Serum total cholesterol level as a potential predictive biomarker for neurological outcomes in cardiac arrest survivors who underwent target temperature management

Cholesterol is an essential substance to maintain cell membranes. Low levels of total cholesterol (TC) are associated with poor prognosis in critically ill patients. Cardiac arrest-induced whole-body ischemia and reperfusion injury cause a sepsis-like syndrome. The Cholesterol level in post-cardiac arrest patients may indicate the degree of endotoxemia or inflammation caused by ischemic and reperfusion injury. We aimed to investigate the association of TC levels with neurologic outcome of out-of-hospital cardiac arrest (OHCA) survivors who underwent target temperature management (TTM). This was a retrospective single-center observational study from May 2018 to April 2021 on a cohort of 106 patients. TC levels were determined in samples obtained immediately and at 24, 48, and 72 hours after the return of spontaneous circulation (ROSC). The primary outcome was poor neurologic outcome at 3 months after ROSC. Poor neurologic outcome was defined by cerebral performance categories 3 to 5. Sixty patients had a poor neurologic outcome. TC levels were significantly lower in the poor neurologic outcome group at each time point. The TC levels for predicting poor neurologic outcome had a sensitivity of 80.8%, with 67.6% specificity at 48 hours (TC₄₈) after ROSC. The areas under the curve value of TC₄₈ was 0.771 (0.670–0.853), with a cutoff value of 114 mg/dL. TC level at 48 hours after ROSC was a helpful marker for the 3-month poor neurologic outcome. This might be an easily accessible predictive marker of neurologic outcome in OHCA survivors treated with TTM.     

Association between Temporal Muscle Thickness and Overall Survival in Non-Small Cell Lung Cancer Patients with Brain Metastasis

Temporal muscle thickness (TMT) has recently been suggested as a novel biomarker of sarcopenia in head and neck malignancies. However, few studies have evaluated TMT as a prognostic marker in patients with brain metastasis. This study investigated the association of TMT with overall survival (OS) in non-small cell lung cancer (NSCLC) patients with brain metastasis. The records of all NSCLC patients with brain metastasis between 2009 and 2018 at St. Vincent’s Hospital were reviewed retrospectively. A total of 221 patients met our eligibility criteria. In the group with TMT thicker than the median, OS was longer than the group with TMT thinner than the median (240 days versus 139 days, p = 0.014). In multivariate analysis, the thicker TMT group had longer survival (HR 0.73 CI 0.56–0.96, p = 0.024). Male (HR 1.58 CI 1.19–2.09, p = 0.002) and older age (≥65 years) (HR 2.05 CI 1.53–2.74, p < 0.001) also showed statistical significance. We also performed subgroup analysis in older patients (≥65 years). In this subgroup of 107 patients, the thicker TMT group also showed longer OS than the thinner TMT group (209 days versus 82 days, p = 0.009). Our findings suggest that TMT can be a useful biomarker for OS in NSCLC patients with brain metastasis.     

The Role of Systemic Therapy in Resectable Colorectal Liver Metastases: Systematic Review and Network Meta-Analysis

BackgroundDespite multiple randomized trials, the role of perioperative chemotherapy in colorectal cancer liver metastasis (CRLM) is still under debate. In this systematic review and network meta-analysis (NMA), we aim to evaluate the efficacy of perioperative systemic therapies for patients with CRLM.MethodsWe searched various databases for abstracts and full-text articles published from database inception through May 2021.We included randomized controlled trials (RCTs) comparing the addition of perioperative (post, pre, or both) systemic therapies to surgery alone in patients with CRLM. The outcomes were compared according to the chemotherapy regimen using a random effects model. Outcomes of interest included disease-free survival (DFS) and overall survival (OS).ResultsSeven RCTs with a total of 1504 patients with CRLM were included. Six studies included post-operative treatment and one evaluated perioperative (pre- and postoperative) therapy. Fluoropyrimidine-based chemotherapy was the most used systemic therapy. NMA showed benefit of adding perioperative therapy to surgery in terms of DFS (HR 0.73, 95% CI 0.63 to 0.84). However, these findings did not translate into a statistically significant OS benefit (HR 0.88, 95% CI 0.74 to 1.05). NMA did not show any advantage of one regimen over another including oxaliplatin or irinotecan.ConclusionsThis systematic review and NMA of 7 RCTs found that the addition of perioperative systemic treatment for resectable CRLM could improve disease-free survival but not overall survival. Based on the findings, addition of perioperative treatment in resectable CRLM should be individualized weighing the risks and benefits.

The role of perioperative chemotherapy in colorectal cancer liver metastasis is unclear. This review evaluates the efficacy of perioperative systemic therapies for patients with colorectal cancer liver metastasis.

Implications for PracticeThe role of adding systemic therapy to surgery in patients with resectable colorectal liver metastases is unclear. In this network meta-analysis of 7 trials, we found that the addition of systemic therapy improves disease-free survival but not overall survival. Therefore, chemotherapy should not be uniformly recommended in this setting.     

Opto-ultrasound biosensor for wearable and mobile devices: realization with a transparent ultrasound transducer

Mobile and wearable healthcare electronics are widely used for measuring bio-signals using various fusion sensors that employ photoplethysmograms, cameras, microphones, ultrasound (US) sensors, and accelerometers. However, the consumer demand for small form factors has significantly increased as the integration of multiple sensors is difficult in small mobile or wearable devices. This study proposes two novel opto-US sensors, namely (1) a wearable photoplethysmography (PPG)-US device and (2) a PPG sensor built-in mobile smartphone with a US sensor, seamlessly integrated using a transparent ultrasound transducer (TUT). The TUT exhibits a center frequency of 6 MHz with a 50% bandwidth and 82% optical transparency in visible and near-infrared regions. We developed an integrated wearable PPG-US device to demonstrate its feasibility and coupled the TUT sensor with a smartphone. We measured the heart rates optically and acoustically in human subjects and quantified the oxygen saturation optically by passing light through the TUT. The proposed proof-of-concept is a novel sensor fusion for mobile and wearable devices that require a small form factor and aim to improve digital healthcare. The results of this study can form the basis for innovative developments in sensor-based high-tech industrial applications, such as automobiles, robots, and drones, in addition to healthcare applications.     

pH-Dependent Photophysical Properties of Metallic Phase MoSe2 Quantum Dots

Fluorescence properties of quantum dots (QDs) are critically affected by their redox states, which is important for practical applications. In this study, we investigated the optical properties of MoSe₂-metallic phase quantum-dots (MoSe₂-mQDs) depending on the pH variation, in which the MoSe₂-mQDs were dispersed in water with two sizes (Φ~3 nm and 12 nm). The larger MoSe₂-mQDs exhibited a large red-shift and broadening of photoluminescence (PL) peak with a constant UV absorption spectra as varying the pH, while the smaller ones showed a small red-shift and peak broadening, but discrete absorption bands in the acidic solution. The excitation wavelength-dependent photoluminescence shows that the PL properties of smaller MoSe₂-mQDs are more sensitive to the pH change compared to those of larger ones. From the time-resolved PL spectroscopy, the excitons dominantly decaying with an energy of ~3 eV in pH 2 clearly show the shift of PL peak to the lower energy (~2.6 eV) as the pH increases to 7 and 11 in the smaller MoSe₂-mQDs. On the other hand, in the larger MoSe₂-mQDs, the exciton decay is less sensitive to the redox states compared to those of the smaller ones. This result shows that the pH variation is more critical to the change of photophysical properties than the size effect in MoSe₂-mQDs.     

Catechin-7-O-α-L-rhamnopyranoside can reduce α-MSH-induced melanogenesis in B16F10 melanoma cells through competitive inhibition of tyrosinase

Although melanogenesis is a defense mechanism against ultraviolet (UV)-induced skin damage, abnormally excessive melanin production causes pigmentation disorders. Tyrosinase, as a key factor for melanin synthesis, plays an important role in inducing skin pigmentation. Therefore, the inhibition of tyrosinase is crucial in preventing skin pigmentation in the cosmetics and medicine fields. However, the majority of well-known tyrosinase inhibitors have been discontinued due to toxic effects on the skin or lack of selectivity and/or stability. In this study, we evaluated possible anti-melanogenic effects of catechin-7-O-α-L-rhamnopyranoside (C7R) isolated from the stem bark of Ulmus parvifolia, to discover a new tyrosinase inhibitor that has both safety and stability. When C7R was pretreated in B16F10 melanoma cells stimulated by α-melanocyte-stimulating hormone, this compound reduced melanin accumulation and murine tyrosinase activity. In line with these results, C7R inhibits tyrosinase purified from a mushroom in vitro like kojic acid and arbutin. Furthermore, C7R exhibited a competitive inhibition on a Lineweaver-Burk plot. Next, the underlying mechanisms of the C7R-mediated tyrosinase inhibitory effect were sought through docking simulation and pharmacophore analysis between tyrosinase residues and C7R. The results of these analyses showed that C7R had binding energy of -14.5kcal/mol, and indicated that C7R interacts with tyrosinase through an aromatic ring and various hydrophobic and hydrogen bonds. Together, our results suggest that C7R can be applied as a novel natural anti-melanogenic agent that inhibits tyrosinase.     

Antiangiogenic activity of lupeol from Bombax ceiba

In the search for antiangiogenic agents from medicinal plants used in Vietnam, a methanol extract of the stem barks of Bombax ceiba was found to exhibit a significant antiangiogenic activity on in vitro tube formation of human umbilical venous endothelial cells (HUVEC). Bioactivity-guided fractionation and isolation carried out on this extract afforded lupeol as an active principle. At 50 and 30 microg/mL lupeol showed a marked inhibitory activity on HUVEC tube formation while it did not affect the growth of tumor cell lines such as SK-MEL-2, A549, and B16-F10 melanoma.     

SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.