Acute fetal cardiovascular adaptation to artificial placenta in sheep model.

OBJECTIVE: To describe the acute cardiovascular adaptation of the fetus after connection to an artificial placenta (AP) in a sheep model, using ultrasound and invasive and non-invasive hemodynamic assessment. METHODS: This was an experimental study of 12 fetal sheep that were transferred to an AP system, consisting of a pumpless circuit with umbilical cord connection, at 109-117 days' gestation. The study was designed to collect in-utero and postcannulation measurements in all the animals. The first six consecutive fetuses were fitted with intravascular catheters and perivascular probes to obtain invasive physiological data, including arterial and venous intravascular pressures and perivascular blood flows, with measurements taken in utero and at 5 and 30 min after cannulation. These experiments were designed with a survival goal of 1-3 h. The second set of six fetuses were not fitted with catheters, and experiments were aimed at 3-24 h of survival. Echocardiographic assessment of cardiac anatomy and function, as well as measurements of blood flow and pre- and postmembrane pressures recorded by circuit sensors in the AP system, were available for most of the fetuses. These data were acquired in utero and at 30 and 180 min after cannulation. RESULTS: Compared with in-utero conditions, the pulsatility index at 30 and 180 min after connection to the AP system was reduced in the umbilical artery (median, 1.36 (interquartile range (IQR), 1.06-1.50) vs 0.38 (IQR, 0.31-0.50) vs 0.36 (IQR, 0.29-0.41); P < 0.001 for extreme timepoints) and the ductus venosus (median, 0.50 (IQR, 0.41-0.67) vs 0.29 (IQR, 0.22-0.33) vs 0.36 (IQR, 0.22-0.41); P = 0.011 for extreme timepoints), whereas umbilical venous peak velocity increased (median, 20 cm/s (IQR, 18-22 cm/s) vs 39 cm/s (IQR, 31-43 cm/s) vs 43 cm/s (IQR, 34-54 cm/s); P < 0.001 for extreme timepoints) and flow became more pulsatile. Intravascular monitoring showed that arterial and venous pressures increased transiently after connection, with median values for mean arterial pressure at baseline, 5 min and 30 min of 43 mmHg (IQR, 35-54 mmHg), 72 mmHg (IQR, 61-77 mmHg) and 58 mmHg (IQR, 50-64 mmHg), respectively (P = 0.02 for baseline vs 5 min). Echocardiography showed a similar transient elevation of fetal heart rate at 30 and 180 min after connection compared with in utero (median, 145 bpm (IQR, 142-156 bpm) vs 188 bpm (IQR, 171-209 bpm) vs 175 bpm (IQR, 165-190 bpm); P = 0.001 for extreme timepoints). Fetal cardiac structure and function were mainly preserved; median values for right fractional area change were 36% (IQR, 34-41%) in utero, 38% (IQR, 30-40%) at 30 min and 37% (IQR, 33-40%) at 180 min (P = 0.807 for extreme timepoints). CONCLUSIONS: Connection to an AP system resulted in a transient fetal hemodynamic response that tended to normalize over hours. In this short-term evaluation, cardiac structure and function were preserved. However, the system resulted in non-physiologically elevated venous pressure and pulsatile flow, which should be corrected to avoid later impairment of cardiac function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

A Systematic Review and Meta-analysis of the Medical Error Rate in Iran: 2005-2019.

BACKGROUND AND OBJECTIVES: Medical errors (MEs) are one of the main factors affecting the quality of hospital services and reducing patient safety in health care systems, especially in developing countries. The aim of this study was to determine the rate of ME in Iran. METHODS: This is a systematic literature review and meta-analysis of extracted data. The databases MEDLINE, EMBASE, Scopus, Cochrane, SID, Magiran, and Medlib were searched in Persian and English, using a combination of medical subject heading terms ("Medical Error" [Mesh] OR "Medication error" [Mesh] OR "Hospital Error" AND ("Iran" [Mesh]) for observational and interventional studies that reported ME rate in Iran from January 1995 to April 2019. We followed the STROBE checklist for the purpose of this review. RESULTS: The search yielded a total of 435 records, of which 74 articles were included in the systematic review. The rate of MEs in Iran was determined as 0.35%. The rates of errors among physicians and nurses were 31% and 37%, respectively. The error rates during the medication process, including prescription, recording, and administration, were 31%, 27%, and 35%, respectively. Also, incidence of MEs in night shifts was higher than in any other shift (odds ratio [OR] = 38%; 95% confidence interval [CI]: 31%-45%). Moreover, newer nurses were responsible for more errors within hospitals than other nurses (OR = 57%; 95% CI: 41%-80%). The rate of reported error after the Health Transformation Plan was higher than before the Health Transformation Plan (OR = 40%; CI: 33%-49% vs OR = 30%; CI: 25%-35%). CONCLUSION: This systematic review has demonstrated the high ME rate in Iranian hospitals. Based on the error rate attributed solely to night shifts, more attention to the holistic treatment process is required. Errors can be decreased through a variety of strategies, such as training clinical and support staff regarding safe practices and updating and adapting systems and technologies.

Tocol composition and supercritical carbon dioxide extraction of lipids from barley pearling flour.

Samples of whole grain and 35% pearling flour of 20 different barley varieties grown in Alberta were analyzed for their lipid contents. Total lipid contents of whole grains were within 1.9% to 3.0% (w/w), whereas those of the 35% pearling flour were 4.3% to 7.9%. Lipids of 35% pearling flour fraction of Tercel barley were extracted using supercritical carbon dioxide (SC-CO2 ) at different pressures (24, 45, and 58 MPa) and temperatures (40 and 60 °C) for 3 h. Lipid recoveries of 73% to 97% were achieved using SC-CO2 extraction under different operational conditions. Tocol contents and compositions of whole grain, 35% pearling flour, and SC-CO2 extracts were analyzed using HPLC. Tocol content of the whole grain was 53.8 to 124.9 µg/g and that of the pearling flour was 195 to 363 µg/g of flour. The hulless barley varieties were higher in tocols, with waxy, double waxy and Tercel varieties having the highest levels (P < 0.05). The ratios of total tocotrienols to total tocopherols varied within 1.6 to 3.9 range. Tocol concentrations of SC-CO2 extract fractions varied from 1171 to 4391 µg/g extract depending on the operational conditions. Barley oil is a good natural source of different tocol isomers rich in tocotrienols.

Microstructural changes in fat during the ripening of Iranian ultrafiltered Feta cheese.

In this study, fat globules in Iranian ultrafiltered Feta cheese (3 to 60 d) were directly observed during the ripening period by scanning electron microscopy. According to images of ultrafiltered Feta cheese samples obtained by scanning electron microscopy, individual fat globules and aggregates of fat were easily distinguishable on d 3 and had completely disappeared within 20 d of storage. On d 20, only the fingerprints of the fat globules and pools of free fat in the casein matrix remained. After 40 d of ripening, the texture was homogeneous and no fat globules or fat voids were detected. Chemical analysis of cheese samples showed that with an increase in the ripening period, the contents of dry matter and fat decreased significantly, whereas the pH values and salt content did not indicate any significant changes.

Effects of water on enzyme performance with an emphasis on the reactions in supercritical fluids.

Enzymes require a certain level of water in their structures in order to maintain their natural conformation, allowing them to deliver their full functionality. Furthermore, as a modifier of the solvent, up to a certain level, water can modify the solvent properties such as polarity/polarizability as well as the solubility of the reactants and the products. In addition, depending on the type of the reaction, water can be a substrate (e.g., in hydrolysis) or a product (e.g., in esterolysis) of the enzymatic reaction, influencing the enzyme turnover in different ways. It is found that regardless of the type of reaction, the functionality of enzyme itself is maximum at an optimum level of water, beyond which the enzyme performance is declined due to the loss in enzyme stability. Furthermore, mass transfer limitations caused by pathway blockage and/or by reduced solubilities of the reactants and/or products can also affect the enzyme performance at higher water levels. Controlling water content of ingoing CO2 and substrates as well as precise management of enzyme support and salt hydrates are important strategies to adjust water level in reaction media, especially in supercritical environments.

Effects of pressure and temperature on enzymatic reactions in supercritical fluids.

Supercritical fluids (SCFs) are receiving increasing attention as reaction media because they permit higher reaction rates compared with the conventional solvents. The ease of manipulating the physical properties of the SCFs enables easier control of the reaction conditions and easier solvent removal after the reaction. This review focuses on effects of pressure, temperature and the properties of the SCFs, on enzymatic reactions. Phase behavior, reaction rate and activation volume in SCFs are discussed. Within the ranges of pressure (10-40 MPa) and temperature (35-60 degrees C) that typically characterize the supercritical region, an increase in pressure and/or a decrease in temperature lead to a decrease in the enzyme turnover because the diffusion coefficients of the substrates migrating to the active sites of enzymes are affected.

Intrathecal administration of PNA targeting galanin receptor reduces galanin-mediated inhibitory effect in the rat spinal cord.

Peptide nucleic acids (PNA) are nucleic acid analogues containing neutral amide backbone, forming stable and tight complexes with complementary DNA/RNA. However, it is unclear whether unmodified PNA can efficiently penetrate neuronal tissue in order to act as antisense reagent. Here we show that intrathecal (i.t.) injection of an unmodified antisense PNA complementary to the rat galanin receptor type 1 (GalR1) mRNA is able to block the inhibitory effect of i.t. administered galanin on spinal nociceptive transmission. Autoradiographic ligand binding studies using [125I]galanin show that the unmodified PNA is able to reduce the density of galanin binding sites in the dorsal horn. Thus, unmodified PNA applied i.t. appears to function as an effective antisense reagent in rat spinal cord in vivo.

Role of third intracellular loop of galanin receptor type 1 in signal transduction.

To determine the domains essential for G-protein coupling of the human galanin receptor type 1 (GalR1), we have used both GalR1 mutants and synthetic receptor-derived peptides in(125)I-galanin and [(35)S]-GTPgammaS binding studies. Replacement of potential phosphorylation sites by Leu in the third intracellular loop (IC3) of GalR1 did not affect K(D)values for the receptor. Peptides derived form the IC3 loop, and especially the N-terminal part of it were able to increase the rate of [(35)S]-GTPgammaS binding to the trimeric Gialpha1beta1gamma2, but not to Gsalphabeta1gamma2, whereas the peptides corresponding to the IC1 and IC2 loops had no such effect. IC3 loop peptides also inhibited the binding of(125)I-galanin to GalR1 in membranes from Rin m5F cells. Our results suggest that the IC3 loop of GalR1, especially its N-terminal part, defines the coupling of the receptor to the Gialpha1beta1gamma2 protein and consequently, to the signal transduction cascade.

Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo.

Peptide nucleic acids (PNAs) form stable and tight complexes with complementary DNA and/or RNA and would be promising antisense reagents if their cellular delivery could be improved. We show that a 21-mer PNA, complementary to the human galanin receptor type 1 mRNA, coupled to the cellular transporter peptides, transportan or pAntennapedia(43-58), is efficiently taken up into Bowes cells where they block the expression of galanin receptors. In rat, the intrathecal administration of the peptide-PNA construct results in a decrease in galanin binding in the dorsal horn. The decrease in binding results in the inability of galanin to inhibit the C fibers stimulation-induced facilitation of the rat flexor reflex, demonstrating that peptide-PNA constructs act in vivo to suppress expression of functional galanin receptors.

Differential regulation of GTPase activity by mastoparan and galparan.

The chimeric peptide galparan, composed of galanin (1-13) in the N-terminus and mastoparan in the C-terminus, was recently designed and synthesized. The effect of galparan on GTPase activity of rat brain cortical membranes was studied in comparison with the effect of mastoparan and galanin. GTPase was activated by mastoparan but it was noncompetitively inhibited by galparan, while no effect of galanin and galanin (1-13) was found in this tissue. EC50 of 12.1 +/- 2.1 microM and Hill coefficient of 2.1 +/- 0.6 was calculated for galparan from a dose-response curve and Ki of 19.1 +/- 0.3 microM was obtained by fitting the experimental data to the Michaelis-Menten equation valid in the presence of noncompetitive inhibitor. Mastoparan reversed the effect of galparan in a fully competitive manner while benzalkonium chloride did not prevent the inhibition of GTPase activity by galparan. Pertussis-toxin-catalyzed ribosylation of G proteins from rat brain cortical membranes resulted in 15% lower basal GTPase activity of our preparation but did not alter the parameters of the dose-response curve for galparan inhibition. The rate of GTP gamma S binding to G proteins from rat brain cortical membranes was not influenced by galparan. CD spectra revealed predominantly antiparallel beta-structure and unordered secondary structure of galparan in the buffer solution, while in the presence of lipid vesicles it adopted a higher amount of alpha-helix. Critical micelle concentration of galparan in buffer solution of 22 microM was determined. It is suggested that the reversal of GTPase activation by mastoparan to inhibition by galparan is due to different loci of action of these two peptides on G proteins.