Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Prevention of multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) is a top priority for global TB control, given the need to limit epidemic spread and considering the high cost, toxicity and poor treatment outcomes with available therapies. We performed a systematic literature review to evaluate the evidence for strategies to reduce MDR/XDR-TB transmission and disease progression. Rapid detection and timely initiation of effective treatment is critical to rendering MDR/XDR-TB cases non-infectious. The scale-up of rapid molecular testing has transformed the capacity of high-incidence settings to identify and treat patients with MDR/XDR-TB. Optimized infection control measures in hospitals and clinics are critical to protect other patients and healthcare workers, whereas creative measures to reduce transmission within community hotspots require consideration. Targeted screening of high-risk communities may enhance early case-detection and limit the spread of MDR/XDR-TB. Among infected contacts, preventive therapy promises to reduce the risk of disease progression. This is supported by observational cohort studies, but randomized trials are urgently needed to confirm these observations and guide policy formulation. Substantial investment in MDR/XDR-TB prevention and care will be critical if the ambitious global goal of TB elimination is to be realized

Time-to-birth prediction models and the influence of expert opinions

Preterm birth is the leading cause of death among children under five years old. The pathophysiology and etiology of preterm labor are not yet fully understood. This causes a large number of unnecessary hospitalizations due to high--sensitivity clinical policies, which has a significant psychological and economic impact. In this study, we present a predictive model, based on a new dataset containing information of 1,243 admissions, that predicts whether a patient will give birth within a given time after admission. Such a model could provide support in the clinical decision-making process. Predictions for birth within 48 h or 7 days after admission yield an Area Under the Curve of the Receiver Operating Characteristic (AUC) of 0.72 for both tasks. Furthermore, we show that by incorporating predictions made by experts at admission, which introduces a potential bias, the prediction effectiveness increases to an AUC score of 0.83 and 0.81 for these respective tasks

Global data for ecology and epidemiology: a novel algorithm for temporal Fourier processing MODIS data

Background. Remotely-sensed environmental data from earth-orbiting satellites are increasingly used to model the distribution and abundance of both plant and animal species, especially those of economic or conservation importance. Time series of data from the MODerate-resolution Imaging Spectroradiometer (MODIS) sensors on-board NASA's Terra and Aqua satellites offer the potential to capture environmental thermal and vegetation seasonality, through temporal Fourier analysis, more accurately than was previously possible using the NOAA Advanced Very High Resolution Radiometer (AVHRR) sensor data. MODIS data are composited over 8- or 16-day time intervals that pose unique problems for temporal Fourier analysis. Applying standard techniques to MODIS data can introduce errors of up to 30% in the estimation of the amplitudes and phases of the Fourier harmonics. Methodology/Principal Findings. We present a novel spline-based algorithm that overcomes the processing problems of composited MODIS data. The algorithm is tested on artificial data generated using randomly selected values of both amplitudes and phases, and provides an accurate estimate of the input variables under all conditions. The algorithm was then applied to produce layers that capture the seasonality in MODIS data for the period from 2001 to 2005. Conclusions/Significance. Global temporal Fourier processed images of 1 km MODIS data for Middle Infrared Reflectance, day- and night-time Land Surface Temperature (LST), Normalised Difference Vegetation Index (NDVI), and Enhanced Vegetation Index (EVI) are presented for ecological and epidemiological applications. The finer spatial and temporal resolution, combined with the greater geolocational and spectral accuracy of the MODIS instruments, compared with previous multi-temporal data sets, mean that these data may be used with greater confidence in species' distribution modelling

Cerebral aneurysm exclusion by CT angiography based on subarachnoid hemorrhage pattern: a retrospective study

<p>Abstract</p> <p>Background</p> <p>To identify patients with spontaneous subarachnoid hemorrhage for whom CT angiography alone can exclude ruptured aneurysms.</p> <p>Methods</p> <p>An observational retrospective review was carried out of all consecutive patients with non-traumatic subarachnoid hemorrhage who underwent both CT angiography and catheter angiography to exclude an aneurysm. CT angiography negative cases (no aneurysm) were classified according to their CT hemorrhage pattern as "aneurismal", "perimesencephalic" or as "no-hemorrhage."</p> <p>Results</p> <p>Two hundred and forty-one patients were included. A CT angiography aneurysm detection sensitivity and specificity of 96.4% and 96.0% were observed. All 35 cases of perimesencephalic or no-hemorrhage out of 78 CT angiography negatives also had negative angiography findings.</p> <p>Conclusions</p> <p>CT angiography is self-reliant to exclude ruptured aneurysms when either a perimesencephalic hemorrhage or no-hemorrhage pattern is identified on the CT within a week of symptom onset.</p

A Rapid and Simple Procedure for the Establishment of Human Normal and Cancer Renal Primary Cell Cultures from Surgical Specimens

The kidney is a target organ for the toxicity of several xenobiotics and is also highly susceptible to the development of malignant tumors. In both cases, in vitro studies provide insight to cellular damage, and represent adequate models to study either the mechanisms underlying the toxic effects of several nephrotoxicants or therapeutic approaches in renal cancer. The development of efficient methods for the establishment of human normal and tumor renal cell models is hence crucial. In this study, a technically simple and rapid protocol for the isolation and culture of human proximal tubular epithelial cells and human renal tumor cells from surgical specimens is presented. Tumor and normal tissues were processed by using the same methodology, based on mechanical disaggregation of tissue followed by enzymatic digestion and cell purification by sequential sieving. The overall procedure takes roughly one hour. The resulting cell preparations have excellent viabilities and yield. Establishment of primary cultures from all specimens was achieved successfully. The origin of primary cultured cells was established through morphological evaluation. Normal cells purity was confirmed by immunofluorescent staining and reverse transcription-polymerase chain reaction analysis for expression of specific markers

1/f2 Characteristics and Isotropy in the Fourier Power Spectra of Visual Art, Cartoons, Comics, Mangas, and Different Categories of Photographs

Art images and natural scenes have in common that their radially averaged (1D) Fourier spectral power falls according to a power-law with increasing spatial frequency (1/f2 characteristics), which implies that the power spectra have scale-invariant properties. In the present study, we show that other categories of man-made images, cartoons and graphic novels (comics and mangas), have similar properties. Further on, we extend our investigations to 2D power spectra. In order to determine whether the Fourier power spectra of man-made images differed from those of other categories of images (photographs of natural scenes, objects, faces and plants and scientific illustrations), we analyzed their 2D power spectra by principal component analysis. Results indicated that the first fifteen principal components allowed a partial separation of the different image categories. The differences between the image categories were studied in more detail by analyzing whether the mean power and the slope of the power gradients from low to high spatial frequencies varied across orientations in the power spectra. Mean power was generally higher in cardinal orientations both in real-world photographs and artworks, with no systematic difference between the two types of images. However, the slope of the power gradients showed a lower degree of mean variability across spectral orientations (i.e., more isotropy) in art images, cartoons and graphic novels than in photographs of comparable subject matters. Taken together, these results indicate that art images, cartoons and graphic novels possess relatively uniform 1/f2 characteristics across all orientations. In conclusion, the man-made stimuli studied, which were presumably produced to evoke pleasant and/or enjoyable visual perception in human observers, form a subset of all images and share statistical properties in their Fourier power spectra. Whether these properties are necessary or sufficient to induce aesthetic perception remains to be investigated

O2 Level Controls Hematopoietic Circulating Progenitor Cells Differentiation into Endothelial or Smooth Muscle Cells

BACKGROUND:Recent studies showed that progenitor cells could differentiate into mature vascular cells. The main physiological factors implicated in cell differentiation are specific growth factors. We hypothesized that simply by varying the oxygen content, progenitor cells can be differentiated either in mature endothelial cells (ECs) or contractile smooth muscle cells (SMCs) while keeping exactly the same culture medium. METHODOLOGY/PRINCIPAL FINDINGS:Mononuclear cells were isolated by density gradient were cultivated under hypoxic (5% O2) or normoxic (21% O2) environment. Differentiated cells characterization was performed by confocal microscopy examination and flow cytometry analyses. The phenotype stability over a longer time period was also performed. The morphological examination of the confluent obtained cells after several weeks (between 2 and 4 weeks) showed two distinct morphologies: cobblestone shape in normoxia and a spindle like shape in hypoxia. The cell characterization showed that cobblestone cells were positive to ECs markers while spindle like shape cells were positive to contractile SMCs markers. Moreover, after several further amplification (until 3(rd) passage) in hypoxic or normoxic conditions of the previously differentiated SMC, immunofluorescence studies showed that more than 80% cells continued to express SMCs markers whatever the cell environmental culture conditions with a higher contractile markers expression compared to control (aorta SMCs) signature of phenotype stability. CONCLUSION/SIGNIFICANCE:We demonstrate in this paper that in vitro culture of peripheral blood mononuclear cells with specific angiogenic growth factors under hypoxic conditions leads to SMCs differentiation into a contractile phenotype, signature of their physiological state. Moreover after amplification, the differentiated SMC did not reverse and keep their contractile phenotype after the 3rd passage performed under hypoxic and normoxic conditions. These aspects are of the highest importance for tissue engineering strategies. These results highlight also the determinant role of the tissue environment in the differentiation process of vascular progenitor cells

Large-Scale Assessment of the Zebrafish Embryo as a Possible Predictive Model in Toxicity Testing

Background: In the drug discovery pipeline, safety pharmacology is a major issue. The zebrafish has been proposed as a model that can bridge the gap in this field between cell assays (which are cost-effective, but low in data content) and rodent assays (which are high in data content, but less cost-efficient). However, zebrafish assays are only likely to be useful if they can be shown to have high predictive power. We examined this issue by assaying 60 water-soluble compounds representing a range of chemical classes and toxicological mechanisms. Methodology/Principal Findings: Over 20,000 wild-type zebrafish embryos (including controls) were cultured individually in defined buffer in 96-well plates. Embryos were exposed for a 96 hour period starting at 24 hours post fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for LC 50 determination. Zebrafish embryo LC50 (log mmol/L), and published data on rodent LD50 (log mmol/kg), were found to be strongly correlated (using Kendall’s rank correlation tau and Pearson’s product-moment correlation). The slope of the regression line for the full set of compounds was 0.73403. However, we found that the slope was strongly influenced by compound class. Thus, while most compounds had a similar toxicity level in both species, some compounds were markedly more toxic in zebrafish than in rodents, or vice versa. Conclusions: For the substances examined here, in aggregate, the zebrafish embryo model has good predictivity for toxicit

Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis

Objective: Corticosteroids are used in sepsis treatment to benefit outcome. However, discussion remains on which patients will benefit from treatment. Inter-individual variations in cortisol sensitivity, mediated through the glucocorticoid receptor, might play a role in the observed differences. Our aim was to study changes in mRNA levels of three glucocorticoid receptor splice variants in neutrophils of children with sepsis. Patients and design: Twenty-three children admitted to the pediatric intensive care unit with sepsis or septic shock were included. Neutrophils were isolated at days 0, 3 and 7, and after recovery (>3 months). mRNA levels of the glucocorticoid receptor splice variants GR-α (determining most of the cortisol effect), GR-P (increasing GR-α effect) and GR-β (inhibitor of GR-α) were measured quantitatively. Main results: Neutrophils from sepsis patients showed decreased levels of glucocorticoid receptor mRNA of the GR-α and GR-P splice variants on day 0 compared to after recovery. GR-α and GR-P mRNA levels showed a gradual recovery on days 3 and 7 and normalized after recovery. GR-β mRNA levels did not change significantly during sepsis. GR expression was negatively correlated to interleukin-6 (a measure of disease severity, r = -0.60, P = 0.009). Conclusions: Children with sepsis or septic shock showed a transient depression of glucocorticoid receptor mRNA in their neutrophils. This feature may represent a tissue-specific adaptation during sepsis leading to increased cortisol resistance of neutrophils. Our study adds to understanding the mechanism of cortisol sensitivity in immune cells. Future treatment strategies, aiming at timing and tissue specific regulation of glucocorticoids, might benefit patients with sepsis or septic shock

Clinical standards for the assessment, management, and rehabilitation of post-TB lung disease

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR). METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement). RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR. CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD