Mixed Connective Tissue Disease Presenting With Psychosis-A Case Report.

ABSTRACT: Mixed connective tissue disease (MCTD) is a systemic autoimmune disease with features overlapping multiple autoimmune disorders. One study found that over 55% of patients with MCTD experienced neuropsychiatric symptoms, the most common of which was an "aseptic meningitis-like syndrome." We present a case of a 17-year-old adolescent girl presenting with abnormal speech and behavior, auditory hallucinations, and paranoid delusions after an isolated episode of fever. She was treated for her psychotic symptoms but later developed symptoms resembling neuroleptic malignant syndrome. An antibody screen revealed elevated anti-U1-ribonucleoprotein antibodies with a possible diagnosis of MCTD. She finally responded to steroid therapy. To our knowledge, this is the first reported case of MCTD initially presenting with psychosis. A diagnosis of autoimmune disorders should be kept in the differential of similar clinical presentations including connective tissue disorders and autoimmune thyroid conditions.

Novel AI-based HRV analysis (NAIHA) in healthcare automation and related applications.

BACKGROUND: Heart rate variability (HRV) analysis computed on R-R interval series of ECG records with heavy burden of ectopic beats or non-sinus rhythm can significantly distort HRV parameters and hence clinically ineligible for HRV analysis. Yet, existing algorithmic methods of HRV analysis do not check such eligibility and require manual identification of eligible window (portion of ECG record) to ensure reliability. OBJECTIVE: We aimed to propose a robust algorithm with a sliding window feature to automate the identification of an eligible window, if available, which compute HRV parameters within that window obviating manual input. METHODS: The proposed algorithm classifies each window as either eligible or ineligible. With a window classified eligible, we stop sliding through the record, otherwise we move to the next window and repeat the eligibility identification process, until either an eligible window is found, or all windows are exhausted. RESULTS: When evaluated on random subset of 100 records from MIMIC-III waveform database, the proposed algorithm excluded every ineligible record, and missed only 1.25% of eligible ones. The HRV parameters computed using proposed method closely approximated the standard HRV analysis with Pearson correlation coefficients (ideally one) and fractions of variance unexplained (ideally zero) ranging from 96.3% to 99.8% and 0.34% to 7.43%, respectively. CONCLUSIONS: When translated into practice, proposed algorithm will reduce clinicians'' burden without compromising the accuracy of HRV analysis, potentially leading to its wider adoption.

Single-molecule correlated chemical probing reveals large-scale structural communication in the ribosome and the mechanism of the antibiotic spectinomycin in living cells.

The ribosome moves between distinct structural states and is organized into multiple functional domains. Here, we examined hundreds of occurrences of pairwise through-space communication between nucleotides in the ribosome small subunit RNA using RNA interaction groups analyzed by mutational profiling (RING-MaP) single-molecule correlated chemical probing in bacterial cells. RING-MaP revealed four structural communities in the small subunit RNA, each distinct from the organization defined by the RNA secondary structure. The head domain contains 2 structural communities: the outer-head contains the pivot for head swiveling, and an inner-head community is structurally integrated with helix 44 and spans the entire ribosome intersubunit interface. In-cell binding by the antibiotic spectinomycin (Spc) barely perturbs its local binding pocket as revealed by the per-nucleotide chemical probing signal. In contrast, Spc binding overstabilizes long-range RNA-RNA contacts that extend 95 Å across the ribosome that connect the pivot for head swiveling with the axis of intersubunit rotation. The two major motions of the small subunit-head swiveling and intersubunit rotation-are thus coordinated via long-range RNA structural communication, which is specifically modulated by Spc. Single-molecule correlated chemical probing reveals trans-domain structural communication and rationalizes the profound functional effects of binding by a low-molecular-mass antibiotic to the megadalton ribosome.

When is My Baby Going Home? Moderate to Late Preterm Infants are Discharged at 36 Weeks Based on Admission Data.

OBJECTIVE: This study evaluates the effect of admission characteristics of uncomplicated moderate to late preterm infants on timing of discharge. One of the first questions that families of infants admitted to the Neonatal Intensive Care Unit (NICU) ask is, "When is my baby going home?" Moderate to late preterm infants are the largest cohort of NICU patients but little data exist about their length of stay (LOS). STUDY DESIGN: A retrospective electronic chart review was completed on 12,498 infants admitted to our NICU between January 1, 2009 and December 31, 2015. All inborn infants with a gestational age between 320/7 and 366/7 weeks were studied. RESULTS: A total of 3,240 infants met our inclusion criteria. The mean postmenstrual age at discharge was 363/7 weeks. Infants who were small for gestational age were significantly more likely to have an increased LOS. Infants born between 34 and 366/7 weeks had a significantly increased LOS if they had respiratory distress syndrome. Admission diagnoses of neonatal abstinence syndrome, meconium aspiration syndrome, hydrops, hypoxic ischemic encephalopathy, biliary emesis, ABO incompatibly, and a genetic diagnosis all had increased LOS for all late preterm infants. CONCLUSION: For uncomplicated moderate to late preterm infants, clinicians can counsel families that their infants will likely be discharged at 36 weeks of postmenstrual age. Small for gestational age infants and those with specific diagnoses may stay longer.

The regulatory TnaC nascent peptide preferentially inhibits release factor 2-mediated hydrolysis of peptidyl-tRNA.

The tnaC regulatory gene from the tna operon of Escherichia coli controls the transcription of its own operon through an attenuation mechanism relying on the accumulation of arrested ribosomes during inhibition of its own translation termination. This free l-Trp-dependent mechanism of inhibition of translation termination remains unclear. Here, we analyzed the inhibitory effects of l-Trp on the function of two known E. coli translation termination factors, RF1 and RF2. Using a series of reporter genes, we found that the in vivo l-Trp sensitivity of tnaC gene expression is influenced by the identity of its stop codon, with the UGA stop codon producing higher expression efficiency of the tnaA-lacZ gene construct than the UAG stop codon. In vitro TnaC-peptidyl-tRNA accumulation and toe-printing assays confirmed that in the presence of l-Trp, the UGA stop codon generates higher accumulation of both TnaC-peptidyl-tRNA and arrested ribosomes than does the UAG stop codon. RF-mediated hydrolysis assays corroborated that l-Trp blocks RF2 function more than that of RF1. Mutational analyses disclosed that amino acids substitutions at the 246 and 256 residue positions surrounding the RF2-GGQ functional motif reduce l-Trp-dependent expression of the tnaC(UGA) tnaA-lacZ construct and the ability of l-Trp to inhibit RF2-mediated cleavage of the TnaC-peptidyl-tRNA. Altogether, our results indicate that l-Trp preferentially blocks RF2 activity during translation termination of the tnaC gene. This inhibition depends on the identities of amino acid residues surrounding the RF2-GGQ functional motif.

Guidelines for SHAPE Reagent Choice and Detection Strategy for RNA Structure Probing Studies.

Chemical probing is an important tool for characterizing the complex folded structures of RNA molecules, many of which play key cellular roles. Electrophilic SHAPE reagents create adducts at the 2'-hydroxyl position on the RNA backbone of flexible ribonucleotides with relatively little dependence on nucleotide identity. Strategies for adduct detection such as mutational profiling (MaP) allow accurate, automated calculation of relative adduct frequencies for each nucleotide in a given RNA or group of RNAs. A number of alternative reagents and adduct detection strategies have been proposed, especially for use in living cells. Here we evaluate five SHAPE reagents: three previously well-validated reagents 1M7 (1-methyl-7-nitroisatoic anhydride), 1M6 (1-methyl-6-nitroisatoic anhydride), and NMIA ( N-methylisatoic anhydride), one more recently proposed NAI (2-methylnicotinic acid imidazolide), and one novel reagent 5NIA (5-nitroisatoic anhydride). We clarify the importance of carefully designed software in reading out SHAPE experiments using massively parallel sequencing approaches. We examine SHAPE modification in living cells in diverse cell lines, compare MaP and reverse transcription-truncation as SHAPE adduct detection strategies, make recommendations for SHAPE reagent choice, and outline areas for future development.

An evaluation of planarity of the spatial QRS loop by three dimensional vectorcardiography: Its emergence and loss.

AIMS: To objectively characterize and mathematically justify the observation that vectorcardiographic QRS loops in normal individuals are more planar than those from patients with ST elevation myocardial infarction (STEMI). METHODS: Vectorcardiograms (VCGs) were constructed from three simultaneously recorded quasi-orthogonal leads, I, aVF and V2 (sampled at 1000 samples/s). The planarity of these QRS loops was determined by fitting a surface to each loop. Goodness of fit was expressed in numerical terms. RESULTS: 15 healthy individuals aged 35-65years (73% male) and 15 patients aged 45-70years (80% male) with diagnosed acute STEMI were recruited. The spatial-QRS loop was found to lie in a plane in normal controls. In STEMI patients, this planarity was lost. Calculation of goodness of fit supported these visual observations. CONCLUSIONS: The degree of planarity of the VCG loop can differentiate healthy individuals from patients with STEMI. This observation is compatible with our basic understanding of the electrophysiology of the human heart.

Interactions of the TnaC nascent peptide with rRNA in the exit tunnel enable the ribosome to respond to free tryptophan.

A transcriptional attenuation mechanism regulates expression of the bacterial tnaCAB operon. This mechanism requires ribosomal arrest induced by the regulatory nascent TnaC peptide in response to free L-tryptophan (L-Trp). In this study we demonstrate, using genetic and biochemical analyses, that in Escherichia coli, TnaC residue I19 and 23S rRNA nucleotide A2058 are essential for the ribosome's ability to sense free L-Trp. We show that the mutational change A2058U in 23S rRNA reduces the concentration dependence of L-Trp-mediated tna operon induction, whereas the TnaC I19L change suppresses this phenotype, restoring the sensitivity of the translating A2058U mutant ribosome to free L-Trp. These findings suggest that interactions between TnaC residue I19 and 23S rRNA nucleotide A2058 contribute to the creation of a regulatory L-Trp binding site within the translating ribosome.

Efficacy of an online lung ultrasound module on skill acquisition by clinician: a new paradigm.

Introduction: Lung ultrasound (LUS) as an assessment tool has seen significant expansion in adult, paediatric, and neonatal populations due to advancements in point-of-care ultrasound over the past two decades. However, with fewer experts and learning platforms available in low- and middle-income countries and the lack of a standardised supervised training programme, LUS is not currently effectively used to the best of its potential in neonatal units. Methodology: A cross-sectional survey assessed the efficacy of learning LUS via a mentor-based online teaching module (NEOPOCUS). The questionnaire comprised the clinicians' demographic profile, pre-course skills, and self-assessment of skill acquisition after course completion with ongoing hands-on practice. Results: A total of 175 clinicians responded to the survey, with the majority (87.9%) working in level 3 and 4 neonatal intensive care units. Clinicians had variable clinical experience. Of them, 53.2% were consultant paediatricians/neonatologists with over 10 years of experience. After the course, there was a significant increase in clinician confidence levels in diagnosing and assessing all LUS pathology, as evidenced by the increase in median cumulative scores [from baseline 6 (interquartile range, IQR, 6-9) to 20 (IQR 16-24), p < 0.001] with half of them gaining confidence within 3 months of the course. Conclusion: An online curriculum-based neonatal lung ultrasound training programme with clinician image demonstration and peer review of images for image optimisation increases self-reported confidence in diagnosing and managing neonatal lung pathology. Web-based online training in neonatal lung ultrasound has merits that can help with the delivery of training globally, and especially in low- and middle-income countries.

Detection of Twin Pregnancies using Fetal Phonocardiogram.

Fetal phonocardiogram (fPCG), or the electronic recording of fetal heart sounds, is a safe and easily available signal that can be used to monitor fetal wellbeing. In the proposed work an attempt is made to identify twin pregnancies using fPCG data recorded from the fetus with 1/3rd power in octave band filtered output as features to train K-Nearest Neighbor (KNN) and support vector machine (SVM) classifiers. The SVM classifier with the quadratic kernel is able to identify singletons and twins with a positive predictive value of 100% and 79.1% respectively. The KNN classifier with k=10 neighbors is able to identify singletons and twins with a positive predictive value of 100% and 81.8% respectively.Clinical Relevance: Identifying twin pregnancies from singleton is an essential clinical protocol followed during late pregnancy as there may be complications like twin-twin transfusion syndrome, selective fetal growth restriction, and preterm labor in twin pregnancy [1], [2]. Ultrasound imaging is the most commonly used technique for twin pregnancy detection, though it is often not affordable or available in rural or low-income populations. Utilization of fPCG in such circumstances has immense clinical potential.

Synchrosqueezed Transform based Click Event Segmentation in Phonocardiogram of Mitral Valve Prolapse.

Phonocardiogram (PCG) signal of the mitral valve prolapse (MVP) patients is characterized by transient audio events which include a systolic click (SC) followed by a murmur of varying intensity. Physicians detect these auscultation clues in regular auscultation before ordering expensive echocardio-graphy test. But auscultation is often error prone and even physicians with considerable experience might end up missing these clues. Therefore developing machine learning techniques to help clinicians is the need of the hour. A segmentation technique using Fourier synchrosqueezed transform (FSST) features with a long short term memory (LSTM) network is proposed in this study. An accuracy of 99.8% on MVP dataset demonstrates the potential of the proposed method in clinical diagnosis.

Central line-associated bloodstream infection in hospitalized children with peripherally inserted central venous catheters: extending risk analyses outside the intensive care unit.

BACKGROUND: Increasingly, peripherally inserted central venous catheters (PICCs) are placed for prolonged intravenous access. Few data exist regarding risk factors for central line-associated bloodstream infection (CLABSI) complicating PICCs in hospitalized children, especially children hospitalized outside the intensive care unit (ICU). METHODS: We identified all children with a PICC inserted at The Johns Hopkins Hospital (Baltimore, MD) from 1 January 2003 through 31 December 2009 and used Poisson regression models to identify risk factors for PICC-associated CLABSIs. RESULTS: A total of 2592 PICCs were placed in 1819 children. One hundred sixteen CLABSIs occurred over 44,972 catheter-days (incidence rate [IR], 2.58 cases per 1000 catheter-days; 95% confidence interval [CI], 2.07-3.00 cases per 1000 catheter-days). Independent predictors of CLABSI in the entire cohort included PICC dwell time of > 21 days (IR ratio [IRR], 1.53; 95% CI, 1.05-2.26), parenteral nutrition as indication for insertion (IRR, 2.24; 95% CI, 1.31-3.84), prior PICC-associated CLABSI (IRR, 2.48; 95% CI, 1.18-5.25), underlying metabolic condition (IRR, 2.07; 95% CI, 1.14-3.74), and pediatric ICU exposure during hospitalization (IRR, 1.80; 95% CI, 1.18-2.75). Risk factors for CLABSI in children without PICU exposure included younger age, underlying malignancy and metabolic conditions, PICCs inserted in the lower extremity, and a prior PICC-associated CLABSI. CONCLUSIONS: Prolonged catheter dwell time, pediatric ICU exposure, and administration of parenteral nutrition as the indication for PICC insertion are important predictors of PICC-associated CLABSI in hospitalized children. A careful assessment of these risk factors may be important for future success in preventing CLABSIs in hospitalized children with PICCs.

Knowledge, awareness, and attitudes regarding methicillin-resistant Staphylococcus aureus among caregivers of hospitalized children.

OBJECTIVES: To explore knowledge, awareness, and attitudes among caregivers of hospitalized children with regard to methicillin-resistant Staphylococcus aureus (MRSA). STUDY DESIGN: We developed and administered a bedside questionnaire to caregivers of hospitalized children in contact isolation for MRSA colonization or infection. RESULTS: Of 104 caregivers approached, 100 (96%) consented to participate. The caregivers' children included 28 (28%) newly recognized as colonized or infected with MRSA during the hospitalization and 72 (72%) previously identified as colonized or infected with MRSA. Eighteen (18%) caregivers had no knowledge of MRSA. Twenty-nine (29%) were unaware that their child had MRSA, including caregivers of 9 newly identified patients with MRSA and 20 patients with previously identified MRSA. Of the 71 caregivers aware of their child's MRSA status, 89% had concerns; 77% worried about risks of future MRSA infection, 51% worried about spreading MRSA, and 16% described a feeling of stigma. Worries were more common among caregivers of children with newly identified MRSA (P < .05). CONCLUSION: Caregivers of children hospitalized with MRSA are frequently unaware that their child has MRSA. Among those aware of their child's MRSA status, many have concerns and worries. Caregivers of children with newly identified MRSA more often are worried and may need additional education and reassurance.

Wavelet based event detection in the phonocardiogram of prolapsed mitral valve.

Mitral valve prolapse (MVP) is one of the cardiovascular valve abnormalities that occurs due to the stretching of mitral valve leaflets, which develops in around 2 percent of the population. MVP is usually detected via auscultation and diagnosed with an echocardiogram, which is an expensive procedure. The characteristic auscultatory finding in MVP is a mid-to-late systolic click which is usually followed by a high-pitched systolic murmur. These can be easily detected on a phonocardiogram which is a graphical representation of the auscultatory signal. In this paper, we have proposed a method to automatically identify patterns in the PCG that can help in diagnosing MVP as well as monitor its progression into Mitral Regurgitation. In the proposed methodology the systolic part, which is the region of interest here, is isolated by preprocessing and thresholded Teager-Kaiser energy envelope of the signal. Scalogram images of the systole part are obtained by applying continuous wavelet transform. These scalograms are used to train the convolutional neural network (CNN). A two-layer CNN could identify the event patterns with nearly 100% accuracy on the test dataset with varying sizes (20% - 40% of the entire data). The proposed method shows potential in the quick screening of MVP patients.

Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling.

Free L-tryptophan (L-Trp) stalls ribosomes engaged in the synthesis of TnaC, a leader peptide controlling the expression of the Escherichia coli tryptophanase operon. Despite extensive characterization, the molecular mechanism underlying the recognition and response to L-Trp by the TnaC-ribosome complex remains unknown. Here, we use a combined biochemical and structural approach to characterize a TnaC variant (R23F) with greatly enhanced sensitivity for L-Trp. We show that the TnaC-ribosome complex captures a single L-Trp molecule to undergo termination arrest and that nascent TnaC prevents the catalytic GGQ loop of release factor 2 from adopting an active conformation at the peptidyl transferase center. Importantly, the L-Trp binding site is not altered by the R23F mutation, suggesting that the relative rates of L-Trp binding and peptidyl-tRNA cleavage determine the tryptophan sensitivity of each variant. Thus, our study reveals a strategy whereby a nascent peptide assists the ribosome in detecting a small metabolite.

Spatial velocity of the dynamic vectorcardiographic loop provides crucial insight in ventricular dysfunction.

Vectorcardiogram (VCG) represents the trajectory of the tip of cardiac vectors in three dimensional space with varying time. It is a recurring, near-periodic pattern of cardiac dynamics that is constructed by drawing the instantaneous vectors from a zero reference point according to direction, magnitude and polarity in the space. Being a three dimensional entity, it is more informative and more sensitive than conventional ECG as an evaluation tool of the physiology of cardiac dynamics, because of its extra degree of freedom. Accordingly, it is possible to find out even a minute and early electrophysiological alteration in diseases. Each cardiac cycle primarily consists of three loops in VCG corresponding to P, QRS, and T wave activities. The morphological assessment of the QRS loop was carried out in three dimensional space in order to analyze the spatial vectors of the ventricles and their patho-physiological correlation in various cardiac diseases. Spatial Velocity (SV) is a virtual velocity that represents the rate of movement of the tip of the cardiac vector through space, coordinated by three orthogonal leads, and can be estimated by using simple mathematical formula. It is the rate of change in amplitude and the directionality of instantaneous vectors in seriatim in the three dimensional space to quantify their the temporo-spatial characteristic pattern. We propose to evaluate this novel VCG descriptor SV, in normal individuals and patients of ventricular dysfunction. The possible mechanisms consistent with the patho-physiological basis of ventricular dysfunction or heart failure with altered SV would enrich the current understanding of the disease. Heart failure is the final common pathway of multitude of cardiac pathologies. Despite etiological heterogeneity, there are common mechanisms involved in the complex electrophysiological alteration of the failing myocardium. The changes observed as a consequence of ventricular dysfunction involve ion channel remodeling, intercellular uncoupling, myocardial ischemia, alterations in calcium handling, remodeling of the extracellular matrix, the presence of scars, activation of the sympathetic & the renin-angiotensin-aldosterone system, dilatation as well as stretch of viscous etc. The source modulation of the depolarization wave and its propagation in the heart and body fluid volume conductor also influence the visual pattern of cardiac vectors. In addition, patients with heart failure receive pharmacological or non-pharmacological therapies that also influence the electrophysiological changes. We hypothesize that the spatial velocity of ventricular depolarization and repolarization vectors of the VCG loop alters with a characteristic pattern in the patients with ventricular dysfunction and can differentiate healthy individuals from patients with ventricular dysfunction and also differentiate various categories, gradations and severity stratifications of the patients with ventricular dysfunction.

Geometry of the Poincaré plot can segregate the two arms of autonomic nervous system - A hypothesis.

Autonomic Nervous System (ANS) operates to achieve the optimum physiological functioning and maintains homeostasis in a tonic and continuous manner. Evaluation of ANS profile is crucial in assessing autonomic dysfunction. Conventional ANS evaluation procedures fail to capture minute dynamic alterations of ANS activities. The ANS output pattern is appropriately reflected in the fine alteration of the resting heart rate (HR). HR is a non-stationary variable, results from the dynamic interplay between the multiple physiologic mechanisms. The control of cardiac rate or the chronotropic regulation of heart is considered as a coupled network of oscillators, each representing a specific facet of the cardiovascular reflex. The slower vasomotor oscillation via sympathetic system is combined with rapid respiratory oscillation by parasympathetic system to modulate the intrinsic oscillation pattern of the SA Node. Heart Rate Variability (HRV) is used to understand the autonomic influence on cardiovascular system in health and disease. Fourier decomposition of HRV offers us mainly two different frequency components. High frequency (HF) variation indicates parasympathetic variability due to respiration and Low frequency (LF) mainly implicates tonic sympathetic influence, due to slower vasomotor modulation of heart rate. However, different studies show conflicting results and direct recording of sympathetic nerve activity also failed to correlate with LF power in either healthy subjects or in patients with increased cardiac sympathetic drive. A scatter-plot where each R-R interval is plotted against the preceding R-R interval forms a distributed elliptic point cloud in two dimensional plane. The phase space realization of this plot with dimension two and delay one is referred to as Poincaré plot analysis, an emerging quantitative-visual technique where the shape of the plot is categorized into different functional classes. The plot provides summary as well as detailed beat-to-beat information of the heart. This plot can be extended to three dimensions and with multi-lag, offering more insight and information. A mathematical expression was developed by an interventional study by Toichi et al., using pharmacological blockers during different physiological variables that calculated the lengths of transverse and longitudinal axes of the Poincaré plot to derive two quantitative expressions of sympathetic and vagal influence on HRV: 'cardiac sympathetic index' (CSI)) and 'cardiac vagal index' (CVI). In the present study, we emulate Poincaré plot patterns seen in normal range of sympatho-vagal balances and also in Diabetes Mellitus (DM), known to cause autonomic dysfunction. The emerging pattern of R-R interval time series would provide valuable insight into the altered temporal dynamics and also extract crucial features embedded within. DM is a major public health crisis globally and particularly in Indian population. We hypothesize that, CSI and CVI will effectively segregate the two arms of ANS and can be utilized as an effective evaluation tool to explore the disease status in patients of Diabetes Mellitus. We also propose that, the dynamics of fluctuations in physiological rhythms that exhibit long-term correlation and memory, can also be explored and expressed quantitatively by incorporating various degrees of 'lag' in these recurrence plots.

Planarity of the spatial QRS loop of vectorcardiogram is a crucial diagnostic and prognostic parameter in acute myocardial infarction.

Vectorcardiogram (VCG) is a recurring, near-periodic pattern of cardiac dynamics that graphically represents the trajectory of the tip of cardiac vectors in three dimensional space with varying time. VCG is constructed by drawing the instantaneous vectors from a zero reference point according to direction, magnitude and polarity in the space. It is more informative and sensitive than conventional ECG as an evaluation tool of the physiology of cardiac dynamics. Each heart cycle consists of three loops corresponding to P, QRS, and T wave activities in VCG. The morphological assessment of the QRS loop was carried out in order to analyze the spatial vectors of the ventricles and their patho-physiological correlation in various cardiac diseases. It was found that, the three dimensional QRS loop in healthy individuals lies in a plane. It is rather surprising that the normal spatial QRS loop lies in a single plane, considering the complex structure of the ventricular musculature together with the numerous possible pathways along which the depolarization impulse passes. The highly curious phenomenon of planarity of the spatial QRS loop was explained by uniform double layer (UDL) theory, which postulates the phenomenon of activation wave-fronts that propagate with a constant & uniform rate throughout the myocardium. Acute myocardial infarction results in loss of structural and functional integrity of the different layers of heart, perturbation of the uniformity in wave propagation due to the disturbance in directional symmetry, development of nonlinear relationships among the concerned variables, loss of homogeneity and complete loss of planarity of the 3D-QRS loop. The planarity of the 3D-QRS loop is a highly restricted and sensitive parameter and a characteristic feature of normal heart and can be utilized as a test for diagnostic screening of cardiac normalcy and the loss of planarity may be a conspicuous feature of AMI. It will be reasonable to study the morphology of the spatial QRS loop in patients of AMI throughout the course of disease and also in a regular interval through the long-term follow up period. It is expected that with the reperfusion, recovery and salvage of the diseased myocardium; the homogeneity and the intensity of the line density of the membrane current of the UDL would gradually recover with retrieval of the planarity of the spatial QRS loop. The temporal pattern of characteristics alteration of the QRS loop planarity with the natural course of the disease requires intensive evaluation. We propose that, the planarity of the spatial QRS loop, its loss, involution and reversal is a temporal series of events in AMI and also a crucial diagnostic and prognostic parameter.

Effects of paraquat on anti-oxidant system in rats.

The toxic effects of paraquat on the anti-oxidant defense system of male albino rats were evaluated, after administering either a single dose (1.5 and 7.5 mg/kg of body weight) or continuous daily doses (same as above, i.e., 1.5 mg/kg and 7.5 mg/kg of body weight) for 3 and 7 days. Glutathione levels in blood cells, liver, lung and kidney tissues decreased in a dose and time dependent manner. Glutathione reductase and glucose-6-phosphate dehydrogenase activity decreased, whereas the activity of glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase increased in paraquat exposure. Malondialdehyde formation also increased in a dose and time dependent manner. The alterations of anti-oxidant system particularly glutathione can be utilized as biomarkers during management of paraquat poisoning.

Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer.

We have shown earlier that Neem (Azadirachta indica) bark aqueous extract has potent antisecretory and antiulcer effects in animal models and has no significant adverse effect (Bandyopadhyay et al., Life Sciences, 71, 2845-2865, 2002). The objective of the present study was to investigate whether Neem bark extract had similar antisecretory and antiulcer effects in human subjects. For this purpose, a group of patients suffering from acid-related problems and gastroduodenal ulcers were orally treated with the aqueous extract of Neem bark. The lyophilised powder of the extract when administered for 10 days at the dose of 30 mg twice daily caused a significant (p < 0.002) decrease (77%) in gastric acid secretion. The volume of gastric secretion and its pepsin activity were also inhibited by 63% and 50%, respectively. Some important blood parameters for organ toxicity such as sugar, urea, creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, albumin, globulin, hemoglobin levels and erythrocyte sedimentation rate remained close to the control values. The bark extract when taken at the dose of 30-60 mg twice daily for 10 weeks almost completely healed the duodenal ulcers monitored by barium meal X-ray or by endoscopy. One case of esophageal ulcer (gastroesophageal reflux disease) and one case of gastric ulcer also healed completely when treated at the dose of 30 mg twice daily for 6 weeks. The levels of various blood parameters for organ toxicity after Neem treatment at the doses mentioned above remained more or less close to the normal values suggesting no significant adverse effects. Neem bark extract thus has therapeutic potential for controlling gastric hypersecretion and gastroesophageal and gastroduodenal ulcers.