Myocardial biomechanics and the consequent differentially expressed genes of the left atrial ligation chick embryonic model of hypoplastic left heart syndrome

Left atrial ligation (LAL) of the chick embryonic heart is a model of the hypoplastic left heart syndrome (HLHS) where a purely mechanical intervention without genetic or pharmacological manipulation is employed to initiate cardiac malformation. It is thus a key model for understanding the biomechanical origins of HLHS. However, its myocardial mechanics and subsequent gene expressions are not well-understood. We performed finite element (FE) modeling and single-cell RNA sequencing to address this. 4D high-frequency ultrasound imaging of chick embryonic hearts at HH25 (ED 4.5) were obtained for both LAL and control. Motion tracking was performed to quantify strains. Image-based FE modeling was conducted, using the direction of the smallest strain eigenvector as the orientations of contractions, the Guccione active tension model and a Fung-type transversely isotropic passive stiffness model that was determined via micro-pipette aspiration. Single-cell RNA sequencing of left ventricle (LV) heart tissues was performed for normal and LAL embryos at HH30 (ED 6.5) and differentially expressed genes (DEG) were identified.After LAL, LV thickness increased by 33%, strains in the myofiber direction increased by 42%, while stresses in the myofiber direction decreased by 50%. These were likely related to the reduction in ventricular preload and underloading of the LV due to LAL. RNA-seq data revealed potentially related DEG in myocytes, including mechano-sensing genes (Cadherins, NOTCH1, etc.), myosin contractility genes (MLCK, MLCP, etc.), calcium signaling genes (PI3K, PMCA, etc.), and genes related to fibrosis and fibroelastosis (TGF-β, BMP, etc.). We elucidated the changes to the myocardial biomechanics brought by LAL and the corresponding changes to myocyte gene expressions. These data may be useful in identifying the mechanobiological pathways of HLHS

Costs and staffing resource requirements for adaptive clinical trials: quantitative and qualitative results from the Costing Adaptive Trials project

Background Adaptive designs offer great promise in improving the efficiency and patient-benefit of clinical trials. An important barrier to further increased use is a lack of understanding about which additional resources are required to conduct a high-quality adaptive clinical trial, compared to a traditional fixed design. The Costing Adaptive Trials (CAT) project investigated which additional resources may be required to support adaptive trials. Methods We conducted a mock costing exercise amongst seven Clinical Trials Units (CTUs) in the UK. Five scenarios were developed, derived from funded clinical trials, where a non-adaptive version and an adaptive version were described. Each scenario represented a different type of adaptive design. CTU staff were asked to provide the costs and staff time they estimated would be needed to support the trial, categorised into specified areas (e.g. statistics, data management, trial management). This was calculated separately for the non-adaptive and adaptive version of the trial, allowing paired comparisons. Interviews with 10 CTU staff who had completed the costing exercise were conducted by qualitative researchers to explore reasons for similarities and differences. Results Estimated resources associated with conducting an adaptive trial were always (moderately) higher than for the non-adaptive equivalent. The median increase was between 2 and 4% for all scenarios, except for sample size re-estimation which was 26.5% (as the adaptive design could lead to a lengthened study period). The highest increase was for statistical staff, with lower increases for data management and trial management staff. The percentage increase in resources varied across different CTUs. The interviews identified possible explanations for differences, including (1) experience in adaptive trials, (2) the complexity of the non-adaptive and adaptive design, and (3) the extent of non-trial specific core infrastructure funding the CTU had. Conclusions This work sheds light on additional resources required to adequately support a high-quality adaptive trial. The percentage increase in costs for supporting an adaptive trial was generally modest and should not be a barrier to adaptive designs being cost-effective to use in practice. Informed by the results of this research, guidance for investigators and funders will be developed on appropriately resourcing adaptive trials

Body fat measurement by bioelectrical impedance and air displacement plethysmography: a cross-validation study to design bioelectrical impedance equations in Mexican adults

<p>Abstract</p> <p>Background</p> <p>The study of body composition in specific populations by techniques such as bio-impedance analysis (BIA) requires validation based on standard reference methods. The aim of this study was to develop and cross-validate a predictive equation for bioelectrical impedance using air displacement plethysmography (ADP) as standard method to measure body composition in Mexican adult men and women.</p> <p>Methods</p> <p>This study included 155 male and female subjects from northern Mexico, 20–50 years of age, from low, middle, and upper income levels. Body composition was measured by ADP. Body weight (BW, kg) and height (Ht, cm) were obtained by standard anthropometric techniques. Resistance, R (ohms) and reactance, Xc (ohms) were also measured. A random-split method was used to obtain two samples: one was used to derive the equation by the "all possible regressions" procedure and was cross-validated in the other sample to test predicted versus measured values of fat-free mass (FFM).</p> <p>Results and Discussion</p> <p>The final model was: FFM (kg) = 0.7374 * (Ht²/R) + 0.1763 * (BW) - 0.1773 * (Age) + 0.1198 * (Xc) - 2.4658. R²was 0.97; the square root of the mean square error (SRMSE) was 1.99 kg, and the pure error (PE) was 2.96. There was no difference between FFM predicted by the new equation (48.57 ± 10.9 kg) and that measured by ADP (48.43 ± 11.3 kg). The new equation did not differ from the line of identity, had a high R²and a low SRMSE, and showed no significant bias (0.87 ± 2.84 kg).</p> <p>Conclusion</p> <p>The new bioelectrical impedance equation based on the two-compartment model (2C) was accurate, precise, and free of bias. This equation can be used to assess body composition and nutritional status in populations similar in anthropometric and physical characteristics to this sample.</p

Comparing factors affecting commencement and cessation of betel quid chewing behavior in Taiwanese adults

<p>Abstract</p> <p>Background</p> <p>Betel quid is the fourth most common used substance in the world after tobacco, alcohol and caffeine. Although factors related to betel quid chewing or cessation of behaviors were reported previously, few studies simultaneously compared both behaviors in the same population. In addition, it is essential to consider time-to-event concept, since the chance of developing or stopping habit may vary over time. The purpose of this study was to compare the risk factors for commencement and cessation of betel quid chewing behaviors in a time-to-event setting.</p> <p>Methods</p> <p>A stratified multi-stage cluster sampling with selection probabilities proportional to size (PPS) was designed for Taiwanese adults with aged 18 years old and above. Kaplan-Meier estimates and Cox proportional hazard regression models were used to compare and calculate the hazard rate ratios for related factors to commencement or cessation of chewing habits.</p> <p>Results</p> <p>In Taiwan, men had a higher betel quid chewing rate (M: 20.9%, W: 1.2%), but woman chewers had a lower cessation rate (M: 27.5%, W: 12.7%). The hazard rate ratio (HRR) of having chewing habit changed from 4.22 (men vs women) univariately to 1.38 multivariablely, which indicated gender differences were confounded by other factors. In multivariable analysis, the risk factors of gender, education and ethnicity were significantly associated with both starting and cessation of betel quid chewing behavior. The factors of occupation, cigarette smoking and alcohol drinking were only associated with starting habit.</p> <p>Conclusion</p> <p>Commencement or cessation of chewing behavior involves a scenario of time, hence it is preferable to use a time-to-event approach for the comparison. The cessation rates of betel quid chewing were decreasingly associated with the daily consumption of betel quid. Hence, reducing of daily amount in betel quid cessation program may be associated with future stopping habit.</p

Kocuria kristinae infection associated with acute cholecystitis

BACKGROUND: Kocuria, previously classified into the genus of Micrococcus, is commonly found on human skin. Two species, K. rosea and K. kristinae, are etiologically associated with catheter-related bacteremia. CASE PRESENTATION: We describe the first case of K. kristinae infection associated with acute cholecystitis. The microorganism was isolated from the bile of a 56-year old Chinese man who underwent laparoscopic cholecystectomy. He developed post-operative fever that resolved readily after levofloxacin treatment. CONCLUSION: Our report of K. kristinae infection associated with acute cholecystitis expands the clinical spectrum of infections caused by this group of bacteria. With increasing number of recent reports describing the association between Kocuria spp. and infectious diseases, the significance of their isolation from clinical specimens cannot be underestimated. A complete picture of infections related to Kocuria spp. will have to await the documentation of more clinical cases

Ethnic Differences in Survival after Breast Cancer in South East Asia

Background: The burden of breast cancer in Asia is escalating. We evaluated the impact of ethnicity on survival after breast cancer in the multi-ethnic region of South East Asia. Methodology/Principal Findings Using the Singapore-Malaysia hospital-based breast cancer registry, we analyzed the association between ethnicity and mortality following breast cancer in 5,264 patients diagnosed between 1990 and 2007 (Chinese: 71.6%, Malay: 18.4%, Indian: 10.0%). We compared survival rates between ethnic groups and calculated adjusted hazard ratios (HR) to estimate the independent effect of ethnicity on survival. Malays (n = 968) presented at a significantly younger age, with larger tumors, and at later stages than the Chinese and Indians. Malays were also more likely to have axillary lymph node metastasis at similar tumor sizes and to have hormone receptor negative and poorly differentiated tumors. Five year overall survival was highest in the Chinese women (75.8%; 95%CI: 74.4%–77.3%) followed by Indians (68.0%; 95%CI: 63.8%–72.2%), and Malays (58.5%; 95%CI: 55.2%–61.7%). Compared to the Chinese, Malay ethnicity was associated with significantly higher risk of all-cause mortality (HR: 1.34; 95%CI: 1.19–1.51), independent of age, stage, tumor characteristics and treatment. Indian ethnicity was not significantly associated with risk of mortality after breast cancer compared to the Chinese (HR: 1.14; 95%CI: 0.98–1.34). Conclusion: In South East Asia, Malay ethnicity is independently associated with poorer survival after breast cancer. Research into underlying reasons, potentially including variations in tumor biology, psychosocial factors, treatment responsiveness and lifestyle after diagnosis, is warranted

Psychosocial impact of implantable cardioverter defibrillators (ICD) in young adults with Tetralogy of Fallot

Item does not contain fulltextOBJECTIVE: To investigate the psychosocial impact of having an implantable cardioverter defibrillator (ICD) in adults with Tetralogy of Fallot (ToF). METHODS: Included were 26 ToF-patients with an ICD (age 44 +/- 12 years), and two control groups consisting of 28 ToF-patients without an ICD (age 40 +/- 10 years) and a group of 35 ICD-patients of older age without ToF (age 72.0 +/- 8 years). This last control group was chosen to represent the "older general ICD population" with acquired heart disease seen at the out-patient clinic. Psychosocial functioning encompassed daily functioning, subjective health status, quality of life, anxiety, depression, coping and social support. RESULTS: ToF-patients with ICD showed diminished psychosocial functioning in comparison to ToF-patients without ICD. This was reflected by diminished subjectively perceived physical functioning (p = 0.01), general health perception (p < 0.01) and a lower satisfaction with life (p = 0.02). In comparison to older ICD-patients, ToF-patients with ICD showed less satisfaction with life (p = 0.03), experienced more anxiety (p = 0.01) and showed less favourable coping styles, although physical functioning was better for ToF-patients with ICD than for older ICD-patients (p = 0.01). More inappropriate shocks were found in ToF-patients with ICD compared to the older ICD-patients. CONCLUSION: In patients with ToF, ICD implantation had a major impact on psychosocial functioning which should be taken into account when considering ICD implantation in these young patients. To help improve psychosocial functioning, psychological counselling attuned to the specific needs of these patients may be useful.1 juli 201