Understanding patient preferences for student clinician attire: a cross-sectional study of a student chiropractic clinic in Australia.

Objectives: Previous studies have investigated the role of clinical attire in establishing patient-held perceptions of professionalism and knowledgeability across various healthcare settings. This study aimed to understand patients' preferences for chiropractic student attire.

Methods: Three hundred and twenty patients were recruited from a university chiropractic clinic and asked to complete an online questionnaire.

NTRK point mutations and their functional consequences.

The neurotrophic receptor tyrosine kinase (NTRK) family of genes, including NTRK1, NTRK2, and NTRK3, encodes membrane-bound receptors that normally regulate cell survival and differentiation upon binding of growth factors. Not surprisingly, mutations in these genes are known to contribute to the growth of a diverse number of cancers. With the recent FDA approval of two first-generation tyrosine-kinase inhibitors (TKIs) for adult and pediatric patients with solid tumors harboring NTRK gene fusions, much of the literature has focused on the biology behind these types of NTRK abnormalities; however, point mutations can also contribute to oncogenesis or resistance to TKI therapy, albeit at a lower frequency than fusions.

A review of inherited cancer susceptibility syndromes.

Inherited cancer syndromes are caused by genetic mutations that place patients at an increased risk for developing cancer. Although most cancers are not caused by genetic inheritance, clinicians must understand these syndromes and be able to recognize their common characteristics. A thorough family history and identification of common patterns as well as specific clinical signs and symptoms can help with early recognition.

Gasdermins in Apoptosis: New players in an Old Game.

Apoptosis is a form of programmed cell death (PCD) that plays critical physiological roles in removing superfluous or dangerous cell populations that are unneeded or threatening to the health of the host organism. Although the molecular pathways leading to activation of the apoptotic program have been extensively studied and characterized starting in the 1970s, new evidence suggests that members of the gasdermin superfamily are novel pore-forming proteins that augment apoptosis by permeabilizing the mitochondria and participate in the final stages of the apoptotic program by inducing secondary necrosis/pyroptosis. These findings may explain outstanding questions in the field such as why certain gasdermin members sensitize cells to apoptosis, and why some apoptotic cells also show morphological features of necrosis.

Mutant BRAF and MEK Inhibitors Regulate the Tumor Immune Microenvironment via Pyroptosis.

Combinations of BRAF inhibitors and MEK inhibitors (BRAFi + MEKi) are FDA-approved to treat -mutant melanoma. Efficacy of BRAFi + MEKi associates with cancer cell death and alterations in the tumor immune microenvironment; however, the links are poorly understood. We show that BRAFi + MEKi caused durable melanoma regression in an immune-mediated manner.

Gasdermins: novel mitochondrial pore-forming proteins.

Gasdermin proteins have been extensively characterized for their ability to form necrotic pores in the plasma membrane, however, their interactions with other organelles have yet to be described. We recently demonstrated that some gasdermin proteins can also permeabilize the mitochondria to augment apoptotic signaling which may be important in the context of cancer and hearing loss.

Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation.

Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells.

Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3.

TLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1.