Guidelines of care for the management of acne vulgaris.

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

Moving forward with teledermatology: Operational challenges of a hybrid in-person and virtual practice.

Since the COVID-19 outbreak, teledermatology services have become an integral part of our daily practice. In this study, we compared three practice models of an academic department in an urban setting: 1) in-person only, 2) teledermatology only, and 3) hybrid of in-person and teledermatology. Our study demonstrated that older patients prefer in-person visits over teledermatology visits, while non-English-speaking patients prefer teledermatology visits over in-person visits. In addition, teledermatology services can be better utilized for evaluation of acne and psoriasis, as these diagnoses do not require in-person reevaluation, unlike the evaluation of concerning lesions. Considering these findings, our study highlights the need to continuously examine our practice models to understand patient preferences, overcome practice-driven barriers, and ensure the sound allocation of limited health care resources.

Targeted Stimulation of Human Orbitofrontal Networks Disrupts Outcome-Guided Behavior.

Outcome-guided behavior requires knowledge about the current value of expected outcomes. Such behavior can be isolated in the reinforcer devaluation task, which assesses the ability to infer the current value of specific rewards after devaluation. Animal lesion studies demonstrate that orbitofrontal cortex (OFC) is necessary for normal behavior in this task, but a causal role for human OFC in outcome-guided behavior has not been established. Here, we used sham-controlled, non-invasive, continuous theta-burst stimulation (cTBS) to temporarily disrupt human OFC network activity by stimulating a site in the lateral prefrontal cortex that is strongly connected to OFC prior to devaluation of food odor rewards. Subjects in the sham group appropriately avoided Pavlovian cues associated with devalued food odors. However, subjects in the stimulation group persistently chose those cues, even though devaluation of food odors themselves was unaffected by cTBS. This behavioral impairment was mirrored in changes in resting-state functional magnetic resonance imaging (rs-fMRI) activity such that subjects in the stimulation group exhibited reduced OFC network connectivity after cTBS, and the magnitude of this reduction was correlated with choices after devaluation. These findings demonstrate the feasibility of indirectly targeting the human OFC with non-invasive cTBS and indicate that OFC is specifically required for inferring the value of expected outcomes.

Olfactory connectivity mediates sleep-dependent food choices in humans.

Sleep deprivation has marked effects on food intake, shifting food choices toward energy-dense options. Here we test the hypothesis that neural processing in central olfactory circuits, in tandem with the endocannabinoid system (ECS), plays a key role in mediating this relationship. We combined a partial sleep-deprivation protocol, pattern-based olfactory neuroimaging, and ad libitum food intake to test how central olfactory mechanisms alter food intake after sleep deprivation. We found that sleep restriction increased levels of the ECS compound 2-oleoylglycerol (2-OG), enhanced encoding of food odors in piriform cortex, and shifted food choices toward energy-dense food items. Importantly, the relationship between changes in 2-OG and food choices was formally mediated by odor-evoked connectivity between the piriform cortex and insula, a region involved in integrating feeding-related signals. These findings describe a potential neurobiological pathway by which state-dependent changes in the ECS may modulate chemosensory processing to regulate food choices.

Inducible pesticide tolerance in Daphnia pulex influenced by resource availability.

Pesticides are a ubiquitous contaminant in aquatic ecosystems. Despite the relative sensitivity of aquatic species to pesticides, growing evidence suggests that populations can respond to pesticides by evolving higher baseline tolerance or inducing a higher tolerance via phenotypic plasticity. While both mechanisms can allow organisms to persist when faced with pesticides, resource allocation theory suggests that tolerance may be related to resource acquisition by the organism. Using Daphnia pulex, we investigated how algal resource availability influenced the baseline and inducible tolerance of D. pulex to a carbamate insecticide, carbaryl. Individuals reared in high resource environments had a higher baseline carbaryl tolerance compared to those reared in low resource environments. However, D. pulex from low resource treatments exposed to sublethal concentrations of carbaryl early in development induced increased tolerance to a lethal concentration of carbaryl later in life. Only individuals reared in the low resource environment induced carbaryl tolerance. Collectively, this highlights the importance of considering resource availability in our understanding of pesticide tolerance.

Perceptions of U.S. dermatology residency program directors regarding the adequacy of phototherapy training during residency.

BACKGROUND/PURPOSE: Phototherapy utilization has declined over the last 20 years despite its efficacy and cost-effectiveness. Adequacy of phototherapy training in residency may be a contributing factor. The purpose of this study was to evaluate perceptions of U.S. dermatology residency program directors (PDs) regarding the effectiveness of their programs' phototherapy training and what constitutes adequate phototherapy education. METHODS: A questionnaire was sent to PDs to assess phototherapy training within their program; aspects such as dedicated time, exposure to different modalities, and barriers to resident education were surveyed. We assessed the statistical association between these aspects and the perception by PDs that a program's training was adequate. Statistical testing was reported using Fisher's exact tests. RESULTS: A total of 42 PDs responded. Residency training in oral psoralen and ultraviolet A therapy (PUVA), home phototherapy, and excimer laser, respectively, is not provided in 19.0%, 31.0%, and 47.6% of programs. 38.1% of programs provide ≤5 hours of phototherapy training over 3 years of training. 59.5% of PDs cited lack of curriculum time as the most common barrier to phototherapy education. 19.0% of PDs reported completely adequate phototherapy training, which was significantly associated with inclusion of faculty-led didactics, assigned reading, or hands-on clinical training in the curriculum. CONCLUSIONS: There is a mismatch between the resources devoted to phototherapy education and the need for dedicated training reported by PDs. Limited time is allocated to phototherapy training during dermatology residency, and a large majority of PDs do not feel that the phototherapy training offered is completely adequate.

Guidelines of care for the management of acne vulgaris.

Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.

Polycystic ovary syndrome: a review for dermatologists: Part I. Diagnosis and manifestations.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women who are of reproductive age. The pathogenesis involves several associated hormonal pathways that culminate in metabolic, reproductive, and cardiovascular effects. The hallmark features of hyperandrogenism and hyperinsulinemia have systemic long-term implications. Dermatologists frequently evaluate and manage the cutaneous manifestations of PCOS (ie, acanthosis nigricans, hirsutism, acne, and alopecia), and therefore play a key role in its diagnosis and management. In part I of this continuing medical education article, we review the definition, etiology, pathogenesis, and clinical features of PCOS.

Polycystic ovary syndrome: a review for dermatologists: Part II. Treatment.

Dermatologists are in a key position to treat the manifestations of polycystic ovary syndrome (PCOS). The management of PCOS should be tailored to each woman's specific goals, reproductive interests, and particular constellation of symptoms. Therefore, a multidisciplinary approach is recommended. In part II of this continuing medical education article, we present the available safety and efficacy data regarding treatments for women with acne, hirsutism, and androgenetic alopecia. Therapies discussed include lifestyle modification, topical therapies, combined oral contraceptives, antiandrogen agents, and insulin-sensitizing drugs. Treatment recommendations are made based on the current available evidence.

Recent advances in acne pathogenesis: implications for therapy.

Acne pathogenesis is a multifactorial process that occurs at the level of the pilosebaceous unit. While acne was previously perceived as an infectious disease, recent data have clarified it as an inflammatory process in which Propionibacterium acnes and innate immunity play critical roles in propagating abnormal hyperkeratinization and inflammation. Alterations in sebum composition, and increased sensitivity to androgens, also play roles in the inflammatory process. A stepwise approach to acne management utilizes topical agents for mild to moderate acne (topical retinoid as mainstay ± topical antibiotics) and escalation to oral agents for more resistant cases (oral antibiotics or hormonal agents in conjunction with a topical retinoid or oral isotretinoin alone for severe acne). Concerns over antibiotic resistance and the safety issues associated with isotretinoin have prompted further research into alternative medications and devices for the treatment of acne. Radiofrequency, laser, and light treatments have demonstrated modest improvement for inflammatory acne (with blue-light photodynamic therapy being the only US FDA-approved treatment). However, limitations in study design and patient follow-up render these modalities as adjuncts rather than standalone options. This review will update readers on the latest advancements in our understanding of acne pathogenesis and treatment, with emphasis on emerging treatment options that can help improve patient outcomes.

Terbinafine-induced acute generalized exanthematous pustulosis (AGEP) responsive to high dose intravenous corticosteroid.

Acute generalized exanthematous pustulosis (AGEP) is a febrile pustular drug eruption. Terbinafine, an allylamine fungicidial agent, is the most common anti-mycotic associated with AGEP. Here, we report a case of terbinafine-induced AGEP that was recalcitrant to oral corticosteroid but responsive to high-dose intravenous corticosteroid.

Pityriasis rubra pilaris exacerbation with topical use of imiquimod.

The role of immune response modifiers is increasing in the treatment of dermatologic diseases. Imiquimod, a toll-like receptor agonist, results in up-regulation of proinflammatory cytokines for improved immune surveillance. Although topical use is generally well-tolerated, imiquimod can potentially result in systemic effects and exacerbate generalized inflammatory papulosquamous diseases of the skin. We report the case of a 67-year-old man who was treated with imiquimod for actinic keratosis and developed fever and a progressive erythematous papulosquamous eruption that was histologically consistent with pityriasis rubra pilaris.

Optimization of monocarboxylate transporter 1 blockers through analysis and modulation of atropisomer interconversion properties.

We have previously described a novel series of potent blockers of the monocarboxylate transporter, MCT1, which show potent immunomodulatory activity in an assay measuring inhibition of PMA/ionomycin-induced human PBMC proliferation. However, the preferred compounds had the undesirable property of existing as a mixture of slowly interconverting rotational isomers. Here we show that variable temperature NMR is an effective method of monitoring how alteration to the nature of the amide substituent can modulate the rate of isomer exchange. This led to the design of compounds with increased rates of rotamer interconversion. Moreover, some of these compounds also showed improved potency and provided a route to further optimization.

Efficient and regiospecific one-pot synthesis of substituted 1,2,4-triazoles.

An efficient one-pot, three-component synthesis of substituted 1,2,4-triazoles has been developed, utilizing a wide range of substituted primary amines and acyl hydrazides.