In vivo multicolor molecular MR imaging using diamagnetic chemical exchange saturation transfer liposomes

A variety of (super)paramagnetic contrast agents are available for enhanced MR visualization of specific tissues, cells, or molecules. To develop alternative contrast agents without the presence of metal ions, liposomes were developed containing simple bioorganic and biodegradable compounds that produce diamagnetic chemical exchange saturation transfer MR contrast. This diamagnetic chemical exchange saturation transfer contrast is frequency-dependent, allowing the unique generation of "multicolor" images. The contrast can be turned on and off at will, and standard images do not show the presence of these agents. As an example, glycogen, L-arginine, and poly-L-lysine were encapsulated inside liposomes and injected intradermally into mice to image the lymphatic uptake of these liposomes. Using a frequency-dependent acquisition scheme, it is demonstrated that multicolor MRI can differentiate between different contrast particles in vivo following their homing to draining lymph nodes. Being nonmetallic and bioorganic, these diamagnetic chemical exchange saturation transfer liposomes form an attractive novel platform for multicolor imaging in vivo.     

Early-life factors and adult anti-Müllerian hormone levels

Journal of Assisted Reproduction and Genetics - This study aims to examine whether early-life factors are associated with adult ovarian reserve, measured by anti-Müllerian hormone (AMH)...     

Ghrelin secretion is modulated in a nutrient- and gender-specific manner

BACKGROUND: Ghrelin is a potent GH secretagogue that also plays an important role in appetite and weight regulation. Ghrelin increases hunger and food intake, and its levels decrease after a standard meal or glucose. OBJECTIVE: To examine the effects of standard oral glucose, lipid and protein loads on ghrelin levels, investigating the possibility that these responses may be modulated by several anthropometric and metabolic factors. SUBJECTS AND METHODS: There were 24 adult nondiabetic subjects (13 men/11 women; mean age 55.3 +/- 2.9 years, range 26-74 years). Each participant underwent one or more of the following nutrient loads: (i) a standard oral glucose (75 g) load (n = 18); (ii) an oral lipid load (40 g, with 24 g saturated fat; n = 13); (iii) an oral protein load (40 g; n = 11). RESULTS: Fasting ghrelin levels were negatively related to body mass index (BMI; r =-0.47; P = 0.02), waist circumference (r = -0.58; P = 0.0028), waist/hip ratio (r = -0.56; P = 0.0046), fasting insulin (r = -0.44, P = 0.03), and homeostasis model assessment insulin resistance index (HOMA-R; r = -0.43, P = 0.034). Glucose load induced a decrease in ghrelin levels (P < 0.0001), and this response was modulated by sex (P < 0.0001), in that levels were significantly higher in females. The presence of obesity affected ghrelin response to glucose (< 0.0217), in that log-transformed ghrelin levels started to increase back to baseline after its initial decline earlier in obese than in lean subjects. Ghrelin levels after a glucose load were lower over time in subjects with more pronounced insulin resistance (P < 0.0001). Similarly, ghrelin levels decreased significantly following the lipid meal (P = 0.035), and were modulated by HOMA-R (P = 0.027) and gender (P = 0.029). Protein did not affect ghrelin levels. CONCLUSIONS: This study demonstrates that ghrelin levels respond in a different manner to glucose, lipid and protein loads, and are subject to modulation according to gender, obesity and insulin sensitivity.     

Identifying incidents of suboptimal care during paediatric emergencies–an observational study utilising in situ and simulation centre scenarios

Aim

Life threatening paediatric emergencies are relatively uncommon events. When they do occur staff caring for these children must have the ability to recognise the deterioration, evaluate and simultaneously treat these patients. The aim of this study was to identify suboptimal care during standardised simulated scenarios and to identify the potential causation factors.

Methods

Participants were emergency department and operating theatre staff in Sydney, Australia. Incidents of suboptimal care were identified during scenarios and were analysed by thematic qualitative assessment methods. Potential causation factors were elicited both during and immediately after the scenarios and during facilitated debriefings. Causation factors were attributed to any of seven pre-defined categories.

Results

Seventy-three simulations occurred over 9 month period in 2011. 270 doctors, 235 nurses and 11 students participated. 194 incidents of suboptimal care were observed and attributed to 325 causation factors. There were 76 knowledge deficits, 39 clinical skill deficits, 36 leadership problems, 84 communication failures, 20 poor resource utilisations, 23 preparation and planning failures and 47 incidents of a loss of situational awareness. Clinically important themes were: paediatric life support, drug choice and doses, advanced airway and ventilation, intravenous fluids and recognition of the deteriorating patient. Recurring incidents included the failure to recognise a cardiac arrest, inadequate fluid resuscitation and incorrect medication dose administration.

Conclusions

During standardised paediatric simulations multiple incidents of suboptimal care have been identified and multiple causation factors attributed to these. Educators should use this information to adapt current training programs to encompass these factors.     

Sperm quality is not affected by the BNT162b2 mRNA SARS-CoV-2 vaccine: results of a 6–14 months follow-up

Purpose We aimed to investigate the possible effect of SARS-CoV-2 vaccination on sperm quality by evaluating semen analyses of men prior to vaccination and 6–14 months after vaccination.MethodsThis was a retrospective cohort study, conducted in a university-affiliated in vitro fertilization center between October 2021 and March 2022, including men not previously infected with the SARS-CoV-2 virus who received at least 2 doses of the Pfizer-BioNTech (BNT162b2) SARS-CoV-2 vaccine. Semen analyses of samples given pre-vaccination and 6–14 months post-vaccination were analyzed for the parameters of volume, concentration, motility, morphology, and total motile count (TMC) and compared. These parameters were also compared separately for men who received a third (booster) dose and for men with pre-vaccination normal and abnormal sperm. Correlations between time from vaccination and post-vaccination sperm parameters were also assessed.ResultsFifty-eight men were included in the final analysis. Semen volume (2.9 ± 1.4 vs. 2.9 ± 1.6 ml), sperm concentration (42.9 ± 37.9 vs. 51.5 ± 46.2 million/ml), motility (42.5 ± 23.1 vs. 44.3 ± 23.4 percent), morphology (8.8 ± .16.6 vs. 6.6 ± 8.8 percent), and TMC (55.7 ± 57.9 vs. 71.1 ± 77.1 million) were comparable between the pre- and post-vaccination samples. This was true for the entire study cohort, for the subgroup of men who received a third dose and for the subgroups of men with a pre-vaccination normal and abnormal semen samples. No correlation was found between time from vaccination and post-vaccination sperm parameters.ConclusionsThe Pfizer-BioNTech (BNT162b2) SARS-CoV-2 vaccine does not impair any of the sperm parameters over a relatively long-time interval of 6 to 14 months from vaccination.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-022-02621-x.     

Is parotidectomy justified in elderly patients with pleomorphic adenoma? A decision analysis model

PurposeThe value of parotidectomy in older patients is unclear. This study presents a decision model to help resolve this question.Materials & methodsA Markov model with Monte Carlo simulation was used to compare outcomes in patients of different ages with pleomorphic adenoma of the parotid gland treated by surgery or surveillance.ResultsIn 30-year-old patients, surgery conferred a 3.5-year gain in life expectancy whereas in 75-year-olds, it was only 0.74 months. The expected rate of malignant transformation at age 30 years was 6.5% after surgery and 26.5% after surveillance; at age 65, corresponding rates were 0.8% and 10.7%. Sensitivity analysis showed that age was the only parameter that significantly contributed to life expectancy. The benefit of surgery was restricted in older patients.ConclusionOur Markov decision-analysis model suggests that patients older than 65 years with pleomorphic adenoma have a limited survival advantage with surgery compared to surveillance.     

Early polyamine treatment accelerates regeneration of rat sympathetic neurons

After injury of their axons, damaged neurons shift their metabolic activity into a reparative mode aimed at survival and regeneration or, alternatively, they undergo degeneration and die. Previous reports have shown that at the initial stages of the response to axonal injury, polyamines are essential for neuronal survival and can accelerate functional recovery. In this study we examined the ability of exogenous polyamines to accelerate regeneration following crush of the pre- or postganglionic sympathetic nerves of the superior cervical ganglion in adult rats. We found that early treatment with polyamines after pre- or postganglionic nerve crush, accelerated the reappearance of choline acetyltransferase activity in the superior cervical ganglion, and of [3H]norepinephrine uptake in the iris, respectively. Functional recovery from eyelid ptosis was also accelerated. We conclude that treatment with polyamines can enhance regeneration of peripheral sympathetic neurons.