L-glutamic acid-g-poly hydroxyethyl methacrylate nanoparticles: acute and sub-acute toxicity and biodistribution potential in mice

The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD₅₀ was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS^® spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.KEY WORDS: biocompatibility, blood biochemistry, genotoxicity, histology, in vivo toxicity, micronucleus test, polymers     

Impact of COVID-19 Pandemic on Organ Donation in Hong Kong: A Single-Center Observational Study

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic was expected to have a negative impact on organ donation. With the differences in health care systems and lockdown policies in various regions, the pandemic's effect on organ donation and transplant service may vary. Most of the deceased donor organ referrals in our hospital came from non–intensive care units (ICUs). The objective of this study is to report our experience and quantify the effects of the COVID-19 pandemic on deceased donor organ donation in our center.MethodsThis was a retrospective observational study comparing the deceased donor organ donation activity during the period January 23 to November 30, 2020 with the same period in 2018 in Queen Elizabeth Hospital, Hong Kong.ResultsThere was a 26.9% reduction in deceased donor organ donor referral in 2020 compared with 2018. No significant difference in the proportion of referrals from ICU or non-ICU areas between the 2 time periods was observed. The brain death confirmation rate was significantly higher in 2020 (40.8% vs 20.2%, P = .003). Nine patients had family consent for organ donation in 2020 (vs 7 patients in the same period in 2018). There were no significant differences in consent rate and number of recovered organs between the 2 periods.ConclusionsWith effective measures to limit the spread of COVID-19 in a community, it is possible to support the needs of both patients with COVID-19 and deceased donor organ donation services.     

Antibody-based immunotherapies for Parkinsonian syndromes

<正>what is the rationale for immunotherapies in Parkinsonian syndromes(PS)? PS are neurodegenerative diseases which are clinically characterized by a hypokinetic phenotype in combination with additional motor and non-motor symptoms. One major patholog-     

Quantifying breast milk intake by term and preterm infants for input into paediatric physiologically based pharmacokinetic models

Despite the many benefits of breast milk, mothers taking medication are often uncertain about the risks of drug exposure to their infants and decide not to breastfeed. Physiologically based pharmacokinetic models can contribute to drug‐in‐milk safety assessments by predicting the infant exposure and subsequently, risk for toxic effects that would result from continuous breastfeeding. This review aimed to quantify breast milk intake feeding parameters in term and preterm infants using literature data for input into paediatric physiologically based pharmacokinetic models designed for drug‐in‐milk risk assessment. Ovid MEDLINE and Embase were searched up to July 2, 2019. Key study reference lists and grey literature were reviewed. Title, abstract and full text were screened in nonduplicate. Daily weight‐normalized human milk intake (WHMI) and feeding frequency by age were extracted. The review process retrieved 52 studies. A nonlinear regression equation was constructed to describe the WHMI of exclusively breastfed term infants from birth to 1 year of age. In all cases, preterm infants fed with similar feeding parameters to term infants on a weight‐normalized basis. Maximum WHMI was 152.6 ml/kg/day at 19.7 days, and weighted mean feeding frequency was 7.7 feeds/day. Existing methods for approximating breast milk intake were refined by using a comprehensive set of literature data to describe WHMI and feeding frequency. Milk feeding parameters were quantified for preterm infants, a vulnerable population at risk for high drug exposure and toxic effects. A high‐risk period of exposure at 2–4 weeks of age was identified and can inform future drug‐in‐milk risk assessments.     

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).     

Description of Leprosy Classification at Baseline among Patients Enrolled at the Uniform Multidrug Therapy Clinical Trial for Leprosy Patients in Brazil

The uniform multidrug therapy clinical trial, Brazil (U-MDT/CT-BR), database was used to describe and report the performance of available tools to classify 830 leprosy patients as paucibacillary (PB) and multibacillary (MB) at baseline. In a modified Ridley and Jopling (R&J) classification, considering clinical features, histopathological results of skin biopsies and the slit-skin smear bacterial load results were used as the gold standard method for classification. Anti-phenolic glycolipid-I (PGL-I) serology by ML Flow test, the slit skin smear bacterial load, and the number of skin lesions were evaluated. Considering the R&J classification system as gold standard, ML Flow tests correctly allocated 70% patients in the PB group and 87% in the MB group. The classification based on counting the number of skin lesions correctly allocated 46% PB patients and 99% MB leprosy cases. Slit skin smears properly classified 91% and 97% of PB and MB patients, respectively. Based on U-MDT/CT-BR results, classification of leprosy patients for treatment purposes is unnecessary because it does not impact clinical and laboratories outcomes. In this context, the identification of new biomarkers to detect patients at a higher risk to develop leprosy reactions or relapse remains an important research challenge.