The Regulation of Cbf1 by PAS Kinase Is a Pivotal Control Point for Lipogenesis Versus Respiration in Saccharomyces cerevisiae

PAS kinase 1 (Psk1) is a key regulator of respiration in Saccharomyces cerevisiae. Herein the molecular mechanisms of this regulation are explored through the characterization of its substrate, Centromere binding factor 1 (Cbf1). CBF1-deficient yeast displayed a significant decrease in cellular respiration, while PAS kinase-deficient yeast, or yeast harboring a Cbf1 phosphosite mutant (T211A) displayed a significant increase. Transmission electron micrographs showed an increased number of mitochondria in PAS kinase-deficient yeast consistent with the increase in respiration. Although the CBF1-deficient yeast did not appear to have an altered number of mitochondria, a mitochondrial proteomics study revealed significant differences in the mitochondrial composition of CBF1-deficient yeast including altered Atp3 levels, a subunit of the mitochondrial F₁-ATP synthase complex. Both beta-galactosidase reporter assays and western blot analysis confirmed direct transcriptional control of ATP3 by Cbf1. In addition, we confirmed the regulation of yeast lipid genes LAC1 and LAG1 by Cbf1. The human homolog of Cbf1, Upstream transcription factor 1 (USF1), is also known to be involved in lipid biogenesis. Herein, we provide the first evidence for a role of USF1 in respiration since it appeared to complement Cbf1 in vivo as determined by respiration phenotypes. In addition, we confirmed USF1 as a substrate of human PAS kinase (hPASK) in vitro. Combined, our data supports a model in which Cbf1/USF1 functions to partition glucose towards respiration and away from lipid biogenesis, while PAS kinase inhibits respiration in part through the inhibition of Cbf1/USF1.

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Broadening the operative field: the extent of surgery beyond the patient`s informed consent (the so-called therapeutic exception)

W artykule omówiono przesłanki tzw. wyjątku terapeutycznego, uregulowanego w art. 35 ustawy z dnia 5 grudnia 1996 r. o zawodach lekarza i lekarza dentysty. Konstrukcja ta pozwala lekarzowi, w trakcie operacji, na zmianę zakresu zabiegu ponad zgodę wyrażoną przez pacjenta. Ponadto poruszono kwestię tzw. zgody antycypacyjnej oraz warunki jej skuteczności oraz wyjaśniono, czy w wypadku realizacji przesłanek wyjątku terapeutycznego lekarz jedynie może dokonać odpowiedniej modyfikacji czynności operacyjnych, czy też jest to jego obowiązek. Wskazano również, że w omawianej sytuacji lekarz nie może powoływać się na tzw. stan wyższej konieczności. Prezentowane treści zostały wzbogacone o przedstawienie konkretnych spraw sądowych i ich rozstrzygnięć.

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Inter-arm differences in blood pressure among subjects with disseminated atherosclerosis scheduled for vascular surgery

Background: The measurement of blood pressure (BP) is routinely performed in perioperative care. The reliability of results is essential for the implementation of treatment ensuring haemodynamic stability. The aim of the present study was to assess the prevalence and basic determinants of inter-arm BP differences among patients with advanced peripheral atherosclerosis undergoing vascular surgical procedures of the lower limbs. Methods: The prospective study was carried out in patients scheduled for elective lower limb vascular surgery. One-time non-invasive BP measurements were performed sequentially on the brachial arteries of both upper extremities before the induction of anaesthesia, maintaining the shortest possible interval between measurements. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded. Results: The results of 173 patients (including 123 men aged 67 ± 8 years) were analysed. In 16 (9.3%) patients, an inter-arm difference in BP was already observed during the preoperative examination. SBP and DBP was higher in the right limb in 86 (49.7%) an 80 (46.3%) patients, respectively. Moreover, the medians of inter-arm differences in SBP, DBP and MAP were 9 (IQR 4–17), 5 (IQR 3–10) and 7 mm Hg (IQR 3–12), respectively. An evaluation of the determinants of BP differences related to the presence of additional diseases demonstrated that patients with arterial hypertension were characterised by higher SBP and MAP disproportions (P = 0.04 and P = 0.01). Conclusions: In the population of patients with disseminated atherosclerosis, the inter-arm differences in BP substantially exceed the measurement error limits and are likely to be associated with arterial hypertension. If in doubt about BP disproportions, intraoperative monitoring of BP should be recommended using an invasive method on the limb presenting higher non-invasively measured values.

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Risk factors for occurrence of failed interscalene brachial plexus blocks for shoulder arthroscopy using 20 mL 0.5% ropivacaine: a randomised trial

Background: The red blood cell distribution width index (RDW) is one of several parameters routinely analysed in peripheral blood counts. The aim of the study was to assess the usefulness of RDW in the prediction of in-hospital mortality in patients undergoing high-risk gastroenterological surgery. Methods: Prospective observation covered 229 patients who underwent surgery, for whom the risk of cardiovascular complications was high due to the type of procedure. The patient's individual risk was assessed using the criteria of the American Society of Anesthesiologists (ASA-PS). Peripheral blood for morphological examination was collected preoperatively. The following parameters of the red blood cell system were evaluated: red blood cell count (RBC), haemoglobin (Hgb), haematocrit (Hct), mean corpuscular volume (MCV), RDW expressed as a standard deviation (SD) and a coefficient of variation (CV). The occurrence of hospital death was the main endpoint. Results: Patients who died had had statistically significantly lower RBC, Hgb and Hct values, as well as higher RDW-SD and RDW-CV values. Both the preoperative RDW-SD and RDW-CV values predicted the outcome, respectively: AUC_RDW-SD = 0.744 (95% CI: 0.683–0.799; P RDW-CV = 0.762 (95% CI: 0.702–0.816; P RDW-SD = 1.21; P RDW-CV = 1.62; P = 0.01), even after adjustment for individual risk and other erythrocyte parameters. Conclusion: RDW is a valuable screening predictor of in-hospital mortality in patients undergoing high-risk gastroenterological surgery, regardless of the estimated individual risk and the value of other erythrocyte parameters. Evaluation of the RDW may be helpful in the identification of patients requiring correction of haematological disorders in the pre-operative period, as well as, in particular, surveillance in the perioperative period.

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Use of noninvasive mechanical ventilation with pressure support guaranteed with average volume in de novo hypoxaemic respiratory failure. A pilot study

Background: This study was designed to determine the results associated with the use of noninvasive mechanical ventilation (NIV) using the BiPAP S/T-AVAPS ventilation strategy in subjects with mild to moderate de novo hypoxaemic respiratory failure. Methods: This is a prospective study that includes subjects with de novo hypoxaemic respiratory failure (not produced by acute exacerbations of COPD, chronic lung disease, or congestive heart failure) with mild to moderate PaO₂/FiO₂, who were admitted to the Intensive Care Unit (ICU) of Santa Maria Clinic in Guayaquil, Ecuador. Subjects were divided into two groups and compared according to their PaO₂/FiO₂: higher than 100 and up to 200 mm Hg (moderate ARDS) or between 200 and 300 mm Hg (mild ARDS) (both groups were ventilated with the BiPAP S/T-AVAPS strategy). A value of P Results: A total of 38 subjects were analysed in this study. The total rate of intubation was 34.2% while the mortality rate was 28.9%. Significant differences were observed when comparing success versus failure in exhaled tidal volumes (P = 0.04), peak inspired pressure (P 2 (P 2 (P 2/FiO₂ (P P P = 0.029) measured at baseline and at 12-hour, 24-hour and 48-hour intervals. Conclusion: The BiPAP S/T-AVAPS ventilatory mode can be used in subjects with de novo hypoxaemic respiratory failure with special vigilance concerning exhaled tidal volumes and inspired pressure.

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Peri-anaesthetic cardiac arrest with administration of enalapril, spironolactone and β-blocker

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Postoperative pain after spinal surgery in the paediatric population

Introduction: Postoperative pain is a major aftereffect of surgery. Especially severe occurs after extensive operations within the spine. The goal of the study was to investigate the laboratory predictive factors of intensive postoperative pain in children undergoing extensive surgery Patients and methods: We recruited 41 children, age median 13 years (IQR:10-15 years) undergoing extensive spine surgery. The subjects were divided into two groups based on the intensity of postoperative pain measured using the 10-point numerical rating scale (NRS), visual analog scale (VAS) or faces pain scale-revised (FPS-R). Patients with a score of 5 or higher were included in the study group and those with NRS of less than 5 were included in the control group. We collected detailed clinical and laboratory data before, during and after surgery. Results: The highest intensity of pain was observed in the first 6 hours after surgery. The postoperative pain was associated with a higher drop in hemoglobin concentration and hematocrit level in peri-operative period (p=0.006 and p=0.019 respectively) as well as higher changes in mean arterial pressure during surgery. Additionally, we found that children with intensive pain had higher total protein concentration after surgery. Conclusions: We reported that the drop in hemoglobin and hematocrit level, fluctuation in mean arterial pressure as well as total protein concentration could be useful prognostic factors of early postoperative pain.

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