Postpartum physiology, psychology and paediatric follow up study (P4 Study) – Study protocol

© 2016 International Society for the Study of Hypertension in Pregnancy Background Women who have had hypertension in pregnancy are at greater risk of long term cardiovascular disease (CVD). Little is known about their cardiovascular risk postpartum or the effects on the woman's mental health and the outcomes of their infants. In this project we will study the physiological and psychological health of women and the physical health and development of their infants six months, two years and five years after birth. We will establish normal blood pressure (BP) and metabolic function for women who were normotensive in pregnancy and use these to assess women who had gestational hypertension (GH) or preeclampsia (PE). Design/methods Women will be asked to participate if they have given birth in the preceding six months. They will be excluded if they had diabetes, hypertension, renal or other serious maternal disease prior to pregnancy or congenital anomaly in the pregnancy. We will recruit 292 women who were normotensive and their babies, 100 who had GH and 100 who had PE and their babies. They will be assessed at six months, two and five years after birth. At each assessment mothers will have their blood pressure (BP) assessed peripherally with a liquid crystal sphygmomanometer and 24 h ambulatory blood pressure monitoring (ABPM), and centrally with non-invasive applanation tonometry. Additional physiological testing will include: body composition; energy balance; vascular compliance; cardiac function; liver and renal function, lipids and biochemistry; glucose and insulin; and urinalysis. Psychological status will be assessed with validated self-report questionnaires for depression, anxiety, post-traumatic stress disorder (PTSD) and mother-infant bonding. The babies will have a medical examination by a paediatrician at each assessment. Their behavioural development will be assessed with an Ages and Stages Questionnaire completed by their mother at each assessment and a developmental assessment by a child psychologist at two and five years. Conclusions This study will re-define normal BP and other physiological parameters for young parous women thereby permitting a more sensitive assessment of post-partum BP and other cardiovascular risk markers in women who have had GH or PE. It will also determine the extent, if any, of psychological disorders in these women and developmental or other concerns in their babies. Trials registration Australian and New Zealand Clinical Trials Registry Number: ACTRN12613001260718

The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

Background: Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. Objective: We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Design, setting, and participants: Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. Outcome measures and statistical analysis: We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Results and limitations: Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Conclusions: Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. Patient summary: We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy

Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

Background: The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods: Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results: Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the noninjured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions: This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases

A fatal case of recurrent amiodarone-induced thyrotoxicosis after percutaneous tracheotomy: a case report

<p>Abstract</p> <p>Background</p> <p>Amiodarone is a widely used antiarrythmic drug, which may produce secondary effects on the thyroid. In 14–18% of amiodarone-treated patients, there is overt thyroid dysfunction, usually in the form of amiodarone-induced thyrotoxicosis, which can be difficult to manage with standard medical treatment.</p> <p>Case presentation</p> <p>Presented is the case of a 65-year-old man, under chronic treatment of atrial fibrillation with amiodarone, who was admitted to the Intensive Care Unit with acute cardio-respiratory failure and fever. He was recently hospitalized with respiratory distress, attributed to amiodarone-induced pulmonary fibrosis. Clinical and laboratory investigation revealed thyrotoxicosis due to amiodarone treatment. He was begun on thionamide, prednisone and beta-blockers. After a short term improvement of his clinical status the patient underwent percutaneous tracheotomy due to weaning failure from mechanical ventilation, which led to the development of recurrent thyrotoxicosis, unresponsive to medical treatment. Finally, the patient developed multiple organ failure and died, seven days later.</p> <p>Conclusion</p> <p>We suggest that percutaneous tracheotomy could precipitate a thyrotoxic crisis, particularly in non-euthyroid patients suffering from concurrent severe illness and should be performed only in parallel with emergency thyroid surgery, when indicated.</p

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space

Expense and benefit of neoadjuvant treatment in squamous cell carcinoma of the esophagus

BACKGROUND: The effectiveness of neoadjuvant treatment (NT) prior to resection of squamous cell carcinoma of the esophagus (SCCE) in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patient's remaining survival time, this study aims to provide rationales for pretreating resection candidates. METHODS: From March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival. RESULTS: Two hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.). The response to NT was detected in 23 patients (70%). In 11 instances (33%), the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193). The average pretreatment time was 113 ± 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834. CONCLUSIONS: NT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival

Solution Structure and Dynamics of the I214V Mutant of the Rabbit Prion Protein

Background: The conformational conversion of the host-derived cellular prion protein (PrP C) into the disease-associated scrapie isoform (PrP Sc) is responsible for the pathogenesis of transmissible spongiform encephalopathies (TSEs). Various single-point mutations in PrP C s could cause structural changes and thereby distinctly influence the conformational conversion. Elucidation of the differences between the wild-type rabbit PrP C (RaPrP C) and various mutants would be of great help to understand the ability of RaPrP C to be resistant to TSE agents. Methodology/Principal Findings: We determined the solution structure of the I214V mutant of RaPrP C (91–228) and detected the backbone dynamics of its structured C-terminal domain (121–228). The I214V mutant displays a visible shift of surface charge distribution that may have a potential effect on the binding specificity and affinity with other chaperones. The number of hydrogen bonds declines dramatically. Urea-induced transition experiments reveal an obvious decrease in the conformational stability. Furthermore, the NMR dynamics analysis discloses a significant increase in the backbone flexibility on the pico- to nanosecond time scale, indicative of lower energy barrier for structural rearrangement. Conclusions/Significance: Our results suggest that both the surface charge distribution and the intrinsic backbone flexibility greatly contribute to species barriers for the transmission of TSEs, and thereby provide valuable hints fo

The efficacy of a comprehensive lifestyle modification programme based on yoga in the management of bronchial asthma: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is a substantial body of evidence on the efficacy of yoga in the management of bronchial asthma. Many studies have reported, as the effects of yoga on bronchial asthma, significant improvements in pulmonary functions, quality of life and reduction in airway hyper-reactivity, frequency of attacks and medication use. In addition, a few studies have attempted to understand the effects of yoga on exercise-induced bronchoconstriction (EIB) or exercise tolerance capacity. However, none of these studies has investigated any immunological mechanisms by which yoga improves these variables in bronchial asthma.</p> <p>Methods</p> <p>The present randomized controlled trial (RCT) was conducted on 57 adult subjects with mild or moderate bronchial asthma who were allocated randomly to either the yoga (intervention) group (n = 29) or the wait-listed control group (n = 28). The control group received only conventional care and the yoga group received an intervention based on yoga, in addition to the conventional care. The intervention consisted of 2-wk supervised training in lifestyle modification and stress management based on yoga followed by closely monitored continuation of the practices at home for 6-wk. The outcome measures were assessed in both the groups at 0 wk (baseline), 2, 4 and 8 wk by using Generalized Linear Model (GLM) repeated measures followed by post-hoc analysis.</p> <p>Results</p> <p>In the yoga group, there was a steady and progressive improvement in pulmonary function, the change being statistically significant in case of the first second of forced expiratory volume (FEV₁) at 8 wk, and peak expiratory flow rate (PEFR) at 2, 4 and 8 wk as compared to the corresponding baseline values. There was a significant reduction in EIB in the yoga group. However, there was no corresponding reduction in the urinary prostaglandin D₂metabolite (11β prostaglandin F2α) levels in response to the exercise challenge. There was also no significant change in serum eosinophilic cationic protein levels during the 8-wk study period in either group. There was a significant improvement in Asthma Quality of Life (AQOL) scores in both groups over the 8-wk study period. But the improvement was achieved earlier and was more complete in the yoga group. The number-needed-to-treat worked out to be 1.82 for the total AQOL score. An improvement in total AQOL score was greater than the minimal important difference and the same outcome was achieved for the sub-domains of the AQOL. The frequency of rescue medication use showed a significant decrease over the study period in both the groups. However, the decrease was achieved relatively earlier and was more marked in the yoga group than in the control group.</p> <p>Conclusion</p> <p>The present RCT has demonstrated that adding the mind-body approach of yoga to the predominantly physical approach of conventional care results in measurable improvement in subjective as well as objective outcomes in bronchial asthma. The trial supports the efficacy of yoga in the management of bronchial asthma. However, the preliminary efforts made towards working out the mechanism of action of the intervention have not thrown much light on how yoga works in bronchial asthma.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN00815962</p