Prenatal exposure to diagnostic ultrasound impacts blood-brain barrier permeability in rats

The central nervous system vasculature consists of a tightly sealed endothelium that forms the blood-brain barrier (BBB); these blood vessels are impermeable to large-molecular-size agents. The aim of this study was to determine the influence of prenatal ultrasound exposure on blood-brain barrier (BBB) integrity as measured by the permeation of Evans blue (EB) through the BBB during the postnatal development of the rat. Diagnostic levels of ultrasound (2.89 MHz, mechanical index = 1.1, acoustic output power = 70.5 mW) for 1 h and 2 h per day, for 9 consecutive days were used on Sprague-Dawley rats. Offspring were assessed postnatally on days 10, 17, 24 and 38. Our analysis of over 139 animals reveals that, when exposed to diagnostic levels of ultrasound during embryonic development, a statistically significant amount of EB extravasation into the cerebrum and cerebellum could be detected on postnatal day 10 but not later. In addition, small changes in pup body weight, cerebrum weight and cerebellum weight were observed after relatively prolonged ultrasound exposure on all postnatal days. Taken together, these results emphasize the need for further investigation of the effects of ultrasound exposure during the potentially vulnerable period of intense BBB development in the human fetus.     

The aging heart, myocardial fibrosis, and its relationship to circulating C-type natriuretic Peptide

Myocardial aging is characterized by left ventricular (LV) fibrosis leading to diastolic and systolic dysfunction. Studies have established the potent antifibrotic and antiproliferative properties of C-type natriuretic peptide (CNP); however, the relationship between circulating CNP, LV fibrosis, and associated changes in LV function with natural aging are undefined. Accordingly, we characterized the relationship of plasma CNP with LV fibrosis and function in 2-, 11-, and 20-month-old male Fischer rats. Further in vitro, we established the antiproliferative actions of CNP and the participation of the clearance receptor using adult human cardiac fibroblasts. Here we establish for the first time that a progressive decline in circulating CNP characterizes natural aging and is strongly associated with a reciprocal increase in LV fibrosis that precedes impairment of diastolic and systolic function. Additionally, we demonstrate in cultured adult human cardiac fibroblasts that the direct antiproliferative actions of high-dose CNP may involve a non-cGMP pathway via the clearance receptor. Together, these studies provide new insights into myocardial aging and the relationship to the antifibrotic and antiproliferative peptide CNP.     

Primary surveillance of spotted fever group antibodies on rats in the Kinmen area

The positive rate of rickettsial antibodies of 107 rats in the Kinmen area by indirect immunofluorescent antibody (IFA) technique was 0% (0/107) in typhus fever, 38.3% (41/107) in scrub typhus and 66.4% (71/107) in spotted fever group; the positive rate (42.9%) of spotted fever group of 21 rats in Taiwan island also higher than scrub typhus (19.0). It suggests that spotted fever group patients may be present in our country but have not been discovered.     

Epigallocatechin gallate sensitizes cisplatin‐resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling

Epigallocatechin gallate (EGCG) is a green tea polyphenol that presents anticancer activities in multiple cancer cells, but no available report was addressed for the underling molecular mechanism of cytotoxic impacts on drug‐resistant oral squamous cell carcinoma cells. In the present study, the inhibitory effects of EGCG were experienced on cisplatin‐resistant oral cancer CAR cells. EGCG inhibited cell viability in a time‐ and concentration‐dependent manner by a sulforhodamine B (SRB) assay. EGCG induced CAR cell apoptosis and autophagy by 4′,6‐diamidino‐2‐phenylindole (DAPI) dye, acridine orange (AO) staining and green fluorescent protein (GFP)‐tagged LC3B assay, respectively. EGCG also significantly enhanced caspase‐9 and caspase‐3 activities by caspase activity assay. EGCG markedly increased the protein levels of Bax, cleaved caspase‐9, cleaved caspase‐3, Atg5, Atg7, Atg12, Beclin‐1, and LC3B‐II, as well as significantly decreased the expression of Bcl‐2, phosphorylated AKT (Ser473) and phosphorylation of STAT3 on Tyr705 by western blotting in CAR cells. Importantly, the protein and gene expression of multidrug resistance 1 (MDR1) were dose‐dependently inhibited by EGCG. Overall, downregulation of MDR1 levels and alterations of AKT/STAT3 signaling contributed to EGCG‐induced apoptosis and autophagy in CAR cells. Based on these results, EGCG has the potential for therapeutic effect on oral cancer and may be useful for long‐term oral cancer prevention in the future. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 845–855, 2017.     

B-type natriuretic peptide: beyond a diagnostic

The concept of the heart as an endocrine organ has been attractive since the discovery of atrial natriuretic peptide. This review focuses on the second discovered natriuretic peptide from the heart - B-type natriuretic peptide (BNP), widely used as a tool in the diagnosis of heart failure (HF). Controversy remains regarding its use as a therapeutic agent in HF. This article places into perspective some of the debate and provides insights into the therapeutics of BNP and the importance of its second messenger 3'5' cyclic guanosine monophosphate, which also is the second messenger for nitric oxide and is modulated by renal phosphodiesterases.     

Predicting outcomes after trauma: Prognostic model development based on admission features through machine learning

In an overcrowded emergency department (ED), trauma surgeons and emergency physicians need an accurate prognostic predictor for critical decision-making involving patients with severe trauma. We aimed to develope a machine learning-based early prognostic model based on admission features and initial ED management.We only recruited patients with severe trauma (defined as an injury severity score >15) as the study cohort and excluded children (defined as patients <16 years old) from a 4-years database (Chi-Mei Medical Center, from January 2015, to December 2018) recording the clinical features of all admitted trauma patients. We considered only patient features that could be determined within the first 2 hours after arrival to the ED. These variables included Glasgow Coma Scale (GCS) score; heart rate; respiratory rate; mean arterial pressure (MAP); prehospital cardiac arrest; abbreviated injury scales (AIS) of head and neck, thorax, and abdomen; and ED interventions (tracheal intubation/tracheostomy, blood product transfusion, thoracostomy, and cardiopulmonary resuscitation). The endpoint for prognostic analyses was mortality within 7 days of admission.We divided the study cohort into the early death group (149 patients who died within 7 days of admission) and non-early death group (2083 patients who survived at >7 days of admission). The extreme Gradient Boosting (XGBoost) machine learning model provided mortality prediction with higher accuracy (94.0%), higher sensitivity (98.0%), moderate specificity (54.8%), higher positive predict value (PPV) (95.4%), and moderate negative predictive value (NPV) (74.2%).We developed a machine learning-based prognostic model that showed high accuracy, high sensitivity, and high PPV for predicting the mortality of patients with severe trauma.