Inhibition of ␤-site APP cleaving enzyme 1 (BACE1) is being pursued as a therapeutic target for treating patients with Alzheimer's disease because BACE1 is the sole ␤-secretase for generating ␤-amyloid peptide. Knowledge regarding the other cellular functions of BACE1 is therefore critical for the safe use of BACE1 inhibitors in human patients. BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination in injured sciatic nerves. Since BACE1 is expected to be ubiquitously expressed, we asked whether axonal or Schwann cell BACE1 is required for optimal remyelination. By swapping sciatic nerve segments from BACE1-null mice with the corresponding wild-type nerve segments or vice versa, we tested how a deficiency of BACE1 in Schwann cells or axons affects remyelination. Our results show that BACE1 in axons and Schwann cells is similarly important for remyelination of regenerated axons. Nerve injury induces BACE1 transcription and protein levels are elevated in Schwann cells. Expression of type I neuregulin 1 (Nrg1), rather than type III Nrg1, was induced by Schwann cells, and the abolished Nrg1 cleavage in BACE1-null Schwann cells contributed to decreased remyelination of regenerated axons. Hence, this study is the first to demonstrate the equal importance of axonal and Schwann cell BACE1 for remyelination of injured nerves.

Background. During cold storage, some red blood cell (RBC) units age more rapidly than others. Yet, the Food and Drug Administration has set a uniform storage limit of 42 days. Objectives of this review are to present evidence for an RBC storage lesion and suggest that functional measures of stored RBC quality-which we call real age-may be more appropriate than calendar age. Methods. During RBC storage, biochemical substances and byproducts accumulate and RBC shape alters. Factors that influence the rate of degradation include donor characteristics, bio-preservation conditions, and vesiculation. Better understanding of markers of RBC quality may lead to standardized, quantifiable, and operationally practical measures to improve donor selection, assess quality of an RBC unit, improve storage conditions, and test efficacy of the transfused product. Results. The conundrum is that clinical trials of younger versus older RBC units have not aligned with in vitro aging data; that is, the units transfused were not old enough. In vitro changes are considerable beyond 28 to 35 days, and average storage age for older transfused units was 14 to 21 days. Conclusions. RBC product real age varies by donor characteristics, storage conditions, and biological changes during storage. Metrics to measure temporal changes in quality of the stored RBC product may be more appropriate than the 42-day expiration date. Randomized trials and observational studies are focused on average effect, but, in the evolving age of precision medicine, we must acknowledge that vulnerable populations and individuals may be harmed by aging blood.

In this retrospective study, the authors found that ITB therapy is effective in reducing spasticity and related symptoms in ambulatory patients with MS. Because the use of ITB therapy is increasing in ambulatory patients with MS, randomized, prospective studies are important to help provide a more useful characterization of the effects of ITB therapy on ambulation.

Acute aortic dissection is one of the most lethal cardiovascular disease. The major histopathological feature of AAD is medial degradation, especially breakdown of elastin and collagen. However, the underlying mechanism remains a mystery. Platelets expressed CD40 Ligand (CD40L) is recently recognised as a key effector of cardiovascular disease development through its pro-inflammatory effect. To clarify the role of CD40L in AAD, we examined level of CD40L in human blood serum samples and found that it is significantly higher in AAD patients compared with healthy subjects (26.8±5.52 ng/mL versus 13.4±4.00 ng/mL). To further investigate if CD40L is involve in the development of AAD, we applied β-aminopropionitrile (BAPN) induced mouse model of AAD. Consistent with the human data, circulating CD40L in AAD mice much higher than normal mice (148.40±75.96 pg/mL versus 44.09±19.65 pg/mL). Meanwhile, multiple pro-inflammatory chemokines significantly increased in AAD mice. Importantly, the CD40L-/- mice treated with BAPN did not develop these phenotypes. Lastly, we confirmed that endothelial cells migration was significantly inhibited by CD40L, suggesting impaired recovery from intimal injury. In summary, we found that CD40L promoted AAD development through its pro-inflammatory effects and inhibition of endothelial cell function.

Cardiac surgical patients are often anemic. Demographic characteristics, comorbidities, and outcomes are dissimilar according to red cell size. Patients with microcytic anemia had the lowest hemoglobin levels, yet the best clinical outcomes among anemic patients. MCV from the standard complete blood count adds additional information beyond hemoglobin for targeted intervention.

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Ulcer perforation in the excluded stomach and duodenum is a rare complication after Roux-en-Y gastric bypass (RYGB). Pathogenesis of these ulcers are multifactorial. We report a case of perforated gastric remnant ulcer in a 54-year-old woman who had undergone a laparoscopic RYGB 5 years previously. The perforation was successfully repaired with an omental patch. We also present a review of the literature of similar cases.

Many adult patients with congenital ventricular septal defect (VSD) also developed ascending aortic dilation, but few report the clinical features and surgical management of these patients. This study was designed to study ascending aortic dilation in adult patients with congenital VSD, and summarized the treatment experience and prognosis.To assess the clinical features and surgical management, we performed a retrospective analysis on preoperative data, intraoperative data, and postoperative data from the adult patients with congenital VSD who developed ascending aortic dilation in our institution from February 2010 to December 2016.From February 2010 to December 2016, we operated on 13 adult patients (12 males, 92.31%) with VSD who developed ascending aortic dilation. Median age was 37 (interquartile range 14) years. All patients suffered from perimembranous VSD and received surgical treatment. Their symptoms were all improved after surgery, no deaths occurred.Surgery is feasible for the ascending aortic dilation in adult patients with congenital VSD. Both proper perioperative treatment and close monitoring are required for the successful surgery.