The length dependence of the series elasticity of pig bladder smooth muscle

Strips of urinary bladder smooth muscle were subjected to a series of quick release measurements. Each measurement consisted of several releases and resets to the original length, made during one contraction. The complete length-force characteristic of series elasticity was quantified by estimating H, the amplitude of quick release necessary to reduce the active force to exactly zero, and Db, a measure for the deviation of the characteristic from a straight line. By measuring a series of contractions at increasing stretched strip lengths, the length dependence of these parameters was studied. It was found that H depends linearly on stretched strip length. On average H/length amounted to 0.04. Db decreased when strips were stretched, i.e. a straight line was more closely approximated. Both parameter dependencies support the concept of two separate elastic mechanisms, a linear true passive elasticity in series with a non-linear elasticity in the cross-bridges. For the latter, H amounts to 3.8% of the initial strip length

Isolation and individual electrical stimulation of single smooth-muscle cells from the urinary bladder of the pig

In contrast to striated muscle, measurements on strips of smooth muscle cannot be uniquely interpreted in terms of an array of contractile units. Therefore scaling down to the single-cell level is necessary to gain detailed understanding of the contractile process in this type of muscle. The present study describes the development of a method for isolating contractile single smooth muscle cells from pig urinary bladders. Contractile responses evoked by individual electrical stimulation were used as a measure of cell quality during development of the method. Responses were evaluated by measuring latency, contraction and relaxation times, as indicated by visible length changes, and stored on-line in a computer. Initial length, relative shortening and shortening speed were determined by measuring cell lengths in previously timed still video frames using a computer-controlled crosshair device. Increase of stimulus pulse duration resulted in improved responses, indicating that the observed shortening represented a physiological contractile response. Ultimately this method of evaluation was applied to two sets of cell preparations obtained by two different methods, one using only collagenase digestion, the other using mechanical manipulation as well. Both sets showed two main patterns of response to electrical stimulation: a pattern of contraction upon stimulation followed by enhanced contraction when stimulation was switched off (CK), and a pattern of contraction upon stimulation followed by relaxation when the stimulus was switched off (CR). The set of preparations containing the highest percentage of CR cells was found to be superior (i.e. greater initial length, shorter latency and contraction times, increased shortening and higher shortening speed). The method of isolation used for this set gives a high yield of contractile cells available for experimental use over a long span of time

External validity and assignment of experimental vs. control treatment providers within small work groups: a research note

Funder: University of CambridgeAbstract Objectives When offenders or victims are randomly assigned to receive experimental vs. current treatments, the external validity of results may depend on whether different treatments are delivered by similar kinds of treatment providers. When treatment providers volunteer to deliver innovative practices in an experiment, it is unclear whether outcomes depend on the content of the treatment, enthusiasm of the providers for the new practice, or both. In such situations, the potential for what we describe as differential predisposition of volunteers for a new treatment raises a question of external validity. Methods We describe the process by which 14 out of 29 mediators across seven Danish police districts came to deliver a new, restorative conferencing method of conducting face-to-face meetings between offenders and their victims, in comparison to longstanding mediation methods. Results We negotiated with all seven District mediation leaders and all 29 of their mediators to use partial random assignment of 14 of the mediators to deliver the new, restorative model. The 14 trained providers of the new method were substantially similar in several measureable characteristics to the 15 other mediators who continued to use the preexisting model, but we cannot measure directly the extent or balance of their predispositions for delivering each model. Conclusions While small work teams pose obstacles to simple random assignment of treatment providers to deliver experimental practices, the random assignment of victims and offenders to two different models of service might be made more externally valid by use of partial random assignment of service providers. </jats:sec

The economic impact of mental healthcare consumption before and after stroke in a cohort of stroke patients in the Netherlands:a record linkage study

BACKGROUND: Post-stroke healthcare consumption is strongly associated with a mental health diagnosis. This study aimed to identify stroke patients who utilised mental healthcare facilities, explored their mental healthcare consumption pre-stroke and post-stroke, and examined possible predictors of costs incurred by mental healthcare consumption post-stroke. METHODS: Three databases were integrated, namely the Maastricht University Medical Centre (MUMC) Medical Administration, the Stroke Registry from the Department of Neurology at MUMC, and the Psychiatric Case Registry South-Limburg. Patients from the MUMC who suffered their first-ever stroke between January 1 2000 and December 31 2004 were included and their records were analysed for mental healthcare consumption from 5 years preceding to 5 years following their stroke (1995-2009). Regression analysis was conducted to identify possible predictors of mental healthcare consumption costs. RESULTS: A total of 1385 patients were included and 357 (25.8%) received services from a mental healthcare facility during the 10-year reference period around their stroke. The costs of mental healthcare usage increased over time and peaked 1 year post-stroke (€7057; 22% of total mental healthcare costs). The number of hospitalisation days and mental healthcare consumption pre-stroke were significant predictors of mental healthcare costs. Explained variances of these models (costs during the 5 years post-stroke: R (2) = 15.5%, costs across a 10 year reference period: R (2) = 4.6%,) were low. CONCLUSION: Stroke patients have a significant level of mental healthcare comorbidity leading to relatively high mental healthcare costs. There is a relationship between stroke and mental healthcare consumption costs, but results concerning the underlying factors responsible for these costs are inconclusive

The pathology of co-infection with Usutu virus and Plasmodium spp. in naturally infected Eurasian blackbirds (Turdus merula)

Usutu virus (USUV) is a mosquito-borne zoonotic flavivirus causing mortality in Eurasian blackbirds ( Turdus merula) in Europe. In dead blackbirds, avian malaria co-infection due to mosquito-borne hemosporidians (e.g., Plasmodium spp.) has been reported. In humans, a similar co-infection of a flavivirus, Dengue virus, and Plasmodium spp. is causing increased severity of clinical disease. Currently, the effects of co-infection of arboviruses and hemosporidians in blackbirds remain unclear. This study investigates the rate of USUV and Plasmodium spp. co-infection in found-dead blackbirds ( n = 203) from 2016 to 2020 in the Netherlands. Presence of Plasmodium spp. was evaluated by cytology (43/203; 21,2%), histopathology (94/186; 50,5%) and qPCR (179/203; 88,1%). The severity of histological lesions in USUV and Plasmodium spp. co-infected dead blackbirds (121/203; 59,6%) were compared with those in Plasmodium spp. single-infected cases. Additionally, since no knowledge is present on the infection rate on live birds and mosquitoes in the Netherlands, a small group of live blackbirds ( n = 12) and selected in the field-collected mosquito pools ( n = 96) in 2020 were tested for the presence of Plasmodium spp. The latter was detected in the tested live blackbirds by qPCR (8/10; 80%), and cytology (3/11; 27,3%) and in the mosquito pools by qPCR (18/96; 18,7%). For this study, co-infection between USUV and Plasmodium spp. was observed only in the dead blackbirds. The high Plasmodium spp. presence, associated with lower lesions score, in single infected found dead birds suggest a predominantly smaller pathogenic role as single agent. On the other hand, the higher histological lesion scores observed in USUV and Plasmodium spp. co-infected birds suggests a major pathogenic role for the virus or an increased severity of the lesions due to a possible interplay of the two agents

Neurophysiological modeling of bladder afferent activity in the rat overactive bladder model

The overactive bladder (OAB) is a syndrome-based urinary dysfunction characterized by “urgency, with or without urge incontinence, usually with frequency and nocturia”. Earlier we developed a mathematical model of bladder nerve activity during voiding in anesthetized rats and found that the nerve activity in the relaxation phase of voiding contractions was all afferent. In the present study, we applied this mathematical model to an acetic acid (AA) rat model of bladder overactivity to study the sensitivity of afferent fibers in intact nerves to bladder pressure and volume changes. The afferent activity in the filling phase and the slope, i.e., the sensitivity of the afferent fibers to pressure changes in the post-void relaxation phase, were found to be significantly higher in AA than in saline measurements, while the offset (nerve activity at pressure ~0) and maximum pressure were comparable. We have thus shown, for the first time, that the sensitivity of afferent fibers in the OAB can be studied without cutting nerves or preparation of single fibers. We conclude that bladder overactivity induced by AA in rats is neurogenic in origin and is caused by increased sensitivity of afferent sensors in the bladder wall

Health-related quality of life after fast-track treatment results from a randomized controlled clinical equivalence trial

Purpose This randomized clinical equivalence trial was designed to evaluate health-related quality of life (HRQoL) after fast-track treatment for low-risk coronary artery bypass (CABG) patients. Methods Four hundred and ten CABG patients were randomly assigned to undergo either short-stay intensive care treatment (SSIC, 8 h of intensive care stay) or control treatment (care as usual, overnight intensive care stay). HRQoL was measured at baseline and 1 month, and one year after surgery using the multidimensional index of life quality (MILQ), the EQ-5D, the Beck Depression Inventory and the State-Trait Anxiety Inventory. Results At one month after surgery, no statistically significant difference in overall HRQoL was found (MILQ-score P-value = .508, overall MILQ-index P-value = .543, EQ-5D VAS P-value = .593). The scores on the MILQ-domains, physical, and social functioning were significantly higher at one month postoperatively in the SSIC group compared to the control group (P-value = .049; 95% CI: 0.01-2.50 and P-value =.014, 95% CI:0.24-2.06, respectively). However, these differences were no longer observed at long-term follow-up. Conclusions According to our definition of clinical equivalence, the HRQoL of SSIC patients is similar to patients receiving care as usual. Since safety and the financial benefits of this intervention were demonstrated in a previously reported analysis, SSIC can be considered as an adequate fast-track intensive care treatment option for low-risk CABG patients

The laboratory parameters-derived CoLab score as an indicator of the host response in ICU COVID-19 patients decreases over time: a prospective cohort study

The CoLab score was developed and externally validated to rule out COVID-19 among suspected patients presenting at the emergency department. We hypothesized a within-patient decrease in the CoLab score over time in an intensive care unit (ICU) cohort. Such a decrease would create the opportunity to potentially rule out the need for isolation when the infection is overcome. Using linear mixed-effects models, data from the Maastricht Intensive Care COVID (MaastrICCht) cohort were used to investigate the association between time and the CoLab score. Models were adjusted for sex, APACHE II score, ICU mortality, and daily SOFA score. The CoLab score decreased by 0.30 points per day (95% CI − 0.33 to − 0.27), independent of sex, APACHE II, and Mortality. With increasing SOFA score over time, the CoLab score decreased more strongly (− 0.01 (95% CI − 0.01 to − 0.01) additional decrease per one-point increase in SOFA score.) The CoLab score decreased in ICU patients on mechanical ventilation for COVID-19, with a one-point reduction per three days, independent of sex, APACHE II, and ICU mortality, and somewhat stronger with increasing multi-organ failure over time. This suggests that the CoLab score would decrease below a threshold where COVID-19 can be excluded. Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL

Bedside breath tests in children with abdominal pain: a prospective pilot feasibility study

Background: There is no definitive method of accurately diagnosing appendicitis before surgery. We evaluated the feasibility of collecting breath samples in children with abdominal pain and gathered preliminary data on the accuracy of breath tests. Methods: We conducted a prospective pilot study at a large tertiary referral paediatric hospital in the UK. We recruited 50 participants with suspected appendicitis, aged between 5 and 15 years. Five had primary diagnosis of appendicitis. The primary outcome was the number of breath samples collected. We also measured the number of samples processed within 2 h and had CO2 ≥ 3.5%. Usability was assessed by patient-reported pain pre- and post-sampling and user-reported sampling difficulty. Logistic regression analysis was used to predict appendicitis and evaluated using the area under the receiver operator characteristic curve (AUROC). Results: Samples were collected from all participants. Of the 45 samples, 36 were processed within 2 h. Of the 49 samples, 19 had %CO2 ≥ 3.5%. No difference in patient-reported pain was observed (p = 0.24). Sampling difficulty was associated with patient age (p = 0.004). The logistic regression model had AUROC = 0.86. Conclusions: Breath tests are feasible and acceptable to patients presenting with abdominal pain in clinical settings. We demonstrated adequate data collection with no evidence of harm to patients. The AUROC was better than a random classifier; more specific sensors are likely to improve diagnostic performance. Trial registration: ClinicalTrials.gov, NCT03248102. Registered 14 Aug 2017