Effects of Audio Brain Entrainment on Korean People with Mild Insomnia.

Sleep health has become an important healthy lifestyle. Research has shown that almost one-fifth of the Korean adult population does not have sufficient sleep. The lack of sleep is associated with significant medical, psychological, social, and economic issues. People are not only yearning for sufficient sleep but the quality of sleep as well. Usually, the obvious choice will be the use of pharmaceuticals however, these often have various side effects, and the lasting use of these medications could become a concern. Therefore, new non-drug alternatives are sought after. Audio brain entrainment is a procedure that modules neural activities by synchronizing brainwave frequency with pulse tones. By producing frequency tones for the deep sleep stage, it promotes a good night's sleep. In this paper, we developed a pillow integrated with the audio speakers that produce alpha and theta beats that should help improve sleep. Sleep polysomnography was performed on 10 people to compare the effects of the audio stimulus. Initial results showed a positive effect on sleep onset latency, indicating that sleep induction happened. This noninvasive stimulation technique can be a promising candidate for wearable bioelectronics medicine and further neuroscience research.

pSlugS158 immunohistochemistry is a novel promising mitotic marker for FFPE samples: a pilot study.

Slug is a transcription factor belonging to the slug/snail superfamily. The protein is involved in embryonic development and epithelial-mesenchymal transition of tumors. Slug is also under temporal regulation during cell cycle. Here, we examined relationship between pSlugS158 (site-specific phosphorylation) and the cell cycle, and checked whether its phosphorylation level reflects mitotic activity in tissue specimens. Cell cycle analysis was performed after cell synchronization. To evaluate pSlugS158 identifying mitotic figures, we performed immunohistochemistry (IHC) for pSlugS158 in various formalin-fixed paraffin-embedded tissues; in addition, mitotic counts were compared with those in sections stained with hematoxylin and eosin (HE) and IHC for PHH3, a mitotic marker. We found that the level of pSlugS158 protein increased specifically at M phase and decreased at the G1/S phases in vitro. In almost all tested tissues, nuclear stain of pSlugS158 was identified in the cell with mitotic figures. There was no significant difference in mitotic counts between HE- and pSlugS158-stained sections. In conclusion, pSlugS158 may be a novel and practical immunohistochemical marker for detecting mitotic figures in human tissues.

Analysis of EGFR mutation status in malignant pleural effusion and plasma from patients with advanced lung adenocarcinoma.

Background: Cell-free DNA (cfDNA) is emerging as a surrogate sample type for mutation analyses. We investigated the suitability of malignant pleural effusion (MPE) and plasma as a biomaterial for analyzing epidermal growth factor receptor (EGFR) mutation by peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve (PANAMutyper™) analysis. Methods: Matched tissue, MPE cell block (MPE-CB), MPE supernatant, and plasma samples were collected from patients with advanced lung adenocarcinoma who had a MPE at the time of diagnosis. EGFR mutation was assessed by PANAMutyper™. Results: Mutation analyses in matched tumor tissues, MPE-CB, MPE supernatant, and/or plasma samples were available for 67 patients. In comparison with tumor tissue and MPE-CB, MPE supernatant exhibited 84.4% sensitivity, 97.1% specificity, 96.4% positive predictive value (PPV), and 87.2% negative predictive value (NPV). In the same comparison, plasma exhibited 70.6% sensitivity, 100.0% specificity, 100.0% PPV, and 73.7% NPV. When sorted by mutation type, MPE supernatant had better sensitivity than plasma for the detection of two major EGFR mutations: 93.8% vs. 75.0% for exon 19 deletion and 73.3% vs. 60.0% for L858R. Conclusions: In this cohort of patients with MPEs, MPE supernatant demonstrated superior diagnostic performance compared with plasma using a PNA-based real-time PCR method.

Characteristics of Renal Cell Carcinoma Harboring TPM3-ALK Fusion.

The World Health Organization 2016 edition assigned anaplastic lymphoma kinase (ALK) rearrangement-associated renal cell carcinoma (ALK-RCC) as an emerging renal tumor entity. Identifying ALK-RCC is important because ALK inhibitors have been shown to be effective in treatment. Here, we report the case of a 14-year-old young man with ALK-RCC. Computed tomography revealed a well-demarcated 5.3-cm enhancing mass at the upper pole of the left kidney. There was no further history or symptoms of the sickle-cell trait. The patient underwent left radical nephrectomy. Pathologically, the mass was diagnosed as an unclassified RCC. Targeted next-generation sequencing identified a TPM3-ALK fusion gene. The present report and literature review demonstrate that TPM3-ALK RCC may be associated with distinct clinicopathological features. Microscopically, the tumors showed diffuse growth and tubulocystic changes with inflammatory cell infiltration. Tumor cells were dis-cohesive and epithelioid with abundant eosinophilic cytoplasm and cytoplasmic vacuoles. If morphological features and TFE3 expression are present in adolescent and young patients, molecular tests for ALK translocation should be performed. This awareness is critically important, because ALK rearrangement confers sensitivity to ALK inhibitors.

Therapeutic Effect of pHLIP-mediated CEACAM6 Gene Silencing in Lung Adenocarcinoma.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays an important role in lung cancer progression. Here, we examined the therapeutic efficacy of CEACAM6 gene silencing using an siRNA delivery platform targeting the acidic tumour microenvironment in a lung adenocarcinoma xenograft mouse model. An siRNA delivery vector was constructed by tethering the peptide nucleic acid form of an siRNA targeting CEACAM6 (siCEACAM6) to a peptide with a low pH-induced transmembrane structure (pHLIP) to transport siRNAs across the plasma membrane. Specific binding of the pHLIP-siCEACAM6 conjugate to A549 lung adenocarcinoma cells at low pH was demonstrated by flow cytometry. A549 cells incubated with pHLIP-siCEACAM6 at an acidic pH showed downregulated expression of endogenous CEACAM6 protein and reduced cell viability. The in vivo tumour-suppressing effects of pHLIP-siCEACAM6 in lung adenocarcinoma were assessed in a xenograft model generated by injecting BALB/c nude mice with A549 cells. pHLIP-siCEACAM6 treatment alone resulted in tumour growth inhibition of up to 35.5%. When combined with cisplatin treatment, pHLIP-siCEACAM6 markedly enhanced tumour growth inhibition by up to 47%. In conclusion, the delivery of siCEACAM6 to lung adenocarcinoma using the pHLIP peptide has therapeutic potential as a unique cancer treatment approach.

Diagnostic benefits of the combined use of liquid-based cytology, cell block, and carcinoembryonic antigen immunocytochemistry in malignant pleural effusion.

BACKGROUND: Malignant pleural effusion (MPE) is a common complication of cancer cell metastasis to the pleura. Discrimination between MPE and benign pleural effusion is necessary to design treatment strategies. Cytology is important for the diagnosis of MPE. Carcinoembryonic antigen (CEA) is an epithelial biomarker with a strong staining pattern in adenocarcinomas. Here, the diagnostic performances of liquid-based cytology (LBC), cell block (CB) preparation, and CEA immunostaining for the detection of malignancy in effusion cytology were compared in a large case series. METHODS: In a single institution, 1,014 cytology samples from 862 patients were retrospectively collected and reviewed between January 2013 and November 2015. Ethanol-fixed, paraffin embedded CB of pleural effusions was analyzed by CEA immunostaining. Diagnostic values were compared among LBC, CB, CEA immunostaining, and the combination of two methods. RESULTS: The sensitivity and specificity of the CB preparation were 94.3% and 98.7%, respectively, compared with 81.3% and 99.4% for LBC preparations, respectively. Combination of LBC and CB increased sensitivity by 98.3%. Although the accuracy of CEA staining itself was moderate (sensitivity, 89.8%), the combined use of CB and CEA tumor marker increased the detection rate of malignancy (sensitivity, 100%; specificity, 100%), compared with that of cytology (LBC or CB) alone. CONCLUSIONS: The sensitivity and specificity for the diagnosis of MPE could be improved by integrating the CB and CEA staining into LBC in routine clinical practice to improve diagnostic accuracy.