Exploring the Impact of a Trauma-informed Yoga and Mindfulness Curriculum for Multiple Populations: A Pilot Study.

Individuals with trauma experience negative mental health impacts and are at risk of poor cardiovascular outcomes. Unmanaged, these conditions may worsen, compromising healing and wellbeing. Yoga, particularly trauma-informed, may improve outcomes. The current pilot study explores the impact of a novel trauma-informed yoga and mindfulness curriculum on wellbeing in two parts. The first examined mental health (stress, mood) outcomes in four trauma-impacted populations: adults who were incarcerated (INC), individuals in recovery from substance use disorders (SU), veterans (VA), and vulnerable youth (YTH) assessing both the impact of individual class participation and impact of attending at least four curriculum sessions. For the subgroup of incarcerated individuals, impact by theme was examined. After curriculum sessions, stress was reduced, and mood improved. Across multiple sessions both the largest decreases in stress and greatest increase in mood occurred after participant in the first session. Further, a specific exploration of curriculum class impact by theme for participants who were incarcerated indicated no difference in impact by theme. The second part of this study explored cardiovascular outcomes for the population of those in recovery from substance use. Reductions in systolic blood pressure occurred immediately after the first curriculum session, and diastolic blood pressure reduced over three consecutive sessions.

Evaluating H295R steroidogenesis assay data for robust interpretation.

The in vitro H295R steroidogenesis assay (OECD TG 456) is used to determine a chemical's potential to interfere with steroid hormone synthesis/metabolism. As positive outcomes in this assay can trigger significant higher tiered testing, we compiled a stakeholder database of reference and test item H295R data to characterize assay outcomes. Information concerning whether a Level 5 reproductive toxicity study was triggered due to a positive outcome in the H295R assay was also included. Quality control acceptance criteria were not always achieved, suggesting this assay is challenging to conduct within the guideline specifications. Analysis of test item data demonstrated that pairwise significance testing to controls allowed for overly sensitive statistically significant positive outcomes, which likely contribute to the assay's high positive hit rate. Complementary interpretation criteria (e.g., 1.5-fold change threshold) markedly reduced the rate of equivocal and positive outcomes thus improving identification of robust positive effects in the assay. Finally, a case study (positive H295R outcome and no endocrine adversity in vivo) is presented, which suggests that stricter data interpretation criteria could refine necessary in vivo follow-up testing. Overall, the described additional criteria could improve H295R data interpretation and help inform on how to best leverage this assay for regulatory purposes.

The Relationship of Lightning Radio Pulse Amplitudes and Source Altitudes as Observed by LOFAR.

When a lightning flash is propagating in the atmosphere it is known that especially the negative leaders emit a large number of very high frequency (VHF) radio pulses. It is thought that this is due to streamer activity at the tip of the growing negative leader. In this work, we have investigated the dependence of the strength of this VHF emission on the altitude of such emission for two lightning flashes as observed by the Low Frequency ARray (LOFAR) radio telescope. We find for these two flashes that the extracted amplitude distributions are consistent with a power-law, and that the amplitude of the radio emissions decreases very strongly with source altitude, by more than a factor of 2 from 1 km altitude up to 5 km altitude. In addition, we do not find any dependence on the extracted power-law with altitude, and that the extracted power-law slope has an average around 3, for both flashes.

A distinct negative leader propagation mode.

The common phenomenon of lightning still harbors many secrets such as what are the conditions for lightning initiation and what is driving the discharge to propagate over several tens of kilometers through the atmosphere forming conducting ionized channels called leaders. Since lightning is an electric discharge phenomenon, there are positively and negatively charged leaders. In this work we report on measurements made with the LOFAR radio telescope, an instrument primarily build for radio-astronomy observations. It is observed that a negative leader rather suddenly changes, for a few milliseconds, into a mode where it radiates 100 times more VHF power than typical negative leaders after which it spawns a large number of more typical negative leaders. This mode occurs during the initial stage, soon after initiation, of all lightning flashes we have mapped (about 25). For some flashes this mode occurs also well after initiation and we show one case where it is triggered twice, some 100 ms apart. We postulate that this is indicative of a small (order of 5 km[Formula: see text]) high charge pocket. Lightning thus appears to be initiated exclusively in the vicinity of such a small but dense charge pocket.

Determining Electric Fields in Thunderclouds With the Radiotelescope LOFAR.

An analysis is presented of electric fields in thunderclouds using a recently proposed method based on measuring radio emission from extensive air shower events during thunderstorm conditions. This method can be regarded as a tomography of thunderclouds using cosmic rays as probes. The data cover the period from December 2011 till August 2014. We have developed an improved fitting procedure to be able to analyze the data. Our measurements show evidence for the main negative-charge layer near the -10° isotherm. This we have seen for a winter as well as for a summer cloud where multiple events pass through the same cloud and also the vertical component of the electric field could be reconstructed. On the day of measurement of some cosmic-ray events showing evidence for strong fields, no lightning activity was detected within 100 km distance. For the winter events, the top heights were between 5 and 6 km, while in the summer, typical top heights of 9 km were seen. Large horizontal components in excess of 70 kV/m of the electric fields are observed in the middle and top layers.

Radio Emission Reveals Inner Meter-Scale Structure of Negative Lightning Leader Steps.

We use the Low Frequency Array (LOFAR) to probe the dynamics of the stepping process of negatively charged plasma channels (negative leaders) in a lightning discharge. We observe that at each step of a leader, multiple pulses of vhf (30-80 MHz) radiation are emitted in short-duration bursts (<10 µs). This is evidence for streamer formation during corona flashes that occur with each leader step, which has not been observed before in natural lightning and it could help explain x-ray emission from lightning leaders, as x rays from laboratory leaders tend to be associated with corona flashes. Surprisingly, we find that the stepping length is very similar to what was observed near the ground, however with a stepping time that is considerably larger, which as yet is not understood. These results will help to improve lightning propagation models, and eventually lightning protection models.

Essential medicines containing ethanol elevate blood acetaldehyde concentrations in neonates.

UNLABELLED: Neonates administered ethanol-containing medicines are potentially at risk of dose-dependent injury through exposure to ethanol and its metabolite, acetaldehyde. Here, we determine blood ethanol and acetaldehyde concentrations in 49 preterm infants (median birth weight = 1190 g) dosed with iron or furosemide, medicines that contain different amounts of ethanol, and in 11 control group infants (median birth weight = 1920 g) who were not on any medications. Median ethanol concentrations in neonates administered iron or furosemide were 0.33 (range = 0-4.92) mg/L, 0.39 (range = 0-72.77) mg/L and in control group infants were 0.15 (range = 0.03-5.4) mg/L. Median acetaldehyde concentrations in neonates administered iron or furosemide were 0.16 (range = 0-8.89) mg/L, 0.21 (range = 0-2.43) mg/L and in control group infants were 0.01 (range = 0-0.14) mg/L. There was no discernible relationship between blood ethanol or acetaldehyde concentrations and time after medication dose. CONCLUSION: Although infants dosed with iron or furosemide had low blood ethanol concentrations, blood acetaldehyde concentrations were consistent with moderate alcohol exposure. The data suggest the need to account for the effects of acetaldehyde in the benefit-risk analysis of administering ethanol-containing medicines to neonates. WHAT IS KNOWN: • Neonates are commonly treated with ethanol-containing medicines, such as iron and furosemide. • However, there is no data on whether this leads to appreciable increases in blood concentrations of ethanol or its metabolite, acetaldehyde. What is New: • In this study, we find low blood ethanol concentrations in neonates administered iron and/or furosemide but markedly elevated blood acetaldehyde concentrations in some infants receiving these medicines. • Our data suggest that ethanol in drugs may cause elevation of blood acetaldehyde, a potentially toxic metabolite.

Prioritization of active antimalarials using structural interaction profile of Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR)-triclosan derivatives.

An empirical relationship between the experimental inhibitory activities of triclosan derivatives and its computationally predicted Plasmodium falciparum enoyl-acyl carrier protein (ACP) reductase (PfENR) dock poses was developed to model activities of known antimalarials. A statistical model was developed using 57 triclosan derivatives with significant measures (r = 0.849, q(2) = 0.619, s = 0.481) and applied on structurally related and structurally diverse external datasets. A substructure-based search on ChEMBL malaria dataset (280 compounds) yielded only two molecules with significant docking energy, whereas eight active antimalarials (EC(50) < 100 nM, tested on 3D7 strain) with better predicted activities (pIC(50) ~ 7) from Open Access Malaria Box (400 compounds) were prioritized. Further, calculations on the structurally diverse rhodanine molecules (known PfENR inhibitors) distinguished actives (experimental IC(50) = 0.035 µM; predicted pIC(50) = 6.568) and inactives (experimental IC(50) = 50 µM; predicted pIC50 = -4.078), which showed that antimalarials possessing dock poses similar to experimental interaction profiles can be used as leads to test experimentally on enzyme assays.

An observational study of blood concentrations and kinetics of methyl- and propyl-parabens in neonates.

PURPOSE: Systemic exposure to parabens in the neonatal population, in particular propyl-parabens (PPB), remains a concern. Blood concentrations and kinetics of methyl-parabens (MPB) and PPB were therefore determined in neonates receiving medicines containing these excipients. METHODS: A multi-centre, non-interventional, observational study of excipient-kinetics in neonates. 'Dried Blood Spot' samples were collected opportunistically at the same time as routine samples and the observations modelled using a non-linear mixed effects approach. RESULTS: A total of 841 blood MPB and PPB concentration data were available for evaluation from 181 pre- and term-neonates. Quantifiable blood concentrations of MPB and PPB were observed in 99% and 49% of patients, and 55% and 25% of all concentrations were above limit of detection (10 ng/ml), respectively. Only MPB data was amenable to modelling. Oral bioavailability was influenced by type of formulation and disposition was best described by a two compartment model with clearance (CL) influenced by post natal age (PNA); CL PNA<21 days 0.57 versus CL PNA>21 days 0.88 L/h. CONCLUSIONS: Daily repeated administration of parabens containing medicines can result in prolonged systemic exposure to the parent compound in neonates. Animal toxicology studies of PPB that specifically address the neonatal period are required before a permitted daily exposure for this age group can be established.

Emerging antimicrobial resistance pattern of Helicobacter pylori in central Gujarat.

BACKGROUND: Antimicrobial resistance is a growing problem in H. pylori treatment. The study was intended to evaluate the prevalence of resistance amongst 80 H.pylori isolates cultured from biopsy taken during routine endoscopies in 2008-2011. MATERIALS AND METHODS: 855 gastro duodenal biopsies were collected and cultured on H.pylori selective medium (containing Brucella agar and Columbia agar (Hi media), with Skirrow's supplement (antibiotic supplement) and 7% human blood cells). H.pylori was isolated from 80 specimens. The antimicrobial susceptibility of H.pylori isolates was carried out by the Kirby Bauer technique against metronidazole (5 µg), clarithromycin (15 µg), ciprofloxacin (5 µg), amoxicillin (10 µg), tetracycline (30 µg), erythromycin (15 µg), levofloxacin (5 µg), and furazolidone (50 µg) (Sigma- Aldrich, MO). RESULTS: 83.8% isolates were resistant to metronidazole, 58.8% were resistant to Clarithromycin 72.5% were resistant to Amoxicillin, 50% to Ciprofloxacin and 53.8% to tetracycline. furazolidone, erythromycin and Levofloxacin showed only 13.8% resistance to H.pylori. Multi drug resistance with metronidazole+clarithromycin+tetracycline was 85%. For all the drugs Antimicrobial resistance rate was found higher in males compare to females. Metronidazole and amoxicillin resistance was found noteworthy in patients with duodenal ulcer (p=0.018), gastritis (P=0.00), and in reflux esophagitis (P=0.00). clarithromycin and tetracycline resistance was suggestively linked with duodenitis (P=0.018), while furazolidone, erythromycin and levofloxacin showed excellent sensitivity in patients with duodenitis (P value--0.018), gastritis (P=0.00) and reflux esophagitis (P=0.00). Resistance with metronidazole (P=0.481), clarithromycin (P=0.261), amoxicillin (P=0.276), tetracycline (P=0.356), ciprofloxacin (P=0.164) was not correlated well with Age-group and Gender of the patients. CONCLUSION: A very high percentage of patients were infected with metronidazole and clarithromycin resistant strains. The use of antibiotics for other indications seems to be the major risk factor for the development of primary resistance. High incidence should alarm the gastroenterologist while prescribing the eradication regimen.

Intravenous salbutamol for childhood asthma: evidence-based medicine?

Intravenous salbutamol is commonly used to treat children with severe asthma unresponsive to inhaled ß2-agonist therapy. However, in this setting, there is little clinical trial data demonstrating its effectiveness. Additionally, there are significant concerns that intravenous salbutamol-dosing recommendations for children with acute asthma are excessive, and unnecessarily raise the potential for adverse reactions, such as lactic acidosis and tachycardia which, by increasing respiratory workload, exacerbate respiratory failure. Here, we review salbutamol clinical pharmacology and toxicology, evidence relating to its use in acute asthma and highlight gaps in the evidence base.

MEMS based Low Cost Piezoresistive Microcantilever Force Sensor and Sensor Module.

In the present work, we report fabrication and characterization of a low-cost MEMS based piezoresistive micro-force sensor with SU-8 tip using laboratory made silicon-on-insulator (SOI) substrate. To prepare SOI wafer, silicon film (0.8 µm thick) was deposited on an oxidized silicon wafer using RF magnetron sputtering technique. The films were deposited in Argon (Ar) ambient without external substrate heating. The material characteristics of the sputtered deposited silicon film and silicon film annealed at different temperatures (400-1050°C) were studied using atomic force microscopy (AFM) and X-ray diffraction (XRD) techniques. The residual stress of the films was measured as a function of annealing temperature. The stress of the as-deposited films was observed to be compressive and annealing the film above 1050°C resulted in a tensile stress. The stress of the film decreased gradually with increase in annealing temperature. The fabricated cantilevers were 130 µm in length, 40 µm wide and 1.0 µm thick. A series of force-displacement curves were obtained using fabricated microcantilever with commercial AFM setup and the data were analyzed to get the spring constant and the sensitivity of the fabricated microcantilever. The measured spring constant and sensitivity of the sensor was 0.1488N/m and 2.7mV/N. The microcantilever force sensor was integrated with an electronic module that detects the change in resistance of the sensor with respect to the applied force and displays it on the computer screen.

A computational model for non-conserved mature miRNAs from the rice genome.

Several computational approaches employ the high complementarity of plant miRNAs to target mRNAs as a filter to recognize miRNA. Numerous non-conserved miRNAs are known with more recent evolutionary origin as a result of target gene duplication events. We present here a computational model with knowledge inputs from reported non-conserved mature miRNAs of Oryza sativa (rice). Sequence- and structure-based approaches were used to retrieve miRNA features based on rice Argonaute protein and develop a multiple linear regression (MLR) model (r(2) = 0.996, q(2)cv = 0.989) which scored mature miRNAs as predicted by the MaturePred program. The model was validated by scoring test set (q(2) = 0.990) and computationally predicted mature miRNAs as external test set (q(2)test = 0.895). This strategy successfully enhanced the confidence of retrieving most probable non-conserved miRNAs from the rice genome. We anticipate that this computational model would recognize unknown non-conserved miRNA candidates and nurture the current mechanistic understanding of miRNA sorting to unveil the role of non-conserved miRNAs in gene silencing.

Risk assessment of neonatal excipient exposure: lessons from food safety and other areas.

Newborn babies can require significant amounts of medication containing excipients intended to improve the drug formulation. Most medicines given to neonates have been developed for adults or older children and contain excipients thought to be safe in these age groups. Many excipients have been used widely in neonates without obvious adverse effects. Some excipients may be toxic in high amounts in which case they need careful risk assessment. Alternatively, it is conceivable that ill-founded fears about excipients mean that potentially useful medicines are not made available to newborn babies. Choices about excipient exposure can occur at several stages throughout the lifecycle of a medicine, from product development through to clinical use. Making these choices requires a scalable approach to analysing the overall risk. In this contribution we examine these issues.

Adverse effects of systemic immunosuppression in keratolimbal allograft.

Purpose. Keratolimbal allograft (KLAL) is a treatment for limbal stem cell deficiency. One disadvantage is systemic immunosuppression to avoid rejection. Our purpose was to examine the adverse effects of systemic immunosuppression in KLAL. Methods. A retrospective case review of 16 patients with KLAL who received systemic immunosuppression consisting of a corticosteroid, an antimetabolite, and/or a calcineurin inhibitor was performed. Patients were monitored for signs, symptoms, or laboratory evidence of toxicity. Results. Eleven of 16 patients (68%) experienced an adverse effect. The average age of those with adverse effects was 43.5 years and without was 31.4 years. Ten of 11 patients (91%) had resolution during mean followup of 16.4 months. No serious adverse effects occurred. The most common included anemia, hyperglycemia, elevated creatinine, and elevated liver function tests. Prednisone and tacrolimus were responsible for the most adverse effects. Patients with comorbidities were more likely to experience an adverse effect (82% versus 20%, P = 0.036). Conclusions. KLAL requires prolonged systemic immunosuppression. Our data demonstrated that systemic immunosuppression did not result in serious adverse effects in our population and is relatively safe with monitoring for toxicity. In addition, we demonstrated that adverse effects are more likely in older patients with comorbidities.

Biological mesh reconstruction of perineal wounds following enhanced abdominoperineal excision of rectum (APER).

INTRODUCTION: An abdominoperineal excision of rectum (APER) may be required for rectal tumours less than 6 cm from the anal verge. Recently, the cylindrical APER has been used to prevent the "surgical waist" and so decrease margin involvement. However, removal of the levators leaves a large defect. Myocutaneous flaps [e.g. vertical rectus abdominis (VRAM)] are often used to fill the cylindrical resection defect, but have disadvantages associated with operative time, expertise and morbidity. We report our early experience of pelvic floor reconstruction with a biological mesh following cylindrical APER. METHODS: Data on consecutive patients having cylindrical APER between January 2008 and November 2010 were collected. Outcomes were compared between a VRAM reconstruction group and a mesh group. RESULTS: In 15 consecutive patients with low rectal cancer, five patients had VRAM pelvic floor reconstruction prior to ten patients having biosynthetic mesh repairs. The median operative time for the VRAM cohort was 405 min, compared with 259 min for the mesh (p = 0.0013). The median length of postoperative stay was 20 days for VRAM and 10 days for the mesh group (p = 0.067). There were four early complications for the VRAM group compared with seven for the mesh cohort (p = 0.37). The median cost per patient for the VRAM cohort was £11,075 compared to a median cost of £6,513 for the Mesh (p = 0.0097). CONCLUSION: The use of a biological mesh for pelvic floor reconstruction following cylindrical APER is feasible with morbidity comparable to VRAM reconstruction. There is significant cost-saving using a biosynthetic mesh, mainly due to reduced length of stay.

Assessment of liquid captopril formulations used in children.

OBJECTIVE: Unlicensed liquid captopril formulations are commonly used to treat children with heart disease. This study assessed the bioequivalence of two liquid preparations against a licensed tablet form. DESIGN: An open label, single dose, three-treatment, three-period, crossover trial. SETTING: Outpatient. PATIENTS: Healthy adult volunteers (n=18). INTERVENTIONS: Each subject was randomly assigned to one of six dosing sequences, and dosed with 25 mg captopril on each of three dosing visits separated by a washout of at least 14 days. Blood samples for pharmacokinetic analysis were taken at regular intervals (0 min to 10 h) post-dose. MAIN OUTCOME MEASURES: Bioequivalence of the formulations would be concluded if the 90% CI for the estimated ratio of the means of C(max) (maximum plasma concentrations) and area under curve(AUC) (extent of absorption) lay entirely within the range 0.8 to 1.25 RESULTS: Both liquid formulations failed the bioequivalence assessment with respect to C(max) and AUC. The 90% CI of the mean ratios of liquid/licensed tablet for both C(max) and AUC, fell outside the 0.8 to 1.25 limits. There was also considerable within-subject variability in C(max) (97.5%) and AUC (78.5%). CONCLUSIONS: Unlicensed captopril formulations are not bioequivalent to the licensed tablet form, or to each other, and so cannot be assumed to behave similarly in therapeutic use. Thus formulation substitution must be done with care and may require a period of increased monitoring of the patient. There is also significant within-subject variability in performance which has clinical implications with respect to titrating to an optimum therapeutic dose.

Novel Fe (III) heterochelates: synthesis, structural features and fluorescence studies.

Fluorescence properties of five 4-acyl pyrazolone based hydrazides (H(2)SB(n)) and their Fe (III) heterochelates of the type [Fe(SB(n))(L)(H(2)O)].mH(2)O [H(2)SB(n)=nicotinic acid [1-(3-methyl-5-oxo-1-phenyl-4,5-di hydro-1H-pyrazol-4yl)-acylidene]-hydrazide; where acyl=-CH(3), m=4 (H(2)SB(1)); -C(6)H(5), m=2 (H(2)SB(2)); -CH(2)-CH(3), m=3 (H(2)SB(3)); -CH(2)-CH(2)-CH(3), m=1.5 (H(2)SB(4)); -CH(2)-C(6)H(5), m=1.5 (H(2)SB(5)) and HL=1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid] were studied at room temperature. The fluorescence spectra of heterochelates show red shift, which may be due to the chelation by the ligands to the metal ion. It enhances ligand ability to accept electrons and decreases the electron transition energy. The kinetic parameters such as order of reaction (n), energy of activation (E(a)), entropy (S*), pre-exponential factor (A), enthalpy (H*) and Gibbs free energy (G*) have been reported.