R. Isseroff

Single cell mechanics of keratinocyte cells

Keratinocytes represent the major cell type of the uppermost layer of human skin, the epidermis. Using AFM-based single cell compression, the ability of individual keratinocytes to resist external pressure and global rupturing forces is investigated and compared with various cell types. Keratinocytes are found to be 6-70 times stiffer than other cell types, such as white blood, breast epithelial, fibroblast, or neuronal cells, and in contrast to other cell types they retain high mechanic strength even after the cells death. The absence of membrane rupturing peaks in the force-deformation profiles of keratinocytes and their high stiffness during a second load cycle suggests that their unique mechanical resistance is dictated by the cytoskeleton. A simple analytical model enables the quantification of Youngs modulus of keratinocyte cytoskeleton, as high as 120-340 Pa. Selective disruption of the two major cytoskeletal networks, actin filaments and microtubules, does not significantly affect keratinocyte mechanics. F-actin is found to impact cell deformation under pressure. During keratinocyte compression, the plasma membrane stretches to form peripheral blebs. Instead of blebbing, cells with depolymerized F-actin respond to pressure by detaching the plasma membrane from the cytoskeleton underneath. On the other hand, the compression force of keratinocytes expressing a mutated keratin (cell line, KEB-7) is 1.6-2.2 times less than that for the control cell line that has normal keratin networks. Therefore, we infer that the keratin intermediate filament network is responsible for the extremely high keratinocyte stiffness and resilience. This could manifest into the rugged protective nature of the human epidermis.

TLR2 expression and signaling-dependent inflammation impair wound healing in diabetic mice

Toll-like receptor-2 (TLR2) is a pivotal pathogen recognition receptor that has a key role in inflammation, diabetes, and injury. Hyperglycemia, inflammation, and oxidative stress induce TLR2-myeloid differentiation factor-88 (MyD88) expression and signaling, and are major pathophysiological mechanisms in the impaired diabetic wound-healing process. The aim of the study was to examine the contribution of TLR2-MyD88 expression and signaling to the prolonged inflammation observed in diabetic wounds. Diabetes was induced in male C57BL/6J and TLR2−/− mice using streptozotocin (STZ) with matching nondiabetic mice as control. In addition, nonobese diabetic (NOD) mice were used to represent the spontaneous type 1 diabetes condition. After 2 weeks of persistent hyperglycemia in the mice, full-thickness excision wounds were made on the backs aseptically. Total RNA and protein were subjected to real-time PCR and western blot analyses. Wound sizes were measured using digital planimetry. TLR2 mRNA and protein expression increased significantly in wounds of C57BL/6J+STZ and NOD mice (P<0.05) compared with nondiabetic C57BL/6J mice. MyD88 expression, interleukin receptor-associated kinase-1 phosphorylation, and nuclear factor-κ B (NF-κB) activation were increased in diabetic wounds compared with nondiabetic wounds. Wounds of TLR2−/−+STZ mice showed less oxidative stress, decreased MyD88 signaling, NF-κB activation, and cytokine secretion. The wound closure was significant in TLR2−/−+ STZ mice compared with C57BL/6J+STZ mice. Collectively, our findings show that increased TLR2 mRNA and protein expression, signaling, and activation contribute to the prolonged inflammation in the diabetic wounds and that absence of TLR2 may result in decreased inflammation and improved wound healing.

Does class attendance matter? Results from a second-year medical school dermatology cohort study.

Little is known about the impacts of class attendance and learning preferences on academic performance in dermatology.

Multiple Firm Nodules and Tender, Indurated Plaques

Aman in his 30swith a history of multiple medical conditions, includinghypertension, congestiveheart failure (receiving chronicdiuretic therapy), chronic renal insufficiency, andpulmonaryembolus (receiving warfarin therapy), presented with multiple firm nodules that extruded a thin, white, milky fluid within tender, hyperpigmented, induratedplaquesonthe lowerabdomen(Figure,A).Healso hadnumerous smallernondraining, yellow-whitenodulesonanerythematous to hyperpigmented base on the bilateral medial thighs (Figure, B). A few scattered firm, yellow-white subcutaneous nodules were also seen on the extensor upper extremities. The lesions appeared approximately 1 year prior to our evaluation of his lower abdomen, where he had injected enoxaparin sodium subcutaneously for4days. Sixmonths later, similar lesionsappearedonhismedial thighs and upper extremities without prior trauma or injection. The patient reported no fevers, chills, joint pain, or swelling. He admitted to social alcohol use. A punch biopsywas obtained of a nondraining yellow-white nodule on the left upper arm (Figure, C). What is your diagnosis?

Short-term exposure of human sebocytes to 13-cis-retinoic acid induces acnegenic changes

Acne vulgaris is the most common skin disorder and contributes an estimated 0.29% of the global burden of disease. The pathophysiology of acne involves excess sebum production and altered lipid composition by the sebaceous glands, follicular hyperkeratinization, bacterial colonization by Cutibacterium acnes (C. acnes), and perifollicular inflammation. 13-cis Retinoic Acid (13-cis RA), also known as isotretinoin, is the only acne therapy that targets all four pathologic mechanisms and is often prescribed to patients with severe acne. This article is protected by copyright. All rights reserved.

Acute Exacerbation of Carpal Tunnel Syndrome After Radiesse® Injection for Hand Rejuvenation

A calcium hydroxyapatite filler (CaHA, Radiesse® ; Merz Aesthetics, Franksville, WI, USA) became the first FDA-approved injectable filler for volume loss correction of the dorsal hands during rejuvenation.1 Within three months, the filler is processed by macrophage phagocytosis, and CaHA stimulates neocollagenesis for sustained results. The material does not stimulate calcifications or foreign body reactions, and allergy testing is not required. In fact, its chemically inert behavior contributes to its high degree of biocompatibility and favorable safety profile. Marmur etxa0al. reported no long-term adverse events at 6 month follow-up. This article is protected by copyright. All rights reserved.