Impact of donor extracellular vesicle release on recipient cell “cross-dressing” following clinical liver and kidney transplantation

In several murine models of transplantation, the “cross-dressing” of recipient antigen presenting cells (APCs) with intact donor major histocompatibility complex (MHC) derived from allograft-released small extracellular vesicles (sEVs) has been recently described as a key mechanism in eliciting and sustaining alloimmune responses. Investigation of these processes in clinical organ transplantation has, however, been hampered by the lack of sensitivity of conventional instruments and assays. We have employed advanced imaging flow cytometry (iFCM) to explore the kinetics of allograft sEV release and the extent to which donor sEVs might induce cross-dressing following liver and kidney transplantation. We report for the first time that recipient APC cross-dressing can be transiently detected in the circulation shortly after liver, but not kidney, transplantation in association with the release of HLA-bearing allograft-derived sEVs. In liver transplant recipients the majority of circulating cells exhibiting donor HLA are indeed cross-dressed cells and not passenger leukocytes. In keeping with experimental animal data, the downstream functional consequences of the transfer of circulating sEVs harvested from human transplant recipients varies depending on the type of transplant and time posttransplant. sEVs released shortly after liver, but not kidney, transplantation exhibit immunoinhibitory effects that could influence liver allograft immunogenicity.     

Association of sleep duration and quality with immunological response after vaccination against severe acute respiratory syndrome coronavirus-2 infection

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer–BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38–54) years and body mass index of 24·84 (22.6–28.51) kg/m² were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6–7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = −0.178, p < 0.001), poor sleep quality (r = −0.094, p < 0.05), insomnia (r = −0.098, p < 0.05), and nap frequency per week (r = −0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination.     

Benign paroxysmal torticollis of infancy: An underdiagnosed condition

Benign paroxysmal torticollis is probably an under‐diagnosed condition of infancy. It is a self‐limiting disorder characterised by periods of unusual, sustained posture of the head and neck, during which the head tilts to one side. Episodes are often accompanied by marked autonomic features, irritability, ataxia, apathy and drowsiness. They last several hours to a few days and are often recurring every few weeks. They subside within the pre‐school years; however, during later childhood, there is a tendency to develop migraine. Three cases of benign paroxysmal torticollis are presented and are compared with cases in the literature. A telephone survey has been conducted to determine what is the general awareness of paediatricians of this condition in Cyprus. Eighty‐two paediatricians were randomly selected out of 235 paediatricians. All of them agreed to participate. Our cases revealed that benign paroxysmal torticollis may coexist with other problems during infancy. The telephone survey showed that only two out of eighty‐two (2.4%) of the paediatricians are aware of the condition, and none of them was confident regarding the management. Our telephone survey clearly shows that Cypriot paediatricians are not familiar with benign paroxysmal torticollis in infancy which is a benign, self‐limiting disorder. It is essential to recognise the condition and to reassure parents of its benign course and not to be misdiagnosed for other disorders, such as epileptic seizures. We have shown again that benign paroxysmal torticollis in infancy may coexist with motor delay and hearing problems.     

Anthropometry and Body Composition of Preterm Neonates in the Light of Metabolic Programming

The improved survival of preterm infants has led to increased interest regarding their health as adults. In the context of metabolic programming, the connection between perinatal and early postnatal nutrition and growth with health in later life has brought to the fore the role of catch-up growth during the first months of preterm infants' lives and its association with body fat and obesity in childhood or puberty. A state-of-the art review was conducted in order to assess the way catch-up is evaluated, in terms of timing and rate. Adequate growth is of major importance for neurodevelopment; however, it may compete with adiposity or metabolic health. Studies based on body composition assessment have given conflicting results as regards the effect of early versus late and rapid versus slow catch-up growth on later health, mainly attributed to the lack of established criteria and definitions. Given that adequate early nutrition is crucial for the neurodevelopment of preterm infants, further studies are needed on the role of catch-up growth in long-term outcome, using generally accepted qualitative and quantitative criteria.     

Cardiomyocyte-specific desmin rescue of desmin null cardiomyopathy excludes vascular involvement

Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals. To determine whether altered capillary function or an intrinsic cardiomyocyte defect is responsible for desmin null DCM, transgenic mice were generated to rescue desmin expression specifically to cardiomyocytes. Desmin rescue mice display a wild-type cardiac phenotype with no fibrosis or calcification in the myocardium and normalization of coronary flow. Cardiomyocyte ultrastructure is also restored to normal. Markers of hypertrophy upregulated in desmin null hearts return to wild-type levels in desmin rescue mice. Working hearts were perfused to assess coronary flow and cardiac power. Restoration of a wild-type cardiac phenotype in a desmin null background by expression of desmin specifically within cardiomyocyte indicates that defects in the desmin null heart are due to an intrinsic cardiomyocytes defect rather than compromised coronary circulation.     

Today’s Mediterranean Diet in Greece: Findings from the National Health and Nutrition Survey—HYDRIA (2013–2014)

Background: This study aimed to investigate the food and macronutrient intake of the population in Greece and evaluate its adherence to the Greek traditional Mediterranean diet. Methods: Adults over 18 years old (n = 4011) were included from the 2013–2014 National Health and Nutrition survey—HYDRIA. Dietary intake was collected using two 24-h recall interviews and a nonquantitative food frequency questionnaire. Macronutrient intakes were calculated using an updated version of the Greek FCT. Results: Only 28.3% of the adult population had high adherence to the Greek traditional Mediterranean diet, with a higher percentage (39.7%) observed for participants over 65 years compared to those under 65 years (25.5%). Differences in adherence to the MD were observed among the four geographical regions in Greece. Younger adults had a higher intake of meat, cereals, alcoholic and nonalcoholic beverages, and sugar products than older individuals who consumed more vegetables, fruits, legumes, dairy, fish, and lipids (mainly from olive oil). Adults do not meet the international dietary recommendations for the intake of several foods and macronutrients. Conclusions: The adult Greek population, especially younger people, has headed away from the Greek traditional Mediterranean diet. These observations indicate potential detrimental consequences in terms of morbidity and mortality.     

NOSH-Aspirin: A Novel Nitric Oxide-Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals

A series of new hybrids of aspirin (ASA), bearing both nitric oxide (NO) and hydrogen sulfide (H(2)S)-releasing moieties were synthesized and designated as NOSH compounds (1-4). NOSH-1 (4-(3-thioxo-3H-1,2-dithiol-5-yl) phenyl 2-((4-(nitrooxy)-butanoyl)oxy) benzoate); NOSH-2 (4-(nitrooxy)butyl (2-((4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)carbonyl)phenyl)); NOSH-3 (4-carbamothioylphenyl 2-((4-(nitrooxy)butanoyl)-oxy)benzoate); and NOSH-4 (4-(nitrooxy)butyl 2-(5-((R)-1,2-dithiolan-3-yl)pentanoyloxy)-benzoate). The cell growth inhibitory properties of compounds 1-4 were evaluated in eleven different human cancer cell lines of six different tissue origins. These cell lines are of adenomatous (colon, pancreatic, lung, prostate), epithelial (breast), and lymphocytic (leukemia) origin. All NOSH compounds were extremely effective in inhibiting the growth of these cell lines. NOSH-1 was the most potent, with an IC(50) of 48 ± 3 nM in HT-29 colon cancer cells. This is the first NSAID-based compound with such potency. This compound was also devoid of any cellular toxicity, as determined by LDH release. NOSH-1 was comparable to aspirin in its anti-inflammatory properties, using the carrageenan rat paw edema model.     

Aberrant p16 promoter methylation among Greek lung cancer patients and smokers: correlation with smoking.

Genetic and environmental factors (dietary and smoking) influence lung cancer epidemiology and induce epigenetic modifications that should be assessed in individual populations. We analyzed p16 methylation among Greek non-small cell lung carcinoma patients and smokers using two-stage methylation-specific polymerase chain reaction. One hundred and fifty specimens from cancerous and adjacent non-cancerous tissue, bronchial washings and sputum from patients and 48 specimens, mostly sputum, from disease-free smokers were included. p16 methylation was very frequent in biopsies (82.85%) and bronchial washings (non-small cell lung carcinoma, 80.35%; small cell lung carcinoma, 16.66%) from patients, but also in adjacent non-cancerous tissue (45.71%). Concordance of p16 methylation and positivity by cytological examination was 51.78%. Methylation was also observed in sputum from asymptomatic cytology-negative smokers (22.5%) and chronic obstructive pulmonary disease patients (three of eight). Among disease-free individuals, methylation correlated only with heavy smoking (>50 pack-years, P<0.001) and differed among male and female disease-free smokers. In summary, p16 methylation is very frequent among non-small cell lung carcinoma patients, and correlates with heavy cigarette consumption only in disease-free smokers.     

Oprimizing the protocol for the calculation of the doses of (131)I administered for the treatment of benign thyroid disease

The administration of (131)I for the treatment of benign thyroid disease is widely used in clinical practice. The appropriate dose of (131)I, so as the gland could receive the specified absorbed dose, is determined by various methods. The mostly used is the one based on the 24 h uptake. In the present study we examined the time to measure (131)I uptake which better represents the total accumulated activity in the thyroid gland and consequently is more reliable for dose calculation. Fourteen patients, who were referred to the Nuclear Medicine Department of AHEPA University Hospital, were included in the study. 1.85 MBq of (131)I were administered and the uptake at 24, 48, 72 and 192 h was measured. From the curve of the activity vs time we calculated the area under it, which represents the total accumulated thyroid activity. We compared the uptakes of every individual with the total area and we found that the 192 h uptake was best correlated with it (r=0.996). The absorbed dose to the thyroid was calculated in the following ways: a) was based on the 24 h uptake and b) was based on the total accumulated activity on the 192 h uptake. We found differences from -19.9% to +33.7%. In conclusion, the 192 h uptake consists the most representative and reliable parameter for the estimated activity of (131)I given to the thyroid for the treatment of hyperthyroidism.