Readiness of future teachers for sociocultural education of children in modern conditions of society development

The modern sociocultural situation of the development of society involves taking into account all aspects of human life in the educational process. Are our students - future preschool teachers - ready to build their activities taking into account socio-cultural aspects. The authors consider the characteristic of readiness, highlighting motivational and value-based component (awareness of the importance of their process, readiness for continuous improvement and professional development, highlighting the values of professional activity), activity-technological component (knowledge of the ways of interaction with the subjects of the pedagogical process, design of the educational and educational process, the use of modern teaching tools (IT), information and knowledge component (knowledge of the specifics of preschool childhood, modern trends in the development of society and education, learning technologies). The study shows the insufficient level of development of the 2nd and the 3rd components of the readiness of future teachers. The proposed methods of professional training of future teachers of preschool education are associated with the use of business games, conducting master classes, studying the technological component of the educational process

Loss of ATP-Sensitive Potassium Channel Surface Expression in Heart Failure Underlies Dysregulation of Action Potential Duration and Myocardial Vulnerability to Injury.

The search for new approaches to treatment and prevention of heart failure is a major challenge in medicine. The adenosine triphosphate-sensitive potassium (KATP) channel has been long associated with the ability to preserve myocardial function and viability under stress. High surface expression of membrane KATP channels ensures a rapid energy-sparing reduction in action potential duration (APD) in response to metabolic challenges, while cellular signaling that reduces surface KATP channel expression blunts APD shortening, thus sacrificing energetic efficiency in exchange for greater cellular calcium entry and increased contractile force. In healthy hearts, calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates the Kir6.2 KATP channel subunit initiating a cascade responsible for KATP channel endocytosis. Here, activation of CaMKII in a transaortic banding (TAB) model of heart failure is coupled with a 35-40% reduction in surface expression of KATP channels compared to hearts from sham-operated mice. Linkage between KATP channel expression and CaMKII is verified in isolated cardiomyocytes in which activation of CaMKII results in downregulation of KATP channel current. Accordingly, shortening of monophasic APD is slowed in response to hypoxia or heart rate acceleration in failing compared to non-failing hearts, a phenomenon previously shown to result in significant increases in oxygen consumption. Even in the absence of coronary artery disease, failing myocardium can be further injured by ischemia due to a mismatch between metabolic supply and demand. Ischemia-reperfusion injury, following ischemic preconditioning, is diminished in hearts with CaMKII inhibition compared to wild-type hearts and this advantage is largely eliminated when myocardial KATP channel expression is absent, supporting that the myocardial protective benefit of CaMKII inhibition in heart failure may be substantially mediated by KATP channels. Recognition of CaMKII-dependent downregulation of KATP channel expression as a mechanism for vulnerability to injury in failing hearts points to strategies targeting this interaction for potential preventives or treatments

Molecular autopsy: using the discovery of a novel de novo pathogenic variant in the KCNH2 gene to inform healthcare of surviving family

Background: Molecular testing of the deceased (Molecular Autopsy) is an overlooked area in the United States healthcare system and is not covered by medical insurance, leading to ineffective care for surviving families of thousands of sudden unexpected natural deaths each year. We demonstrated the precision management of surviving family members through the discovery of a novel de novo pathogenic variant in a decedent. Methods: Forensic investigation and molecular autopsy were performed on an 18-year-old female who died suddenly and unexpectedly. Co-segregation family study of the first-degree relatives and functional characterization of the variant were conducted. Findings: We identified a novel nonsense variant, NP_000229.1:p.Gln1068Ter, in the long QT syndrome type II gene KCNH2 in the decedent. This finding correlated with her ante-mortem electrocardiograms. Patch clamp functional studies using transfected COS-7 cells show that hERG-ΔQ1068 has a mixed phenotype, with both gain- (negative voltage shift of steady-state activation curve, the positive shift of the steady-state inactivation curve, and accelerated activation) and loss-of function (reduced current density, reduced surface expression and accelerated deactivation) hallmarks. Loss of cumulative activation during rapid pacing demonstrates that the loss-of-function phenotype predominates. The wild-type channel did not rescue the hERG-ΔQ1068 defects, demonstrating haploinsufficiency of the heterozygous state. Targeted variant testing in the family showed that the variant in KCNH2 arose de novo, which eliminated the need for exhaustive genome testing and annual cardiac follow-up for the parents and four siblings. Interpretation: Molecular testing enables accurate determination of natural causes of death and precision care of the surviving family members in a time and cost-saving manner. We advocate for molecular autopsy being included under the healthcare coverage in US

K_ATP channel surface expression is down-regulated in ventricles of hearts after transverse aortic banding.

<p>A) Representative western blots of the K_ATP Kir6.2 subunit and the sodium-potassium pump (Na⁺-K⁺ pump) from the biotinylated membrane fraction of ventricular tissue from isolated hearts of sham and TAB mice. <b>B)</b> Summary of ventricular membrane Kir6.2 expression normalized to Na⁺-K⁺ pump expression in hearts of sham and TAB mice (*p<0.05 <i>vs</i>. sham). <b>C)</b> Representative current profiles of isolated left ventricular myocytes before and after application of the K_ATP channel activators, pinacidil (PIN, 100 μM) and 2,4-dinitrophenol (DNP, 200 μM). <b>D)</b> Summary of K_ATP channel current density (after-before K_ATP channel activations) from isolated ventricular cardiomyocytes of sham and TAB mice (**p<0.01 <i>vs</i>. sham).</p

Monophasic action potential duration shortening is blunted in failing hearts.

<p>Monophasic action potentials were measured from a single left ventricular epicardial position in isolated hearts from TAB and sham mice before and during exposure to hypoxia or abrupt heart rate acceleration from 400 beats per minute (bpm) to 667 bpm (150 msec cycle length to 90 msec cycle length) driven by pacing. <b>A)</b> Representative normalized monophasic action potentials at baseline (solid lines) and in response to hypoxia (dotted lines) from hearts of sham (left panel) and TAB (right panel) mice. A horizontal line designates the point at which monophasic action potential duration at 90% repolarization (MAPD₉₀) was measured. <b>B)</b> Summary of MAPD₉₀ shortening (left), half-time (t_1/2) of MAPD₉₀ shortening (middle), and rate of MAPD₉₀ shortening (right) in hearts from sham and TAB mice in response to hypoxia (*p < .05). <b>C)</b> Summary of MAPD₉₀ shortening (left), half-time (t_1/2) of MAPD₉₀ shortening (middle), and rate of MAPD₉₀ shortening (right) in hearts from sham and TAB mice in response to heart rate acceleration (*p < .05).</p

CaMKII is activated in ventricles of hearts following transverse aortic banding.

<p><b>A)</b> Representative western blots of phosphorylated CaMKII (P-CaMKII), oxidized CaMKII (Ox-CaMKII), total CaMKII (T-CaMKII) and GAPDH in ventricles of sham and TAB mice as labelled by whole-heart biotinylation. <b>B)</b> Summary of P-CaMKII, Ox-CaMKII and T-CaMKII quantification from western blots in ventricles of sham and TAB mice (*p<0.05, **p < .01 <i>vs</i>. sham).</p