Clinicopathologic characteristics of early-onset Becker's nevus in Korean children and adolescents

Abstract

Background

Becker's nevus (BN) presents as a hairy patch or plaque with or without proliferation of the dermal smooth muscles. BN has been described as acquired as found in a similar entity, congenital smooth muscle hamartoma (CSMH). This study was aimed at evaluating the clinicopathological aspects of BN in Korean cases in differential diagnosis with CSMH.

Methods

We performed a retrospective study of 103 patients histopathologically diagnosed as having BN or CSMH. The cases included 40 cases diagnosed with BN or CSMH before the age of 10 years who had clinical monitoring and a second skin biopsy after puberty to determine the disease course.

Results

Among cases of children to adolescents (<18 years), we observed a slight male predominance. Among children aged <14 years, sex ratio converged at 1:1. Early-onset BN showed a female predominance and hyperpigmented skin lesions. All BN cases showed hyperpigmentation, and face and neck involvement tended to make severe cosmetic concerns. In contrast, hypertrichosis was more frequent in CSMH. Either skin-colored lesion or pseudo-Darier's sign was not seen in early-onset BN. BN showed less dermal smooth muscle than CSMH.

Conclusions

Androgens themselves do not seem to be related to the development of BN but play only an aggravating role especially in male patients. Considering high occurrence in exposed areas, BN may distress patients severely. As early laser treatment may be helpful in some patients with BN, early-onset BN in comparison to CSMH should be diagnosed appropriately.

Detection of somatic mutations in secondary tumors associated with nevus sebaceus by targeted next generation sequencing. Comment on Kitamura et al.

Furuncular myiasis for the Western dermatologist: treatment in outpatient consultation

Abstract

Background

Furuncular myiasis is likely to be seen by Western dermatologists because of the increasing number of international travelers but remains unfamiliar to most of them, who tend to refer these patients to hospitals. Different treatments have been proposed, but many of them are not achievable in outpatient consultation.

Methods

We reported three typical cases of furuncular myiasis, according to each species involved, and proposed diagnostic and therapeutic guidelines for dermatologists in outpatient consultation.

Results

One patient, complaining of an inflammatory nodule of the leg with a central punctum, was diagnosed with Dermatobia hominis infection, after a forest walk in French Guiana. One woman returned from Senegal with a nodule of the left buttock. She had been infected by a Cordylobia anthropophaga larva after drying her underwear under a mango tree. One woman living in Cameroon presented with scalp nodules, pain, fatigue, and facial edema. She had been infected by more than 40 larvae of Cordylobia rodhaini after drying her sheets under a mango tree. Manual extraction ensured complete healing in the three patients. We used neither doppler ultrasound nor occlusive dressing. Diagnosis was immediately made thanks to the typical clinical stories.

Conclusions

The diagnosis of furuncular myiasis requires only clinical skills and basic knowledge of life cycles. The treatment varies slightly depending on the species involved but is achievable in outpatient consultation and does not require occlusive dressing.

Multiple epidermolytic acanthomas mimicking condyloma: a retrospective study of 8 cases

Abstract

Background

Epidermolytic acanthoma (EA) is an uncommon benign cutaneous lesion. Multiple epidermolytic acanthomas (multiple EAs) are rarely reported.

Methods

We retrospectively identified patients diagnosed with multiple EAs between 2005 and 2017 from our dermatopathology database and analyzed their clinical, pathological, and immunohistochemical features. We also evaluated the association of multiple EAs with human papillomavirus (HPV) infection.

Results

In total, eight patients (average age 51 years; 3 : 1 male predominance) with multiple EAs were found. All patients had lesions on the genitocrural area. The two most common clinical diagnoses were condyloma (5/8) and soft fibroma (3/8), which were predominantly skin-colored (5/8) or whitish (2/8). The lesions were less than 1 cm in diameter, and most (6/8) appeared to have a smooth surface. No molecular evidence suggesting HPV infection was found. Immunohistochemical staining showed low mitotic activity. The lesions were removed in one of two patients via cryotherapy, and one patient was treated with electrocauterization. The other five patients were followed without treatment.

Conclusion

The genital area was the most common location for multiple EAs, which was commonly misdiagnosed clinically as condyloma. Patients presenting with uniformly small-sized, skin-colored to whitish, smooth papular lesions in the genitalia should be carefully evaluated. The specific pathological features of epidermolytic hyperkeratosis are diagnostic, and the lesions can be observed without aggressive treatment after confirmed diagnosis.

A narrative review of dermatologic protocols for primary care medical service trips in Latin America and the Caribbean

Abstract

Background

Skin disorders are prevalent on primary care medical service trips in Latin America and the Caribbean and commonly include scabies, superficial mycoses, and pyoderma. There have been no previous attempts to describe protocols that international volunteer clinicians use in managing these patients. The purpose of this study was to collect North American clinical protocols used by sending organizations in their volunteer operations in Latin America and the Caribbean, summarize the most common pharmacologic and nonpharmacologic management strategies, and compare these to published international practice recommendations.

Methods

A systematic web search was used to identify North American medical service trip-sending organizations. Clinical protocols were downloaded from their websites, and organizations were directly contacted to request protocols that were not published online. The protocols obtained were summarized, analyzed thematically, and compared to existing international guidelines.

Results

Of 225 organizations contacted, 112 (49.8%) responded, and 31 of these (27.7%) claimed to possess protocols for their trips, of which 20 were obtained and analyzed. Ten (50%) protocols discussed scabies, eight (40%) discussed superficial mycoses, and five (25%) discussed pyoderma. The protocols discussed clinical assessment, pharmacologic and nonpharmacologic management with variable degrees of accuracy and thoroughness, and with important omissions when compared to international guidelines. None were the product of systematic literature searches, and most were not referenced.

Conclusions

To avoid ineffective treatment and related harms, context-specific clinical guidelines are needed for volunteer clinicians practicing in remote international settings, and such guidelines should be based on best evidence and stakeholder consensus.

Ethnic variations in the epidemiology of bullous pemphigoid in Israel

Abstract

Background

No ethnic or geographic predisposition to bullous pemphigoid (BP) was reported so far.

Objective

To evaluate trends in the incidence of BP in northern Israel, shedding light on differences between two distinct ethnic populations who inhabit the same region, namely Jews and Arabs.

Methods

Bullous pemphigoid incidence was retrospectively estimated from January 2000–December 2015 in two Israeli regions with a total population of 1.56 million inhabitants.

Results

A total of 287 new-onset BP patients (mean age: 77.6 ± 12.1) were identified. The incidence rate was 11.4 per million inhabitants per year (95% CI, 10.2–12.9). The crude incidence rate in Jews was 4.8-fold higher than that in Arabs (16.4 vs. 3.4 cases per million per year, respectively [P < 0.0001]). After adjusting for age, the discrepancy between the two populations diminished (11.7 vs. 8.9 cases per million per year, respectively) but remained statistically significant (P = 0.032). The incidence increased consistently from 7.6 cases per million per year in the calendar period 2000–2005 to 12.6 and 14.3 cases in 2006–2010 and 2011–2015, respectively (P < 0.0001). Bullous pemphigoid patients of Arab ancestry presented with the disease significantly earlier than Jews (69.5 ± 15.3 vs. 78.7 ± 11.1 years, respectively, P = 0.002).

Conclusions

The incidence of BP in northern Israel has increased in the last 16 years and is significantly higher among Jews compared to Arabs. The age of presentation is remarkably different between patients belonging to the two populations.

Cross-sectional study of Treponema pallidum PCR in diagnosis of primary and secondary syphilis

Abstract

Background

Syphilis remains a major challenge and a complex diagnosis. We aim to evaluate the role of polymerase chain reaction (PCR) in Treponema pallidum (Tp) detection in various types of biological samples in the diagnosis of early syphilis.

Methods

We conducted a cross-sectional study including all attendees of the STI clinic with clinical suspicion of early syphilis. One or more specimens for the detection of Tp by PCR testing were collected.

Results

The overall sensitivity of Tp PCR test was 82.61% (95% CI: 68.6–92.2%). Tp PCR test had sensitivity of 84.6% (95% CI: 54.6–98.1%) in primary syphilis cases and 81.8% (95% CI: 64.5–93%) in secondary syphilis cases. PCR test performance was independent of HIV status.

Conclusion

Tp PCR test is a fast and reliable method for the detection of Tp in skin lesions of early syphilis, and it is a powerful tool in clinical settings.

Social media and modern dermatology

Prospective, pilot evaluation of the performance of nanofractional radiofrequency for improvement of skin texture via skin resurfacing

Summary

Background

The latest generation of radiofrequency, nanofractional radiofrequency, allows the heat energy to be delivered through the use of pins or needles as electrodes, facilitating increased efficacy and reduced pain, downtime, and side effects.

Objective

The objective of this prospective pilot clinical study was to evaluate the efficacy of nanofractional radiofrequency in skin resurfacing.

Methods and materials

Seventeen subjects were enrolled in the study, and each received three nanofractional radiofrequency (160-pin tip) treatments in the facial area at 3-week intervals. Follow-up visits were scheduled at 1 and 2 months after the final treatment. Clinical photography, patient, and investigator assessments were conducted during the treatment visits and follow-up.

Results

All subjects completed the study. At the 1- and 2-month follow-up, there was a moderate to significant improvement (2.6 and 3.5, respectively, P = .01) according to the investigator global esthetic improvement scale rating. Most subjects reported that they were satisfied or very satisfied with the outcome and level of comfort.

Conclusion

Nanofractional radiofrequency is a safe and effective strategy for improving texture, tone, and skin laxity with high patient satisfaction and tolerable safety profile.

Posicionamiento de la Academia Española de Dermatología y Venereología sobre la teledermatología

Publication date: Available online 31 October 2017
Source:Actas Dermo-Sifiliográficas
Author(s): D. Moreno-Ramírez, G. Romero-Aguilera, P. Pasquali, S. Vaño, L. Ríos-Buceta, J. Malvehy, L. Ferrándiz

Hemangioma microvenular: estudio morfológico de 3 casos

Publication date: Available online 31 October 2017
Source:Actas Dermo-Sifiliográficas
Author(s): A. Giacaman, L.J. del Pozo, A. Bauzá, C. Saus

Leishmaniasis mucocutánea en pacientes inmunocomprometidos: reporte de 4 casos autóctonos

Publication date: Available online 31 October 2017
Source:Actas Dermo-Sifiliográficas
Author(s): S. Habibi Naderizadeh, C. Valcárcel Sierra, L. Medrano Gallego, B.J. Flores Robles, L.G. Roustán-Gullón

Cyclin D1 promoter -56 and -54bp CpG un-methylation predicts invasive progression in arsenic-induced Bowen’s disease

Globally, hundreds of millions of people are under the challenge of environmental arsenic exposure (WHO 2008). Epidemiological studies have demonstrated that long-term exposure to arsenic is associated with an increased risk of malignant tumors in many organs, such as the skin, lung, and urinary bladder [1]. Arsenic-induced Bowen's disease (As-BD), an intraepidermal carcinoma, is the most prevalent arsenic-induced skin cancer [2–4]. As-BD lesions are able to progress to invasive squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in the skin [4–6].

US Food and Drug Administration Approval of Soft-Tissue Fillers

This systematic review examines the quality of evidence leading to US Food and Drug Administration approval of soft-tissue fillers.

The Impact and Influence of JAMA Facial Plastic Surgery

Meaningful and influential articles written by leading thought leaders in the field are the lifeblood of a journal. I am pleased to announce that the Impact Factor (IF) of JAMA Facial Plastic Surgery has reached a new high of 2.70 (up 58% from last year's IF of 1.74). This places our journal near the top of all journals in our comparative group of journals that publish similar content. Although this metric is imperfect, it is often recognized by the scientific and publishing community as one important measure of comparing journals in its scientific impact and influence. Recall that IF is calculated by counting all of the citations to every article published in a journal divided by the number of full-length articles (Original Investigations, Special Communications, Reviews) published in that journal during the 2 preceding years.

September-October Issue Highlights

Safety and Efficacy of Bilateral Submental Cryolipolysis

This nonrandomized interventional cohort study investigates the safety and efficacy of cryolipolysis for reduction of lateral and central submental fat.

Capsular Contracture in Silicone Implant Rhinoplasty

This case series study examines the immunohistochemical features of capsular contracture in patients who have undergone silicone implant rhinoplasty.

Perceived Benefits of Facial Rejuvenation Beyond Restoring Youth

This survey study examines whether face-lift and upper facial rejuvenation surgery improve observer ratings of age, attractiveness, success, and health.

Emerging Goals in Aesthetic Medicine

I applaud Bater et al on their significant contribution in this issue of JAMA Facial Plastic Surgery to the growing body of literature further shaping and defining what the ultimate goal in aesthetic medicine is and should be. During the past decade, we have witnessed an evolution in aesthetic medicine, progressing from medieval standards of success defined by Eurocentrically oriented and canonized somatic ideals to a modern-day aspiration of enhanced social and psychological well-being. Let me be frank: those seeking cosmetic treatments are, at their core, desiring more than a straightened dorsum, a reduced cervical angle, or a projected mentum. They also—and perhaps more importantly—desire the self-satisfying and externally perceived benefits that result from the perception of idealized forms. It is the impression of beauty, whether elicited from the self, another, or both, from which our patients appreciate the aesthetic interventions we offer to them.

Association of Mental Health Status With Perception of Nasal Function

This cross-sectional study assesses the association of poor mental health with perception of nasal function.

A New Nasal Septum Splint

This Surgical Pearl describes a new type of splint designed to sit extremely caudally along the septum, to be left in place for 2 to 3 weeks postoperatively, and to replace other methods of posterior septal angle fixation to the nasal spine.

Neurovascular Characteristics of Facial Skin After Rhytidectomy

This study describes the change in epidermal nerve fibers, neurotransmitters, vasculature, and mast cells in facial skin following primary and revision face-lifts.

Duration of Facial Paralysis in Studies of Emotion and Well-Being—Reply

In Reply We appreciate Chaiet and Carpenter's thoughtful contribution regarding our recently published article "Association Among Facial Paralysis, Depression, and Quality of Life in Facial Plastic Surgery Patients."

Anatomy and Surgical Approaches to the Rabbit Nasal Septum

This ex vivo study examines the anatomy and approaches to rabbit septal surgery.

A Cautious but Optimistic Opinion of Submental Cryolipolysis

The increasing consumer demand for minimally invasive or noninvasive procedures has driven a burgeoning industry of technological advances that cater to this desire. Neck adiposity is an emerging area of interest, driven in large part by the US Food and Drug Administration's clearance of injectable deoxycholic acid in April 2015, along with a juggernaut of related marketing endeavors. As surgeons, we must always be wary of noninvasive methods that might make bold claims, using surgical methods of cervical fat reduction as the criterion standard by which to judge any new entrants into the competitive field. However, we must also embrace methods that may undoubtedly serve as adjuncts, alternatives, or replacements for surgical techniques when they are truly viable. With that spirit, I commend the article in this issue of JAMA Facial Plastic Surgery on submental cryolipolysis by Bernstein and Bloom, who have sought to quantifiably evaluate both the aesthetic improvement and the patients' subjective perception of their results and the nature of their experience. The article serves to expand the current limited body of literature exploring this new application of cryolipolysis.

Two-Dimensional Threshold for Perception of Artificial-Appearing Lips

This survey study characterizes the quantitative measurements for the perceptual threshold of artificial- and unnatural-appearing lips.

Don’t Miss the Fourth Dimension of the Nasal Airway

Nasal obstruction as a symptom is supposedly simple to grasp, with the nasal airway being easy to inspect and objective measures for both its resistance and diameter at hand. Because the nasal cavity is also amenable to enlargement through straightforward surgical procedures, a permanently blocked nose ought to be easy to fix. Yet, how often are physicians intrigued by patient dissatisfaction after surgery with what must be considered a success after nasal endoscopy? Little is known about the incidence of postoperative dissatisfaction after septoplasty, with no failures to be seen or measured. One reason for an incongruent appraisal of the outcome of surgery may be that reducing the cause of nasal obstruction or the sensation of nasal fullness to a septal deviation or mucosal edema and to swelling may be simplistic in light of the advances in our understanding of nasal pathologic conditions and mucosal neural regulation. Few studies have shown highly correlated associations of the sensation of nasal fullness with any of the objective parameters measured in routine clinical practice. The cause may be that the sensation of fullness is the computational end product of a complex neurologic integrative process. This process encompasses interoceptive sensation on the basis of the currently assessed severity relative to other competing sensory and emotional stimuli. Recollections of the difficulties experienced in breathing through the nose in the recent and more distant past also play a role. The sensation of fullness or blockage attributed to the nasal mucosa is a highly integrated interpretation of afferent information from multiple subsets of nociceptive and other neurons, with the perception of cooling during inspiration likely playing a central role.

Association of Diet With Skin Histological Features in UV-B–Exposed Mice

This animal model study examines the influence of a calorie-restricted diet and an obesity diet in mice exposed to long-term UV-B irradiation to assess if there is an association between diet and histopathological response to UV-B irradiation.

Nonsurgical Rhinoplasty

This Surgical Pearl demonstrates how fillers can be used to add volume to the soft tissues of the nose.

Association of Velopharyngeal Insufficiency With Quality of Life

This study uses the Velopharyngeal Insufficiency Effects on Life Outcomes instrument to assess the association of improved speech with quality of life in patients who underwent secondary speech surgery.

Negative and Positive Online Patient Reviews of Physicians

This study explores reasons for both excellent and poor patient reviews on websites rating physicians.

Patterns of Change in Facial Skeletal Aging

This case series study of 14 adults documents patterns of change in the facial skeleton and develops a methodology for measuring these changes.

Polyglutamine tracts as autophagy regulators

By Yoskaly Lazo-Fernandez, PhD

Polyglutamine tracts (polyQ tracts) are long chains of glutamine amino acidspresent in the sequence of many proteins. The length of polyQ tracts within proteins varies significantly as normal alleles of specific genes usually contain different number of the cytosine-adenine-guanine (CAG) nucleotide repeats¹.

It has long been known that polyQ tracts play a role in the etiology of several inheritable neurodegenerative disorders, including spinocerebellar ataxia, and Huntington's disease². These 'polyglutamine diseases' result from the excessive elongation of a polyQ tract in a particular gene which causes the resultant protein to become toxic. The toxicity of mutated polyQ tracts has been extensively studied and several explanatory hypotheses have been proposed: aggregation of polyQ tract proteins, transcriptional dysregulation, mitochondrial dysfunction, and impairment of both the ubiquitin-proteasome and autophagy-lysosome protein degradation systems.

Western blot analysis of Htt in four different lymphoblast HD cell lines extracts each expressing ~65 (mutant) and ~20 (normal) CAG repeats. Lanes 1-4  (A), HTT mAb clone 1A771 recognizes only the expanded or long form of Htt. (B), A different Htt antibody recognizing both normal and mutant Htt.

Interestingly, the physiological function of polyQ tracts in normal proteins remained unclear until very recently.  This breakthrough has been published in a Nature paper³ that depicted very detailed and exhaustive studies performed by David Rubinsztein's group at the University of Cambridge in the UK. This group uncovered an interesting regulatory function of normal polyQ tract-containing protein ataxin 3 on autophagy.

In their experiments, Ashkenazi et al.³ explored whether the knockdown or overexpression of genes involved in polyQ diseases like ataxin 3 (related to spinocerebellar ataxia) and huntingtin (Huntington's disease) affected autophagosome formation, an essential step for proper autophagy function⁴. The knockdown of wild type ataxin 3 impaired autophagosome formation in different biological models including cultured mouse neurons and liver cells, as well as in immortalized human cultured cells. Conversely, the overexpression of ataxin 3 in the same models stimulated autophagosome formation. Most importantly, the authors identified the key component of autophagosome biogenesis that is affected by the modulation of ataxin 3 expression, beclin 1, which is a particularly important protein for the induction of autophagy after nutrient depletion^4,5. Ataxin 3 was shown to be essential for the protection of beclin 1 from polyubiquitination and degradation, which made much sense since ataxin 3 is a deubiquitinating enzyme involved in the regulation of protein homeostasis. In fact, the polyQ tracts in ataxin 3 are necessary for its binding to and deubiquitination of beclin 1. Interestingly, longer polyQ tracts diminished the deubiquitinating activity of ataxin 3 and created a much stronger binding affinity of the mutated ataxin 3 to beclin 1. Longer polyQ tracts in huntingtin and other polyQ proteins also bonded strongly to beclin 1, leading to a competitive blockade of the functional interaction between wild type ataxin 3 and beclin 1, and thus resulting in excessive beclin 1 degradation and autophagy impairment.

Overall, this new study provides insight into the physiological function of normal polyQ tracts as binding domains to beclin 1, and therefore as regulators of autophagy. Also, this insight reveals a new integrative model by which mutated polyQ tract-containing proteins may cause disease. According to this new model, mutated polyQ tracts create a stronger than normal binding to beclin 1, which then blocks ataxin 3's binding and deubiquitination of beclin 1, causing beclin 1's excessive degradation. This sequence of events results in impaired basal levels of autophagy in polyQ disease patients which could explain the progressive toxic protein accumulation and aggregation observed in their neurons. Moreover, since impaired autophagy has been implicated in many chronic diseases like cancer and diabetes, perhaps the use of modulators targeting this new mechanism of autophagy regulation may provide alternative pharmacological treatments.

Learn more about autophagy regulation

References

1. Rinaldi & Fischbeck. Pathological Mechanisms of Polyglutamine Diseases. Nature Education 8, (2015).
   
2. Fan et al. Polyglutamine (PolyQ) Diseases: Genetics to Treatments. Cell Transplantation 23, 441–458(18)
3. Ashkenazi et al. Polyglutamine tracts regulate beclin 1-dependent autophagy. Nature 545, 108–111 (2017).
4. Cohen-Kaplan, Livneh, Avni, Cohen-Rosenzweig & Ciechanover. The ubiquitin-proteasome system and autophagy: Coordinated and independent activities. The International Journal of Biochemistry & Cell Biology 79, 403–418 (2016).
5. Kang, Zeh, Lotze & Tang. The Beclin 1 network regulates autophagy and apoptosis. Cell Death & Differentiation 18, 571–580 (2011).

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Comparative Transcriptomics of Seasonal Phenotypic Flexibility in Two North American Songbirds

Abstract

Phenotypic flexibility allows organisms to reversibly alter their phenotypes to match the changing demands of seasonal environments. Because phenotypic flexibility is mediated, at least in part, by changes in gene regulation, comparative transcriptomic studies can provide insights into the mechanistic underpinnings of seasonal phenotypic flexibility, and the extent to which regulatory responses to changing seasons are conserved across species. To begin to address these questions, we sampled individuals of two resident North American songbird species, American goldfinch (Spinus tristis) and black-capped chickadee (Poecile atricapillus) in summer and winter to measure seasonal variation in pectoralis transcriptomic profiles and to identify conserved and species-specific elements of these seasonal profiles. We found that very few genes exhibited divergent responses to changes in season between species, and instead, a core set of over 1200 genes responded to season concordantly in both species. Moreover, several key metabolic pathways, regulatory networks, and gene functional classes were commonly recruited to induce seasonal phenotypic shifts in these species. The seasonal transcriptomic responses mirror winter increases in pectoralis mass and cellular metabolic intensity documented in previous studies of both species, suggesting that these seasonal phenotypic responses are due in part to changes in gene expression. Despite growing evidence of muscle nonshivering thermogenesis (NST) in young precocial birds, we did not find strong evidence of upregulation of genes putatively involved in NST during winter in either species, suggesting that seasonal modification of muscular NST is not a prominent contributor to winter increases in thermogenic capacity for adult passerine birds. Together, these results provide the first comprehensive overview of potential common regulatory mechanisms underlying seasonally flexible phenotypes in wild, free-ranging birds.

Commentary on: Adipose-Derived Stem Cells in Aesthetic Surgery: A Mixed Methods Evaluation of the Current Clinical Trial, Intellectual Property, and Regulatory Landscape

Adipose-derived stem cells (ADSC) continue to incite controversy in the medical profession, are highly sought after by the public, incite excitement in commercial companies, and are seen as a lucrative income generator in clinics. This interesting analysis of ADSC registered trials as well as registered intellectual properties further illustrates these points.¹

Sclerotherapy for Reticular Veins in the Lower Limbs

This randomized clinical trial compares sclerotherapy of reticular veins of the lower limb with 2% polidocanol diluted in 70% hypertonic glucose vs hypertonic glucose alone.

Prior Authorizations for Diagnostic Skin Biopsies

This Viewpoint outlines how managed care policies on prior authorization for diagnostic skin biopsies are affecting costs, access to care, and quality of care for patients.

Use of a Physician Extender and Dermatology Appointment Wait Times

This cross-sectional analysis of responses to a telephone algorithm finds that dermatology appointment wait times have doubled over the past decade and appointment wait time may have an influence on dermatology office management.

Descriptive Error in the Text

In the Original Investigation titled "Prevalence of Pubic Hair Grooming–Related Injuries and Identification of High-Risk Individuals in the United States," published online August 16, 2017, there was a descriptive error in the text. The term vagina was used rather than the more accurate labia majora in 4 instances. This article has been corrected online.

Nonhealing Leg Ulcer in a Middle-aged Indian Man

A middle-aged Indian man with multiple, ill-defined, hypopigmented, asymptomatic lesions on his face and scalp presents with a painful foot ulcer having well-defined margins and a yellowish slough that remained unhealed after 1 year. Treatment with rifampicin, dapsone, and clofazimine after an earlier diagnosis of multibacillary leprosy failed. What is your diagnosis?

Factors Associated With Chronic Urticaria in Children

This cohort study examined the resolution rate of chronic urticaria in children and whether there are biomarkers that can predict resolution.

Chronic Urticaria in Children

Six years ago, we reviewed what was then known about chronic urticaria (CU) in children. We came to the conclusion that many important and interesting questions were unanswered. These included, but were not limited to, how common chronic spontaneous urticaria (CSU) and inducible urticaria are in children, the clinical presentation, underlying causes, impact on everyday life of CU in children, and the natural course of pediatric CU. We also suggested strategies to address and answer these questions and encouraged further studies to do so.

Thyroid Function in Children With Alopecia Areata

This study characterizes thyroid function in children with alopecia areata to establish guidelines for thyroid dysfunction screening.

The Epidemic of Guns

The shooting in Las Vegas, Nevada, that left 59 people dead, 10 times that number wounded, and thousands of people with the psychological distress from being present at the scene during and after the massacre has once again raised the issue of what we as a nation can and should do about guns. The solution lies in not just focusing on Las Vegas and the hundreds of other mass shootings that have occurred in the United States in the last 14 months, but rather to underscore that on average almost 100 people die each day in the United States from gun violence. The 36 252 deaths from firearms in the United States in 2015 exceeded the number of deaths from motor vehicle traffic crashes that year (36 161). That same year, the US Centers for Disease Control and Prevention reported that 5 people died from terrorism. Since 1968, more individuals in the United States have died from gun violence than in battle during all the wars the country has fought since its inception.

Anesthesia Duration and Head and Neck Microvascular Reconstruction Complications

This study examines the association of anesthesia duration with complications after microvascular reconstruction of the head and neck.

Combining Rhinoplasty With Upper Lip–Lift Using a Single Incision Line

This Surgical Pearl describes a procedure that combines the columellar incision with the incision for the upper lip–lift, resulting in harmonious nasolabial proportions and a smaller surgical scar.

Outcomes of Buccinator Treatment With Botulinum Toxin in Facial Synkinesis

This cohort study evaluates outcomes for patients treated with botulinum toxin applied to the buccinator muscle in the setting of facial synkinesis.

Botulinum Neuromodulators in Facial Synkinesis Management

This randomized clinical trial evaluates the effectiveness of 3 commercially available botulinum toxin neuromodulators in the treatment of facial synkinesis.

THE NON-NEURONAL AND NON-MUSCULAR EFFECTS OF BOTULINUM TOXIN: A Graceful Opportunity for a Deadly Molecule to Treat a Human Disease in the Skin and Beyond

Abstract

There is growing evidence that botulinum neurotoxins (BoNTs) exhibit biological effects on various human cell types with a host of associated clinical implications. The BoNT receptors and intracellular targets are not unique for neurotransmission. They have been found in both neuronal and non-neuronal cells, but there are differences in the way BoNT binds to, and acts on neuronal vs. non-neuronal cells. The non-neuronal cells expressing one or more BoNT/A-binding proteins and/or cleavage target SNAP-25 include epidermal keratinocytes, mesenchymal stem cells from subcutaneous adipose, nasal mucosal cells, urothelial cells, intestinal epithelial cells, neutrophils, macrophages, and prostate, breast and alveolar epithelial cells, BoNT/A can also elicit specific biological effects in dermal fibroblasts, sebocytes and vascular endothelial cells. The reported non-traditional applications of BoNT in dermatologic conditions include hyperhidrosis, Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita, multiple eccrine hydrocystomas, eccrine angiomatous hamartoma, eccrine sweat gland nevi, congenital eccrine nevus, Raynaud phenomenon and cutaneous leiomyomas. Experimental studies demonstrated BoNT/A ability to protect skin flaps, facilitate wound healing, decrease thicknesses of hypertrophic scars, produce an anti-aging effect, and improve a mouse model of psoriasiform dermatitis. Furthermore, experimental studies also have revealed extracutaneous effects of BoNT arising from its anti-inflammatory and anti-cancer properties. Therefore, it is clear that BoNTs have a much wider zone of influence than originally understood, and that these ubiquitous events are based on individual cellular responses to the cholinergic impacts of BoNTs, which represents fertile grounds for future studies that are highly likely to result in impactful discoveries.

This article is protected by copyright. All rights reserved.

Incentivized goodness

Abstract

It will be argued that humans have a rational self-interest in voluntarily opting to subject themselves to moral bioenhancement. This interest is based on the fact that goodness appears to be conducive to happiness. Those who understand that will be more inclined to opt for safe and effective moral bioenhancement technologies that have the potential to augment our motivation to become better. The more people decide to follow this path, the likelier it is that states will adopt suitable policies that incentivize moral bioenhancement. Hence, goodness, happiness and state incentivized moral bioenhancement can operate in a circularly supportive fashion.

Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma Presenting with Vaginal Sloughing and Ulcerated Skin Nodule

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma (NHL) with subtypes that can be distinguished on the basis of clinical, immunophenotypic, morphologic, and molecular characteristics. The genital tract as a primary site for NHL is very rare (1).

High calcium enhances the expression of double-stranded RNA sensors and antiviral activity in epidermal keratinocytes

Abstract

Double-stranded RNA (dsRNA) sensors including TLR3, MDA5, and RIG-I are expressed in epidermal keratinocytes, and play an important immunological role by enhancing various innate and adaptive immune responses. Although the role of elevated extracellular calcium concentration in keratinocyte differentiation is well understood, the effect of high calcium on dsRNA sensors is not well studied.

We investigated alterations in dsRNA sensor expression and antiviral activity induced by a high extracellular concentration of calcium in epidermal keratinocytes. Normal human epidermal keratinocytes (NHEKs) were stimulated with high calcium and/or synthetic dsRNA, poly (I:C). TLR3, IFIH1 (MDA5), and DDX58 (RIG-I) expression were measured via qPCR, and IFN-β and human beta defensin 2 (HBD2) levels were measured using ELISA. TLR3 localization was evaluated with immunocytofluorescence. Antiviral activity was quantified with virus plaque assays using herpes simplex virus type-1 (HSV-1). High calcium significantly upregulated mRNA expression of TLR3, IFIH1, and DDX58 in NHEKs. In addition, high calcium significantly enhanced poly (I:C)-induced anti-HSV-1 activity in NHEKs. The anti-viral molecule, HBD2 but not IFN-β induction by poly (I:C) was enhanced by high calcium.

Our findings indicate that high levels of extracellular calcium enhance the expression of dsRNA sensors and augment antiviral activity in epidermal keratinocytes.

This article is protected by copyright. All rights reserved.

Development of an asporogenic Bacillus cereus strain to improve keratinase production in exponential phase by switching sigmaH on and sigmaF off

Abstract

Many bacteria, including the genus Bacillus are able to produce proteases (keratinase). In Bacillus, proteases are produced in the stationary phase and initial stages of sporulation. Protease production is coordinated with sporulation in which expression of various genes by different sigma factors manages the transition from exponential to the stationary phase. In the present study the sigma-F gene of an indigenous Bacillus cereus strain, which is involved in transcription of maintaining sporulation genes was deleted. Meanwhil the sigma-H, which its product activates the genes that function in the zero phase of sporulation and inhibits suppression of protease production, and spo0B genes were expressed in the exponential phase under the control of a sucrose inducible promoter from Bacillus sacPA operon. For the first time, an asporogenic strain of B. cereus was generated that produced higher keratinase (390 U in compare to the 198 U of wild strain) and protease (450 U in compare to the 290 U of wild strain) activities in the exponential growth phase by induction with sucrose. The new strain is promising for production of keratinase for degradation of feather waste to produce feather meal for poultry feed and decrease environmental pollution of poultry industry.

Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC)

Several data indicate that migraine, especially migraine with aura, is associated with an increased risk of ischemic stroke and other vascular events. Of concern is whether the risk of ischemic stroke in migra...

Immunohistochemical markers informing the diagnosis of sebaceous carcinoma and its distinction from its mimics: Adipophilin and Factor XIIIa to the rescue?

In this issue of the Journal of Cutaneous Pathology, Tjarks et al. present a study that advances our understanding of the diagnosis of sebaceous neoplasms (in particular, sebaceous carcinoma) and the lesions that mimic them (1).

Calciphylaxis with Pseudoxanthoma Elasticum-like Changes: A Case Series

BACKGROUND

Calciphylaxis and pseudoxanthoma elasticum (PXE) are rare, clinically distinct, disorders that share a common feature of cutaneous calcification that vary widely in their cutaneous presentation.

METHODS

We conducted a descriptive, retrospective review of biopsy specimens collected over a two-year period. Only specimens with a histologic and clinical diagnosis of calciphylaxis were included in the review. Specimens were then histologically examined for features of pseudoxanthoma elasticum in the dermis and/or subcutaneous fat, utilizing hematoxylin and eosin staining. Von Kossa and Verhoeff-Van Gieson special stains were also performed to examine calcification and elastic fibers, respectively.

RESULTS

We reviewed 13 biopsy specimens from 9 patients with known clinical and histologic evidence of calciphylaxis, both uremic and non-uremic types. Upon reexamination, we found that 46.2% (n=6/13) of the specimens demonstrated concomitant PXE-like changes uniquely localized to the subcutaneous fat.

CONCLUSION

The presence of PXE-like changes in the subcutis may heighten suspicion for a diagnosis of calciphylaxis in the appropriate clinical setting and be helpful when classic histologic features are subtle or absent.

Folliculotropic mycosis fungoides presenting with a solitary lesion: clinicopathological features and long-term follow-up data in a series of nine cases

Folliculotropic mycosis fungoides (FMF) is a rare but distinct variant of mycosis fungoides (MF), histologically characterized by the presence of folliculotropic infiltrates, often with sparing of the epidermis, and clinically by the preferential involvement of the head and neck region.¹

Me and I Are Not Friends, Just Aquaintances: on Thought Insertion and Self-Awareness

Abstract

A group of philosophers suggests that a sense of mineness intrinsically contained in the phenomenal structure of all conscious experiences is a necessary condition for a subject to become aware of himself as the subject of his experiences i.e. self-awareness. On this view, consciousness necessarily entails phenomenal self-awareness. This paper argues that cases of delusions of thought insertion undermine this claim and that such a phenomenal feature plays little role in accounting for the most minimal type of self-awareness entailed by phenomenal consciousness. First, I clarify the main view endorsing this claim i.e. the Self-Presentational View of Consciousness and formulate the challenge from thought insertion. After, I offer a systematic evaluation of all the strategies used by the advocates of this view to deal with this challenge. Finally, I conclude that most of these strategies are unsatisfactory for they rest in unwarranted premises, imprecisions about the agentive nature of cognitive experiences, and especially, lack of distinction between the different ways in which subjects can become aware of their own thoughts.

Acknowledgment of Reviewers

Testicular torsion and reperfusion: evidences for biochemical and molecular alterations

Abstract

This study was done in order to determine the molecular and biochemical alterations following testicular torsion (TT) and torsion-reperfusion (TR). For this purpose, 54 male Wistar rats were divided into five groups as control group (n = 6) and experimental group subjected to 1, 2, 4, and 8 h unilateral left torsion induction (n = 12 in each group). After induction of TT, testicular samples were collected from each group (n = 6), and the other six rats of each group underwent the same period of reperfusion after TT and then were sampled. Histological changes, the mRNA and protein expression of heat shock protein-70 (Hsp70), and caspase-3 were examined using reverse transcriptase-PCR (RT-PCR) and immunohistochemistry, respectively. Testicular total antioxidant capacity (TAC), glutathione peroxidase (GSH-px), and malondialdehyde (MDA) levels were evaluated. The mRNA damage and DNA fragmentation were assessed. The TT and TR significantly reduced differentiation and spermiogenesis indices (p < 0.05). The TT- and TR-induced groups exhibited a severe reduction in Hsp70 expression as well as remarkable enhancement in caspase-3 expression. The TAC and GSH-px levels were decreased and the MDA content was increased in TT- and TR-induced groups. Finally, the TT and TR enhanced mRNA damage and DNA fragmentation. The TT- and TR-induced damaging oxidative stress, diminished Hsp70 expression, and enhanced caspase-3 mRNA and protein levels result in apoptosis following 1, 2, and 4 h. Whereas, following 8 h, TT and TR initiate the necrosis by inducing energy depletion as well as severe mRNA damage.

Taking Multiple Exposure Into Account Can Improve Assessment of Chemical Risks

Abstract

During work, operators may be exposed to several chemicals simultaneously. Most exposure assessment approaches only determine exposure levels for each substance individually. However, such individual-substance approaches may not correctly estimate the toxicity of 'cocktails' of chemicals, as the toxicity of a cocktail may differ from the toxicity of substances on their own. This study presents an approach that can better take into account multiple exposure when assessing chemical risks. Almost 30000 work situations, monitored between 2005 and 2014 and recorded in two French databases, were analysed using MiXie software. The algorithms employed in MiXie can identify toxicological classes associated with several substances, based on the additivity of the selected effects of each substance. The results of our retrospective analysis show that MiXie was able to identify almost 20% more potentially hazardous situations than identified using a single-substance approach. It therefore appears essential to review the ways in which multiple exposure is taken into account during risk assessment.

Seven years of clinical experience with the Yeast Traffic Light PNA FISH: assay performance and possible implications on antifungal therapy

Abstract

We evaluated the performance of Yeast Traffic Light PNA FISH (YTL PNA FISH) in identification of Candida spp. from blood cultures. A total of 200 new episodes of candidemia were analysed prospectively. The YTL PNA FISH results were reported to the clinicians and data on antifungal therapy was documented. In total, there were 164/200 (82%) positive blood culture bottles with monomicrobial growth. Coverage of monomicrobial yeasts was 150/164 (91.5%). YTL PNA FISH could identify 23/24 (95.8%) Candida spp. in bottles with concomitant growth of bacteria and one yeast. Growth of two or more different yeasts was observed in 12/200 (6%) blood culture bottles and the method could identify all yeasts in 8/12 (66.7%). Data on antifungal treatment was available for 181/200 patients (90.5%). In 132/137 (96.4%) samples from patients without antifungal treatment, YTL PNA FISH could identify the Candida spp. or gave a negative result for yeasts not included in panel, and based on the result guide appropriate antifungal therapy the same day when the blood culture bottle signaled positive. The present study shows that YTL PNA FISH is a rapid, reliable diagnostic method which significantly reduces time delay for choice of appropriate antifungal therapy for critically ill patients.

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Undiagnosed Diabetes Mellitus in Community-Acquired Pneumonia: A Prospective Cohort Study

Abstract

Background

Diabetes mellitus is an important risk factor for community-acquired pneumonia, whereas the prevalence of undiagnosed diabetes mellitus and prediabetes in patients with community-acquired pneumonia is largely unknown. We aimed to determine the prevalence of prediabetes, undiagnosed diabetes mellitus, and risk factors associated with undiagnosed diabetes mellitus in a large European community-acquired pneumonia cohort.

Methods

This was a multicenter prospective cohort study of hospitals and private practices in Germany and Austria encompassing 1961 adults with community-acquired pneumonia included in the German Community-Acquired Pneumonia Competence Network (CAPNETZ) study between 2007 and 2014. The prevalence of undiagnosed diabetes mellitus and prediabetes was estimated based on hemoglobin A1c measurements. Logistic regression was used to assess risk factors for undiagnosed diabetes mellitus.

Results

Fifteen percent of patients had known diabetes mellitus. Among patients without known diabetes mellitus, 5.0% had undiagnosed diabetes mellitus and 37.5% had prediabetes. Male sex (odds ratio [OR], 2.45 [95% confidence interval {CI}, 1.35–4.45]), body mass index ≥25 kg/m² (OR, 2.64 [95% CI, 1.48–4.72]), and hyperglycemia at admission (6–11 mM: OR, 2.93 [95% CI, 1.54–5.60] and ≥11 mM: OR, 44.76 [95% CI, 17.58–113.98]) were associated with undiagnosed diabetes mellitus. Patients with undiagnosed diabetes mellitus had a higher 180-day mortality rate compared to patients without diabetes mellitus (12.1% vs 3.8%, respectively; P = .001).

Conclusions

Undiagnosed diabetes mellitus was prevalent among community-acquired pneumonia. Male sex, overweight, and hyperglycemia at admission were associated with undiagnosed diabetes mellitus. The long-term mortality among patients with undiagnosed diabetes mellitus was high compared to patients without diabetes mellitus.