Medical Education in Costa Rica. From Flexner to COVID-19: Integrative Answers for Old and New Challenges.

Unlabelled: This monograph describes key aspects of medical education in a middle-income country such as Costa Rica, with an emphasis on public education. The main strengths and challenges of our curriculum are presented, as well as some recently implemented modernization measures to address the challenges described. Special attention is given to simulation training in medicine to promote systematic and integrative medical education in a problem-solving context.

Alterations of the skeletal muscle contractile apparatus in necrosis induced by myotoxic snake venom phospholipases A: a mini-review.

Skeletal muscle necrosis is a common clinical manifestation of snakebite envenoming. The predominant myotoxic components in snake venoms are catalytically-active phospholipases A (PLA) and PLA homologs devoid of enzymatic activity, which have been used as models to investigate various aspects of muscle degeneration. This review addresses the changes in the contractile apparatus of skeletal muscle induced by these toxins.

Skeletal muscle fiber hypercontraction induced by Bothrops asper myotoxic phospholipases A ex vivo does not involve a direct action on the contractile apparatus.

Myonecrosis is a frequent clinical manifestation of envenomings by Viperidae snakes, mainly caused by the toxic actions of secreted phospholipase A (sPLA) enzymes and sPLA-like homologs on skeletal muscle fibers. A hallmark of the necrotic process induced by these myotoxins is the rapid appearance of hypercontracted muscle fibers, attributed to the massive influx of Ca resulting from cell membrane damage. However, the possibility of myotoxins having, in addition, a direct effect on the contractile machinery of skeletal muscle fibers when internalized has not been investigated.

Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus.

Viperid snake venoms contain a unique family of cytotoxic proteins, the Lys49 PLA homologs, which are devoid of enzymatic activity but disrupt the integrity of cell membranes. They are known to induce skeletal muscle damage and are therefore named 'myotoxins'. Single intact and skinned (devoid of membranes and cytoplasm but with intact sarcomeric proteins) rat cardiomyocytes were used to analyze the cytotoxic action of a myotoxin, from the venom of Bothrops asper.

Chemotherapy triggers cachexia by deregulating synergetic function of histone-modifying enzymes.

Background: Chemotherapy is the first line of treatment for cancer patients. However, the side effects cause severe muscle atrophy or chemotherapy-induced cachexia. Previously, the NF-κB/MuRF1-dependent pathway was shown to induce chemotherapy-induced cachexia.

The Positively Charged C-Terminal Region of Human Skeletal Troponin T Retards Activation and Decreases Calcium Sensitivity.

Calcium binding to troponin C (TnC) activates striated muscle contraction by removing TnI (troponin I) from its inhibitory site on actin. Troponin T (TnT) links TnI with tropomyosin, causing tropomyosin to move from an inhibitory position on actin to an activating position. Positive charges within the C-terminal region of human cardiac TnT limit Ca activation.

Hypertrophic and Dilated Cardiomyopathy-Associated Troponin T Mutations R130C and ΔK210 Oppositely Affect Length-Dependent Calcium Sensitivity of Force Generation.

Length-dependent activation of calcium-dependent myocardial force generation provides the basis for the Frank-Starling mechanism. To directly compare the effects of mutations associated with hypertrophic cardiomyopathy and dilated cardiomyopathy, the native troponin complex in skinned trabecular fibers of guinea pigs was exchanged with recombinant heterotrimeric, human, cardiac troponin complexes containing different human cardiac troponin T subunits (hcTnT): hypertrophic cardiomyopathy-associated hcTnT, dilated cardiomyopathy-associated hcTnT or the wild type hcTnT (hcTnT) serving as control. Force-calcium relations of exchanged fibers were explored at short fiber length defined as 110% of slack length ( ) and long fiber length defined as 125% of (1.

Cycling Cross-Bridges Contribute to Thin Filament Activation in Human Slow-Twitch Fibers.

It has been shown that not only calcium but also strong binding myosin heads contribute to thin filament activation in isometrically contracting animal fast-twitch and cardiac muscle preparations. This behavior has not been studied in human muscle fibers or animal slow-twitch fibers. Human slow-twitch fibers are interesting since they contain the same myosin heavy chain isoform as the human heart.