Paediatric Residents and Fellows Ethics (PERFEct) survey: perceptions of European trainees regarding ethical dilemmas.

With an increasingly complex healthcare environment, ethics is becoming a more critical part of medical education. We aimed to explore European paediatric trainees' experiences of facing ethical dilemmas and their medical ethics education whilst assessing their perceptions of ethical dilemmas in current and future practice. The Young Sections of the European Academy of Paediatrics and European Society of Paediatric and Neonatal Intensive Care developed an explorative online survey covering demographics, ethical dilemmas faced and ethics training. The survey was made available in nine languages from November 2019 to January 2020 via newsletters and social media. Participants (n = 253) from 22 countries, predominantly female (82%) and residents (70%), with a median age of 29-years, completed the survey. The majority (58%) faced ethical dilemmas monthly or more frequently. Most ethics training was received by ethics lectures in medical school (81%) and on the job (60%). A disagreement between the healthcare team and patient/family was the most frequently faced moral dilemma (45%); the second was withholding/withdrawing life-prolonging measures (33%). The latter was considered the most challenging dilemma to resolve (50%). Respondents reported that ethical issues are not sufficiently addressed during their training and wished for more case-based teaching. Many have been personally affected by moral dilemmas, especially regarding withholding/withdrawing life-prolonging measures, and often felt inadequately supported.Conclusion: Paediatric trainees face many moral issues in daily practice and consider that training about managing current and future ethical dilemmas should be improved, such as by the provision of a core European paediatric ethics curriculum. What is Known: • Paediatric services are becoming more complex with an increase in ethical dilemmas asking for rigorous training in ethics. • Ethics training is often lacking or covered poorly in both pre- and postgraduate medical education curricula. • Existing ethics training for European paediatric trainees is haphazard and lacks standardisation. What is New: • The PaEdiatric Residents and Fellows Ethics (PERFEct) survey provides insight into the European paediatric trainees' views regarding ethical dilemmas in their current and future practice. • European paediatric trainees report a lack of ethics training during paediatric residency and fellowship. • This study provides content suggestions for standardised medical ethics training for paediatric trainees in Europe.

Melatonin reduces excitotoxic blood-brain barrier breakdown in neonatal rats.

The blood-brain barrier (BBB) is a complex structure that protects the central nervous system from peripheral insults. Understanding the molecular basis of BBB function and dysfunction holds significant potential for future strategies to prevent and treat neurological damage. The aim of our study was (1) to investigate BBB alterations following excitotoxicity and (2) to test the protective properties of melatonin. Ibotenate, a glutamate analog, was injected intracerebrally in postnatal day 5 (P5) rat pups to mimic excitotoxic injury. Animals were than randomly divided into two groups, one receiving intraperitoneal (i.p.) melatonin injections (5mg/kg), and the other phosphate buffer saline (PBS) injections. Pups were sacrificed 2, 4 and 18 h after ibotenate injection. We determined lesion size at 5 days by histology, the location and organization of tight junction (TJ) proteins by immunohistochemical studies, and BBB leakage by dextran extravasation. Expression levels of BBB genes (TJs, efflux transporters and detoxification enzymes) were determined in the cortex and choroid plexus by quantitative PCR. Dextran extravasation was seen 2h after the insult, suggesting a rapid BBB breakdown that was resolved by 4h. Extravasation was significantly reduced in melatonin-treated pups. Gene expression and immunohistochemical assays showed dynamic BBB modifications during the first 4h, partially prevented by melatonin. Lesion-size measurements confirmed white matter neuroprotection by melatonin. Our study is the first to evaluate BBB structure and function at a very early time point following excitotoxicity in neonates. Melatonin neuroprotects by preventing TJ modifications and BBB disruption at this early phase, before its previously demonstrated anti-inflammatory, antioxidant and axonal regrowth-promoting effects.

Metric similarity of dynamic commutation processes in situ and in vitro.

The dynamics of string growth was studied in model homochiral solutions of biomimetics, trifluoroacetylated amino alcohols (TFAAA) in heptane, water, and inverted heptane-water emulsion. In heptane and water, a thick (~1 µ in diameter) string had a crown of thin strings on its growing terminal and these thin strings effectively adsorbed dissolved TFAAA. In emulsion, the strings grew inside the water droplets, in which this TFAAA cannot be solved, presumably due to transport of TFAAA molecules from heptane into water in the surface layer surrounding the string. Applications of these phenomena to in vivo cell commutation were discussed.

Effects of physicochemical forms of phenazepam and Panavir on their action at ultra-low doses.

A concept of physicochemical forms of biologically active substances introduced in investigation of the action mechanism of ultra-low doses allows qualitative explanation of the main effects of ultra-low doses, chemical diversity of biologically active substances, and physical boundaries for these effects. Phenazepam was shown to possess activity in ultra-low doses only in disperse state, in the form of nanoparticles with a diameter <100-300 nm; these nanoparticles appear as micelles of surface active substances and solvated. Panavir possesses pharmacological activity in ultra-low doses and appears as nanoparticles with a diameter of 200-300 nm, which have uncompensated negative surface charge and polymer nature.

Superspiralization of chiral strings.

A phenomenon of superspiralization was revealed in homochiral solutions of biomimetics with strings lengths from 10(2) nm to 10(2) µ and longer: strings of greater size spontaneously formed in solution are twined of the smaller strings, which also have a helical structure. The chiral pitch depends on the conditions of formation of a particular string and can vary by several times in different strings of the same specimen.

Short-term bisphosphonate therapy could ameliorate osteonecrosis: a complication in childhood hematologic malignancies.

Osteonecrosis (ON) is a critical complication in the treatment of childhood leukemia and lymphoma. It particularly affects survivors of acute lymphoblastic leukemia and non-Hodgkin lymphoma reflecting the cumulative exposure to glucocorticosteroid therapy. ON is often multiarticular and bilateral, specially affecting weight-bearing joints. A conventional approach suggests a surgical intervention even if pharmacological options have also recently been investigated. We reported two cases of long time steroid-treated patients who underwent Bone Marrow Transplantation (BMT) for hematological disease. Both patients developed femoral head osteonecrosis (ON) that was diagnosed by magnetic resonance imaging (MRI) and the ON was also accompanied with pain and a limp. Despite of the conventional strategies of therapy, we successfully started a short-term treatment with bisphosphonates in order to decrease the pain and the risk of fracture.

Rotating hexagonal pattern in a dielectric barrier discharge system.

Here, we report on the experimental observation of a rotating hexagonal pattern in a continuous dissipative medium. The system under investigation is a planar dielectric barrier gas-discharge cell. The pattern consists of a set of current filaments occupying the whole discharge area and rotating as a rigid body. The symmetry of the rotating hexagons is lower than the symmetry of the stationary hexagonal pattern. We study the dynamics of the pattern, especially peculiarities of its rotational velocity. The temperature of the gas is found to be an important quantity influencing the rotating hexagons.

Concentric-ring patterns in a dielectric barrier discharge system.

We report on the first experimental observation of a concentric-ring pattern in a short planar dielectric barrier gas-discharge system and study its spatiotemporal behavior. While increasing the gas pressure the destabilization of the rings into a filamentary structure is observed. The charge carriers deposited on the dielectric electrodes determine the spatiotemporal behavior of the pattern.

The FX enzyme is a functional component of lymphocyte activation.

Fucose is an essential constituent of selectin ligands. These molecules mediate the initial contact between extravasating leukocytes and endothelial cells. The generation of GDP-L-fucose by the FX enzyme is the final step of fucose biosynthesis. Recently, we demonstrated that outside-in signaling regulates the expression of the FX enzyme in certain cancer cells. The present study demonstrates that the polyclonal activation of T and B cells significantly up-regulated the expression of the FX enzyme and of the fucosylated selectin ligands sLe-x and CLA. Treatment of T cells with FX antisense oligonucleotides significantly decreased selectin ligand expression upon activation. We conclude that FX is regulated by outside-in signals also in lymphocytes and that this enzyme is involved in the biosynthesis of selectin ligands in such cells. We propose that FX takes part in the cascade of events leading to the extravasation of activated lymphocytes.

The GPI-linked Ly-6 antigen E48 regulates expression levels of the FX enzyme and of E-selectin ligands on head and neck squamous carcinoma cells.

By differential display we demonstrated that antibody-mediated ligation of the GPI-linked protein product of E48, a newly discovered human Ly-6 gene, up-regulates the expression of the FX enzyme in 3 lines of head and neck squamous carcinoma cells. FX is responsible for the last step in the synthesis of GDP-L-fucose. The up-regulation of FX was E48 ligand-specific. 22AWT head and neck squamous carcinoma cells expressing high levels of E48 expressed significantly higher levels of FX than the E48 antisense transfected 22AWT cells (8-3 cells). The former cells also expressed higher levels of two major fucosylated glycans (the selectin ligand, Sialyl Lewis a, and VIM-2) than the E48 antisense transfectants. Conversely, transfection of cells from the 14CWT line expressing very low levels of E48 with E48 cDNA caused an up-regulated expression of FX and of the two fucosylated glycans in the 14C-CMV16 transfectants. Moreover, the expression levels of Sialyl Lewis a was significantly up-regulated on HNSCC upon ligation of E48 by anti-E48 antibodies. The functional significance of the E48-mediated up-regulation of Sialyl Lewis a was demonstrated in rolling experiments on E-selectin bearing surfaces under physiological conditions of shear flow and on tumor necrosis factor alpha-activated human umbilical venous endothelial cells. Only high E48/FX/Sialyl Lewis a expressing 14C-CMV16 cells could roll on purified E-selectin or establish E-selectin dependent rolling on the activated human umbilical venous endothelial cells. Low E48/FX/Sialyl Lewis a expressing 14CWT cells did not roll. These results show that E48 controls the expression of the FX enzyme and of certain fucosylated E-selectin ligands by HNSCC. E48 may thus function as a key regulator of the adhesiveness of these tumor cells to inflamed vessel walls expressing E-selectin.

Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation.

To quantify the number of goblet cells and inflammatory cells in the epithelium of peripheral airways in smokers with both symptoms of chronic bronchitis and chronic airflow limitation, we examined surgical specimens obtained from 25 subjects undergoing lung resection for localized pulmonary lesions: 10 smokers with symptoms of chronic bronchitis and chronic airflow limitation, six asymptomatic smokers with normal lung function, and nine nonsmoking control subjects. Peripheral airways were examined with histochemical methods to identify goblet cells and with immunohistochemical methods to identify total leukocytes (CD45(+) cells), neutrophils, macrophages, CD4(+) and CD8(+) cells in the epithelium. When compared with nonsmokers, smokers with both symptoms of chronic bronchitis and chronic airflow limitation had an increased number of goblet cells (p < 0.01), CD45(+) cells (p < 0. 01), macrophages (p < 0.05), and CD8(+) cells (p < 0.01) in the epithelium of peripheral airways. When all the smokers were grouped together, they showed an increased number of neutrophils (p < 0.05) along with an increased number of goblet cells, CD45(+) cells, macrophages and CD8(+) cells (p < 0.05) compared with nonsmokers. In conclusion, smokers with both symptoms of chronic bronchitis and chronic airflow limitation have an increased number of goblet cells and inflammatory cells in the epithelium of peripheral airways.

Ki-67 scores and AgNor counts in transitional cell carcinoma of the bladder: apparent lack of prognostic value.

The cellular proliferative state of 18 incident cases of transitional cell carcinomas of the bladder treated with transurethral resection was blindly determined by two independent observers using Ki-67 monoclonal antibody and silver stain for nucleolar organizer regions (AgNORs). Ki-67 scores were significantly related to histological grade (WHO) (rs = 0.65, p < 0.01) and clinical stage (UICC) (rs = 0.46, p < 0.05). However, the follow-up analysis over a six year period did not demonstrate significant relationship between Ki-67 values and survival. AgNOR counting did not show significant association with any of the variables under study. The results of this investigation and the review of the pertinent literature suggest that the assessment of cell proliferation of bladder carcinoma by means of Ki-67 and AgNOR techniques is far from having immediate direct influence on patient management.

[Tumor grading in urinary cytology. A study of the cytohistological relationship with evaluation of the kappa statistic for concordance]. / Il grading tumorale in citologia urinaria. Studio della correlazione cito-istologica con valutazione del kappa statistico per la concordanza.

In order to verify both usefulness and reliability of cytologic grading evaluated on urinary sediment, we designed a study to test the ability to distinguish consistently between different degrees of neoplastic abnormalities of urothelial cells from voided urine, in relation to the histologic findings of bladder biopsies performed after cytologic reading. Kappa measures were calculated in 112 cytohistologic pairs representative of first disease detection (A) and in 35 pairs representative of disease recurrence (B). Cytology was able to correctly identify a cancer in 70.5% and 80.0% of group A and group B lesions, respectively. Unweighted kappa values of both groups A and B were poor (0.298 and 0.324 respectively). When we considered the weighted kappa, values suggesting fair agreement were obtained (0.576 and 0.500). Our data confirm that urinary cytology shows a good sensitivity in detecting bladder cancer, but it does not seem to give reliable results for the assessment of the tumor grading.

[Correlation between histological grading and cell growth fraction in bladder tumors]. / Correlazione tra grading istologico e frazione di crescita nei carcinomi vescicali.

30 carcinomas and 1 papilloma of bladder were studied by immunohistochemical method with a monoclonal antibody Ki-67 (Dako-PC) reacting with a nuclear antigen present in cells of the mitotic phases G1, S, G2 and M. Authors would like determine the growth ratio (correlation between the number of cells in mitotic cycle and the total number of cells) of the neoplastic cell populations to compare it to the grading of themselves established by traditional parameters. It was shown, as in other carcinoma type, that the down grading correspondent with augmentation of cell growth fraction. It is of interest to verify that among carcinoma of different grading there are values partially corresponding for the growth fraction. This confirm what are going to demonstrate all those studies by means of flow cytometry and image analysis: grading of neoplasias as now fixed, doesn't give a satisfactory index for prognosis.

[Temporal resolving capacity of the auditory analyzer of the dolphin Tursiops truncatus]. / K voprosu o razreshaiushchei sposobnosti po vremeni slukhovogo analizatora del'fina Tursiops truncatus.

Differential threshold of discrimination of paired stimuli in relation to interimpulse interval has been investigated in man and porpoise. Similar features in mechanisms of discrimination of paired impulses in man and porpoise are noted. It was shown that threshold-interimpulse interval surve may be divided into several parts: two zones in which discrimination is made by different characters, and single transitional zone from one character to another.