Identification of mycolic acid forms using surface-enhanced Raman scattering as a fast detection method for tuberculosis

Background: Tuberculosis (TB) is the ninth leading cause of death worldwide and the leading cause from a single infectious agent, based on the WHO Global Tuberculosis Report in 2017. TB causes massive health care burdens in many parts of the world, specifically in the resource constrained developing world. Most deaths from TB could be prevented with cost effective early diagnosis and appropriate treatment. Purpose: Conventional TB detection methods are either too slow as it takes a few weeks for diagnosis or they lack the specificity and accuracy. Thus the objective of this study was to develop a fast and efficient detection for TB using surface enhanced Raman scattering (SERS) technique. Methods: SERS spectra for different forms of mycolic acids (MAs) that are both synthetic origin and actual extracts from the mycobacteria species were obtained by label-free direct detection mode. Similarly, we collected SERS spectra for γ-irradiated whole bacteria (WB). Measurements were done using silver (Ag) coated silicon nanopillar (Ag SNP) as SERS substrate. Results: We report the SERS based detection of MA, which is a biomarker for mycobacteria species including Mycobacterium tuberculosis. For the first time, we also establish the SERS spectral characterization of the three major forms of MA – αMA, methoxy-MA, and keto-MA, in bacterial extracts and also in γ-irradiated WB. We validated our findings by mass spectrometry. SERS detection of these three forms of MA could be useful in differentiating pathogenic and nonpathogenic Mycobacterium spp. Conclusions: We have demonstrated the direct detection of three major forms of MA – αMA, methoxy-MA, and keto-MA, in two different types of MA extracts from MTB bacteria, namely delipidated MA and undelipidated MA and finally in γ-irradiated WB. In the near future, this study could pave the way for a fast and efficient detection method for TB, which is of high clinical significance

The relationship between obesity, hyperglycemia symptoms, and health-related quality of life among Hispanic and non-Hispanic white children and adolescents

BACKGROUND: The current study was conducted to evaluate the effects of overweight, hyperglycemia symptoms, Hispanic ethnicity, and language barriers on health-related quality of life (HRQoL) among children and adolescents. METHODS: Parents'/guardians of a population based sample of 5530 children between ages 3 and 18 were administered the parents' version of the KINDL(® )survey instrument to assess HRQoL in children and adolescents. Multiple linear regression analysis was used to assess relationships between HRQoL, body mass index, and hyperglycemia symptoms categories. RESULTS: The mean age of children was 10.6 (SD = 4.3). The mean KINDL(® )total score was 79.7 (SD = 11.6) and the mean physical functioning score was 81.9 (SD = 20.3). Male children exhibited better physical health as compared to the female children (p < 0.001). Overweight children had lower overall HRQoL (p = 0.008). However, the association was not significant for the four of the six subscales including the physical health domain. Children with hyperglycemia symptoms and a family history of diabetes also had significantly lower overall and physical health HRQoL (p < 0.05). Children diagnosed with diabetes and in lower income strata also had significantly lower overall HRQoL (p < 0.05). No significant association between the Hispanic ethnicity and HRQoL was observed. However, those who reported mostly speaking Spanish exhibited significantly lower overall HRQoL (p = 0.001). CONCLUSION: Results suggest that overweight may reduce overall quality of life among children, though it does not directly influence physical functioning. However, hyperglycemia symptoms may affect both overall health and physical functioning. Findings also suggest the need for developing programs directed at overcoming language barriers that may face Spanish-speaking children or their parents. Furthermore, targeting children who have hyperglycemia symptoms with public information campaigns may be more appropriate than targeting overweight children

Association of dialysis facility-level hemoglobin measurement and erythropoiesis-stimulating agent dose adjustment frequencies with dialysis facility-level hemoglobin variation: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>A key goal of anemia management in dialysis patients is to maintain patients' hemoglobin (Hb) levels consistently within a target range. Our aim in this study was to assess the association of facility-level practice patterns representing Hb measurement and erythropoiesis-stimulating agent (ESA) dose adjustment frequencies with facility-level Hb variation.</p> <p>Methods</p> <p>This was a retrospective observational database analysis of patients in dialysis facilities affiliated with large dialysis organizations as of July 01, 2006, covering a follow-up period from July 01, 2006 to June 30, 2009. A total of 2,763 facilities representing 436,442 unique patients were included. The predictors evaluated were facility-level Hb measurement and ESA dose adjustment frequencies, and the outcome measured was facility-level Hb variation.</p> <p>Results</p> <p>First to 99th percentile ranges for facility-level Hb measurement and ESA dose adjustment frequencies were approximately once per month to once per week and approximately once per 3 months to once per 3 weeks, respectively. Facility-level Hb measurement and ESA dose adjustment frequencies were inversely associated with Hb variation. Modeling results suggested that a more frequent Hb measurement (once per week rather than once per month) was associated with approximately 7% to 9% and 6% to 8% gains in the proportion of patients with Hb levels within a ±1 and ±2 g/dL range around the mean, respectively. Similarly, more frequent ESA dose adjustment (once per 2 weeks rather than once per 3 months) was associated with approximately 6% to 9% and 5% to 7% gains in the proportion of patients in these respective Hb ranges.</p> <p>Conclusions</p> <p>Frequent Hb measurements and timely ESA dose adjustments in dialysis patients are associated with lower facility-level Hb variation and an increase in proportion of patients within ±1 and ±2 g/dL ranges around the facility-level Hb mean.</p

Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis

BACKGROUND The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. METHODOLOGY We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. PRINCIPAL FINDINGS Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. CONCLUSIONS/SIGNIFICANCE Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. PROTOCOL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42012003338

Requirement Text Detection from Contract Packages to Support Project Definition Determination

Project requirements are wishes and expectations of the client toward the design, construction, and other project management processes. The project definition is typically specified in a contract package including a contract document and many other related documents such as drawings, specifications, and government codes. Project definition determination is critical to the success of a project. Due to the lack of efficient tools for requirement processing, the current practices regarding project scoping still heavily rely on a manual basis which is tedious, time-consuming, and error-prone. This study aims to fill that gap by developing an automated method for identifying requirement texts from contractual documents. The study employed Naïve Bayes to train a classification model that can be used to separate requirement statements from non-requirement statements. An experiment was conducted on a manually labeled dataset of 1191 statements. The results revealed that the developed requirement detection model achieves a promising accuracy of over 90%

Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks

Cells modulate themselves in response to the surrounding environment like substrate elasticity, exhibiting structural reorganization driven by the contractility of cytoskeleton. The cytoskeleton is the scaffolding structure of eukaryotic cells, playing a central role in many mechanical and biological functions. It is composed of a network of actins, actin cross-linking proteins (ACPs), and molecular motors. The motors generate contractile forces by sliding couples of actin filaments in a polar fashion, and the contractile response of the cytoskeleton network is known to be modulated also by external stimuli, such as substrate stiffness. This implies an important role of actomyosin contractility in the cell mechano-sensing. However, how cells sense matrix stiffness via the contractility remains an open question. Here, we present a 3-D Brownian dynamics computational model of a cross-linked actin network including the dynamics of molecular motors and ACPs. The mechano-sensing properties of this active network are investigated by evaluating contraction and stress in response to different substrate stiffness. Results demonstrate two mechanisms that act to limit internal stress: (i) In stiff substrates, motors walk until they exert their maximum force, leading to a plateau stress that is independent of substrate stiffness, whereas (ii) in soft substrates, motors walk until they become blocked by other motors or ACPs, leading to submaximal stress levels. Therefore, this study provides new insights into the role of molecular motors in the contraction and rigidity sensing of cells

Efficacy of orally administered fluralaner (BravectoTM) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs

BACKGROUND : This laboratory study compared the efficacy of Bravecto™ (fluralaner), formulated as a chewable tablet, with the efficacy of Advocate® (imidacloprid/moxidectin), formulated for topical administration, against naturally acquired generalized demodicosis in dogs. METHODS : Sixteen dogs, all diagnosed with generalized demodectic mange, were randomly allocated to two equal groups. Bravecto™ chewable tablets were administered once orally at a minimum dose of 25 mg fluralaner/kg body weight to one group of dogs, while the second group was treated topically on three occasions at 28-day intervals with Advocate® at a minimum dose of 10 mg imidacloprid/kg body weight and 2.5 mg moxidectin/kg body weight. Mites were counted in skin scrapings and demodectic lesions were evaluated on each dog before treatment and at 28-day intervals thereafter over a 12 week study period. Deep skin scrapings (~4 cm2) were made from the same five sites on each dog at each subsequent examination. RESULTS : After single oral administration of Bravecto™ chewable tablets, mite numbers in skin scrapings were reduced by 99.8% on Day 28 and by 100% on Days 56 and 84. Mite numbers in the dogs treated topically on three occasions at 28-day intervals with Advocate® were reduced by 98.0% on Day 28, by 96.5% on Day 56 and by 94.7% on Day 84. Statistically significantly (P ≤ 0.05) fewer mites were found on Days 56 and 84 on the Bravecto™ treated dogs compared to Advocate® treated dogs. A marked decrease was observed in the occurrence of erythematous patches, crusts, casts and scales in the dogs treated with Bravecto™ and in the occurrence of erythematous patches in the dogs treated with Advocate®. With the exception of one dog in each treated group, all dogs exhibited hair regrowth ≥ 90% at the end of the study in comparison with their hair-coat at study start. CONCLUSIONS : Single oral administration of Bravecto™ chewable tablets is highly effective against generalized demodicosis, with no mites detectable at 56 and 84 days following treatment. In comparison, Advocate®, administered three times at 28-day intervals, is also highly effective against generalized demodicosis, but most dogs still harboured mites at all assessment time points. Both treatments resulted in a marked reduction of skin lesions and increase of hair re-growth 12 weeks after the initial treatment.http://www.parasitesandvectors.comam201

Factors affecting the use of patient survey data for quality improvement in the Veterans Health Administration

<p>Abstract</p> <p>Background</p> <p>Little is known about how to use patient feedback to improve experiences of health care. The Veterans Health Administration (VA) conducts regular patient surveys that have indicated improved care experiences over the past decade. The goal of this study was to assess factors that were barriers to, or promoters of, efforts to improve care experiences in VA facilities.</p> <p>Methods</p> <p>We conducted case studies at two VA facilities, one with stable high scores on inpatient reports of emotional support between 2002 and 2006, and one with stable low scores over the same period. A semi-structured interview was used to gather information from staff who worked with patient survey data at the study facilities. Data were analyzed using a previously developed qualitative framework describing organizational, professional and data-related barriers and promoters to data use.</p> <p>Results</p> <p>Respondents reported more promoters than barriers to using survey data, and particularly support for improvement efforts. Themes included developing patient-centered cultures, quality improvement structures such as regular data review, and training staff in patient-centered behaviors. The influence of incentives, the role of nursing leadership, and triangulating survey data with other data on patients' views also emerged as important. It was easier to collect data on current organization and practice than those in the past and this made it difficult to deduce which factors might influence differing facility performance.</p> <p>Conclusions</p> <p>Interviews with VA staff provided promising examples of how systematic processes for using survey data can be implemented as part of wider quality improvement efforts. However, prospective studies are needed to identify the most effective strategies for using patient feedback to improve specific aspects of patient-centered care.</p