Isolated Scaphoid Dislocation From Low-Energy Wrist Trauma.

Isolated scaphoid dislocation is an extremely rare injury typically caused by high-energy trauma. We present the first observed case of isolated scaphoid dislocation resulting from a non-traumatic injury of the wrist in power-grip tension in a patient with a questionable history of Marfan Syndrome. A 20-year-old right-hand dominant man presented to the emergency department with right wrist pain and deformation after carrying a table. The patient reported a possible history of Marfan Syndrome, but it had never been definitively diagnosed. Imaging revealed radial dislocation of the scaphoid. Bedside closed reduction was performed followed by outpatient ligament reconstruction with return to normal activities at 6 months. Early diagnosis and management lead to an improved prognosis for isolated scaphoid dislocation. Regardless of patient history or mechanism of injury, treatment options include closed reduction, percutaneous fixation, and/or open reduction with internal fixation and ligamentous reconstruction.

Simultaneous Bilateral Patellar Tendon Rupture in a Young Adult Male: A Case Report and Review of the Literature.

A bilateral patellar tendon rupture is extremely rare and has only been documented in case reports. Although the etiology remains unknown, predisposing factors include steroid usage, systemic diseases, and tendinopathies. In the present case, a healthy 33-year-old male with a prior history of bilateral patellar tendonitis and a diagnosis of Osgood-Schlatter disease during adolescence experienced simultaneous bilateral patellar tendon rupture after playing volleyball. He underwent bilateral patellar repair without complications. In the absence of trauma, spontaneous bilateral patellar tendon ruptures are associated with several predisposing factors, including systemic diseases, prior corticosteroid or fluoroquinolone usage, and history of tendinopathy. Injuries can be classified based on the location of the rupture. Bilateral patellar tendon ruptures can be misdiagnosed due to the rarity of cases and the lack of a normal comparative knee. Radiographic techniques can aid in the diagnosis, leading to early surgical treatment and improved outcomes. Early diagnosis and prompt surgical repair contribute to good functional outcomes in this potentially debilitating injury pattern.

Lymphomatoid Papulosis and Other Lymphoma-Like Diseases.

Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica are the 2 main subtypes of pityriasis lichenoides. They represent the acute and chronic forms of the disease; both may have clonal T cells. Several treatment modalities are used, but it has been difficult to determine efficacy because of the possibility of spontaneous remission. Cutaneous CD30+ lymphoproliferative disorders constitute many cutaneous T-cell lymphomas and comprise lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (ALCL). Both have an excellent prognosis. Lymphomatoid papulosis often only requires observation or treatment of symptoms. First-line therapies for primary cutaneous ALCL are surgical excision or radiotherapy.

The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma.

Despite major advances in targeted melanoma therapies, drug resistance limits their efficacy. Long noncoding RNAs (lncRNAs) are transcriptome elements that do not encode proteins but are important regulatory molecules. LncRNAs have been implicated in cancer development and response to different therapeutics and are thus potential treatment targets; however, the majority of their functions and molecular interactions remain unexplored. In this study, we identify a novel cytoplasmic intergenic lincRNA (MIRAT), which is upregulated following prolonged MAPK inhibition in NRAS mutant melanoma and modulates MAPK signaling by binding to the MEK scaffold protein IQGAP1. Collectively, our results present MIRAT's direct modulatory effect on the MAPK pathway and highlight the relevance of cytoplasmic lncRNAs as potential targets in drug resistant cancer.

A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations.

BACKGROUND: Food fortification has been recommended to improve a population's micronutrient status. Biofortification techniques modestly elevate the zinc content of cereals, but few studies have reported a positive impact on functional indicators of zinc status. OBJECTIVE: We determined the impact of a modest increase in dietary zinc that was similar to that provided by biofortification programs on whole-body and cellular indicators of zinc status. DESIGN: Eighteen men participated in a 6-wk controlled consumption study of a low-zinc, rice-based diet. The diet contained 6 mg Zn/d for 2 wk and was followed by 10 mg Zn/d for 4 wk. To reduce zinc absorption, phytate was added to the diet during the initial period. Indicators of zinc homeostasis, including total absorbed zinc (TAZ), the exchangeable zinc pool (EZP), plasma and cellular zinc concentrations, zinc transporter gene expression, and other metabolic indicators (i.e., DNA damage, inflammation, and oxidative stress), were measured before and after each dietary-zinc period. RESULTS: TAZ increased with increased dietary zinc, but plasma zinc concentrations and EZP size were unchanged. Erythrocyte and leukocyte zinc concentrations and zinc transporter expressions were not altered. However, leukocyte DNA strand breaks decreased with increased dietary zinc, and the level of proteins involved in DNA repair and antioxidant and immune functions were restored after the dietary-zinc increase. CONCLUSIONS: A moderate 4-mg/d increase in dietary zinc, similar to that which would be expected from zinc-biofortified crops, improves zinc absorption but does not alter plasma zinc. The repair of DNA strand breaks improves, as do serum protein concentrations that are associated with the DNA repair process. This trial was registered at clinicaltrials.gov as NCT02861352.

Acyl protein thioesterase 1 and 2 (APT-1, APT-2) inhibitors palmostatin B, ML348 and ML349 have different effects on NRAS mutant melanoma cells.

Oncogenic NRAS mutations are frequent in melanoma and lead to increased downstream signaling and uncontrolled cell proliferation. Since the direct inhibition of NRAS is not possible yet, modulators of NRAS posttranslational modifications have become an area of interest. Specifically, interfering with NRAS posttranslational palmitoylation/depalmitoylation cycle could disturb proper NRAS localization, and therefore decrease cell proliferation and downstream signaling. Here, we investigate the expression and function of NRAS depalmitoylating acyl protein thioesterases 1 and 2 (APT-1, APT-2) in a panel of NRAS mutant melanoma cells. First, we show that all melanoma cell lines examined express APT-1 and APT-2. Next, we show that siRNA mediated APT-1 and APT-2 knock down and that the specific APT-1 and -2 inhibitors ML348 and ML349 have no biologically significant effects in NRAS mutant melanoma cells. Finally, we test the dual APT-1 and APT-2 inhibitor palmostatin B and conclude that palmostatin B has effects on NRAS downstream signaling and cell viability in NRAS mutant melanoma cells, offering an interesting starting point for future studies.

Synergy of molecular targeted approaches and immunotherapy in melanoma: preclinical basis and clinical perspectives.

INTRODUCTION: Targeted therapy and immunotherapies are the novel pharmacologic treatment strategies for metastatic melanoma. BRAF and MEK inhibitors effectively block the hyperactivation of the MAPK pathway in BRAF mutant melanomas and also have several other effects on melanoma cells and on the immune response. The aim of this work is to discuss the rationale, evidence and perspectives of approaches combining target and immunotherapy against melanoma. AREAS COVERED: We first review the effects of BRAF and MEK inhibitors on melanoma cells and on the different components of the immune system. Afterwards, we summarize the results of the preclinical and clinical studies that have combined targeted therapy and immunotherapy for the treatment of melanoma. EXPERT OPINION: Clinical applications of immunotherapy strategies have recently changed the therapeutic mainstay for metastatic melanoma. Biologic and initial preclinical data support their integration with innovative molecular targeted therapies, opening enormous perspectives for researchers in the effort of finding a definitive cure. Main open challenges are the definition of reliable research models, assessment of effective schedules, safety issues and designing of personalized approaches.