Elevated abeta42 in skeletal muscle of Alzheimer disease patients suggests peripheral alterations of AbetaPP metabolism

The levels of amyloid-beta40 (Abeta40) and Abeta42 peptides were quantified in temporalis muscles and brain of neuropathologically diagnosed Alzheimer disease (AD) and of nondemented individuals. This was achieved by using a novel analytical approach consisting of a combination of fast-performance liquid chromatographic (FPLC) size exclusion chromatography developed under denaturing conditions and europium immunoassay on the 4.0- to 4.5-kd fractions. In the temporalis muscles of the AD and nondemented control groups, the average values for Abeta42 were 15.7 ng/g and 10.2 ng/g (P = 0.010), and for Abeta40 they were 37.8 ng/g and 29.8 ng/g (P = 0.067), respectively. Multiple regression analyses of the AD and control combined populations indicated that 1) muscle Abeta40 and muscle Abeta42 levels were correlated with each other (P < 0.001), 2) muscle Abeta40 levels were positively correlated with age (P = 0. 036), and 3) muscle Abeta42 levels were positively correlated with Braak stage (P = 0.042). Other forms of the Abeta peptide were discovered by mass spectrometry, revealing the presence of Abeta starting at residues 1, 6, 7, 9, 10, and 11 and ending at residues 40, 42, 44, 45, and 46. It is possible that in AD the skeletal muscle may contribute to the elevated plasma pool of Abeta and thus indirectly to the amyloid deposits of the brain parenchyma and cerebral blood vessels. The increased levels of Abeta in the temporalis muscles of AD patients suggest that alterations in AbetaPP and Abeta metabolism may be manifested in peripheral tissues.     

Human Mannose-Binding Protein Inhibits Infection of HeLa Cells by Chlamydia trachomatis

The role that collectin (mannose-binding protein) may play in the host’s defense against chlamydial infection was investigated. Recombinant human mannose-binding protein was used in the inhibition of cell culture infection by Chlamydia trachomatis (C/TW-3/OT, E/UW-5/Cx, and L₂/434/Bu), Chlamydia pneumoniae (AR-39), and Chlamydia psittaci (6BC). Mannose-binding protein (MBP) inhibited infection of all chlamydial strains by at least 50% at 0.098 μg/ml for TW-3 and UW-5, and at 6.25 μg/ml for 434, AR-39, and 6BC. The ability of MBP to inhibit infection with strain L₂ was not affected by supplementation with complement or addition of an L₂-specific neutralizing monoclonal antibody. Enzyme-linked immunosorbent assay and dot blot analyses showed MBP bound to the surface of the organism to exert inhibition, which appeared to block the attachment of radiolabeled organisms to HeLa cells. Immunoblotting and affinity chromatography indicated that MBP binds to the 40-kDa glycoprotein (the major outer membrane protein) on the outer surface of the chlamydial elementary body. Hapten inhibition assays with monosaccharides and defined oligosaccharides showed that the inhibitory effects of MBP were abrogated by mannose or high-mannose type oligomannose-oligosaccharide. The latter carbohydrate is the ligand of the 40-kDa glycoprotein of C. trachomatis L₂, which is known to mediate attachment, suggesting that the MBP binds to high mannose moieties on the surface of chlamydial organisms. These results suggest that MBP plays a role in first-line host defense against chlamydial infection in humans.     

Serological response to Chlamydia pneumoniae infection.

The human serological response was analyzed by using sera from patients who were serologically positive but isolation negative for Chlamydia pneumoniae and from patients with proven C. pneumoniae infection based on serology and isolation. To assess whether seroreactivity to C. pneumoniae proteins had potential diagnostic value, the cross-reactivities of these sera to other Chlamydia species and of sera from patients infected with C. trachomatis and C. psittaci to C. pneumoniae proteins were determined. In all serum samples from patients with proven C. pneumoniae infections, reactivities were seen with 98-, 68-, 60-, 39.5-, and 30-kilodalton proteins. Similar patterns were seen in sera from patients who were serologically positive and isolation negative. The onset of seropositivity for C. pneumoniae was accompanied by reactivities against presumably shared chlamydial antigens and a C. pneumoniae-specific 98-kilodalton protein.     

Associations between Circulating Markers of Cholesterol Homeostasis and Macrovascular Events among Patients Undergoing Hemodialysis

Current strategies targeting serum cholesterol bring limited benefits to mortality and macrovascular events prevention among hemodialysis patients. Direct measurements and analysis on circulating markers of cholesterol homeostasis could be promising solutions to this bottleneck. We prospectively enrolled 90 maintenance hemodialysis patients and 9 healthy controls in 2019 for 1 year. We measured circulating desmosterol and lathosterol as markers for cholesterol synthesis and campesterol and sitosterol for cholesterol absorption. At baseline, hemodialysis patients showed higher levels of campesterol (p = 0.023) compared to healthy controls. During follow-up, we identified 14 (15.4%) patients who experienced macrovascular events. Comparisons of cholesterol homeostasis markers between cohorts with and without macrovascular events showed no significant differences in markers of cholesterol synthesis or absorption. Using logistic regression analysis, the odds ratio was not statistically significant for the prediction of macrovascular events after full-adjusting for age, sex, diabetes, serum albumin, cholesterol, and triglyceride. We concluded that hemodialysis patients demonstrated higher level of cholesterols absorption, indicated by circulating campesterol compared to healthy subjects. Markers for cholesterol homeostasis were not significantly associated with macrovascular events during a 1-year follow-up. Our results shed light on the novel therapeutic target of modulating cholesterol absorption in HD patients.     

Nasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and treatment modalities

Nasal NK/T cell lymphoma is a distinctive type of extranodal lymphoma with an unique immunophenotype and a strong association with Epstein-Barr virus (EBV). It is one of the common extranodal lymphomas in Taiwan. We studied 22 cases of nasal NK/T cell lymphoma to characterize their clinicopathologic features and to explore the possible differences between histologic subtypes and their clinical behavior as well as the prevalence of 30-base pair (bp) deleted latent membrane protein-1 (LMP-1) gene of the EBV. They consisted of 5 cases of small cell type (SC), 6 cases of medium-sized cell type (MC), 6 cases of large cell type (LC), and 5 cases of pleomorphic cell type (PC). Twelve patients were men and 10 were women (1.2 to 1), and their ages ranged from 34 to 75 years with a median age of 55.5 years. The median ages of the LC type and PC type were older than the other 2 types. No other clinical features differed significantly among the 4 subtypes. Nasal obstruction was the most common initial presenting symptom. All but 1 case had stage IE disease at the time of diagnosis. Five cases developed extranasal involvement and skin was the most common site. No bone marrow involvement was detected. The majority of patients received local radiotherapy and chemotherapy. Local irradiation was more effective than chemotherapy alone. We achieved an overall survival of 63.6% at 5 years as estimated by the Kaplan-Meier analysis, which was better than other series. All cases displayed an immunophenotypic profile of CD3(epsilon)+, CD20-, CD56+, and TIA-1+ except that 1 case was CD3(epsilon)-. Fourteen of 22 cases (64%) expressed LMP-1. Nine cases of various cell types (41%) were also CD30+. Among the 4 histologic subtypes, the SC type differed from the other types by the absence of angiodestruction and necrosis, although angioinvasive growth was seen in 2 of them. Pseudoepitheliomatous hyperplasia was seen in only 3 cases of the SC type, and all 5 cases of the SC type were CD30-. No statistical difference in survival was found among the 4 histologic subtypes or between CD30+ and CD30- cases. All 22 cases were positive for EBV by polymerase chain reaction and Epstein-Barr virus early RNA (EBER) in-situ hybridization. A high prevalence rate of 86% (19/22) of the 30-base pair (bp) deleted LMP-1 gene was found, but 81.5% (22/27) of the EBV-positive control reactive lymphoid tissues also had the 30-bp deleted LMP-1 gene. Therefore, the high prevalence of the 30-bp deleted LMP-1 gene found in NK/T cell lymphoma could be due to the high prevalence of the deleted variant in this geographic region. However, it remains possible that the high prevalence of the deleted LMP-1 gene contributed to the increased incidence of EBV-associated nasal NK/T cell lymphoma in Taiwan.     

Opportunities and challenges of cloud computing to improve health care services

Cloud computing is a new way of delivering computing resources and services. Many managers and experts believe that it can improve health care services, benefit health care research, and change the face of health information technology. However, as with any innovation, cloud computing should be rigorously evaluated before its widespread adoption. This paper discusses the concept and its current place in health care, and uses 4 aspects (management, technology, security, and legal) to evaluate the opportunities and challenges of this computing model. Strategic planning that could be used by a health organization to determine its direction, strategy, and resource allocation when it has decided to migrate from traditional to cloud-based health services is also discussed.     

Star Block Copolymers Through Nitroxide‐Mediated Radical Polymerization From Polyhedral Oligomeric Silsesquioxane (POSS) Core

A series of star block copolymers were prepared through nitroxide‐mediated radical polymerization (NMRP) from polyhedral oligomeric silsesquioxanes (POSS) nanoparticle by core‐first polymerization. Eight N‐alkoxyamine groups were incorporated onto the eight corners of a POSS cube through quantitative hydrosilylation through addition of octakis(dimethylsiloxy)silsesquioxane (Q₈M POSS) with 1‐(2‐(allyloxy)‐1‐phenylethoxy)‐2,2,6,6‐tetramethylpiperidine (allyl‐TEMPO) and Karstedt's agent (a platinum divinylsiloxane complex) was used as a catalyst. Octa‐N‐alkoxyamines POSS (OT‐POSS) were used as platform to synthesize star polystyrene‐POSS ((PS)₈‐POSS) homopolymer and diblock copolymers of poly(styrene‐block‐4‐vinylpyridine)‐POSS ((PS‐b‐P4VP)₈‐POSS) and poly(styrene‐block‐acetoxystyrene) ((PS‐b‐PAS)₈‐POSS) through NMRP. In addition, subsequent selective hydrolysis of the acetyl protective group of (PS‐b‐PAS)₈‐POSS, the poly(styrene‐block‐vinyl phenol) ((PS‐b‐PVPh)₈‐POSS) with strong hydrogen bonding group was obtained. The detailed chemical structure and self‐assembled structures of these star block copolymers based on POSS were characterized by ¹H NMR, FTIR, SEC, TEM, and SAXS analyses.

     

Modified Z-palatoplasty with one-layer closure in one-stage multilevel surgery for severe obstructive sleep apnea

Objective

The meticulous two-layer closure is a step to complete the modified Z-palatoplasty, which has been reported to serve as an effective element in multilevel sleep surgery for patients with severe obstructive sleep apnea, especially with Friedman anatomical stages II and III diseases. A single layer closure—the suture closure as originally described in uvulopalatopharyngoplasty by Fujita et al., is an alternative of the two-layer closure, featured by simplicity while its efficacy has not been completely proved in patients with severe obstructive sleep apnea.