Automated adaptive analysis of tagged magnetic resonance images of the mouse heart

The full potential of tagged MRI of the mouse heart for non-invasive evaluation of cardiac mechanics in transgenic animals has not been realized due to excessive user involvement with available image processing algorithms. Therefore, we developed an automated, rapid, high-resolution analysis technique, called High Density Mapping (HDM), that uses spectral correlation to efficiently quantify regional wall deformation, does not entail tracking of individual tags, and involves minimal user interaction. HDM analysis distinguishes regional mechanics in healthy and infarcted mice within 2 minutes. This new method may help promote the practical use of tagged MRI in mice and other species.published_or_final_versio

Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target

Background: The role of microRNAs (miRNAs) in regulating gene expression is currently an area of intense interest. Relatively little is known, however, about the role of miRNAs in inflammatory and immunologically-driven disorders. In a mouse model, we have previously shown that miRNAs are potentially important therapeutic targets in allergic asthma, because inhibition of miR-126, one of a small subset of miRNAs upregulated in the airway wall, effectively suppressed Th2-driven airway inflammation and other features of asthma. In the present study, we extended investigation of the therapeutic potential of miRNA inhibition to our well-established model of chronic asthma. Methods: Female BALB/c mice were systemically sensitised with ovalbumin (OVA) and chronically challenged with low mass concentrations of aerosolised OVA for up to 6 weeks. Airway tissue was obtained by blunt dissection and RNA was isolated for miRNA profiling. On the basis of the results obtained, animals were subsequently treated with either an antagomir to miR-126 (ant-miR-126) or a scrambled control antagomir once weekly during the 6 weeks of chronic challenge, and the effects on airway inflammation and remodelling were assessed using established morphometric techniques. Results: Compared to naïve mice, there was selective upregulation of a modest number of miRNAs, notably miR-126, in the airway wall tissue of chronically challenged animals. The relative increase was maximal after 2 weeks of inhalational challenge and subsequently declined to baseline levels. Compared to treatment with the scrambled control, ant-miR-126 significantly reduced recruitment of intraepithelial eosinophils, but had no effect on the chronic inflammatory response, or on changes of airway remodelling. Conclusions: In this model of chronic asthma, there was an initial increase in expression of a small number of miRNAs in the airway wall, notably miR-126. However, this later declined to baseline levels, suggesting that sustained changes in miRNA may not be essential for perpetuation of chronic asthma. Moreover, inhibition of miR-126 by administration of an antagomir suppressed eosinophil recruitment into the airways but had no effect on chronic inflammation in the airway wall, or on changes of remodelling, suggesting that multiple miRNAs are likely to regulate the development of these lesions

Effect of biomechanical footwear on knee pain in people with knee osteoarthritis : the BIOTOK randomized clinical trial

Importance: Individually calibrated biomechanical footwear therapy may improve pain and physical function in people with symptomatic knee osteoarthritis, but the benefits of this therapy are unclear. Objective: To assess the effect of a biomechanical footwear therapy vs control footwear over 24 weeks of follow-up. Design, Setting, and Participants: Randomized clinical trial conducted at a Swiss university hospital. Participants (N = 220) with symptomatic, radiologically confirmed knee osteoarthritis were recruited between April 20, 2015, and January 10, 2017. The last participant visit occurred on August 15, 2017. Interventions: Participants were randomized to biomechanical footwear involving shoes with individually adjustable external convex pods attached to the outsole (n = 111) or to control footwear (n = 109) that had visible outsole pods that were not adjustable and did not create a convex walking surface. Main Outcomes and Measures: The primary outcome was knee pain at 24 weeks of follow-up assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore standardized to range from 0 (no symptoms) to 10 (extreme symptoms). The secondary outcomes included WOMAC physical function and stiffness subscores and the WOMAC global score, all ranging from 0 (no symptoms) to 10 (extreme symptoms) at 24 weeks of follow-up, and serious adverse events. Results: Among the 220 randomized participants (mean age, 65.2 years [SD, 9.3 years]; 104 women [47.3%]), 219 received the allocated treatment and 213 (96.8%) completed follow-up. At 24 weeks of follow-up, the mean standardized WOMAC pain subscore improved from 4.3 to 1.3 in the biomechanical footwear group and from 4.0 to 2.6 in the control footwear group (between-group difference in scores at 24 weeks of follow-up, -1.3 [95% CI, -1.8 to -0.9]; P < .001). The results were consistent for WOMAC physical function subscore (between-group difference, -1.1 [95% CI, -1.5 to -0.7]), WOMAC stiffness subscore (between-group difference, -1.4 [95% CI, -1.9 to -0.9]), and WOMAC global score (between-group difference, -1.2 [95% CI, -1.6 to -0.8]) at 24 weeks of follow-up. Three serious adverse events occurred in the biomechanical footwear group compared with 9 in the control footwear group (2.7% vs 8.3%, respectively); none were related to treatment. Conclusions and Relevance: Among participants with knee pain from osteoarthritis, use of biomechanical footwear compared with control footwear resulted in an improvement in pain at 24 weeks of follow-up that was statistically significant but of uncertain clinical importance. Further research would be needed to assess long-term efficacy and safety, as well as replication, before reaching conclusions about the clinical value of this device

A comparative study on approximate entropy measure and poincaré plot indexes of minimum foot clearance variability in the elderly during walking

Background: Trip-related falls which is a major problem in the elderly population, might be linked to declines in the balance control function due to ageing. Minimum foot clearance (MFC) which provides a more sensitive measure of the motor function of the locomotor system, has been identified as a potential gait parameter associated with trip-related falls in older population. This paper proposes nonlinear indexes (approximate entropy (ApEn) and Poincaré plot indexes) of MFC variability and investigates the relationship of MFC with derived indexes of elderly gait patterns. The main aim is to find MFC variability indexes that well correlate with balance impairments. Methods: MFC data during treadmill walking for 14 healthy elderly and 10 elderly participants with balance problems and a history of falls (falls risk) were analysed using a PEAK-2D motion analysis system. ApEn and Poincaré plot indexes of all MFC data sets were calculated and compared. Results: Significant relationships of mean MFC with Poincaré plot indexes (SD1, SD2) and ApEn (r = 0.70, p < 0.05; r = 0.86, p < 0.01; r = 0.74, p < 0.05) were found in the falls-risk elderly group. On the other hand, such relationships were absent in the healthy elderly group. In contrast, the ApEn values of MFC data series were significantly (p < 0.05) correlated with Poincaré plot indexes of MFC in the healthy elderly group, whereas correlations were absent in the falls-risk group. The ApEn values in the falls-risk group (mean ApEn = 0.18 ± 0.03) was significantly (p < 0.05) higher than that in the healthy group (mean ApEn = 0.13 ± 0.13). The higher ApEn values in the falls-risk group might indicate increased irregularities and randomness in their gait patterns and an indication of loss of gait control mechanism. ApEn values of randomly shuffled MFC data of falls risk subjects did not show any significant relationship with mean MFC. Conclusion: Results have implication for quantifying gait dynamics in normal and pathological conditions, thus could be useful for the early diagnosis of at-risk gait. Further research should provide important information on whether falls prevention intervention can improve the gait performance of falls risk elderly by monitoring the change in MFC variability indexes

A comparative study on approximate entropy measure and poincaré plot indexes of minimum foot clearance variability in the elderly during walking

Background: Trip-related falls which is a major problem in the elderly population, might be linked to declines in the balance control function due to ageing. Minimum foot clearance (MFC) which provides a more sensitive measure of the motor function of the locomotor system, has been identified as a potential gait parameter associated with trip-related falls in older population. This paper proposes nonlinear indexes (approximate entropy (ApEn) and Poincaré plot indexes) of MFC variability and investigates the relationship of MFC with derived indexes of elderly gait patterns. The main aim is to find MFC variability indexes that well correlate with balance impairments. Methods: MFC data during treadmill walking for 14 healthy elderly and 10 elderly participants with balance problems and a history of falls (falls risk) were analysed using a PEAK-2D motion analysis system. ApEn and Poincaré plot indexes of all MFC data sets were calculated and compared. Results: Significant relationships of mean MFC with Poincaré plot indexes (SD1, SD2) and ApEn (r = 0.70, p < 0.05; r = 0.86, p < 0.01; r = 0.74, p < 0.05) were found in the falls-risk elderly group. On the other hand, such relationships were absent in the healthy elderly group. In contrast, the ApEn values of MFC data series were significantly (p < 0.05) correlated with Poincaré plot indexes of MFC in the healthy elderly group, whereas correlations were absent in the falls-risk group. The ApEn values in the falls-risk group (mean ApEn = 0.18 ± 0.03) was significantly (p < 0.05) higher than that in the healthy group (mean ApEn = 0.13 ± 0.13). The higher ApEn values in the falls-risk group might indicate increased irregularities and randomness in their gait patterns and an indication of loss of gait control mechanism. ApEn values of randomly shuffled MFC data of falls risk subjects did not show any significant relationship with mean MFC. Conclusion: Results have implication for quantifying gait dynamics in normal and pathological conditions, thus could be useful for the early diagnosis of at-risk gait. Further research should provide important information on whether falls prevention intervention can improve the gait performance of falls risk elderly by monitoring the change in MFC variability indexes

Mesoscopic organization reveals the constraints governing C. elegans nervous system

One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations, such as optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis, we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key functional role as a processor of information.Comment: Published version, Minor modifications, 16 pages, 9 figure

Of cattle, sand flies and men : a systematic review of risk factor analyses for South Asian visceral leishmaniasis and implications for elimination

Background: Studies performed over the past decade have identified fairly consistent epidemiological patterns of risk factors for visceral leishmaniasis (VL) in the Indian subcontinent. Methods and Principal Findings: To inform the current regional VL elimination effort and identify key gaps in knowledge, we performed a systematic review of the literature, with a special emphasis on data regarding the role of cattle because primary risk factor studies have yielded apparently contradictory results. Because humans form the sole infection reservoir, clustering of kala-azar cases is a prominent epidemiological feature, both at the household level and on a larger scale. Subclinical infection also tends to show clustering around kala-azar cases. Within villages, areas become saturated over a period of several years; kala-azar incidence then decreases while neighboring areas see increases. More recently, post kalaazar dermal leishmaniasis (PKDL) cases have followed kala-azar peaks. Mud walls, palpable dampness in houses, and peridomestic vegetation may increase infection risk through enhanced density and prolonged survival of the sand fly vector. Bed net use, sleeping on a cot and indoor residual spraying are generally associated with decreased risk. Poor micronutrient status increases the risk of progression to kala-azar. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting the complexity of the effect of bovines on sand fly abundance, aggregation, feeding behavior and leishmanial infection rates. Poverty is an overarching theme, interacting with individual risk factors on multiple levels. Conclusions: Carefully designed demonstration projects, taking into account the complex web of interconnected risk factors, are needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid resurgence when interventions are scaled back. More effective, short-course treatment regimens for PKDL are urgently needed to enable the elimination initiative to succeed

Procedures’ costs related to outpatient chemotherapy treatment of women suffering from breast cancer

To identify the direct cost of procedures related to an outpatient chemotherapy treatment for women with breast cancer. Method: This is a quantitative research, using the case study methodology, performed in an outpatient chemotherapy of a private hospital. The total cost was calculated by multiplying the time spent by professionals involved in therapeutic procedures, the unit cost of direct labor, adding to the cost of materials, drugs and solutions. For performing the calculations, we used the Brazilian currency (R$). Results: The average total cost per chemotherapy session corresponded to R$ 1,783.01 (100%), being R$1,671.66 (93,75$ 74,98 (4.21%) with materials, R$28.49 (1.60$ 7.88 (0.44%) with solutions. Conclusion: The results may support discussions and decision making for the management of costs related to chemotherapy aimed at reducing expenses and eliminating waste without harm to the care provided

Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance