Anesthesia and cognitive performance in children: No evidence for a causal relationship

* Both authors contributed evenly to the manuscript Recent findings of an association between anesthesia administration in the first three years of life and later learning disabilities have created concerns that anesthesia has neurotoxic effects on synaptogenesis, causing later learning problems. An alternative hypothesis is that those children who are likely to undergo surgery early in life have significant medical problems that are associated with a vulnerability to learning disabilities. These two hypotheses were evaluated in a monozygotic concordant–discordant twin design. Data on anesthesia administration and learning abilities and disabilities were available for 1,143 monozygotic twin pairs (56 % female) from the Netherlands Twin Registry. Parents of the twins reported on anesthesia use before age 3 and again between ages 3 and 12 years. Near age 12, educational achievement and cognitive problems were assessed with standardized tests and teacher ratings. Results showed that twins who were exposed to anesthesia before age 3 had significantly lower educational achievement scores and significantly more cognitive problems than twins not exposed to anesthesia. However, there was one important exception: the unexposed co-twin from discordant pairs did not differ from their exposed cotwin. Thus, there is no evidence for a causal relationship between anesthesia administration and later learning-related outcomes in this sample. Rather, there is evidence for early anesthesia being a marker of an individual’s vulnerability for later learning problems, regardless of their exposure to anesthesia

Cardiorespiratory fitness in volleyball athletes following a covid-19 infection: A cross-sectional study

Athletes’ lifestyles have been dramatically affected by the coronavirus disease 2019 (COVID-19) pandemic. Since COVID-19 primarily affects the respiratory system and to a lesser degree the cardiovascular system, the goal of this study was to examine the effects of COVID-19-caused detraining on cardiorespiratory fitness (CRF) of recently recovered volleyball athletes. Sixteen experienced volleyball athletes (age 24 ± 4.5 years) who were recently diagnosed and recovered from a COVID-19 infection volunteered to participate in this study and were tested for CRF and spirometry. Given that participants had only mild symptoms of infection, the primary focus of this study was on the effects of detraining on CRF. On average, the time to exhaustion was 9.4 ± 1.4 min. VE, VCO2, RER and oxygen pulse increased, heart rate exceeded 90% of predicted values, and peak VO2 values were typical for this level of athlete (44.1 ± 3.4 mL/kg). Pulmonary function reflected in FVC, FEV1/FVC and MVV values were well above 80% of predicted values for each of the participants while electrocardiography revealed no ischemia, arrythmias or conduction and repolarization abnormalities were found in the tested subjects. Conclusions: participants experienced typical consequences of detraining. Due to a lack of CRF data prior to COVID-19 infection, we were unable to estimate the magnitude detraining had on CRF. Complete CRF assessment after COVID-19 infection in athletes can be useful for screening of residual myocardial and/or respiratory system damage for safe return-to-play decisions

Selenotriapine – An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors

Triapine, the most studied α-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay

From Davydov solitons to decoherence-free subspaces: self-consistent propagation of coherent-product states

The self-consistent propagation of generalized $D_{1}$ [coherent-product] states and of a class of gaussian density matrix generalizations is examined, at both zero and finite-temperature, for arbitrary interactions between the localized lattice (electronic or vibronic) excitations and the phonon modes. It is shown that in all legitimate cases, the evolution of $D_{1}$ states reduces to the disentangled evolution of the component $D_{2}$ states. The self-consistency conditions for the latter amount to conditions for decoherence-free propagation, which complement the $D_{2}$ Davydov soliton equations in such a way as to lift the nonlinearity of the evolution for the on-site degrees of freedom. Although it cannot support Davydov solitons, the coherent-product ansatz does provide a wide class of exact density-matrix solutions for the joint evolution of the lattice and phonon bath in compatible systems. Included are solutions for initial states given as a product of a [largely arbitrary] lattice state and a thermal equilibrium state of the phonons. It is also shown that external pumping can produce self-consistent Frohlich-like effects. A few sample cases of coherent, albeit not solitonic, propagation are briefly discussed.Comment: revtex3, latex2e; 22 pages, no figs.; to appear in Phys.Rev.E (Nov.2001

Stability of Terrestrial Planets in the Habitable Zone of Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208

We have undertaken a thorough dynamical investigation of five extrasolar planetary systems using extensive numerical experiments. The systems Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208 were examined concerning the question of whether they could host terrestrial like planets in their habitable zones (=HZ). First we investigated the mean motion resonances between fictitious terrestrial planets and the existing gas giants in these five extrasolar systems. Then a fine grid of initial conditions for a potential terrestrial planet within the HZ was chosen for each system, from which the stability of orbits was then assessed by direct integrations over a time interval of 1 million years. The computations were carried out using a Lie-series integration method with an adaptive step size control. This integration method achieves machine precision accuracy in a highly efficient and robust way, requiring no special adjustments when the orbits have large eccentricities. The stability of orbits was examined with a determination of the Renyi entropy, estimated from recurrence plots, and with a more straight forward method based on the maximum eccentricity achieved by the planet over the 1 million year integration. Additionally, the eccentricity is an indication of the habitability of a terrestrial planet in the HZ; any value of e>0.2 produces a significant temperature difference on a planet's surface between apoapse and periapse. The results for possible stable orbits for terrestrial planets in habitable zones for the five systems are summarized as follows: for Gl 777 A nearly the entire HZ is stable, for 47 Uma, HD 72659 and HD 4208 terrestrial planets can survive for a sufficiently long time, while for Gl 614 our results exclude terrestrial planets moving in stable orbits within the HZ.Comment: 14 pages, 18 figures submitted to A&

Pazopanib and trametinib as a synergistic strategy against osteosarcoma: Preclinical activity and molecular insights

Receptor tyrosine kinases (RTKs) inhibitors’ activity in advanced osteosarcoma is significant but short-lived. To prevent or at least delay drug resistance, we explored a vertical inhibition by combining drugs acting at different levels of the RTK pathways (pazopanib + trametinib). We studied pazopanib + trametinib antitumor activity both in vitro and in vivo (MNNG-HOS and KHOS xenografts in NOD/SCID mice) investigating the molecular mechanisms and potential escapes. The involvement of MAPK-PI3K pathways was validated by Nanostring technology, western blot and by silencing/overexpression experiments. Pazopanib targets were expressed on seven osteosarcoma cell lines and their pathways were activated. Pazopanib + trametinib exhibited synergistic antitumor activity by inducing apoptosis and inhibiting ERK1/2 and Akt. In vivo antitumor activity was shown in osteosarcoma-bearing mice. The drug combination significantly down-modulated RTK Ephrin Type-A Receptor 2 (EphA2) and Interleukin-7 Receptor (IL-7R), whereas induced mitogen-activated protein-kinase kinase (MAPKK) MEK6. EphA2 silencing significantly reduced osteosarcoma cell proliferation and migration, while impeding MEK6 up-regulation in the treated cells significantly increased the antitumor effect of the studied drugs. Moreover, the up-regulation of MEK6 reduced combination activity. Pazopanib + trametinib demonstrated synergistic antitumor effects in osteosarcoma models through ERK and Akt inhibition and EphA2 and IL-7R down-modulation. MEK6 up-regulation might evoke escaping mechanism

Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar

Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approache

The utility of Tc-99m-EDDA/HYNIC-TOC scintigraphy for assessment of lung lesions in patients with neuroendocrine tumors

Our aim was to assess clinical utility of Tc-99m-EDDA/HYNIC-TOC scintigraphy for evaluation of lung lesions in patients with neuroendocrine tumors (NETs). Single photon emission computed tomography (SPECT) of the thorax and whole body scintigraphy were performed in 34 patients using Tc-99m-EDDA/HYNIC-TOC. Visual assessment was complemented by semiquantitative evaluation based on tumor to non-tumor (TINT) ratio. Clinical, laboratory, and histological findings served as the standard for comparison. Enhanced tracer uptake was observed on both SPECT and whole body scintigraphy in 29 of 34 patients (88% sensitivity). TINT ratios were significantly higher on SPECT than whole body images (2.96 +/- 1.07 vs. 1.70 +/- 0.43, p LT 0.01) and did not correlate with NET proliferation index Ki-67 (r= - 0.36, p=0.27). Conclusion: Tc-99m-EDDA/HYNIC-TOC scintigraphy is useful for evaluation of NET tissue in the lungs. SPECT provides better visualization of lung lesions than whole body scintigraphy. The intensity of tracer uptake, however, does not relate to the proliferation rate of NETs. Tc-99m-EDDA/HYNIC-TOC scintigraphy may be helpful for selecting and monitoring treatment options, particularly when radiolabeled somatostatin analogue therapy becomes available