. 0.91-1.64), respectively. LIMITATIONS: There was significant data heterogeneity across studies, possibly because of differences in histological techniques and absence of standardized microanatomy definitions. CONCLUSIONS: We established summary estimates for normal human skin microanatomy parameters.

Factors in Early Adolescence Associated With a Mole-Prone Phenotype in Late Adolescence.

Importance: Nevi are important phenotypic risk factors for melanoma in adults. Few studies have examined the constitutional and behavioral factors associated with a mole-prone phenotype in adolescents. Objective: To identify host, behavioral, and dermoscopic factors in early adolescence (age, 14 years) that are associated with a mole-prone phenotype in late adolescence (age, 17 years). Design, Setting, and Participants: A prospective observational cohort study from the Study of Nevi in Children was conducted from January 1, 2009, to December 31, 2014, with a 2- to 3-year follow-up. A total of 569 students from the school system in Framingham, Massachusetts, were enrolled in the 8th or 9th grade (baseline; mean [SD] age, 14.4 [0.7] years). The overall retention rate was 73.3%, and 417 students were reassessed in the 11th grade. Main Outcome and Measures: Mole-prone phenotype in the 11th grade, defined as total nevus count of the back and 1 randomly selected leg in the top decile of the cohort or having any nevi greater than 5 mm in diameter. Results: Of the 417 students assessed at follow-up in the 11th grade (166 females and 251 males; mean [SD] age, 17.0 [0.4] years), 111 participants (26.6%) demonstrated a mole-prone phenotype: 69 students (62.2%) with 1 nevus greater than 5 mm in diameter, 23 students (20.7%) with total nevus count in the top decile, and 19 students (17.1%) with both characteristics. On multivariate analysis, baseline total nevus count (adjusted odds ratio, 9.08; 95% CI, 4.0-23.7; P < .001) and increased variability of nevus dermoscopic pattern (adjusted odds ratio, 4.24; 95% CI, 1.36-13.25; P = .01) were associated with a mole-prone phenotype. Conclusions and Relevance: This study found clinically recognizable factors associated with a mole-prone phenotype that may facilitate the identification of individuals at risk for melanoma. These findings could have implications for primary prevention strategies and help target at-risk adolescents for higher-intensity counseling about sun protection and skin self-examination.

Lettuce and marigold intercropping: crops productivity and marigold's flavonoid content / Consórcio entre alface e calêndula: produtividade das culturas e teor de flavonóides em calêndula

ABSTRACT: Intercropping of vegetables and medicinal plants might produce favorable interactions for both crops, resulting in increased production and profit per unit area. It is known that active compounds can change because of several factors, including the cropping system. Therefore, the goal of this study was to evaluate the effect of intercropping of lettuce and marigold on the productivity of these crops and on the flavonoid content of marigold flowers. The experiment was conducted in the experimental area of EPAMIG in Oratorios-MG. Treatments consisted of lettuce + marigolds intercropping between rows, lettuce + marigold intercropping between plants, and monocultures of each species. Spacing was 0.3x0.3m. The experimental design consisted of randomized blocks with ten repetitions. Harvest of lettuce and marigold flowers started 45 days after transplantation (DAT) and extended up to 72 DAT for marigolds. Lettuce and marigold intercropping appears feasible because lettuce production did not differ between the monoculture and intercropped cultivations, and marigold productivity was higher when intercropped with lettuce. No change in the flavonoid (active chemicals of medicinal interest) content in the floral capitula of marigolds was observed.

RESUMO: O cultivo consorciado entre hortaliças e plantas medicinais pode promover interação benéfica entre as duas culturas, resultando em aumento na produção e no lucro por unidade de área. Sabe-se também que os princípios ativos podem ser alterados por vários fatores, incluindo o sistema de cultivo. Dessa forma, o objetivo do presente trabalho foi avaliar o efeito do consórcio entre alface e calêndula na produtividade destas culturas e no teor de flavonoides em flores de calêndula. O experimento foi conduzido na área experimental da EPAMIG, em Oratórios-MG. Os tratamentos consistiram em: alface + calêndula entre linhas, alface + calêndula entre plantas e os monocultivos de alface e de calêndula. O espaçamento utilizado foi de 0,3x0,3m. O delineamento experimental foi em blocos casualizados com dez repetições. A colheita de alface e das flores de calêndula iniciou-se 45 dias após o transplantio (DAT), sendo a colheita de calêndula estendida até os 72 DAT. O consórcio entre alface e calêndula é viável, pois a produção da alface é semelhante entre sistemas consorciados e cultivo solteiro, e a produtividade da calêndula é maior quando consorciada com a alface, não havendo alteração no teor de flavonoides (princípio ativo de interesse medicinal) dos capítulos florais de calêndula.

Effect of Accessions and Environment Conditions on Coumarin, O-Coumaric and Kaurenoic Acids Levels of Mikania laevigata.

Coumarin, o-coumaric, and kaurenoic acid are bioactive compounds usually found in the leaves of Mikania laevigata. Genetic and environmental variations in the secondary metabolites of plants may have implications for their biological effects. Three different accessions of M. laevigata cultivated in four sites between the Equator and the Tropic of Capricorn in Brazil were evaluated aiming to present potential raw materials and discuss relationships among these three bioactive compounds. The results revealed effects of plant accessions and environmental factors and suggested two contrasting chemical phenotypes of M. laevigata. The first phenotype presented the highest levels of kaurenoic acid (2283 ± 316 mg/100 g) besides lower levels of coumarin (716 ± 61 mg/100 g), which was also stimulated by the environment and mild climate at the site nearest to the Tropic of Capricorn. The other phenotype presented the lowest levels of kaurenoic acid (137 ± 17 mg/100 g) besides higher levels of coumarin (1362 ± 108 mg/100 g), which was also stimulated by the environment and tropical climate at the site nearest to the Equatorial beach.

The Role of Isotretinoin Therapy for Cushing's Disease: Results of a Prospective Study.

Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6-12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6-12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism.

Growth-Curve Modeling of Nevi With a Peripheral Globular Pattern.

IMPORTANCE: Although nevi with a peripheral rim of globules (peripheral globular nevi [PGN]) observed with dermoscopy are associated with enlarging melanocytic nevi, their actual growth dynamics remain unknown. Because change is a sensitive but nonspecific marker for melanoma, beginning to understand the growth patterns of nevi may improve the ability of physicians to differentiate normal from abnormal growth and reduce unnecessary biopsies. OBJECTIVE: To study the growth dynamics and morphologic evolution of PGN on dermoscopy. DESIGN, SETTING, AND PARTICIPANTS: A total of 84 participants with 121 PGN from September 1, 1999, through May 1, 2013, were identified retrospectively. Cohorts were recruited from the Memorial Sloan Kettering Cancer Center; Melanoma Unit of the Hospital Clinic, University of Barcelona; and Study of Nevi in Children. All 3 cohorts underwent longitudinal monitoring with serial dermoscopic imaging of their PGN. Data analysis was performed from May 1, 2014, through April 1, 2015. MAIN OUTCOMES AND MEASURES: Establishment of the natural growth curve of PGN. The secondary aim was to establish the median time to growth cessation in those PGN for which the size eventually stabilized and/or had begun to decrease during the study period. RESULTS: The median duration of follow-up was 25.1 (range, 2.0-114.4) months. Most of the nevi (116 [95.9%]) enlarged at some point during sequential monitoring. The rate of increase in the surface area of PGN varied among cohorts and ranged from -0.47 to 2.26 mm2/mo (mean rate, 0.25 [95% CI, 0.14-0.36] mm2/mo). The median time to growth cessation in the 26 PGN that stabilized or decreased in size (21.5%) was 58.6 months. All lesions changed in a symmetric manner and 91 (75.2%) displayed a decrease in the density of peripheral globules over time. CONCLUSIONS AND RELEVANCE: Nevi displaying a peripheral globular pattern enlarged symmetrically with apparent growth cessation occurring during a span of 4 to 5 years. Our results reiterate the important concept that not all growth is associated with malignancy.

Second Attempt of Cabergoline Withdrawal in Patients with Prolactinomas after a Failed First Attempt: Is it Worthwhile?

Successful discontinuation of cabergoline (CAB) treatment has been reported in 31-75% of prolactinomas patients treated for at least 2 years. In contrast, it is not well established whether CAB therapy can be successfully withdrawn after a failed first attempt. This prospective open trial was designed to address this topic and to try to identify possible predictor factors. Among 180 patients with prolactinomas on CAB therapy, the authors selected those who fulfilled very strict criteria, particularly additional CAB therapy for at least 2 years, normalization of serum prolactin (PRL) levels following CAB restart, no tumor remnant >10 mm, no previous pituitary radiotherapy or surgery; and current CAB dose ≤1.0 mg/week. Recurrence was defined as an increase of PRL levels above the upper limit of normal. A total of 34 patients (70.6% female) treated with CAB for 24-30 months were recruited. Ten patients (29.4%) remained without evidence of recurrence after 24-26 months of follow-up. Twenty-four patients (70.6%) recurred within 15 months (75% within 12 months) after drug withdrawal and ~80% were restarted CAB. Median time to recurrence was 10.5 months (range, 3-15). Despite overlapping values, non-recurring patients had significantly lower mean PRL levels before withdrawal. Moreover, the recurrence rate was lower in subjects without visible tumor on pituitary magnetic resonance imaging (MRI) than in those with small remnant tumor (60 vs. 79%), though the difference was not statistically significant (P = 0.20). No other characteristic could be identified as a predictor of successful CAB discontinuation. In conclusion, a second attempt of CAB withdrawal after two additional years of therapy may be successful, particularly in patients with lower PRL levels and no visible tumor on pituitary MRI. Close monitoring of PRL level is mandatory, especially within the first year after withdrawal, where most recurrences are detected.

Dermatoscopic imaging of skin lesions by high school students: a cross-sectional pilot study.

BACKGROUND: The ability of novices to perform imaging of skin lesions is not well studied. OBJECTIVES: To determine the ability of 12th grade high school students without formal training to take clinical and dermatoscopic images of skin lesions on patient-actors. PATIENTS/METHODS: Nineteen participants were divided into 11 gender-specific groups of 1-2 students. Groups were provided written instructions and assessed in their ability to (a) identify 8 pre-specified skin lesions, (b) take overview clinical images, and (c) take contact, polarized dermatoscopic images. Groups captured the same images twice using two different cameras [Nikon TM 1 J1 / VEOS HD1 and a VEOS DS3 (Canfield Scientific, Inc.)]. The sequence of camera use was determined using block randomization. If students made visibly poor skin contact during dermatoscopic imaging using their first camera, study investigators provided verbal instructions to place the second camera directly onto the skin. Students completed anonymous surveys before and after the imaging activity. RESULTS: Students were proficient at identifying the correct pre-specified skin lesions (86/88, 98%), capturing sufficient quality overview clinical images of the back and legs (41/42, 98%), and taking dermatoscopic images of the entire skin lesion (174/176, 99%). Regarding dermatoscopic image quality, 116 of 175 (66%) images were in focus. Out of focus images were attributed to poor skin contact. Groups that received feedback (n=4) were able to obtain a significantly higher proportion of in focus dermatoscopic images using their second camera compared to their first camera (16% to 72%, P<0.001). CONCLUSIONS: We identified several barriers that exist for participant-acquired dermatoscopic imaging. Instructions emphasizing the importance of skin contact are useful. Our results may help guide future patient-acquired teledermatoscopy efforts.