Enhancing the Reliability in the Noninvasive Measurement of the His Bundle Magnetic Field Using a Novel Signal Averaging Methodology

Background: Extraction of the weak electrical activity of the “His Bundle” (HB) by noninvasive methods has not been very successful in the past. The study reassesses the use of signal averaged magnetocardiography (SAMCG), overcoming some of the limitations in earlier studies including in the signal averaging methodology. Methods: SAMCG on healthy subjects (14 male and 1 female) were performed using R‐peak as the fiducial point in all cases and also using QRS‐onset as the fiducial point in select cases. Results: A conspicuous feature (H) with a magnitude up to 200 femto Tesla (fT) attributed to the HB activity was observed in the PR segment at several spatial positions on the thorax, with onset at 35–50 ms before the QRS‐onset (V) in 15 out of 18 trials constituting 83% of cases studied. The QRS‐onset as the fiducial point resolved the feature better compared to the conventionally used R‐peak, especially in trials exhibiting spread in heart rate (HR). This is attributed to the fluctuations in Q_onRD (the time interval between QRS‐onset and R‐peak) compared to the temporal stability of the H‐V duration. Conclusions: SAMCG reveals a well‐resolved H feature. The double hump morphology of the feature extended at least up to a frequency of 150 Hz. The importance of the choice of QRS‐onset as the fiducial point is unequivocally demonstrated, illustrated by measurements on subjects exhibiting considerable heart rate variability. The latter has a general validity and should be applicable to SAECG as well.     

Correlation between time lag of arterial–plethysmographic waveforms and systemic vascular resistance: a prospective study

Blood pressure (BP), a surrogate of cardiac output (CO), is also dependent on systemic vascular resistance (SVR). But SVR is not routinely monitored in daily clinical practice. We hypothesise that the time difference between the peripheral arterial waveform and the finger plethysmographic waveform (time lag index - TLi) could indicate the systemic vascular resistance. In this study, we correlated TLi with the systemic vascular resistance measured by minimally invasive CO monitor (pulse contour analysis). SVR changes in response to administration of mannitol were studied. American Society of Anesthesiologists (ASA) class I and II patients undergoing major intracranial surgeries were recruited. Arterial cannulation and pulse-oximetry recordings were done in the same limb. Arterial and plethysmographic waveforms were recorded before mannitol infusion (baseline) and at every 10 minutes for 60 minutes after the termination of mannitol infusion. Simultaneously, SVR was recorded from the Vigileo FLotrac CO monitor. Using custom-made programme, the time difference between both waveforms was calculated and corrected for heart rate (TLi). The correlation between time lag and the systemic vascular resistance was assessed using a mixed effect model, adjusting for the subject. Data of one hundred subjects were analysed. Following mannitol administration, there was a significant decrease in the SVR and the TLi (p?β?=?877.16, p?=?.008). The high beta coefficient suggests that when SVR increases, the TLi also increase and vice versa. A strong correlation between SVR and TLi was demonstrated for a given patient. Further studies are needed to explore the possibility of utilising this parameter to follow up changes in SVR in an individual patient at a particular point in time in different clinical scenarios.     

Butyrate Hastens Restoration of Barrier Function after Thermal and Detergent Injury to Rat Distal Colon in Vitro

Background: Epithelial migration restores barrier function after superficial injury to any mucosa. The present study aimed to determine whether butyrate, important to colonic epithelial physiology in diverse ways, influences restoration of barrier function in the injured rat colon. Methods: Rat distal colon was transiently exposed in vitro to heat (55°C for 10 sec) or to detergent (deoxycholic acid, 7.5 mM, for 15 min), and tissue damage was verified histologically. Epithelial barrier function was assessed, in colon tissue mounted in Ussing chambers, by measuring electric resistance and passive serosa-to-mucosa fluxes of ²²Na and of ¹⁴C PEG 4000 under voltage clamp conditions. Studies were done in the absence and presence of 25 mM butyrate in the bathing solutions. Results: Heat exposure induced superficial epithelial damage, and the electric resistance decreased significantly. This was accompanied by increase in flux of­¹4C PEG and increased passive flux of 22Na. Electric resistance was significantly higher, and PEG flux significantly lower, in tissues bathed with butyrate. Exposure to deoxycholic acid also induced superficial epithelial damage, reduced tissue electric resistance, and increased passive flux of Na and PEG. Electric resistance was significantly higher, and PEG flux significantly lower, in injured tissues bathed in butyrate, than in injured tissues bathed in butyrate-free solution. The effect of butyrate on restoration of electric resistance towards normal was seen in colon both from adult rats and from younger rats that were 2 or 6 weeks old. Conclusions: Butyrate enhanced restoration of mucosal barrier function in rat distal colon in response to heat and detergent injury.     

False Discovery Rates for Rare Variants From Sequenced Data

The detection of rare deleterious variants is the preeminent current technical challenge in statistical genetics. Sorting the deleterious from neutral variants at a disease locus is challenging because of the sparseness of the evidence for each individual variant. Hierarchical modeling and Bayesian model uncertainty are two techniques that have been shown to be promising in pinpointing individual rare variants that may be driving the association. Interpreting the results from these techniques from the perspective of multiple testing is a challenge and the goal of this article is to better understand their false discovery properties. Using simulations, we conclude that accurate false discovery control cannot be achieved in this framework unless the magnitude of the variants' risk is large and the hierarchical characteristics have high accuracy in distinguishing deleterious from neutral variants.     

Multipotent Plant Probiotic Rhizobacteria from Western Ghats and Its Effect on Quantitative Enhancement of Medicinal Natural Product Biosynthesis

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Understanding the chemical basis of rhizobacterial-plant interaction provides immense opportunities for the...