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PurposeThe phosphodiesterase inhibitor sildenafil is a promising treatment for neurodegenerative disease, but it can cause oxidative stress in photoreceptors ex vivo and degrade visual performance in humans. Here, we test the hypotheses that in wildtype mice sildenafil causes i) wide-spread photoreceptor oxidative stress in vivo that is linked with ii) impaired vision.MethodsIn dark or light-adapted C57BL/6 mice ± sildenafil treatment, the presence of oxidative stress was evaluated in retina laminae in vivo by QUEnch-assiSTed (QUEST) magnetic resonance imaging, in the subretinal space in vivo by QUEST optical coherence tomography, and in freshly excised retina by a dichlorofluorescein assay. Visual performance indices were also evaluated by QUEST optokinetic tracking.ResultsIn light-adapted mice, 1 hr post-sildenafil administration, oxidative stress was most evident in the superior peripheral outer retina on both in vivo and ex vivo examinations; little evidence was noted for central retina oxidative stress in vivo and ex vivo. In dark-adapted mice 1 hr after sildenafil, no evidence for outer retina oxidative stress was found in vivo. Evidence for sildenafil-induced central retina rod cGMP accumulation was suggested as a panretinally thinner, dark-like subretinal space thickness in light-adapted mice at 1 hr but not 5 hr post-sildenafil. Cone-based visual performance was impaired by 5 hr post-sildenafil and not corrected with anti-oxidants; vision was normal at 1 hr and 24 hr post-sildenafil.ConclusionsThe sildenafil-induced spatiotemporal pattern of oxidative stress in photoreceptors dominated by rods was unrelated to impairment of cone-based visual performance in wildtype mice.

A 75‐year‐old Black man presented for evaluation of a skin lesion on his right shoulder. The lesion had been present for 3 months and was bleeding. A physical exam demonstrated a 2.7 cm exophytic, crusted, blue‐to‐purple plaque. A shave biopsy was performed, and histopathological examination revealed anastomosing strands of basaloid cells in the dermis, leading to a diagnosis of fibroepithelioma of pinkus (FeP). FeP is a rare variant of basal cell carcinoma. It typically presents as a solitary, pink, pedunculated papule on the lower back, but the presentation can vary. This case contributes to the scarce literature on the occurrence of FeP in skin of color populations. Here, we raise the possibility that FeP may present differently in skin of color patients compared to white patients. Greater clinician awareness can foster improved identification, management, and understanding of FeP in diverse populations. [ABSTRACT FROM AUTHOR]

Background: PRAME (PReferentially expressed Antigen in MElanoma) is an antigen that shows marked overexpression in melanoma compared to normal skin melanocytes. PRAME immunohistochemistry has proven effective in distinguishing melanocytic nevi from melanoma, but it is unclear if it may be used to distinguish melanoma in situ from other benign pigmented lesions. In particular, differentiating from melanocytic hyperplasia in sun‐damaged skin is sometimes clinically and histopathologically challenging. We hypothesized that PRAME staining of solar lentigo, sun‐damaged skin, and melanoma in situ would aid in setting a threshold of positivity that could be useful in evaluating such conditions. Methods: We collected and stained typical examples of solar lentigo, melanoma in situ, and non‐lesional sun‐damaged skin by PRAME immunohistochemistry to assess a potential cutoff of PRAME positivity. Results: Solar lentigo and non‐lesional sun‐damaged skin had 10 or fewer PRAME‐positive cells per millimeter (mean 1.2), on the other hand melanoma in situ had at least 16 (mean 75.1). Conclusions: PRAME immunostaining appears sensitive and specific in the current series. This could be clinically useful for distinguishing melanoma in situ from benign melanocytic hyperplasia in sun‐damaged skin. However, further studies are required to determine if 10 cells per millimeter is an acceptable threshold of positivity. [ABSTRACT FROM AUTHOR]

Telogen effluvium (TE) is characterized by diffuse hair shedding 2‐3 months after a stressor, and COVID‐19 infection is potentially one such stressor. Those who were infected with the virus were under immense psychosocial and physiologic stress. We retrospectively reviewed electronic medical records of 552 patients who were evaluated by a Henry Ford Health System dermatologist between February 2020 and September 2020 and had a diagnosis of COVID‐19 infection. Ten patients were identified with TE attributed to COVID‐19 infection and described their presentations as a case series. For the ten patients selected, the mean age was 48.5 years old and 90% were female. Six of the patients were Black, one Middle Eastern, and three White. On average, the hair shedding began 50 days after the first symptom of COVID‐19 infection. About 80% of these patients were treated with antibiotics, systemic corticosteroids, and/or hydroxychloroquine for their COVID‐19 infection and 70% were hospitalized. The presentations of these patients suggest that COVID‐19 infection may be a significant trigger of TE. TE caused by hydroxychloroquine, azithromycin or other medications cannot be ruled out, and the global pandemic itself is a source of psychosocial stress. Further studies will be needed to understand the long‐term prevalence and prognosis of TE associated with COVID‐19 infection. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that imaging biomarkers are useful for evaluating in vivo rod photoreceptor cell responses to a mitochondrial protonophore. Methods: Intraperitoneal injections of either the mitochondrial uncoupler 2,4 dinitrophenol (DNP) or saline were given to mice with either higher [129S6/eVTac (S6)] or lower [C57BL/6J (B6)] mitochondrial reserve capacities and were studied in dark or light. We measured: (i) the external limiting membrane–retinal pigment epithelium region thickness (ELM-RPE; OCT), which decreases substantially with upregulation of a pH-sensitive water removal co-transporter on the apical portion of the RPE, and (ii) the outer retina R1 (= 1/(spin lattice relaxation time (T1), an MRI parameter proportional to oxygen / free radical content. Results: In darkness, baseline rod energy production and consumption are relatively high compared to that in light, and additional metabolic stimulation with DNP provoked thinning of the ELM-RPE region compared to saline injection in S6 mice; ELM-RPE thickness was unresponsive to DNP in B6 mice. Also, dark-adapted S6 mice given DNP showed a decrease in outer retina R1 values compared to saline injection in the inferior retina. In dark-adapted B6 mice, transretinal R1 values were unresponsive to DNP in superior and inferior regions. In light, with its relatively lower basal rod energy production and consumption, DNP caused ELM-RPE thinning in both S6 and B6 mice. Conclusions: The present results raise the possibility of non-invasively evaluating the mouse rod mitochondrial energy ecosystem using new DNP-assisted OCT and MRI in vivo assays. [ABSTRACT FROM AUTHOR]

GLO:DIF/01jan21:ijd15113-fig-0001.jpg PHOTO (COLOR): 1 Hyperpigmented macules and papules on the bilateral chest gl GLO:DIF/01jan21:ijd15113-fig-0002.jpg PHOTO (COLOR): 2 Café au lait macule with superimposed hyperpigmented macules and papules on the left lower back gl After a robust review of the literature, we concluded that our patient's skin findings are most consistent with speckled lentiginous nevi, also called nevus spilus. It is thought that this is a subtype of congenital melanocytic nevus, but because these nevi are not always clinically obvious at birth, there is debate as to whether they are truly congenital or acquired.1 This condition presents as café au lait macules with superimposed melanocytic nevi. Patients with speckled lentiginous nevi, whether associated with a syndrome or not, are at increased risk for melanoma, so regular skin checks for any suspicious lesions are crucial.1 In addition, the nevi may progress with pregnancy or sun exposure, so patients should be aware that the appearance may change over time and new macules and papules may develop. [Extracted from the article]