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re susceptible to immune therapy-based treatment strategies and should be recognized as a unique molecular subgroup in future immune therapy trials.Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence, and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike, prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for patients with melanoma and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome, and offer recommendations for the best path forward.Short-chain fatty acids (SCFAs) are metabolites produced almost exclusively by the gut microbiota and are an essential mechanism by which gut microbes influence host physiology. Given that SCFAs induce vasodilation, we hypothesized that they might have additional cardiovascular effects. In this study, novel mechanisms of SCFA action were uncovered by examining the acute effects of SCFAs on cardiovascular physiology in vivo and ex vivo. Acute delivery of SCFAs in conscious radiotelemetry-implanted mice results in a simultaneous decrease in both mean arterial pressure and heart rate (HR). Inhibition of sympathetic tone by the selective β-1 adrenergic receptor antagonist atenolol blocks the acute drop in HR seen with acetate administration, yet the decrease in mean arterial pressure persists. Treatment with tyramine, an indirect sympathomimetic, also blocks the acetate-induced acute drop in HR. Langendorff preparations show that acetate lowers HR only after long-term exposure and at a smaller magnitude than seenisease states.Previous studies identified a region on chromosome 1 associated with NG-nitro-L-arginine methyl ester (L-NAME) hypertension-induced renal disease in fawn-hooded hypertensive (FHH) rats. This region contains a mutant γ-adducin (Add3) gene that impairs renal blood flow (RBF) autoregulation, but its contribution to renal injury is unknown. The present study evaluated the hypothesis that knockout (KO) of Add3 impairs the renal vasoconstrictor response to the blockade of nitric oxide synthase and enhances hypertension-induced renal injury after chronic administration of L-NAME plus a high-salt diet. The acute hemodynamic effect of L-NAME and its chronic effects on hypertension and renal injury were compared in FHH 1Brown Norway (FHH 1BN) congenic rats (WT) expressing wild-type Add3 gene versus FHH 1BNAdd3 KO rats. RBF was well autoregulated in WT rats but impaired in Add3 KO rats. Acute administration of L-NAME (10 mg/kg) raised mean arterial pressure (MAP) similarly in both strains, but RBF and glomerular filtrat-L-arginine methyl ester-induced hypertensive renal injury by altering the transmission of pressure to the glomerulus.COVID-19 has serious thrombotic complications in critically ill patients; however, thrombus is not a typical presenting symptom. This case report describes a patient with no respiratory symptoms who presented to the emergency department with abdominal pain. The pain was attributed to renal thrombosis, but the patient was found to have no risk factors for thrombotic disease and subsequent hypercoagulable work-up was unremarkable. Pulmonary manifestations of COVID-19 infection were detected incidentally on the abdominal CT scan and confirmed via PCR test. The patient was isolated and went on to develop mild respiratory failure secondary to COVID-19 infection. This case suggests that unexplained thrombus in otherwise asymptomatic patients can be a direct result of COVID-19 infection, and serves as a call to action for emergency department clinicians to treat unexplained thrombotic events as evidence of COVID-19.Carney Complex (CNC) is a rare syndrome characterised by skin pigmentation, endocrine over activity and myxomas, with the median age of detection being 20 years. We present a case of CNC diagnosed in infancy after being noted to have multiple lentigines over his face, abdomen, back and thighs at birth. We consider the differential diagnoses of similar cutaneous presentations in the well neonate and review the prognosis and suggested surveillance of patients with CNC.Oral cavity is an uncommon site for occurrence of metastasis and usually indicates widespread systemic disease. C-176 in vitro Primary tumours from the lung most commonly metastasise to oral soft tissues (31.3%) and jaw bones (22%) among men. It is quite challenging to diagnose a solitary metastatic lesion and to determine the site of primary lesion, due to the rarity of these occurrences. This case report describes the jaw bone as a first sign of occult primary lung adenocarcinoma with multiple metastases in 47-year-old man. The patient was treated with the combination of carboplatin and paclitaxel, and has completed two cycles till date with a stable clinical course. Diagnosis of metastatic carcinoma of jaw is very challenging. The pathologist must have knowledge of ancillary techniques along with clinical, radiological and histological correlation to determine the origin of distant primary.A 75-year-old woman presented with perineal wound dehiscence and small bowel prolapse of a perineal hernia, 6 years after extra-Levator AbdominoPerineal Excision (eLAPE) procedure for rectal cancer. She underwent emergency wound refashioning and perineal hernia repair with Parmacol mesh. Her postoperative recovery was complicated by long-standing ileus, wound infection, and she was discharged to community palliative care services. In this case report, we raise awareness of postoperative eLAPE complications and describe an unfortunate case where a postoperative perineal hernia was not repaired in a patient with multiple comorbidities.