The Effects of Slow Deep Breathing on Measures of Microvascular and Autonomic Function in an Irritable Bowel Syndrome Population

Irritable Bowel Syndrome (IBS) is a functional disorder linked to disruptions in autonomic nervous system regulation, which could impair vascular homeostasis. Studies have shown that slow, deep breathing reduces muscle sympathetic nerve activity and arterial stiffness; however, its effects on autonomic regulation in adults with IBS have not been previously investigated. Moreover, the effects of breathing on microvascular endothelium function are unknown. PURPOSE: To investigate the effects of slow, deep breathing on measures of autonomic function and microvascular endothelial function in adults with IBS. METHODS: Adults (ages 18-65 years) with a formal diagnosis of IBS were enrolled and randomized to 4-week controlled breathing or time-control conditions. The experimental group followed a 20-minute slow, deep breathing video 4 to 6 days per week while the control group maintained their regular activity. To assess autonomic function, heart rate variability (HRV) and exercise heart rate recovery (HRR) were measured at baseline and week 4. The HRV test was accompanied by respiration rate measurements to ensure no significant deviations in respiration occurred between assessments as this could impact HRV. Exercise HRR was assessed 30, 60, and 120 seconds following a Balke treadmill VO2 max test. Laser Doppler flowmetry was assessed at baseline (33°C) and in response to local heating up to 43.5°C while blood pressure was measured throughout for the calculation of cutaneous vascular conductance (CVC). RESULTS: Of the 14 participants enrolled, 12 (n=6 for control and experimental groups) completed the study. At baseline, age (p = 0.47) and body mass index (p=0.14) were similar between groups. Respiration rate was similar between HRV assessments in both groups. In the experimental group, %CVC max significantly increased (p = 0.027) at week 4 while HRR was unchanged. A tendency toward a time by group interaction was observed for HRV low frequency to high frequency (LF/HF) ratio (p = 0.066) with slight reductions in the breathing group and increases in the control group. In the control group, %CVC max and HRR were unaltered, though HRR at 120 seconds tended to improve (p=0.08). CONCLUSIONS: Preliminary results from this ongoing study suggest that microvascular endothelial function can improve with 4 weeks of slow, deep breathing exercises in adults with IBS. These alterations in vascular function were unaccompanied by significant changes in autonomic function though trends were observed in HRV. Results show that slow, deep breathing is a viable alternative to physical exercise for improving microvascular function. Findings also suggest that this intervention could result in improved sympathovagal balance in adults with IBS and potentially other individuals with functional disorders

Adult lifetime cost of hemophilia B management in the US: payer and societal perspectives from a decision analytic model

Aims Hemophilia B (HB) is a rare congenital disorder characterized by bleeding-related complications which are managed by prophylactic or post-bleeding event (“on-demand”) replacement of clotting factor IX (FIX). The standard of care for severe HB is life-long prophylaxis with standard half-life (SHL) or extended half-life (EHL) products given every 2–3 or 7–14 days, respectively. FIX treatment costs in the US have been investigated, but the lifetime costs of HB treatment have not been well characterized, particularly related to the impact of joint health deterioration and associated health resource utilization. We developed a decision-analytic model to explore outcomes, costs and underlying cost drivers associated with FIX treatment options over the lifetime of an adult with severe or moderately severe HB. Materials and methods With participation from clinicians, health technology assessment specialists and patient advocates, a Markov model was constructed to estimate bleeding events and costs associated with health states including “bleed into joint”, “bleed not into joint”, “no bleed” and “death”. Sub-models of joint health were based on 0, 1, or ≥2 areas of chronic joint damage. US third-party payer and societal perspectives were considered with a lifetime horizon; sensitivity analyses tested the robustness of primary findings. Results Total adult lifetime costs per patient with severe and moderately severe HB were $21,086,607 for SHL FIX prophylaxis,$22,987,483 for EHL FIX prophylaxis, and $20,971,826 for on-demand FIX treatment. For FIX prophylaxis, the cost of FIX treatment accounts for >90% of the total HB treatment costs. Conclusions This decision analytic model demonstrated significant economic burden associated with the current HB treatment paradigm

Machine-learning with 18F-sodium fluoride PET and quantitative plaque analysis on CT angiography for the future risk of myocardial infarction

Coronary (18)F-sodium fluoride ((18)F-NaF) PET and CT angiography–based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both of these novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. Methods: Patients with known coronary artery disease underwent coronary (18)F-NaF PET and CT angiography on a hybrid PET/CT scanner. Machine-learning by extreme gradient boosting was trained using clinical data, CT quantitative plaque analysis, measures and (18)F-NaF PET, and it was tested using repeated 10-fold hold-out testing. Results: Among 293 study participants (65 ± 9 y; 84% male), 22 subjects experienced a myocardial infarction over the 53 (40–59) months of follow-up. On univariable receiver-operator-curve analysis, only (18)F-NaF coronary uptake emerged as a predictor of myocardial infarction (c-statistic 0.76, 95% CI 0.68–0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53–0.76) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60–0.84). After inclusion of all available data (clinical, quantitative plaque and (18)F-NaF PET), we achieved a substantial improvement (P = 0.008 versus (18)F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79–0.91). Conclusion: Both (18)F-NaF uptake and quantitative plaque analysis measures are additive and strong predictors of outcome in patients with established coronary artery disease. Optimal risk stratification can be achieved by combining clinical data with these approaches in a machine-learning model

Normal values for nuclear cardiology: Japanese databases for myocardial perfusion, fatty acid and sympathetic imaging and left ventricular function

Myocardial normal databases for stress myocardial perfusion study have been created by the Japanese Society of Nuclear Medicine Working Group. The databases comprised gender-, camera rotation range- and radiopharmaceutical-specific data-sets from multiple institutions, and normal database files were created for installation in common nuclear cardiology software. Based on the electrocardiography-gated single-photon emission computed tomography (SPECT), left ventricular function, including ventricular volumes, systolic and diastolic functions and systolic wall thickening were also analyzed. Normal databases for fatty acid imaging using 123I-beta-methyl-iodophenyl-pentadecanoic acid and sympathetic imaging using 123I-meta-iodobenzylguanidine were also examined. This review provides lists and overviews of normal values for myocardial SPECT and ventricular function in a Japanese population. The population-specific approach is a key factor for proper diagnostic and prognostic evaluation

Coronary Atherosclerotic Plaque Activity and Future Coronary Events

This study was funded by a Wellcome Trust Senior Investigator Award (WT103782AIA). Image analysis was supported by National Institutes for Health (R34HL161195 and 1R01HL135557). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Wellcome Trust or the National Institutes of Health. The British Heart Foundation supports DEN (CH/09/002, RG/16/10/32375, RE/18/5/34216), MRD (FS/SCRF/21/32010), NLM (CH/F/21/90010, RG/20/10/34966, RE/18/5/34216) AJM (AA/18/3/34220) and MCW (FS/ICRF/20/26002) and DD (FS/RTF/20/30009, NH/19/1/34595, PG/18/35/33786, PG/15/88/31780, PG/17/64/33205). MRD is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). PJS is supported by outstanding investigator award National Institutes for Health (R35HL161195). JK is supported by the National Science Centre 2021/41/B/NZ5/02630. EvB is supported by SINAPSE (www.sinapse.ac.uk). AB is supported by a Clinical Research Training Fellowships (MR/V007254/1). DD is supported by Chest Heart and Stroke Scotland (19/53), Tenovus Scotland (G.18.01), and Friends of Anchor and Grampian NHS-Endowments. The Edinburgh Clinical Research Facilities, Edinburgh Imaging facility and Edinburgh Clinical Trials Unit are supported by the National Health Service Research Scotland through National Health Service Lothian Health Board. The Leeds Clinical Research Facilities are supported by the UK National Institute for Health Research (NIHR) via its Clinical Research Facility programme. The work at Cedars-Sinai Medical Center (the Los Angeles site) was supported in part by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. The Chief Investigator and Edinburgh Clinical Trials Unit had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Peer reviewedPostprin

Drowning is an apparent and unexpected recurrent cause of mass mortality of Common starlings (Sturnus vulgaris

Drowning is infrequently reported as a cause of death of wild birds and such incidents typically involve individual, rather than multiple, birds. Over a 21-year period (1993 to 2013 inclusive), we investigated 12 incidents of mortality of multiple (2 − 80+) Common starlings (Sturnus vulgaris) in Great Britain that appeared to be due to drowning. More than ten birds were affected in ten of these reported incidents. These incidents always occurred during the spring and early summer months and usually involved juvenile birds. In all cases, circumstantial evidence and post-mortem examinations indicated drowning to be the most likely cause of death with no underlying disease found. A behavioural explanation seems likely, possibly related to the gregarious nature of this species combined with juvenile inexperience in identifying water hazards. A review of data from the ringed bird recovery scheme across Great Britain (1909–2013 inclusive) of both starlings and Common blackbirds (Turdus merula), also a common garden visitor, identified additional suspected drowning incidents, which were significantly more common in the former species, supporting a species predisposition to drowning. For each species there was a marked seasonal peak from April to August. Drowning should be included as a differential diagnosis when investigating incidents of multiple starling mortality, especially of juveniles

Genital herpes evaluation by quantitative TaqMan PCR: correlating single detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with cross-sectional and longitudinal clinical data

Abstract Objective To evaluate the utility of a single quantitative PCR (qPCR) measurement of HSV (HSV-1&2) DNA in cervicovaginal lavage (CVL) specimens collected from women with predominantly chronic HSV-2 infection in assessing genital HSV shedding and the clinical course of genital herpes (GH) within a cohort with semiannual schedule of follow up and collection of specimens. Methods Two previously described methods used for detection of HSV DNA in mucocutaneous swab samples were adapted for quantification of HSV DNA in CVLs. Single CVL specimens from 509 women were tested. Presence and quantity of CVL HSV DNA were explored in relation to observed cross-sectional and longitudinal clinical data. Results The PCR assay was sensitive and reproducible with a limit of quantification of ~50 copies per milliliter of CVL. Overall, 7% of the samples were positive for HSV-2 DNA with median log10 HSV-2 DNA copy number of 3.9 (IQR: 2.6-5.7). No HSV-1 was detected. Presence and quantity of HSV-2 DNA in CVL directly correlated with the clinical signs and symptoms of presence of active symptomatic disease with frequent recurrences. Conclusion Single qPCR measurement of HSV DNA in CVL fluids of women with chronic HSV-2 infection provided useful information for assessing GH in the setting of infrequent sampling of specimens. Observed positive correlation of the presence and quantity of HSV-2 DNA with the presence of active and more severe course of HSV-2 infection may have clinical significance in the evaluation and management of HSV-2 infected patients

Virological and serological surveillance for type A influenza in the black-legged kittiwake (Rissa tridactyla)

<p>Abstract</p> <p>Background</p> <p>The epidemiology of avian influenza viruses (AIVs) in gulls is only partially known. The role of the world's most numerous gull species, the black-legged kittiwake (<it>Rissa tridactyla</it>), as a potential AIV reservoir species has been unclear. The prevalence of AIV and humoral response against AIV were therefore studied in a colony of apparently healthy black-legged kittiwakes breeding in a nesting cliff in the South West Barents Region of Norway (70°22' N, 31°10' E), in 2008 and 2009.</p> <p>Results</p> <p>AIVs were detected from the oropharynx and cloaca in low amounts, with prevalences of 15% and 5%, in 2008 and 2009, respectively. Direct, partial sequencing of the hemagglutinin (HA) gene revealed that the H4 subtype was present. In 2009, antibodies to influenza A virus were detected in sera from 57 of 80 adult birds. In contrast, none of the three-week-old chicks (n = 18) tested seropositive. Hemagglutination inhibition (HI) assays demonstrated that the adult kittiwakes primarily had antibodies specific to the gull-associated H13 and H16 subtypes, with antibodies to H16 being most common.</p> <p>Conclusions</p> <p>These results support that the highly pelagic black-legged kittiwake is a reservoir of AIV. The serological findings suggest that H16 might be the main AIV subtype in the black-legged kittiwake. Further studies are needed to understand the ecology of AIV in the black-legged kittiwake and in gulls in general.</p