Brain banking in the United States and Europe: Importance, challenges, and future trends.

In recent years, brain banks have become valuable resources for examining the molecular underpinnings of various neurological and psychological disorders including Alzheimer disease and Parkinson disease. However, the availability of brain tissue has significantly declined. Proper collection, preparation, and preservation of postmortem autopsy tissue are essential for optimal downstream brain tissue distribution and experimentation. Collaborations between brain banks through larger networks such as NeuroBioBank with centralized sample request mechanisms promote tissue distribution where brain donations are disproportionately lower. Collaborations between brain banking networks also help to standardize the brain donation and sample preparation processes, ensuring proper distribution and experimentation. Ethical brain donation and thorough processing enhances the responsible conduct of scientific studies. Education and outreach programs that foster collaboration between hospitals, nursing homes, neuropathologists, and other research scientists help to alleviate concerns among potential brain donors. Furthermore, ensuring that biorepositories accurately reflect the true demographics of communities will result in research data that reliably represent populations. Implementing these measures will grant scientists improved access to brain tissue, facilitating a deeper understanding of the neurological diseases that impact millions.

Two-stage reflective self-seeding scheme for high-repetition-rate X-ray free-electron lasers.

X-ray free-electron lasers (XFELs) open a new era of X-ray based research by generating extremely intense X-ray flashes. To further improve the spectrum brightness, a self-seeding FEL scheme has been developed and demonstrated experimentally. As the next step, new-generation FELs with high repetition rates are being designed, built and commissioned around the world. A high repetition rate would significantly speed up the scientific research; however, alongside this improvement comes new challenges surrounding thermal management of the self-seeding monochromator. In this paper, a new configuration for self-seeding FELs is proposed, operated under a high repetition rate which can strongly suppress the thermal effects on the monochromator and provides a narrow-bandwidth FEL pulse. Three-dimension time-dependent simulations have been performed to demonstrate this idea. With this proposed configuration, high-repetition-rate XFEL facilities are able to generate narrow-bandwidth X-ray pulses without obvious thermal concern on the monochromators.

Spinal anaesthesia with a micro-catheter in high-risk patients undergoing colorectal cancer and other major abdominal surgery.

Extended spinal anaesthesia using a spinal micro-catheter was used as a primary method of anaesthesia for elective colorectal cancer surgery in 68 high risk patients over a 14-year period in our institution. The technique was also useful in eight elective and 13 emergency abdominal surgeries. All patients suffered from severe chronic obstructive airway disease requiring multiple inhalers and drugs (ASA III). Thirty nine of these patients also suffered from angina, myocardial infarction, diabetes and other systemic diseases (ASA IV). Surgery included right hemicolectomy, left hemicolectomy, total colectomy, sigmoid colectomy, Hartman's resection, anterior resection of rectum, abdominoperineal resection, cholecystectomy (open and laparoscopic) and obstructed inguinal hernia requiring laparotomy. Spinal anaesthesia was performed under strict aseptic conditions with a 22 gauge spinal needle with a mixture consisting of 2.75ml of 0.5% heavy bupivacaine and 0.25ml of fentanyl (25microg). This was followed by placement of a spinal micro-catheter and the duration of anaesthesia was extended by intermittent injection of 0.5% isobaric bupivacaine. Brief hypotension occurred in 12.4% of patients during the establishment of anaesthetic block height to T6-7 and was duly treated with intravenous administration of fluid and ephedrine hydrochloride. Good anaesthesia resulted in all patients except for brief discomfort in some patients during hemicolectomy surgery possibly due to the dissection and traction on the peritoneum causing irritation to the diaphragm. The use of sedation was avoided. General anaesthesia was administered in one patient and this patient required postoperative ventilation and cardiovascular support in the Intensive Care Unit. The spinal micro-catheter was removed at the end of surgery. Postoperative pain relief was obtained by administering intravenous morphine through a patient controlled analgesia machine in the critical care ward area (High Dependency Unit). There was a low incidence of minor postoperative side effects such as nausea (14.6%), vomiting (7.9%), minor post dural puncture headache (5.6%) and pruritus (5.6%). We conclude that spinal anaesthesia with a micro-catheter may be used as a primary method of anaesthesia for colorectal cancer surgery and other major abdominal surgery in high-risk patients for whom general anaesthesia would be associated with higher morbidity and mortality.

Quality of clinical documentation and anticoagulation control in patients with chronic nonvalvular atrial fibrillation in routine medical care.

OBJECTIVE: Anticoagulation quality and record documentation were retrospectively assessed in patients with chronic nonvalvular atrial fibrillation (CNVAF) managed in a routine care setting. METHODS: Medical record data extraction from physician practices in 4 regions of the United States. RESULTS: Of 686 patients, 59% had an electrocardiogram confirming CNVAF, 84% listed at least 1 stroke risk factor, and 60% indicated the goal target international normalized ratio (INR). Two thirds of INRs>3.0 or <2.0 had no recorded dose change, nor did 45% of INRs>5.0. Vitamin K was given (3%) or anticoagulation was temporarily discontinued (9%) for INRs>5.0. The median interval of INR testing was 21 days, which decreased to 7 days for INRs> 4.60. Patients spent 58% of the time in therapeutic range. CONCLUSION: Serious deficiencies in quality and documentation of routine medical care of anticoagulation for patients with CNVAF continue to exist.

Cost-effectiveness of differing perioperative beta-blockade strategies in vascular surgery patients.

OBJECTIVES: To determine the incremental value of different strategies of both oral and intravenous beta-blockade during the perioperative period in high-risk vascular patients in reducing costs and improving outcomes. DESIGN: Decision analytic model incorporating costs from provider's perspective INTERVENTIONS: Five perioperative strategies in patients undergoing abdominal aortic aneurysm surgery: (1). no routine beta-blockade, (2). preoperative oral bisoprolol for 7 days followed by perioperative intravenous metoprolol and oral bisoprolol based on preoperative titration, (3). immediate preoperative atenolol with postoperative intravenous then oral atenolol, (4). intraoperative esmolol and postoperative intravenous then oral atenolol, and (5). intraoperative and 18 hours of postoperative esmolol then atenolol. MEASUREMENTS AND MAIN RESULTS: Perioperative death was associated with a net increase of US dollars 21909 in charges to Medicare, whereas sustaining a perioperative myocardial infarction was associated with a net increase in charges of US dollars 15000. There is a net hospital saving of US dollars 500 using a strategy of titration of an oral beta-blocker medication for a minimum of 7 days, with a net increase in efficacy of 0.0304. All of the strategies involving acute perioperative blockade were associated with a net cost savings and increase in efficacy, although less than the strategy involving preoperative oral titration. CONCLUSION: Perioperative beta-blockade is both cost effective as well as efficacious from a short-term provider perspective. The optimal strategy of treatment for patients who do not present to surgery already on beta-blockers requires further study, although all strategies save money even accounting for pharmaceutical costs.

Altering substrate specificity of phosphatidylcholine-preferring phospholipase C of Bacillus cereus by random mutagenesis of the headgroup binding site.

PLC(Bc) is a 28.5 kDa monomeric enzyme that catalyzes the hydrolysis of the phosphodiester bond of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine to provide a diacylglycerol and the corresponding phosphorylated headgroup. Because single replacements of Glu4, Tyr56, and Phe66 in the headgroup binding pocket led to changes in substrate specificity [Martin et al. (2000) Biochemistry 39, 3410-3415], a combinatorial library of approximately 6000 maltose binding protein-PLC(Bc) fusion protein mutants containing random permutations of these three residues was generated to identify PLC(Bc) mutants with altered specificity profiles and high catalytic activities. Members of this library were screened for hydrolytic activity toward the water soluble substrates C6PC, C6PE, and C6PS using a novel protocol that was conducted in a 96-well format and featured the in situ cleavage of the fusion protein to release the mutant PLC(Bc)s. Ten mutant enzymes that exhibited significant preferences toward C6PE or C6PS were selected and analyzed by steady-state kinetics to determine their specificity constants, k(cat)/K(M). The C6PS selective clones E4G, E4Q/Y56T/F66Y, and E4K/Y56V exhibited higher specificity constants toward C6PS than wt, whereas Y56T, F66Y, and Y56T/F66Y were C6PE selective and had comparable or higher specificity constants than wt for C6PE. The corresponding wt residues were singly reinserted back into the E4Q/Y56T/F66Y and E4K/Y56V mutants via site-directed mutagenesis, and the E4Q/F66Y mutant thus obtained exhibited a 10-fold higher specificity constant toward C6PS than wt, a value significantly higher than other PLC(Bc) mutants. On the basis of available data, an aromatic residue at position 66 appears important for significant catalytic activity toward all three substrates, especially C6PC and C6PE. The charge of residue 4 also appears to be a determinant of enzyme specificity as a negatively charged residue at this position endows the enzyme with C6PC and C6PE preference, whereas a polar neutral or positively charged residue results in C6PS selectivity. Replacing Tyr56 with Val, Ala, Thr, or Ser greatly reduces activity toward C6PC. Thus, the substrate specificity of PLC(Bc) can be modulated by varying three of the amino acid residues that constitute the headgroup binding pocket, and it is now apparent that this enzyme is not evolutionarily optimized to hydrolyze phospholipids with ethanolamine or serine headgroups.