Thrombomodulin Regulates Keratinocyte Differentiation and Promotes Wound Healing

The membrane glycoprotein thrombomodulin (TM) has been implicated in keratinocyte differentiation and wound healing, but its specific function remains undetermined. The epidermis-specific TM knockout mice were generated to investigate the function of TM in these biological processes. Primary cultured keratinocytes obtained from TMlox/lox; K5-Cre mice, in which TM expression was abrogated, underwent abnormal differentiation in response to calcium induction. Poor epidermal differentiation, as evidenced by downregulation of the terminal differentiation markers loricrin and filaggrin, was observed in TMlox/lox; K5-Cre mice. Silencing TM expression in human epithelial cells impaired calcium-induced extracellular signal–regulated kinase pathway activation and subsequent keratinocyte differentiation. Compared with wild-type mice, the cell spreading area and wound closure rate were lower in keratinocytes from TMlox/lox; K5-Cre mice. In addition, the lower density of neovascularization and smaller area of hyperproliferative epithelium contributed to slower wound healing in TMlox/lox; K5-Cre mice than in wild-type mice. Local administration of recombinant TM (rTM) accelerated healing rates in the TM-null skin. These data suggest that TM has a critical role in skin differentiation and wound healing. Furthermore, rTM may hold therapeutic potential for the treatment of nonhealing chronic wounds

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

EGFR inhibitors as the first-line systemic treatment for advanced non-small-cell lung cancer

Drugs that target the EGFR have a major impact on the treatment of advanced non-small-cell lung cancer (NSCLC). EGFR mutations in NSCLC are associated with a dramatic and sustained response to EGFR tyrosine kinase inhibitors (TKIs). This review summarizes the results of randomized trials using EGFR TKIs or EGFR monoclonal antibodies with chemotherapy in the first-line setting, and discusses several unresolved issues regarding the use of the EGFR TKIs as the first-line therapy in advanced NSCLC

Chlorhexidine for the prevention of bloodstream infection associated with totally implantable venous ports in patients with solid cancers

Purpose To evaluate the preventive effects of topical skin disinfection with chlorhexidine on bloodstream infection (BSI) associated with totally implantable venous port (Port-A). ;Methods Two consecutive cohorts of solid cancer patients were prospectively followed for the occurrence of Port-A associated BSI (PABSI). The first cohort used povidone-iodine as topical skin disinfection and the second cohort used chlorhexidine. The primary endpoint was the time to first PABSI. Propensity score analysis was applied. The preventive effects of chlorhexidine were analyzed by Cox proportional hazards models. ;Results There were 396 patients (81,752 catheter-days) in the iodine cohort and 497 (99,977 catheter-days) in the chlorhexidine cohort. Gram-negative bacteria were the most common pathogens to cause first episode of PABSI (iodine cohort (I) vs chlorhexidine cohort (C) and 0.404 vs 0.450 per 1,000 catheter-day), followed by Gram-positive bacteria (I vs C and 0.269 vs 0.110 per 1,000 catheter-day), and fungi (I vs C and 0.098 vs 0.070 per 1,000 catheter-day). Three hundred forty-three patients were selected from each cohort by propensity score match analysis. Chlorhexidine use was associated with a significant improvement on time to first PABSI caused by Gram-positive bacteria (log-rank test, p =0.00175; HR= 0.35, 95 % CI, 0.14-0.85, p = 0.02). No significant preventive effects of chlorhexidine on time to first PABSI caused by Gram-negative bacteria or fungi was found. ;Conclusions Chlorhexidine topical skin disinfection may prevent PABSI caused by Gram-positive bacteria in patients with solid cancers. The nonsignificant effect on preventing overall PABSI may be attributed to the high incidence of Gram-negative bacteria related PABSI

High Skin Sympathetic Nerve Activity in Patients with Recurrent Syncope

(1) Background: The autonomic imbalance plays a role in vasovagal syncope (VVS) diagnosed by head-up tilting test (HUT). neuECG is a new method of recording skin electrical signals to simultaneously analyze skin sympathetic nerve activity (SKNA) and electrocardiogram. We hypothesize that SKNA is higher in subjects with tilt-positive than tilt-negative and the SKNA surges before syncope. (2) Methods: We recorded neuECG in 41 subjects who received HUT (according to the “Italian protocol”), including rest, tilt-up, provocation and recovery phases. Data were analyzed to determine the average SKNA (aSKNA, μV) per digitized sample. Electrocardiogram was used to calculate standard deviation of normal-to-normal beat intervals (SDNN). The “SKNA-SDNN index” was calculated by rest aSKNA multiplied by the ratio of tilt-up to rest SDNN. (3) Results: 16 of 41 (39%) subjects developed syncope. The aSKNA at rest phase is significantly higher in the tilt-positive (1.21 ± 0.27 µV) than tilt-negative subjects (1.02 ± 0.29 µV) (p = 0.034). There are significant surges and withdraw of aSKNA 30 s before and after syncope (both p ≤ 0.006). SKNA-SDNN index is able to predict syncope (p < 0.001). (4) Conclusion: Higher SKNA at rest phase is associated with positive HUT. The SKNA-SDNN index is a novel marker to predict syncope during HUT