Hidradenitis Suppurativa in Children and Adolescents: An Update on Pharmacologic Treatment Options.

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin condition that manifests as painful, deep-seated, inflamed nodules and abscesses in the axillary, groin, perianal, perineal, and inframammary regions. The associated pain, malodour, and disfigurement contribute to its profound negative impact on psychosocial spheres and overall quality of life in affected individuals. Although the symptoms of HS classically begin in the second or third decade of life, HS affects children and adolescents as well. Despite this, there are limited pediatric data on treatment, which are largely based on expert opinion, extrapolation of efficacy data in adults with HS, and safety information from medication use in other pediatric diseases. On this basis, there exist several pharmacological modalities in the treatment of children and adolescents with HS including topical therapies, systemic therapies, and biologics. The goals of this review article are to: (1) review the efficacy of different pharmacological treatment modalities in children and adolescents with HS, and (2) review the safety and monitoring considerations of the different treatment options in children and adolescents with HS.

Compact Multilayer Extension Actuators for Reconfigurable Soft Robots.

Soft robotic pneumatic actuators generally excel in the specific application they were designed for but lack the versatility to be redeployed to other applications. This study presents a novel and versatile soft compact multilayer extension actuator (MEA) to overcome this limitation. We use the MEA linear output in different hybrid configurations to achieve this versatility. The unique design and fabrication of the MEA allow for a compact elastomeric actuator with innate tension, capable of reverting to its initial state without the need for external stimulus. The MEA is made from alternating elastomers with different Young's modulus, bestowing the MEA with high durability, force, and extension capabilities. In addition, the MEA is lightweight at 4 g, capable of a high force-to-weight ratio of 1000 and an extension ratio of 525%. We also explored varying the MEA parameters, such as its material and dimension, which further enhance its properties. Subsequently, we showed four different design configurations encompassing the MEA to produce four basic motions, that is, push, pull, bend, and twist. Finally, we demonstrated three possible hybrid configurations for manipulation, locomotion, and assistive applications that highlight the versatility, manipulability, and modularity of the MEA.

A Fischer-Type Ruthenium Carbene Complex as a Metathesis Catalyst for the Synthesis of Enol Ethers.

The Grubbs G-I or G-II catalyst gives the ruthenium ethoxy carbene complex, which catalyzes ring-opening cross metathesis (ROCM) of a strained cyclic alkene to give a diene where one of the two alkene moieties in the product contains an ethoxy substituent. No polymeric products are detected. Hydrocarbons such as parent norbornene or substituted cyclopropenes can proceed with the reaction smoothly. Tertiary amines, N-alkylimides, esters, and aryl or alkyl bromides remain intact under the reaction conditions. In addition to vinyl ethers, vinylic esters can also be used. The time required to reach a 50% yield of the ROCM product t50 varies from 0.01 to 140 h depending on the strain and nucleophilicity of the double bond. Anchimeric participation of an electron-rich group would result in significant enhancement of the reactivity, and the t50 could be as short as several minutes. A similar substrate without such a neighboring group shows a much slower rate. An exo-norborne derivative reacts much faster than the corresponding endo-isomer. Alkenes with poor nucleophilicity are less favored for the ROCM process, so is less strained cyclooctene.

Acute transverse myelitis in COVID-19 infection.

A 60-year-old man presented to hospital with bilateral lower limb weakness, urinary retention and constipation. He had been diagnosed with COVID-19 10 days prior. Clinical examination revealed global weakness, increased tone, hyperreflexia and patchy paresthesia in his lower limbs bilaterally. Preliminary blood tests performed revealed a mildly elevated C reactive protein and erythrocyte sedimentation rate but was otherwise unremarkable. MRI scan of his whole spine demonstrated hyperintense T2 signal centrally from T7 to T10, suggestive of acute transverse myelitis. A lumbar puncture showed elevated protein count but normal glucose and white blood cell count. Serological testing for other viruses was negative. His neurological symptoms improved significantly after treatment with intravenous methylprednisone. This case highlights a potential neurological complication of COVID-19 infection.

Development and Validation of a Uremic Pruritus Treatment Algorithm and Patient Information Toolkit in Patients With Chronic Kidney Disease and End Stage Kidney Disease.

CONTEXT: Uremic pruritus (UP) affects up to half of all patients with kidney disease and has been independently associated with poor patient outcomes. UP is a challenging symptom for clinicians to manage as there are no validated guidelines for its treatment. OBJECTIVES: The study aimed to develop and validate an algorithm and patient information toolkit for the treatment of UP in patients with kidney disease. METHODS: The study involved a literature search and development of an initial draft algorithm, followed by content and face validation of this algorithm. Validation entailed three rounds of interviews with six nephrology clinicians per round. Participants assessed the relevance of each component of the algorithm and then rated a series of statements on a scale of 1-5 to assess face validity of the algorithm. After each round, the content validity index (CVI) of each algorithm component was calculated, and the algorithm was revised by the study team in response to findings. This process was followed by a second study that developed and validated a patient information pamphlet and video. RESULTS: Algorithm validation participants were affiliated with three institutions and included seven physicians, four registered nurses, three nurse practitioners, three pharmacists, and a dietician. The average CVI of the algorithm components across all three rounds was 0.89, with 0.80 commonly cited as the lower acceptable limit for content validation. More than 78% of participants rated each face validity statement as "Agree" or "Strongly Agree". For the patient information tools, five clinicians and 15 patients were included in validation. The average CVI was 1.00 for both tools, and the average face validity was 92%. CONCLUSION: A treatment algorithm and patient information toolkit for managing UP in patients with kidney disease were developed and validated through expert review. Further research will be conducted on implementation of the treatment algorithm and evaluating patient-reported outcomes.

VISTA.COMP - an engineered checkpoint receptor agonist that potently suppresses T cell-mediated immune responses.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is a recently discovered immune checkpoint ligand that functions to suppress T cell activity. The therapeutic potential of activating this immune checkpoint pathway to reduce inflammatory responses remains untapped, largely due to the inability to derive agonists targeting its unknown receptor. A dimeric construct of the IgV domain of VISTA (VISTA-Fc) was shown to suppress the activation of T cells in vitro. However, this effect required its immobilization on a solid surface, suggesting that VISTA-Fc may display limited efficacy as a VISTA-receptor agonist in vivo. Herein, we have designed a stable pentameric VISTA construct (VISTA.COMP) by genetically fusing its IgV domain to the pentamerization domain from the cartilage oligomeric matrix protein (COMP). In contrast to VISTA-Fc, VISTA.COMP does not require immobilization to inhibit the proliferation of CD4+ T cells undergoing polyclonal activation. Furthermore, we show that VISTA.COMP, but not VISTA-Fc, functions as an immunosuppressive agonist in vivo capable of prolonging the survival of skin allografts in a mouse transplant model as well as rescuing mice from acute concanavalin-A-induced hepatitis. Collectively, we believe our data demonstrate that VISTA.COMP is a checkpoint receptor agonist and the first agent to our knowledge targeting the putative VISTA-receptor to suppress T cell-mediated immune responses.