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.     

Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. OBJECTIVE: To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. METHODS: Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comté (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. RESULTS: The estimated incidence of DFSP in Franche-Comté was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P=0.004; OR=0.229 (95%, CI=0.103-0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. CONCLUSION: Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.     

Acquired Cutis Laxa in Childhood Sweet's Syndrome

Abstract:  In Sweet's syndrome, the essential features are the characteristic morphology of the lesions, their histologic appearance, the dramatic response to corticosteroids and the absence of scarring. We report an 8-month-old infant in whom Sweet's syndrome was diagnosed and who developed acquired cutis laxa in the skin lesions.     

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.