Spesolimab, A Novel Interleukin-36 Inhibitor for Generalized Pustular Psoriasis Flares in Adult Patients.

Generalized pustular psoriasis (GPP) is a rare, immune-mediated inflammatory disease with characteristic cutaneous and systemic manifestations. Mutations in the interleukin-36 receptor antagonist (IL36RN) gene have been implicated in its pathogenesis. Spesolimab is a novel systemic biologic therapy that selectively inhibits interleukin-36. It was recently approved by Health Canada and the US FDA for the treatment of GPP flares in adults. Results from phase 1 and 2 studies have been promising. Herein, we review the efficacy and safety of spesolimab for the treatment of GPP flares, as demonstrated in clinical trials.

Approach to chronic wrist pain in adults: Review of common pathologies for primary care practitioners.

OBJECTIVE: To develop an approach for identifying, investigating, and initially managing common causes of chronic wrist pain seen by primary care practitioners. SOURCES OF INFORMATION: Relevant clinical evidence and literature were identified using the PubMed database. MAIN MESSAGE: Chronic wrist pain is a common presentation in the primary care setting. The complex anatomy of the wrist leads to a broad differential diagnosis. Elements of history, findings of physical examinations and investigations, and management relevant to the following pathologies are discussed, including scaphoid fracture nonunion, thumb carpometacarpal joint osteoarthritis, scapholunate ligament instability, triangular fibrocartilage complex injuries, de Quervain tenosynovitis, extensor carpi ulnaris tendinopathy, carpal tunnel syndrome, and ganglion cysts. When evaluating chronic wrist pain, diagnostic imaging with x-ray scans can serve as an important ancillary investigation tool but should not override clinical suspicion. Advanced imaging (computed tomography or magnetic resonance imaging) is generally best ordered by a hand surgeon when it will help clarify a diagnosis and guide treatment. CONCLUSION: Chronic wrist pain is a functionally limiting problem best managed with timely diagnosis and treatment. A thorough history and physical examination are the cornerstones of an effective evaluation. When diagnosis is delayed, some wrist pathologies can lead to relatively poor outcomes, such as a scaphoid fracture nonunion resulting in diffuse wrist osteoarthritis.

Tralokinumab for Moderate-to-Severe Atopic Dermatitis in Adults.

Atopic dermatitis (AD) is a common, chronic, recurrent, immune-mediated inflammatory skin disease. Targeted treatment options remain limited. Tralokinumab (Adtralza®) is a promising, new systemic therapy that inhibits interleukin-13. It was recently approved by Health Canada and the US FDA for the treatment of moderate-to-severe AD in adults and may be used alone or with topical corticosteroids. Herein, we review the efficacy and safety of tralokinumab in adults, as demonstrated in clinical trials.

Halobetasol Propionate 0.01% Lotion for Plaque Psoriasis and Corticosteroid-Responsive Dermatoses.

A novel topical corticosteroid, halobetasol propionate (HP) 0.01% lotion (Bryhali™), has recently been introduced for the treatment of plaque psoriasis and corticosteroid-responsive dermatoses in adults. Once daily application of HP 0.01% lotion is indicated for use up to 8 weeks. Treatment success for plaque psoriasis in the pivotal phase 3 clinical trials (defined as an Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] with ≥2-grade improvement from baseline) occurred in over one-third of patients by week 8. Treatment-emergent adverse events were typically mild-to-moderate in intensity and usually limited to the application site(s). No treatment-related cases of skin atrophy have been reported from the studies. Counselling should be considered to optimize treatment outcomes.

Diversification dynamics of mammalian clades during the K-Pg mass extinction.

The Cretaceous/Palaeogene (K-Pg) episode is an iconic mass extinction, in which the diversity of numerous clades abruptly declined. However, the responses of individual clades to mass extinctions may be more idiosyncratic than previously understood. Here, we examine the diversification dynamics of the three major mammalian clades in North America across the K-Pg. Our results show that these clades responded in dramatically contrasting ways to the K-Pg event. Metatherians underwent a sudden rise in extinction rates shortly after the K-Pg, whereas declining origination rates first halted diversification and later drove the loss of diversity in multituberculates. Eutherians experienced high taxonomic turnover near the boundary, with peaks in both origination and extinction rates. These findings indicate that the effects of geological episodes on diversity are context dependent and that mass extinctions can affect the diversification of clades by independently altering the extinction regime, the origination regime or both.

The extended Price equation quantifies species selection on mammalian body size across the Palaeocene/Eocene Thermal Maximum.

Species selection, covariation of species' traits with their net diversification rates, is an important component of macroevolution. Most studies have relied on indirect evidence for its operation and have not quantified its strength relative to other macroevolutionary forces. We use an extension of the Price equation to quantify the mechanisms of body size macroevolution in mammals from the latest Palaeocene and earliest Eocene of the Bighorn and Clarks Fork Basins of Wyoming. Dwarfing of mammalian taxa across the Palaeocene/Eocene Thermal Maximum (PETM), an intense, brief warming event that occurred at approximately 56 Ma, has been suggested to reflect anagenetic change and the immigration of small bodied-mammals, but might also be attributable to species selection. Using previously reconstructed ancestor-descendant relationships, we partitioned change in mean mammalian body size into three distinct mechanisms: species selection operating on resident mammals, anagenetic change within resident mammalian lineages and change due to immigrants. The remarkable decrease in mean body size across the warming event occurred through anagenetic change and immigration. Species selection also was strong across the PETM but, intriguingly, favoured larger-bodied species, implying some unknown mechanism(s) by which warming events affect macroevolution.

Nanoscopy in a living multicellular organism expressing GFP.

We report superresolution fluorescence microscopy in an intact living organism, namely Caenorhabditis elegans nematodes expressing green fluorescent protein (GFP)-fusion proteins. We also superresolve, by stimulated emission depletion (STED) microscopy, living cultured cells, demonstrating that STED microscopy with GFP can be widely applied. STED with GFP can be performed with both pulsed and continuous-wave lasers spanning a wide wavelength range from at least 556-592 nm. Acquiring subdiffraction resolution images within seconds enables the recording of movies revealing structural dynamics. These results demonstrate that numerous microscopy studies of live samples employing GFP as the marker can be performed at subdiffraction resolution.

Case report of hidradenitis suppurativa localized to the face in an HIV patient.

Hidradenitis suppurativa is a chronic, debilitating inflammatory skin disease. Case reports of individuals with hidradenitis suppurativa presenting exclusively on the face, as well as reports of individuals with HIV and hidradenitis suppurativa, are rare. Here, we present the case of an HIV-positive man who presented with hidradenitis suppurativa localized only on his face. We also review facial hidradenitis suppurativa and hidradenitis suppurativa in HIV patients.

Increasing the accessibility and impact of justice-related student and practitioner research.

Much good quality research by pre-doctoral students and case-work focused practitioners remains unpublished. However, their findings could contribute to the evidence base underpinning science and practice within international justice system contexts. There are two main challenges to making findings accessible: reaching all criminal justice stakeholders, and encouraging collaborative efforts in research addressing 'real world' problems. This article presents the rationale for a new, open access repository. The aim is to share good quality pre-doctoral and practitioner criminal justice research across traditional disciplinary and international borders. Such a repository should be easy to use, well maintained and sustainable. Its reach, value and impact also need to be measurable. We present the major considerations relating to the operation and workflow of such a repository, and outline the potential value, benefits and limitations. Our research suggests that the proposed repository could foster interdisciplinary and collaborative work to benefit global justice systems and societies.

STED microscopy with a MHz pulsed stimulated-Raman-scattering source.

We perform stimulated emission depletion (STED) microscopy with a novel light source consisting of a fiber-amplified, frequency doubled laser operating with a 1 MHz repetition rate and a 530 nm output coupled into a standard single mode fiber to produce a tunable spectrum of discrete peaks via stimulated Raman scattering (SRS). Using peaks at 585, 600, and 616 nm as STED light we perform STED microscopy with resolution down to 20-30 nm. The nanosecond pulsed light source should prove valuable for all forms of microscopy requiring both brilliance and multiple wavelengths in the visible range.