Response to a behavioural treatment, biofeedback, in constipated patients is associated with improved gut transit and autonomic innervation

Background: Although behavioural treatment (biofeedback) successfully treats the pelvic floor abnormalities in patients with idiopathic constipation, many patients also normalise their impaired bowel frequency. We postulated that a response may be associated with altered cerebral outflow via extrinsic autonomic nerves to the gut. We investigated whether treatment changes extrinsic innervation, using mucosal laser Doppler flowmetry, whether autonomic changes are gut specific, and whether it changes gut transit. Materials and methods: Forty nine patients (44 female, mean age 39 years) with idiopathic constipation were studied before and after biofeedback treatment (mean five sessions). Rectal mucosal blood flow was measured by laser Doppler flowmetry to assess direct extrinsic gut nerve autonomic activity. To assess general autonomic activity, RR (interval between successive R waves on the electrocardiogram) variability, Valsalva ratio, orthostatic adjustment ratio, and phase II:IV blood pressure ratio (II:IV) of the Valsalva manoeuvre were measured. All autonomic tests were compared with those of 26 healthy volunteers (19 female, mean age 37 years). Results: Twenty nine of 49 patients were symptomatically improved. Treatment reduced those with 3 bowel actions per week (27 v 9, pre v post), need to strain (26 v 9), and laxative or suppository use (34 v 9). Biofeedback reduced retained markers by 32% in those with slow transit and by 20% in those with normal transit. Twenty two had slow transit before treatment14 felt symptomatic improvement of whom 13 developed normal transit. There was a significantly greater increase in rectal mucosal blood flow in patients who subjectively improved compared with those who did not (29% v 7%; p<0.03) and in those with improved bowel frequency (33% v 9%, increased v unchanged bowel frequency; p<0.05). Thirty five patients had abnormal RR variability and 33 an abnormal Valsalva ratio; one had an abnormal orthostatic adjustment ratio and one an abnormal II:IV ratio. None of the general cardiorespiratory autonomic reflexes was changed by treatment. Conclusions: Biofeedback treatment affects more than the pelvic floor. Successful outcome after biofeedback treatment is associated with improved activity of the direct cerebral innervation to the gut and improved gut transit. This effect is gut specific; cardiovascular autonomic reflexes were not altered

Relationship between psychological state and level of activity of extrinsic gut innervation in patients with a functional gut disorder

Background: Anxiety and depression are known to be associated with alterations in central autonomic activity, and this may manifest as a functional gut disturbance. However, the final expression of motility disturbance is non-specific and non-quantifiable. This study examines the relationship between psychological state and psychosocial functioning with a new direct measure of the level of activity of extrinsic autonomic gut innervation, rectal mucosal Doppler blood flow. Materials and methods: Thirty four female patients (mean age 36 years, range 19-45) with constipation for greater than five years and 19 healthy women (mean age 38 years, range 21-60) were studied. They completed the general health questionnaire28 point scale (GHQ-28; psychosocial functioning) and the Bem sex role inventory (BSRI; an index of women's psychological feelings about their own femininity). On the same day they underwent measurement of rectal mucosal Doppler blood flow, a new validated measure of the activity of gut extrinsic nerve innervation. Measurements were made during the follicular phase and in the fasted state. Results: Women with constipation scored higher on the total GHQ-28 score and the somatisation (p=0.05) and anxiety (p=0.05) subscales of the GHQ-28. There was a negative correlation between mucosal blood flow and GHQ somatisation subscale (r=0.45, p<0.005), anxiety (r=0.38, p<0.05), and depression (r=0.40, p<0.01) scores in women with constipation. Although constipated women scored no higher than controls on the BSRI, there was a significant negative correlation between blood flow and BSRI score (r=0.49, p<0.005) for constipated women. Conclusions: General psychosocial function, somatisation, anxiety, depression, and feelings about female role are impaired in women with constipation and associated with altered rectal mucosal blood flow, a measure of extrinsic gut innervation. These findings suggest that psychological factors are likely to influence gut function via autonomic efferent neural pathways

Short Range Ordered Aluminum Foams

Ordering the bubbles of closed cell aluminum foams can contribute to decorative esthetics and create directional mechanical properties that disordered foams do not have. High porosity gt;80 aluminum foams prepared by the traditional static gas injection method usually have large and polyhedral cells, which do not form an ordered stacking. Aluminum foams with relatively uniform and small cells cell size amp; 8776;1.2 amp; 8201;mm have been recently obtained by gas injection through a nozzle rotating at high speed. Herein, the stacking of aluminum foams with different cell sizes and a monodisperse aqueous foam are characterized by X ray tomography and compared with an ideal face centered cubic FCC structure. The aluminum foam featuring the smallest cells has a concentrated distribution of cell coordination number with a peak of 12 and the first peaks of the radial distribution function are found to be consistent with those of the monodisperse aqueous foam and an ideal FCC structure. Furthermore, many aligned bubble chains with more than five bubbles are observed on cross sectional images. Therefore, aluminum foam can become short range ordered whenever the cell size is uniform enough and reduced to around 1.2 amp; 8201;mm. Methods for further improving the order of aluminum foam are discusse

Rethinking organoid technology through bioengineering

In recent years considerable progress has been made in the development of faithful procedures for the differentiation of human pluripotent stem cells (hPSCs). An important step in this direction has also been the derivation of organoids. This technology generally relies on traditional three-dimensional culture techniques that exploit cell-autonomous self-organization responses of hPSCs with minimal control over the external inputs supplied to the system. The convergence of stem cell biology and bioengineering offers the possibility to provide these stimuli in a controlled fashion, resulting in the development of naturally inspired approaches to overcome major limitations of this nascent technology. Based on the current developments, we emphasize the achievements and ongoing challenges of bringing together hPSC organoid differentiation, bioengineering and ethics. This Review underlines the need for providing engineering solutions to gain control of self-organization and functionality of hPSC-derived organoids. We expect that this knowledge will guide the community to generate higher-grade hPSC-derived organoids for further applications in developmental biology, drug screening, disease modelling and personalized medicine.This Review provides an overview of bioengineering technologies that can be harnessed to facilitate the culture, self-organization and functionality of human pluripotent stem cell-derived organoids.Stem cells & developmental biolog

Tomoscopy Time Resolved Tomography for Dynamic Processes in Materials

The structure and constitution of opaque materials can be studied with X ray imaging methods such as 3D tomography. To observe the dynamic evolution of their structure and the distribution of constituents, for example, during processing, heating, mechanical loading, etc., 3D imaging has to be fast enough. In this paper, the recent developments of time resolved X ray tomography that have led to what one now calls tomoscopy are briefly reviewed A novel setup is presented and applied that pushes temporal resolution down to just 1 ms, that is, 1000 tomograms per second tps are acquired, while maintaining spatial resolutions of micrometers and running experiments for minutes without interruption. Applications recorded at different acquisition rates ranging from 50 to 1000 tps are presented. The authors observe and quantify the immiscible hypermonotectic reaction of AlBi10 in wt alloy and dendrite evolution in AlGe10 in wt casting alloy during fast solidification. The combustion process and the evolution of the constituents are analyzed in a burning sparkler. Finally, the authors follow the structure and density of two metal foams over a long period of time and derive details of bubble formation and bubble ageing including quantitative analyses of bubble parameters with millisecond temporal resolutio

Factors associated with time from first-symptoms to diagnosis and treatment initiation of Multiple Sclerosis in Switzerland.

Recent studies emphasise the importance of timely diagnosis and early initiation of disease-modifying treatment in the long-term prognosis of multiple sclerosis. The objective of this study was to investigate factors associated with extended time to diagnosis and time to disease-modifying treatment initiation in the Swiss Multiple Sclerosis Registry. We used retrospective data (diagnoses 1996-2017) of the survey-based Swiss Multiple Sclerosis Registry and fitted logistic regression models (extended time to diagnosis ≥2 years from first symptoms, extended time to disease-modifying treatment initiation ≥1 year from diagnosis) with demographic and a priori defined variables. Our study, based on 996 persons with multiple sclerosis, suggests that 40% had an extended time to diagnosis, and extended time to disease-modifying treatment initiation was seen in 23%. Factors associated with extended time to diagnosis were primary progressive multiple sclerosis (odds ratio (OR) 5.09 (3.12-8.49)), diagnosis setting outside of hospital (neurologist (private practice) OR 1.54 (1.16-2.05)) and more uncommon first symptoms (per additional symptom OR 1.17 (1.06-1.30)). Older age at onset (per additional 5 years OR 0.84 (0.78-0.90)) and gait problems (OR 0.65 (0.47-0.89)) or paresthesia (OR 0.72 (0.54-0.95)) as first symptoms were associated with shorter time to diagnosis. Extended time to disease-modifying treatment initiation was associated with older age at diagnosis (per additional 5 years OR 1.18 (1.09-1.29)). In more recent years, time to diagnosis and time to disease-modifying treatment initiation tended to be shorter. Even in recent periods, substantial and partially systematic variation regarding time to diagnosis and time to disease-modifying treatment initiation remains. With the emerging paradigm of early treatment, the residual variation should be monitored carefully

Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Management of Patients With Crohn's Disease and Ulcerative Colitis During the Coronavirus Disease-2019 Pandemic: Results of an International Meeting

The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) is the only global organization devoted to the study of and management of the inflammatory bowel diseases (IBDs), namely, Crohn?s disease and ulcerative colitis. Membership is composed of physician-scientists who have established expertise in these diseases. The organization hosts an annual meeting and a number of working groups addressing issues of the epidemiology of IBD, diet and nutrition, and the development and use of treatments for IBD. There are currently 89 members of IOIBD representing 26 different countries. The organization has taken particular interest in the coronavirus disease-2019 (COVID-19) pandemic and how it may affect the IBD patient population. This document summarizes the results of 2 recent virtual meetings of the group and subsequent expert guidance for patients and providers