Diagnosis, management and outcomes of primary hypokalemic periodic paralysis during pregnancy.

Primary hypokalaemic periodic paralysis during pregnancy has been rarely reported. Four pregnant women with the acute onset of flaccid paralysis presented between January 2018 and December 2021. Focussed history and physical examination helped an appropriate radiological and laboratory investigation plan to be made. All women recovered within 4-7 days of potassium supplementation. Supplemental potassium continued until delivery. A pain management plan with continuous epidural infusion helped in avoiding stress-induced hypokalaemia. None of the women developed an episode of muscle weakness during the intervening period. In conclusion, a focussed history and targeted laboratory investigation are needed to diagnose primary hypokalaemic periodic paralysis. Early administration of oral or intravenous potassium is crucial in improving fetomaternal outcomes.

Unraveling quantum coherences mediating primary charge transfer processes in photosystem II reaction center.

Photosystem II (PSII) reaction center (RC) is a unique complex that is capable of efficiently separating electronic charges across the membrane. The primary energy- and charge-transfer (CT) processes occur on comparable ultrafast timescales, which makes it extremely challenging to understand the fundamental mechanism responsible for the near-unity quantum efficiency of the transfer. Here, we elucidate the role of quantum coherences in the ultrafast energy and CT in the PSII RC by performing two-dimensional (2D) electronic spectroscopy at the cryogenic temperature of 20 kelvin, which captures the distinct underlying quantum coherences. Specifically, we uncover the electronic and vibrational coherences along with their lifetimes during the primary ultrafast processes of energy and CT. We construct an excitonic model that provides evidence for coherent energy and CT at low temperature in the 2D electronic spectra. The principles could provide valuable guidelines for creating artificial photosystems with exploitation of system-bath coupling and control of coherences to optimize the photon conversion efficiency to specific functions.

Multitype Electronic Interactions in Precursor Solutions of Molecular Doped P3HT Polymer.

Spin-casting of molecularly doped polymer solution mixtures is one of the commonly used methods to obtain conductive organic semiconductor films. In spin-casted films, electronic interaction between the dopant and polymer is one of the crucial factors that dictates the doping efficiency. Here, we investigate excitonic couplings using ultrafast two-dimensional electronic spectroscopy to examine the different types of electronic interactions in ion pairs of the prototype F4TCNQ-doped P3HT polymer system in a precursor solution mixture for spin-casting. Off-diagonal peaks in the 2D spectra clearly establish the excitonic coupling between P3HT+ and F4TCNQ- ions in solution. The observed excitonic coupling is the direct manifestation of a Coulombic interaction between the ion pair. The excited-state lifetime of F4TCNQ- in ion pairs shows biexponential decay at 30 and 200 fs, which hints toward the presence of a heterogeneous population with different interaction strengths. To examine the nature of these different types of interactions in solution mixtures, we study the system using molecular dynamics simulations on a fully solvated model employing the generalized Amber force field. We retrieve three dominant interaction modes of F4TCNQ anions with P3HT: side chain, π-stack, and slipped stack. To quantify these interactions, we complement our studies with electronic structure calculations, which reveal the excitonic coupling strengths of ∼ 75 cm-1 for side chain, ∼ 150 cm-1 for π-π-stack, and ∼69 cm-1 for slipped stack. These various interaction modes provide information about the key geometries of the seed structures in precursor solution mixtures, which may determine the final structures in spin-casted films. The insights gained from our study may guide new strategies to control and ultimately tune Coulomb interactions in polymer-dopant solutions.

Presurgical depressive symptom and anaesthetic requirements in patients undergoing surgery for malignant and non-malignant conditions: A prospective observational cohort study.

The incidence and magnitude of depression are rarely assessed during preanaesthetic evaluation. The shared physiological mechanisms of depression and anaesthetic drugs are likely to alter the pharmacodynamics of propofol. Therefore, the study aimed to evaluate the burden of presurgical depression and its effect on propofol consumption during anaesthesia. This prospective, observational, cross-sectional, analytical study included adult patients (> 18 years) undergoing surgery. During the preoperative period, depressive symptoms were evaluated by the psychiatrist on 9-point Patient Health Questionnaire-9 (PHQ-9). The propofol requirements were recorded during anaesthesia and compared with those for patients without depression. One hundred and seventy-four patients (87 patients each with and without cancer) underwent presurgical evaluation. The prevalence of depression (>4 Patient Health Questionnaire-9) and moderate to severe depression (>9 PHQ-9) among patients with cancer was 58.6% and 35.6%, respectively. The prevalence of depression (>4 PHQ-9) and moderate to severe depression (>9 PHQ-9) among patients without cancer was 18.4% and 3.4%, respectively. In the cancer group, propofol requirement was significantly lower (114.7 ± 22.9mg vs. 126.4 ± 24.3mg; p = 0.025) in patients with depression than that in those without depression. In conclusion, the burden of depression during the preanaesthetic period among patients with cancer is substantial, and depression reduces propofol requirement during surgery.

Effect of Acute Vasodilator Testing Using Oxygen in Pulmonary Hypertension Due to Left Heart Disease.

BACKGROUND: Pulmonary vasodilators, including oxygen, have not shown consistent beneficial effects on pulmonary hypertension due to valvular heart disease (PH-VHD). Therefore, the study aimed to assess the effect of 100% fractional inspiration of oxygen (FiO2) on pulmonary and systemic hemodynamics in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) and isolated post-capillary pulmonary hypertension (IpcPH) due to PH-VHD. METHODS: This prospective study was conducted among patients with PH-VHD undergoing mitral or aortic valve replacement or repair. The study was conducted after induction of anesthesia and pulmonary artery catheterization. Cardiac output was obtained using thermodilution and all direct, and derived hemodynamic variables were obtained at 30% and 100% FiO2. The patients were stratified a priori into responders {(≥10 mmHg fall in mean pulmonary artery pressure (MPAP)} and non-responders. RESULTS: Fifty-seven patients completed the acute vasodilator test. The mean age and body mass index of the study population was 41.8 ± 14.1 years and 21.4 ± 4.6 kg/m2, respectively. There was a significant decrease in MPAP (40.77 ± 12.07 mmHg vs 36.74 ± 13.3 mmHg; P < .001) and pulmonary vascular resistance (PVR) {(median; Interquartile range (IQR); 388; 371 vs 323; 362 dynes sec.cm-5; P < .001) at 100% FiO2. Transpulmonary gradient (TPG) and diastolic pulmonary gradient (DPG) also decreased significantly (P < .001 and P < .001). Cardiac output did not change significantly. The magnitude of decrease in MPAP, PVR, TPG, DPG, and pulmonary artery compliance (PAC) between CpcPH and IpcPH was comparable. Responders did not show a significantly greater fall in MPAP, PVR, TPG, DPG, and PAC after surgery. CONCLUSION: Hyperoxia may lead to reduction in MPAP and PVR in both hemodynamic phenotypes of PH-VHD. A larger sample size is required to support or refute the findings of this study.

Relationship between difference of preoperative and cardiopulmonary bypass mean arterial pressure, and acute kidney injury in cardiac surgical patients undergoing valve surgery.

BACKGROUND: Modifiable and non-modifiable factors contribute to development and progression of acute kidney injury (AKI) during cardiac surgery. We hypothesized that, the difference between preoperative mean arterial pressure (MAP) and the average mean arterial pressure maintained on cardiopulmonary bypass (CPB) would be strongly predictive of AKI. We also measured plasma Neutrophil gelatinase-associated lipocalin (NGAL), to establish its association with cardiac surgery associated-AKI (CSA-AKI). METHODS: One hundred and twelve high-risk patients undergoing valve, and valve plus coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB) were included in this study. Delta mean arterial pressure (MAP) was calculated as the difference between the average of pre-operative and on-bypass MAP, and blood was sampled for NGAL levels, at baseline, and 6-h after CPB. Detailed data collection was done, tabulating most of the factors which might influence development of post-operative cardiac surgery associated-AKI (CSA-AKI). To define CSA-AKI within the first 24-h post-operatively, the Kidney Disease Improving Global Outcomes (KDIGO) classification was used. RESULTS: Out of 112 patients, 44 (39.3%) developed CSA-AKI postoperatively. With an ROC analysis cut-off of delta MAP of more than 25.67 mmHg, 46.4% patients developed post-operative AKI, and the average CPB flows which were 1.8 ± 0.2 were not contributory to the development of early CSA-AKI. In our study, ELISA test for human NGAL was performed on serum samples, and the estimated cut-off value of 1661 ng/mL was found to be significantly associated with early CSA-AKI. CONCLUSIONS: Delta MAP and CPB flows are not related to early post-surgical CSA-AKI in cases with prior high-risk elements. However, baseline serum NGAL, as well as its percent change during the early post-surgical period independently predicted the development of CSA-AKI. This implies that, there may be patients with a higher pre-operative preponderance to develop this complication, which could actually be delineated by the use of serum NGAL estimations at baseline.

Thoracic organ transplantation and pregnancy outcomes: systematic review and meta-analysis.

PURPOSE: Pre-conceptual comorbidities, an inherent risk of graft loss, rejection during pregnancy, and the postpartum period in women with thoracic lung transplant may predispose them to increased risk of adverse feto-maternal outcomes. The study aimed to systematically analyze and assess the risk of adverse pregnancy outcomes in women with thoracic organ transplant. METHODS: MEDLINE, EMBASE, and Cochrane library were searched for publication between January 1990 and June 2020. Risk of bias was assessed using Joanna Briggs critical appraisal tool for case series. The primary outcomes included maternal mortality and pregnancy loss. The secondary outcomes were maternal complications, neonatal complications, and adverse birth outcomes. The analysis was performed using the DerSimonian-Laird random effects model. RESULTS: Eleven studies captured data from 275 parturient with thoracic organ transplant describing 400 pregnancies. The primary outcomes included maternal mortality {pooled incidence (95% confidence interval) 4.2 (2.5-7.1) at 1 year and 19.5 (15.3-24.5) during follow-up}. Pooled estimates yielded 10.1% (5.6-17.5) and 21.8% (10.9-38.8) risk of rejection and graft dysfunction during and after pregnancy, respectively. Although 67% (60.2-73.2) of pregnancies resulted in live birth, total pregnancy loss and neonatal death occurred in 33.5% (26.7-40.9) and 2.8% (1.4-5.6), respectively. Prematurity and low birth weight were reported in 45.1% (38.5-51.9) and 42.7% (32.8-53.2), respectively. CONCLUSIONS: Despite pregnancies resulting in nearly 2/3rd of live births, high incidence of pregnancy loss, prematurity and low birth weight remain a cause of concern. Focused pre-conceptual counseling to avoid unplanned pregnancy, especially in women with transplant-related organ dysfunctions and complications, is vital to improve pregnancy outcomes. PROSPERO NUMBER: CRD42020164020.

Effect of maternal hyperoxygenation on neonatal outcomes among women in labour with pathological cardiotocography: an open-label randomized controlled trial.

BACKGROUND: Hyperoxygenation has shown promise in improving suspicious fetal heart patterns in women in labor. However, the effect of hyperoxygenation on neonatal outcomes in women in labor with pathologic fetal heart rate tracing has not been studied. OBJECTIVE: This study aimed to evaluate the effect of fractional inspiration of oxygen of 80% compared with fractional inspiration of oxygen of 40% on neonatal outcomes in women with pathologic fetal heart rate tracing. STUDY DESIGN: This randomized, open-label, parallel arm, outcome assessor-blinded clinical trial was conducted in a large tertiary care university hospital. Singleton parturients aged ≥18 years at term gestation in active labor (cervical dilatation of ≥6 cm) with pathologic fetal heart rate tracing were recruited in the study. Pathologic fetal heart rate tracing was defined according to the International Federation of Gynecology and Obstetrics 2015 guidelines. The International Federation of Gynecology and Obstetrics classifies fetal heart rate tracings into 3 categories (normal, suspicious, and pathologic) based on rate, variability, and deceleration. Women in the intervention arm received oxygen at 10 L/min via a nonrebreathing mask, and those in the usual care arm received oxygen at 6 L/min with a simple face mask. Oxygen supplementation was continued until cord clamping. The primary outcome measure was a 5-minute Apgar score. The secondary outcome measures were the proportion of neonatal intensive care unit admission, umbilical cord blood gas variables, level of methyl malondialdehyde in the cord blood, and mode of delivery. RESULTS: Overall, 148 women (74 women in the high fractional inspiration of oxygen arm and 74 in the low fractional inspiration of oxygen arm) with pathologic fetal heart rate tracing were analyzed. The demographic data, obstetrical profiles, and comorbidities were comparable. The median 5-minute Apgar scores were 9 (interquartile range, 8-10) in the hyperoxygenation arm and 9 (interquartile range, 8-10) in the usual care arm (P=.12). Furthermore, the rate of neonatal intensive care unit admission (9.5% vs 12.2%; P=.6) and the requirement of positive pressure ventilation (6.8% vs 8.1%; P=.75) were comparable. Concerning cord blood gas parameters, the hyperoxygenation arm had a significantly higher base deficit in the umbilical vein and lactate level in the umbilical artery. The cesarean delivery rate was significantly lower in women who received hyperoxygenation (4.1% [3/74]) than in women who received normal oxygen supplementation (25.7% [19/74]) (P=.00). In addition, umbilical vein malondialdehyde level in the umbilical vein was lower in the hyperoxygenation group (8.28±4.65 µmol/L) than in the normal oxygen supplementation group (13.44±8.34 µmol/L) (P=.00). CONCLUSION: Hyperoxygenation did not improve the neonatal Apgar score in women with pathologic fetal heart rate tracing. In addition, neonatal intensive care unit admission rate and blood gas parameters remained comparable. Therefore, the results of this trial suggest that a high fractional inspiration of oxygen supplementation confers no benefit on neonatal outcomes in women with pathologic fetal heart rate tracings and normal oxygen saturation.

The Transition from Unfolded to Folded G-Quadruplex DNA Analyzed and Interpreted by Two-Dimensional Infrared Spectroscopy.

A class of DNA folds/structures known collectively as G-quadruplexes (G4) commonly forms in guanine-rich areas of genomes. G4-DNA is thought to have a functional role in the regulation of gene transcription and telomerase-mediated telomere maintenance and, therefore, is a target for drugs. The details of the molecular interactions that cause stacking of the guanine-tetrads are not well-understood, which limits a rational approach to the drugability of G4 sequences. To explore these interactions, we employed electron-vibration-vibration two-dimensional infrared (EVV 2DIR) spectroscopy to measure extended vibrational coupling spectra for a parallel-stranded G4-DNA formed by the Myc2345 nucleotide sequence. We also tracked the structural changes associated with G4-folding as a function of K+-ion concentration. To classify the structural elements that the folding process generates in terms of vibrational coupling characteristics, we used quantum-chemical calculations utilizing density functional theory to predict the coupling spectra associated with given structures, which are compared against the experimental data. Overall, 102 coupling peaks are experimentally identified and followed during the folding process. Several phenomena are noted and associated with formation of the folded form. This includes frequency shifting, changes in cross-peak intensity, and the appearance of new coupling peaks. We used these observations to propose a folding sequence for this particular type of G4 under our experimental conditions. Overall, the combination of experimental 2DIR data and DFT calculations suggests that guanine-quartets may already be present before the addition of K+-ions, but that these quartets are unstacked until K+-ions are added, at which point the full G4 structure is formed.

Characterization of an Omnitrap-Orbitrap Platform Equipped with Infrared Multiphoton Dissociation, Ultraviolet Photodissociation, and Electron Capture Dissociation for the Analysis of Peptides and Proteins.

We describe an instrument configuration based on the Orbitrap Exploris 480 mass spectrometer that has been coupled to an Omnitrap platform. The Omnitrap possesses three distinct ion-activation regions that can be used to perform resonant-based collision-induced dissociation, several forms of electron-associated fragmentation, and ultraviolet photodissociation. Each section can also be combined with infrared multiphoton dissociation. In this work, we demonstrate all these modes of operation in a range of peptides and proteins. The results show that this instrument configuration produces similar data to previous implementations of each activation technique and at similar efficiency levels. We demonstrate that this unique instrument configuration is extremely versatile for the investigation of polypeptides.

Transient chiral dynamics revealed by two-dimensional circular dichroism spectroscopy.

Chirality has been considered as one of the key factors in the evolution of life in nature. It is important to uncover how chiral potentials of molecular systems play vital role in fundamental photochemical processes. Here, we investigate the role of chirality in photoinduced energy transfer in a model dimeric system, where the monomers are excitonically coupled. To observe transient chiral dynamics and energy transfer, we employ circularly polarized laser pulses in two-dimensional electronic spectroscopy to construct the two-dimensional circular dichroism (2DCD) spectral maps. Tracking time-resolved peak magnitudes in 2DCD spectra allows one to identify chirality induced population dynamics. The dynamics of energy transfer is revealed by the time-resolved kinetics of cross peaks. However, the differential signal of 2DCD spectra shows the magnitude of cross peaks is dramatically reduced at initial waiting time, which indicates the weak chiral interactions between two monomers. The downhill energy transfer is resolved by presenting a strong magnitude of cross peak in 2DCD spectra after long waiting time. The chiral contribution towards coherent and incoherent energy-transfer pathways in the model dimer system is further examined via control of excitonic couplings between two monomers. Applications are made to study the energy-transfer process in the Fenna-Matthews-Olson complex. Our work uncovers the potential of 2DCD spectroscopy to resolve the chiral-induced interactions and population transfers in excitonically coupled systems.

Ultrasound-Guided Radial Arterial Catheterization in Patients With Regurgitant and Stenotic Left-Sided Cardiac Valvular Lesions.

Background. The pulse characteristics of arterial circulation might affect radial artery catheterization's success rate. Therefore, we hypothesized that the success rate of radial artery catheterization would be lower in the left-sided severe stenotic valvular lesion group than severe regurgitant valvular lesion group. Methods. This prospective study was conducted among patients with left-sided cardiac valvular lesions undergoing cardiac and non-cardiac surgery. The patients with left-sided severe valvular stenosis and left-sided severe valvular regurgitation were included in the study. Radial artery cannulation was performed using an ultrasound-guided out-of-plane short-axis approach. The outcome measures were success rate, number of attempts, and cannulation time. Result. One hundred fifty-two patients were recruited for the study, and all were eligible for final analysis. The first attempt success rate was non-significantly higher in the stenotic valvular lesion group than the regurgitant group (69.7% vs 56.6%; P = .09). Furthermore, the number of attempts (median; 95% CI) was significantly higher in the regurgitant group (1; 1.2-1.43 vs 1; 1.38-1.67; P = .04). However, it may not be of clinical relevance. Moreover, the cannulation time and the number of redirections of the cannula were comparable. Heart rate was significantly higher in the regurgitant group (91.8 ± 13.9 vs 82.26 ± 15.92 beats/min; P = .00), while the incidence of atrial fibrillation was significantly higher in the stenotic lesion (P = .00). No failure was reported, and the incidence of periarterial hematoma was comparable. Conclusion. The success rate of ultrasound-guided radial arterial catheterization is comparable in left-sided stenotic valvular and regurgitant lesion groups.