Lysophosphatidylcholine‐induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells

A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca²⁺ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca²⁺ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation.     

The Associations of Dietary Inflammatory Potential With Musculoskeletal Health in Chinese Community-Dwelling Older People: The Mr. OS and Ms. OS (Hong Kong) Cohort Study

Inflammation, an important contributory factor of muscle and bone aging, is potentially modulated by diet. This study examined the associations of dietary inflammatory index (DII) score with musculoskeletal parameters and related disease outcomes in 3995 community-dwelling Chinese men and women aged ≥65 years in Hong Kong. DII score at baseline was estimated from a food frequency questionnaire. Bone mineral density (BMD) and muscle mass estimated by dual-energy X-ray absorptiometry (DXA), hand grip strength, gait speed, and chair stand test were measured at baseline, year 4, and year 14. The associations of DII score with the longitudinal changes of musculoskeletal parameters, and incidence of osteoporosis, sarcopenia, and fractures were examined by using general linear model, multinomial logistic regression model, and Cox proportional hazards regression model, respectively. After multiple adjustments, each tertile increase in DII score in men was associated with 0.37 (95% confidence interval [CI], 0.10–0.64) kg loss in grip strength and 0.02 (95% CI, 0.01–0.03) m/s loss in gait speed over 4 years. In men, the highest tertile of DII was associated with a higher risk of incident fractures, with adjusted and competing death adjusted hazard ratio (HR) (95% CI) of 1.56 (1.14–2.14) and 1.40 (1.02–1.91), respectively. In women, DII score was not significantly associated with any muscle-related outcomes or incidence of fracture, but a significant association between higher DII score and risk of osteoporosis at year 14 was observed, with the highest tertile of DII score having adjusted odds ratio (OR) (95% CI) of 1.90 (1.03–3.52). In conclusion, pro-inflammatory diet consumption promoted loss of muscle strength and physical function, and increased risk of fractures in older Chinese men. Pro-inflammatory diets had no significant association with muscle related outcomes but increased the long-term risk of osteoporosis in older Chinese women. © 2022 American Society for Bone and Mineral Research (ASBMR).     

International survey of peritoneal dialysis training programs.

OBJECTIVE: To survey nurses around the world about current practices for peritoneal dialysis (PD) home training programs. DESIGN: Random sampling of nurses to complete a written survey from the International Society for Peritoneal Dialysis Nursing Liaison Committee. Settings: United States, Canada, South America (Brazil, Columbia), The Netherlands, Hong Kong. METHODS: Surveys and responses were sent by fax whenever possible, or by regular mail, or hand carried, or conducted by telephone. Results were stratified by geographic areas as well as by cumulative responses and were expressed as medians with ranges. Kruskal-Wallis was used to evaluate differences in responses. Associations between variables were tested with Pearson correlation. Univariate regression analysis was used to evaluate the impact of variables on peritonitis rates. Variables with p < 0.10 were included in a multivariate analysis. RESULTS: A total of 317 nurses responded: 88 in the United States, 46 in Canada, 58 in South America, 58 in Hong Kong, and 67 in The Netherlands. This represented 37% of all surveys distributed. Respondents had a median of 12 years' experience in nephrology (range 1-35 years), but only 31% had a formal background in adult education. Nearly half received their guidance to patient training from a nurse colleague, 11% were guided by a corporate colleague, and 8% were simply self-taught. Clinics responding had a median of 30 PD patients (range 1-400) and reported they trained a median of 8 patients per year (range 0-86). Reported peritonitis rates were a median 0.46 per year or 1 episode every 26 months. Peritonitis rates, however, were not known by 53% of respondents. Total training time per patient had a very wide range of hours, from 6 to 96. There was no correlation between training time and peritonitis rates among the study respondents (p = 0.38), nor with any other variables. CONCLUSIONS: There is wide variation in practices for PD patient training programs within countries and around the world. Training time did not appear to be related to peritonitis rates. Randomized trials of training practices are needed to determine which approaches produce the best outcomes for patients.     

Modified Epworth Sleepiness Scale in Chinese children with obstructive sleep apnea: a retrospective study

Background and objective  The purpose of this study is to assess whether Chinese children with high apnea–hypopnea index (AHI) are sleepier by a modified Epworth Sleepiness Scale (ESS). Materials and methods  Records were retrospectively reviewed. We included children who were between 3 and 12 years old, admitted for overnight polysomnogram because of suspected obstructive sleep apnea syndrome (OSAS). A modified ESS was used to assess excessive daytime sleepiness (EDS) of the children. Results  One hundred ninety-two Chinese children were included. Children with high AHI, defined as AHI > 5.0, were sleepier than children with AHI less than or equal to 5. After adjustment by age, gender, and obesity, children with high AHI remained significantly sleepier. Modified ESS was significantly correlated with AHI (rho = 0.124, 95% CI = 0.004–0.281). Modified ESS score of >8 was the best cutoff point with the sensitivity and specificity of 0.29 and 0.91, respectively. The odds ratio of children with modified ESS > 10 having high AHI was 4.231 (95%CI = 1.248 to 14.338) and children with modified ESS > 8 had the highest odds ratio, 4.295(95%CI = 1.66 to 11.1), of having high AHI. Conclusion   Chinese children with high AHI appear to be sleepier than children with low AHI. Children with suspected OSAS and high modified ESS, i.e., ESS > 8, had significantly higher odds ratio of having high AHI. Increased sleepiness is a specific but not a sensitive symptom in snoring children with high AHI. Screening for EDS in snoring children may help us identify those with high AHI and prioritize the management of those children. All authors worked and the study was carried out in Kwong Wah Hospital in Hong Kong. There was no conflict of interest and no specific source of funding for the study.     

Pharmacokinetics of mycophenolate mofetil in stable pediatric liver transplant recipients receiving mycophenolate mofetil and cyclosporine.

There are few pharmacokinetic data for mycophenolate mofetil (MMF) when used in combination with cyclosporine (CsA) in pediatric liver transplant recipients. The aim of this study was to assess the pharmacokinetics of MMF in stable pediatric liver transplant patients and estimate the dose of MMF required to provide a mycophenolic acid (MPA) exposure similar to that observed in adult liver transplant recipients receiving the recommended dose of MMF (target area under the plasma concentration-time curve from 0 to 12 hours [AUC(0-12)] for MPA of 29 mug.hour/mL in the immediate posttransplantation period and 58 microg x hour/mL after 6 months). A 12-hour pharmacokinetic profile was collected for 8 pediatric patients (mean age 20.9 months) on stable doses of MMF and CsA who had received a liver transplant > or = 6 months prior to entry and who had started on MMF within 2 weeks of transplantation. Mean MMF dosage was 285 mg/m(2) (range, 200-424 mg/m(2)). Of 8 patients, 7 had a MPA AUC(0-12) (range, 11.0-37.2 microg x hour/mL) well below the target. One patient had an AUC(0-12) > or = 58 microg x hour/mL but was considered an outlier and was excluded from analyses. Mean MPA AUC(0-12) and maximum plasma concentration values were 22.7 +/- 10.5 microg x hour/mL and 7.23 +/- 3.27 microg/mL, respectively; values normalized to 600 mg/m(2) (the approved pediatric dose in renal transplantation) were 47.0 +/- 21.8 microg x hour/mL and 14.5 +/- 4.21 microg/mL. In conclusion, assuming that MPA exhibits linear pharmacokinetics, when used in combination with CsA, a MMF dose of 740 mg/m(2) twice daily would be recommended in pediatric liver transplant recipients to achieve MPA exposures similar to those observed in adult liver transplant recipients. This finding should be confirmed by a prospective trial.     

Myoglobinuria from child abuse

A child with myoglobinuria following rhabdomyolysis from child abuse is described. The importance of early recognition and treatment of this condition is emphasized.     

Congenital herpes simplex retinitis

An 1,810-g girl born at 37 weeks of gestation had true congenital herpes simplex virus type 2 infection. The neonate was born with hypo-pigmented skin lesions, brain lesions, and old heavily pigmented retinal scars in the posterior pole. There was no active ocular disease. Viral cultures, immunoperoxidase stains, and antibody determination by enzyme-linked immunosorbent assay were all positive for herpes simplex virus. Treatment with acyclovir healed the lesions within ten days. The clinical and laboratory findings indicated that the herpetic infection probably occurred in the second trimester.     

Invasion of Human Oral Epithelial Cells by Prevotella intermedia

Invasion of oral epithelial cells by pathogenic oral bacteria may represent an important virulence factor in the progression of periodontal disease. Here we report that a clinical isolate of Prevotella intermedia, strain 17, was found to invade a human oral epithelial cell line (KB), whereas P. intermedia 27, another clinical isolate, and P. intermedia 25611, the type strain, were not found to invade the cell line. Invasion was quantified by the recovery of viable bacteria following a standard antibiotic protection assay and observed by electron microscopy. Cytochalasin D, cycloheximide, monodansylcadaverine, and low temperature (4°C) inhibited the internalization of P. intermedia 17. Antibodies raised against P. intermedia type C fimbriae and against whole cells inhibited invasion, but the anti-type-C-fimbria antibody inhibited invasion to a greater extent than the anti-whole-cell antibody. This work provides evidence that at least one strain of P. intermedia can invade an oral epithelial cell line and that the type C fimbriae and a cytoskeletal rearrangement are required for this invasion.