Citations

Low frequency brain rhythms facilitate communication across large spatial regions in the brain and high frequency rhythms are thought to signify local processing among nearby assemblies. A heavily investigated mode by which these low frequency and high frequency phenomenon interact is phase-amplitude coupling (PAC). This phenomenon has recently shown promise as a novel electrophysiologic biomarker, in a number of neurologic diseases including human epilepsy. In 17 medically refractory epilepsy patients undergoing phase-2 monitoring for the evaluation of surgical resection and in whom temporal depth electrodes were implanted, we investigated the electrophysiologic relationships of PAC in epileptogenic (seizure onset zone or SOZ) and non-epileptogenic tissue (non-SOZ). That this biomarker can differentiate seizure onset zone from non-seizure onset zone has been established with ictal and pre-ictal data, but less so with interictal data. Here we show that this biomarker can differentiate SOZ from non-SOZ interictally and is also a function of interictal epileptiform discharges. We also show a differential level of PAC in slow-wave-sleep relative to NREM1-2 and awake states. Lastly, we show AUROC evaluation of the localization of SOZ is optimal when utilizing beta or alpha phase onto high-gamma or ripple band. The results suggest an elevated PAC may reflect an electrophysiology-based biomarker for abnormal/epileptogenic brain regions.

Abstract Primary cardiac sarcoma is a rare type of intracardiac mass. This report describes a patient with atrial flutter who had a new right atrial mass incidentally discovered on transesophageal echocardiography. A thrombus was suspected based on radiographic appearance, but there was minimal change with anticoagulation. The mass was resected and found to be an undifferentiated pleomorphic cardiac sarcoma, an uncommon sub-type within the already rare category of primary cardiac neoplasms. This report highlights the importance of considering primary malignancy and thoroughly correlating radiographic and clinical evidence during the diagnostic workup of patients with intracardiac masses.

Cervical cancer (CC) is women's fourth most occurring malignancy, with a high death rate. Every CC patient is related to infection with high-risk human papillomaviruses (HPV), predominantly transmitted through sexual contact. Early diagnosis of CC helps treat surgical removal of tumours, leading to an increased patient life span. However, existing detection methods of CC, like Pap smear test, have very low sensitivity. Even though preventive vaccines for CC are doing well, they cannot protect against all HPV cancers and potential side effects. Additionally, chemotherapy for CC has had a detrimental impact because of the lack of selective tumour cell toxicity, resulting in higher adverse effects. Despite significant progress in oncology research, efficient CCs treatment is still challenging, and target-selective drug delivery formulations with a systematic release mechanism potentially avoid and reduce biotoxicity. Recent developments in nanomedicine and nanotechnology are creating more interest in developing new treatment strategies for CC treatment. Materials used in nanomedicine development are made up of synthetic or natural. These nanoparticles pointedly impacted therapeutic applications with enhanced specificity and unique personalized assets. Surface-engineered nanoparticles offer a massive possibility for compatibility with biological agents, including nucleic acids, proteins, etc. Surface fictionalization nanoparticles with targeting ligands further help in selective targeting. The present study summarizes recent advancements in surface-modified nanoparticlebased CC treatment methodologies.<br>

Abstract The MHC class I antigen presentation pathway in melanoma cells has a well-established role in immune-mediated destruction of tumors. However, the clinical significance of the MHC class II antigen presentation pathway in melanoma cells is less clear. In antigen presenting cells, gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of multiple melanoma antigens. While not expressed in benign melanocytes of nevi, GILT and MHC class II expression is induced in malignant melanocytes in a portion of melanoma specimens. Analysis of The Cancer Genome Atlas (TCGA) cutaneous melanoma dataset showed that high GILT mRNA expression was associated with improved overall survival. Expression of IFN-γ, TNF-α, and IL-1β was positively associated with GILT expression in the TCGA melanoma specimens. These cytokines were capable of inducing GILT expression in melanoma cells in vitro. GILT protein expression in melanocytes was induced in halo nevi, which are nevi undergoing immune-mediated regression, and is consistent with the association of GILT expression with improved survival in melanoma. To explore potential mechanisms of GILT’s association with patient outcome, we analyzed the mRNA expression pattern in the MHC class II antigen presentation pathway. In contrast to healthy skin where the MHC class II pathway was nearly uniformly expressed and intact, there was substantial variation in the MHC class II pathway of the TCGA melanoma dataset. Both an active and intact MHC class II pathway were associated with improved overall survival in melanoma. These studies support a role for GILT and the MHC class II antigen presentation pathway in melanoma outcome.

A man in his 70s with a history of fatigue, abdominal pain, and a palpable abdominal mass was found to have a peritoneal desmoid tumour. One year after diagnosis, he was prescribed sorafenib to limit tumour growth. Two months later, he developed dyspnoea on exertion and lower extremity weakness and was reported to have supine hypertension and orthostatic hypotension. On formal autonomic testing, he was noted to have severely impaired sympathetic responses and marked orthostatic hypotension without appropriate chronotropic response. A decision to hold sorafenib was made, and treatment was started with graduated compression stockings, liberal fluid and sodium intake, and midodrine. The patient had a modest and gradual improvement in his symptoms. To our knowledge, this is the first reported case of orthostatic hypotension related to sorafenib or any vascular endothelial growth factor inhibitors.