EST is a relatively safe and effective procedure in the treatment of choledocholithiasis. The best prognostic factor is the presence of choledocholithiasis alone. Concurrent choledocholithiasis and cholecystolithiasis carry a more adverse prognosis, and in these cases cholecystectomy should be considered after EST.

Signal transduction is essential for bacteria to adapt to changing environmental conditions. Among many forms of post-translational modifications, reversible protein phosphorylation has evolved as a ubiquitous molecular mechanism of protein regulation in response to specific stimuli. The Ser/Thr protein kinase PknG modulates the fate of intracellular glutamate by controlling the phosphorylation status of the 2-oxoglutarate dehydrogenase regulator OdhI, a function that is conserved among diverse actinobacteria. PknG has a modular organization characterized by the presence of regulatory domains surrounding the catalytic domain. Here we present an investigation through in vivo experiments as well as biochemical and structural methods of the molecular bases of the regulation of PknG from C. glutamicum (CgPknG), in the light of previous knowledge available for the kinase from M. tuberculosis (MtbPknG). We found that OdhI phosphorylation by CgPknG is regulated by a conserved mechanism that depends on a C-terminal domain composed of tetratricopeptide repeats (TPR) essential for metabolic homeostasis. Furthermore, we identified a conserved structural motif that physically connects the TPR domain and a flexible N-terminal extension of the kinase that is involved in docking interactions with OdhI. Based on our results and previous reports, we propose a model in which the TPR domain of PknG couples signal detection to the specific phosphorylation of OdhI. Overall, the available data indicate that conserved PknG domains in distant actinobacteria retain their roles in kinase regulation in response to nutrient availability.IMPORTANCEBacteria control the metabolic processes by which they obtain nutrients and energy in order to adapt to the environment. In this way, the metabolic characteristics of a microorganism determine its ecological role and its usefulness in industrial processes. Here, we use genetic, biochemical, and structural approaches to study a key component in a system that regulates glutamate production in C. glutamicum, a species that is used for the industrial production of amino acids. We elucidated molecular mechanisms involved in metabolic control in C. glutamicum, which are conserved in related pathogenic bacteria. The findings have broader significance for diverse actinobacteria, including microorganisms that cause disease as well as environmental species used to produce billions of dollars of amino acids and antibiotics every year.

. (1975). Thorax, 30,[371][372][373][374][375][376][377][378][379][380][381] Myocardial ultrastructural changes during extracorporeal circulation with anoxic cardiac arrest and its prevention by coronary perfusion. Experimental study. This experimental work has been carried out with the aim of studying the ultrastructural myocardial changes caused by prolonged anoxic cardiac arrest during cardiopulmonary bypass, and their prevention by means of two different techniques of coronary perfusionsystemic-pressure continuous and low-pressure intermittent perfusion.After 30 minutes of cardiac anoxia, the ultrastructural changes of the myocardial cell were reverted to normal by coronary perfusion; when anoxic cardiac arrest was prolonged up to 60 minutes there was severe myocardial damage, with marked mitochondrial changes and dehiscence of intercalated discs, which persisted in spite of restoring coronary flow. These morphological data were in accordance with the fact that no dog which underwent anoxic cardiac arrest for 60 minutes recovered.Both intermittent and continuous coronary perfusion were effective in preventing anoxic damage; cardiac muscle cells were better preserved by low-pressure intermittent perfusion than by systemic-pressure continuous perfusion, which caused intracellular and intramitochondrial oedema.

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BACKGROUND New echocardiographic phenotypes of heart failure (HF) are focused on myocardial systolic involvement of the left ventricle (LV), either endocardial and/or transmural. PURPOSE. To study the pattern of myocardial involvement in patients (p) with HF with preserved left ventricular ejection fraction (pLVEF) and cardiac amyloidosis (CA). METHODS. Comparative study of 16 p with CA and HF with pLVEF, considering as cut point LVEF > 50%, in NYHA class ≥ II / IV, and a control group of 16 healthy people. Longitudinal Strain (LS) and Circumferential Strain (CS) were calculated using 2D speckle-tracking echocardiography, along with Mitral Annulus Plane Systolic Excursion (MAPSE) and Base-Apex distance (B-A). Also, the following indexes were calculated: Twist (apical rotation + basal rotation, º); Classic Torsion (TorC): (twist/B-A, º/cm); Torsion Index (Tor.I): (twist/MAPSE, º/cm) and Deformation Index (Def.I): (twist/LS, º). We suggest the introduction of these dynamic torsion indexes as Tor.I and Def.I that include twist per unit of longitudinal systolic shortening of the LV instead of using TorC which is the normalisation of twist to the end-diastolic longitudinal diameter of the LV. RESULTS There were no differences of age between the groups (68.2 ± 11.5 vs 63.7 ± 2.8 years, p = 0.14). Global values of LS and CS were lower in p with CA indicating endocardial and transmural deterioration during systole, while TorC and Twist of the LV remained conserved in p with CA. However, there is an increase of dynamic torsion parameters such as Tor.I and Def.I that show an increased Twist per unit of longitudinal shortening of the LV in the CA group (Table). CONCLUSIONS In p with CA and HF with pLVEF, the impairment of LS and CS indicates endocardial and transmural systolic dysfunction. In these conditions, LVEF would be preserved at the expense of a greater dynamic torsion of the LV. Table LS (%) CS (%) Twist (º) TorC (º/cm) Tor.I (º/cm) Def.I (º/%) CA pLVEF (n = 16) -11.7 ± 4.2 17.2 ± 4.8 19.8 ± 8.3 2.5 ± 1.1 27.7 ± 13.5 -1.8 ± 0.9 Control Group (n = 15) -20.6 ± 2.5 22.7 ± 4.9 21.7 ± 6.1 2.7 ± 0.8 16.4 ± 4.7 -1.0 ± 0.3 p < 0.001 < 0.01 0.46 0.46 < 0.01 < 0.01 Dynamic Torsion Indexes and Classic Torion Parameters in pLVEF CA patients vs Control group.

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The success of the ST-segment elevation myocardial infarction (STEMI) approach is based on early diagnosis and on the institution of timely reperfusion therapy, with response times remaining variable. The objective of this study was to determine which factors influenced the response time to patients with STEMI until the treatment with coronary reperfusion from the prehospital service or the emergency room in three hospitals in the greater Lisbon area in 2017. An epidemiological, cross-sectional, retrospective, descriptive study with an analytical component was performed, with data from the National Institute of Medical Emergency (INEM) and clinical trials of patients. Patients who were not referred to these hospitals were excluded. Univariate statistical analysis was performed, as well as c2 tests, t-student and logistic regression model (r < 0.05). The population included 95 patients, the majority being male (67.4%), and with a mean age of 63.8 years. 61.1% were hypertensive and the majority (87.4%) had no signs of previous heart failure. The mean door-to-balloon time was 159 minutes, with 57.4% showing time greater than 120 minutes. In patients in whom the INEM Coronary Greenway was activated, mean door-to-balloon time was 99 minutes. Diagnostic, symptom-admission and transport times showed a statistically significant association with the door-to-balloon time in the bivariate analysis. The times are fulfilled in the prehospital service, but in the hospital, services can be improved through the early accomplishment of electrocardiogram and the optimization of interhospital transport. Key messages Reducing ECG time and inter-hospital transport time improves STEMI response and outcome. Time is muscle is the main message for de concern of identifying influence factors of STEMI response time.