Modeling the Measurements of Cochlear Microcirculation and Hearing Function after Loud Noise

Objective: Recent findings support the crucial role of microcirculatory disturbance and ischemia for hearing impairment especially after noise-induced hearing loss (NIHL). The aim of this study was to establish an animal model for in vivo analysis of cochlear microcirculation and hearing function after a loud noise to allow precise measurements of both parameters in vivo. Study Design: Randomized controlled trial. Setting: Animal study. Subjects and Methods: After assessment of normacusis (0 minutes) using evoked auditory brainstem responses (ABRs), noise (106-dB sound pressure level [SPL]) was applied to both ears in 6 guinea pigs for 30 minutes while unexposed animals served as controls. In vivo fluorescence microscopy of the stria vascularis capillaries was performed after surgical exposure of 1 cochlea. ABR measurements were derived from the contralateral ear. Results: After noise exposure, red blood cell velocity was reduced significantly by 24.3% (120 minutes) and further decreased to 44.5% at the end of the observation (210 minutes) in contrast to stable control measurements. Vessel diameters were not affected in both groups. A gradual decrease of segmental blood flow became significant (38.1%) after 150 minutes compared with controls. Hearing thresholds shifted significantly from 20.0 ± 5.5 dB SPL (0 minutes) to 32.5 ± 4.2dB SPL (60 minutes) only in animals exposed to loud noise. Conclusion: With regard to novel treatments targeting the stria vascularis in NIHL, this standardized model allows us to analyze in detail cochlear microcirculation and hearing function in vivo

Reproducibility of fetal heart volume by 3D-sonography using the XI VOCAL method

<p>Abstract</p> <p>Background</p> <p>To assess the reliability of fetal heart volume measurement by three-dimensional sonography (3DUS) using the eXtended Imaging Virtual Organ Computer-aided AnaLysis (XI VOCAL) method.</p> <p>Methods</p> <p>This reliability study enrolled 30 pregnant women with singleton healthy pregnancies between 19 and 34 weeks of gestation. All volume acquirements were performed with a convex volumetric transducer (C3-7ED) coupled to an Accuvix XQ sonography device (Medison, Korea). The XI VOCAL 10 planes was the method of choice for volumetric measurement. 3D datasets were analyzed by two observers (EQSB and HJFM); fetal heart volume was measured twice by the first and once by the second observer to calculate intra and interobserver reproducibility. Statistical analysis used pareated Student's t test (p) and calculated Intraclass correlation coefficients (ICC). Bland-Altman plots were also constructed.</p> <p>Results</p> <p>We observed an excellent intra- and interobserver reliability for fetal cardiac volume assessed by XI VOCAL. For the intraobserver the ICC was 0.998 (95% CI: 0.997; 0.999), with mean of differences of 0.12 cm³(95% limits of agreement: -0.84; +0.84; p = 0.130). For interobserver the ICC was 0.899 (95%CI: 0.996; 0.998), mean of differences 0.05 cm³(95% limits of agreement: -0.84; +0.84; p = 0.175).</p> <p>Conclusion</p> <p>Fetal cardiac volume assessed by 3DUS using XI VOCAL method is highly reproducible between 19 to 34 gestational weeks.</p

Physical activity and health related quality of life

Copyright @ 2012 Anokye et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Research on the relationship between Health Related Quality of Life (HRQoL) and physical activity (PA), to date, have rarely investigated how this relationship differ across objective and subjective measures of PA. The aim of this paper is to explore the relationship between HRQoL and PA, and examine how this relationship differs across objective and subjective measures of PA, within the context of a large representative national survey from England. METHODS: Using a sample of 5,537 adults (40–60 years) from a representative national survey in England (Health Survey for England 2008), Tobit regressions with upper censoring was employed to model the association between HRQoL and objective, and subjective measures of PA controlling for potential confounders. We tested the robustness of this relationship across specific types of PA. HRQoL was assessed using the summary measure of health state utility value derived from the EuroQol-5 Dimensions (EQ-5D) whilst PA was assessed via subjective measure (questionnaire) and objective measure (accelerometer- actigraph model GT1M). The actigraph was worn (at the waist) for 7 days (during waking hours) by a randomly selected sub-sample of the HSE 2008 respondents (4,507 adults – 16 plus years), with a valid day constituting 10 hours. Analysis was conducted in 2010. RESULTS: Findings suggest that higher levels of PA are associated with better HRQoL (regression coefficient: 0.026 to 0.072). This relationship is consistent across different measures and types of PA although differences in the magnitude of HRQoL benefit associated with objective and subjective (regression coefficient: 0.047) measures of PA are noticeable, with the former measure being associated with a relatively better HRQoL (regression coefficient: 0.072). CONCLUSION: Higher levels of PA are associated with better HRQoL. Using an objective measure of PA compared with subjective shows a relatively better HRQoL.This project was funded by the NIHR Health Technology Assessment programme (project number 08/72/01)

Pattern and Outcome of Chest Injuries at Bugando Medical Centre in Northwestern Tanzania.

Chest injuries constitute a continuing challenge to the trauma or general surgeon practicing in developing countries. This study was conducted to outline the etiological spectrum, injury patterns and short term outcome of these injuries in our setting. This was a prospective study involving chest injury patients admitted to Bugando Medical Centre over a six-month period from November 2009 to April 2010 inclusive. A total of 150 chest injury patients were studied. Males outnumbered females by a ratio of 3.8:1. Their ages ranged from 1 to 80 years (mean = 32.17 years). The majority of patients (72.7%) sustained blunt injuries. Road traffic crush was the most common cause of injuries affecting 50.7% of patients. Chest wall wounds, hemothorax and rib fractures were the most common type of injuries accounting for 30.0%, 21.3% and 20.7% respectively. Associated injuries were noted in 56.0% of patients and head/neck (33.3%) and musculoskeletal regions (26.7%) were commonly affected. The majority of patients (55.3%) were treated successfully with non-operative approach. Underwater seal drainage was performed in 39 patients (19.3%). One patient (0.7%) underwent thoracotomy due to hemopericardium. Thirty nine patients (26.0%) had complications of which wound sepsis (14.7%) and complications of long bone fractures (12.0%) were the most common complications. The mean LOS was 13.17 days and mortality rate was 3.3%. Using multivariate logistic regression analysis, associated injuries, the type of injury, trauma scores (ISS, RTS and PTS) were found to be significant predictors of the LOS (P < 0.001), whereas mortality was significantly associated with pre-morbid illness, associated injuries, trauma scores (ISS, RTS and PTS), the need for ICU admission and the presence of complications (P < 0.001). Chest injuries resulting from RTCs remain a major public health problem in this part of Tanzania. Urgent preventive measures targeting at reducing the occurrence of RTCs is necessary to reduce the incidence of chest injuries in this region

Workplace Accidents among Nepali Male Workers in the Middle East and Malaysia: A Qualitative Study

There are many Nepali men working in the Middle East and Malaysia and media reports and anecdotal evidence suggest a high risk of workplace-related accidents and injuries for male Nepali workers. Therefore, this study aims to explore the personal experiences of male Nepali migrants of unintentional injuries at their place of work. In-depth, face-to-face interviews (n = 20) were conducted with male Nepali migrant workers. Study participants were approached at Kathmandu International Airport, hotels and lodges around the airport. Interviews were transcribed and analysed using thematic analysis. Almost half of study participants experienced work-related accident abroad. The participants suggested that the reasons behind this are not only health and safety at work but also poor communication, taking risks by workers themselves, and perceived work pressure. Some participants experienced serious incidents causing life-long disability, extreme and harrowing accounts of injury but received no support from their employer or host countries. Nepali migrant workers would appear to be at a high risk of workplace unintentional injuries owing to a number of interrelated factors poor health and safety at work, pressure of work, risk taking practices, language barriers, and their general work environment. Both the Government of Nepal and host countries need to be better policing existing policies, introduce better legislation where necessary, ensure universal health (insurance) coverage for labour migrants, and improve preventive measures to minimize the number and severity of accidents and injuries among migrant workers

Comparative assessment of viral dynamic models for SARS‐CoV‐2 for pharmacodynamic assessment in early treatment trials

Pharmacometric analyses of time series viral load data may detect drug effects with greater power than approaches using single time points. Because SARS-CoV-2 viral load rapidly rises and then falls, viral dynamic models have been used. We compared different modelling approaches when analysing Phase II-type viral dynamic data. Using two SARS-CoV-2 datasets of viral load starting within 7 days of symptoms, we fitted the slope-intercept exponential decay (SI), reduced target cell limited (rTCL), target cell limited (TCL) and TCL with eclipse phase (TCLE) models using nlmixr. Model performance was assessed via Bayesian information criterion (BIC), visual predictive checks (VPCs), goodness-of-fit plots, and parameter precision. The most complex (TCLE) model had the highest BIC for both datasets. The estimated viral decline rate was similar for all models except the TCL model for dataset A with a higher rate [median (range) day-1: dataset A; 0.63 (0.56 – 1.84); dataset B: 0.81 (0.74-0.85)]. Our findings suggest simple models should be considered during pharmacodynamic model development

What are the living conditions and health status of those who don't report their migration status? a population-based study in Chile

BACKGROUND: Undocumented immigrants are likely to be missing from population databases, making it impossible to identify an accurate sampling frame in migration research. No population-based data has been collected in Chile regarding the living conditions and health status of undocumented immigrants. However, the CASEN survey (Caracterizacion Socio- Economica Nacional) asked about migration status in Chile for the first time in 2006 and provides an opportunity to set the base for future analysis of available migration data. We explored the living conditions and health of self-reported immigrants and respondents who preferred not to report their migration status in this survey. METHODS: Cross-sectional secondary analysis of CASEN survey in Chile in 2006. Outcomes: any disability, illness/accident, hospitalization/surgery, cancer/chronic condition (all binary variables); and the number of medical/emergency attentions received (count variables). Covariates: Demographics (age, sex, marital status, urban/rural, ethnicity), socioeconomic status (education level, employment status and household income), and material standard of living (overcrowding, sanitation, housing quality). Weighted regression models were estimated for each health outcome, crude and adjusted by sets of covariates, in STATA 10.0. RESULTS: About 1% of the total sample reported being immigrants and 0.7% preferred not to report their migration status (Migration Status - Missing Values; MS-MV). The MS-MV lived in more deprived conditions and reported a higher rate of health problems than immigrants. Some gender differences were observed by health status among immigrants and the MS-MV but they were not statistically significant. Regressions indicated that age, sex, SES and material factors consistently affected MS-MVs’ chance of presenting poor health and these patterns were different to those found among immigrants. Great heterogeneity in both the MS-MV and the immigrants, as indicated by wide confidence intervals, prevented the identification of other significantly associated covariates. CONCLUSION: This is the first study to look at the living conditions and health of those that preferred not to respond their migration status in Chile. Respondents that do not report their migration status are vulnerable to poor health and may represent undocumented immigrants. Surveys that fail to identify these people are likely to misrepresent the experiences of immigrants and further quantitative and qualitative research is urgently required

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies