Triple Primary Malignancy Detection in an Elderly Male: A Case Report on Concurrent Prostate Cancer, Clear Cell Renal Cell Carcinoma, and Metastatic Melanoma Identified by PSMA PET-CT.

We report the management of a 76-year-old male presenting with primary metastatic melanoma, prostatic carcinoma, and clear cell renal cell carcinoma. Each of the three cancers was identified via PSMA PET-CT, thought to be unique to prostate cancer identification. Management of this patient included axillary lymph node resection, radiation therapy, radical nephrectomy, and immunotherapy. This case emphasizes the need for a multimodal approach and a broad differential diagnosis when managing cancer patients. Furthermore, the full potential of PSMA PET-CT has yet to be established.

Primary testicular teratoid Wilms tumor in a 40-year-old male with retroperitoneal lymph node involvement: A case report.

We report a 40-year-old male presenting with right testicular pain. Following right orchiectomy demonstrating pT1bS0N0M0 teratoma with extensive necrosis, the patient opted for surveillance. With new retroperitoneal lymphadenopathy, the patient underwent a robotic-assisted laparoscopic retroperitoneal lymph node. After final pathology demonstrated extensive necrosis, the initial orchiectomy specimen was re-reviewed which revealed 60/40 ratio of non-seminomatous teratoma to nephroblastoma. Adult presentation of testicular nephroblastoma is exceedingly rare and such reports contribute to the understanding of adult teratoid Wilms tumor pathogenesis. This case emphasizes the need for comprehensive diagnostic approaches and further research into the pathophysiology of extrarenal teratoid Wilms tumors.

Medical Law and Medical School Curricula: A Systematic Review.

Health law plays a crucial role in the field of medicine, as it dictates appropriate practices, regulations, and rights and responsibilities for healthcare professionals and patients. Despite this undeniable relationship, there is a lack of focus on health law, and an outdated hidden curriculum in medical education has perpetuated long-standing negative perceptions of the legal system. PubMed was searched for articles related to medicolegal education that were published from January 1950 to December 2022. The following search terms were utilized: "(medical student) AND (law OR legal OR medico-legal) AND (education)". Literature that directly or indirectly discussed the relationship between law and medicine as well as the role of medical student education within the medicolegal nexus were reviewed. Additional literature was identified from reference lists of systematic and literature reviews. The authors manually reviewed each included publication to determine key details, study populations, and conclusions. The PubMed search revealed 3,592 papers that were sorted for relevance. Forty-four articles published between 1971 and 2022 were reviewed and analyzed. Three main themes consistently emerged from the discussions in these articles. The first theme concerns the sentiment among medical students that they were ill-prepared to manage the legal aspects of healthcare. The second theme concerns the negative perception of health law by medical students. The third theme details the benefits of including medicolegal courses in medical school curricula. This study sheds light on the notion that medical students feel ill-prepared to handle the legal aspects of healthcare due to limited medicolegal education. Furthermore, negative perceptions of the legal field continue to exist amongst medical students due to a plethora of factors, including an outdated hidden curriculum. Incorporating medicolegal courses into medical school curricula can foster positive attitudes toward the field of law and lead to enhanced professional ethics, increased patient advocacy, and potentially improved patient outcomes.

Smooth Muscle Myosin Localizes at the Leading Edge and Regulates the Redistribution of Actin-regulatory Proteins during Migration.

Airway smooth muscle cell migration plays an essential role in airway development, repair, and remodeling. Smooth muscle myosin II has been traditionally thought to localize in the cytoplasm solely and regulates cell migration by affecting stress fiber formation and focal adhesion assembly. In this study, we unexpectedly found that 20-kDa myosin light chain (MLC20) and myosin-11 (MYH11), important components of smooth muscle myosin, were present at the edge of lamellipodia. The knockdown of MLC20 or MYH11 attenuated the recruitment of c-Abl, cortactinProfilin-1 (Pfn-1), and Abi1 to the cell edge. Moreover, myosin light chain kinase (MLCK) colocalized with integrin ß1 at the tip of protrusion. The inhibition of MLCK attenuated the recruitment of c-Abl, cortactin, Pfn-1, and Abi1 to the cell edge. Furthermore, MLCK localization at the leading edge was reduced by integrin ß1 knockdown. Taken together, our results demonstrate that smooth muscle myosin localizes at the leading edge and orchestrates the recruitment of actin-regulatory proteins to the tip of lamellipodia. Mechanistically, integrin ß1 recruits MLCK to the leading edge, which catalyzes MLC20 phosphorylation. Activated myosin regulates the recruitment of actin-regulatory proteins to the leading edge, and promotes lamellipodial formation and migration.

Cooperativity between ß-agonists and c-Abl inhibitors in regulating airway smooth muscle relaxation.

Current therapeutic approaches to avoid or reverse bronchoconstriction rely primarily on ß2 adrenoceptor agonists (ß-agonists) that regulate pharmacomechanical coupling/cross bridge cycling in airway smooth muscle (ASM). Targeting actin cytoskeleton polymerization in ASM represents an alternative means to regulate ASM contraction. Herein we report the cooperative effects of targeting these distinct pathways with ß-agonists and inhibitors of the mammalian Abelson tyrosine kinase (Abl1 or c-Abl). The cooperative effect of ß-agonists (isoproterenol) and c-Abl inhibitors (GNF-5, or imatinib) on contractile agonist (methacholine, or histamine) -induced ASM contraction was assessed in cultured human ASM cells (using Fourier Transfer Traction Microscopy), in murine precision cut lung slices, and in vivo (flexiVent in mice). Regulation of intracellular signaling that regulates contraction (pMLC20, pMYPT1, pHSP20), and actin polymerization state (F:G actin ratio) were assessed in cultured primary human ASM cells. In each (cell, tissue, in vivo) model, c-Abl inhibitors and ß-agonist exhibited additive effects in either preventing or reversing ASM contraction. Treatment of contracted ASM cells with c-Abl inhibitors and ß-agonist cooperatively increased actin disassembly as evidenced by a significant reduction in the F:G actin ratio. Mechanistic studies indicated that the inhibition of pharmacomechanical coupling by ß-agonists is near optimal and is not increased by c-Abl inhibitors, and the cooperative effect on ASM relaxation resides in further relaxation of ASM tension development caused by actin cytoskeleton depolymerization, which is regulated by both ß-agonists and c-Abl inhibitors. Thus, targeting actin cytoskeleton polymerization represents an untapped therapeutic reserve for managing airway resistance.