Role of diffusion weighted MR imaging in differentiating benign from malignant prostate lesions

Background: The purpose of the study was to determine the diagnostic accuracy of diffusion weighted MR imaging and to propose a cut off ADC value in differentiating benign from malignant prostatic lesions considering histopathology as gold standard.Methods: It is a descriptive type of observational study done on 40 patients with clinical suspicion of prostate carcinoma and elevated PSA level more than 4ng/ml. The patients underwent Multiparametric prostate MRI and ADC values were calculated using ADC maps.Results: Of the 40 cases included in the study histopathology revealed a diagnosis of abscess (1), chronic prostatitis (2), BPH with chronic prostatitis (4), BPH (12), and malignancy (21). The mean and standard deviation (SD) of ADC values for the abscess (0.59), CP (0.83+0.16), BPH with CP (0.94+0.22), BPH (1.14+0.14) and malignancy (0.72+0.15) (x10-3mm2/s) were found in our study. The mean ADC value of malignant lesion was lower (0.727+0.149) as compare to benign lesion (1.034+0.216) and this difference was found to be statistically significant with p<0.001. By using ROC curve, ADC cut off value was calculated as 0.92 x 10-3mm2/s and sensitivity, specificity at this cut off value of ADC were 95.24% and 73.68% respectively. The PPV, NPV, diagnostic accuracy of at this cut off value of ADC were 80%, 93.33%, 85% respectively.Conclusions: Our study shows that DWI with ADC calculation helps in differentiation of Benign from Malignant prostatic lesions with high accuracy and this quantitative analysis should be incorporated in routine MRI evaluation of prostatic lesion

Functional brain activity constrained by structural connectivity reveals cohort-specific features for serum neurofilament light chain

Background: Neuro-axonal brain damage releases neurofilament light chain (NfL) proteins, which enter the blood. Serum NfL has recently emerged as a promising biomarker for grading axonal damage, monitoring treatment responses, and prognosis in neurological diseases. Importantly, serum NfL levels also increase with aging, and the interpretation of serum NfL levels in neurological diseases is incomplete due to lack of a reliable model for age-related variation in serum NfL levels in healthy subjects. Methods: Graph signal processing (GSP) provides analytical tools, such as graph Fourier transform (GFT), to produce measures from functional dynamics of brain activity constrained by white matter anatomy. Here, we leveraged a set of features using GFT that quantified the coupling between blood oxygen level dependent signals and structural connectome to investigate their associations with serum NfL levels collected from healthy subjects and former athletes with history of concussions. Results: Here we show that GSP feature from isthmus cingulate in the right hemisphere (r-iCg) is strongly linked with serum NfL in healthy controls. In contrast, GSP features from temporal lobe and lingual areas in the left hemisphere and posterior cingulate in the right hemisphere are the most associated with serum NfL in former athletes. Additional analysis reveals that the GSP feature from r-iCg is associated with behavioral and structural measures that predict aggressive behavior in healthy controls and former athletes. Conclusions: Our results suggest that GSP-derived brain features may be included in models of baseline variance when evaluating NfL as a biomarker of neurological diseases and studying their impact on personality traits

Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes

Increased renal clearance of thiamine (vitamin B1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: −76% and −53% respectively, p<0.001; transporter protein −77% and −83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy

FOREST CANOPY DENSITY ASSESSMENT USING HIGH RESOLUTION LISS-4 DATA IN YAMUNANAGAR DISTRICT, HARYANA

Forest plays an important role not only in providing ecological services but also economic goods to human beings. However, with increase in population there is a wide gap between demand and supply of these goods and services. This has lead to reduction in forest cover which needs to be taken care on regular time interval. To manage the existing forest area and also to increase the forest cover Forest Canopy Density (FCD) methodology is the main factor which was given by International Tropical timber Organization (ITTO). High resolution remote sensing LISS-4 data gives us chance to assess the quality of forest in terms of FCD as Rikimaru et al (1999) stated that FCD is one important parameter to assess forest cover quality. High resolution LISS-4 data analysis for FCD was never attempted before. Authors here attempted to assess the FCD utilizing methodology adopted by Rikimaru (1999), Huang (2001), Azizia (2008). The adopted methodology is one of the most efficient and cost effective way to derive the FCD. For this study Resourcesat-2 LISS-4 post monsoon data of year 2017 for Yamunanagar district was used to assess FCD within notified forest boundary. Notified forest boundaries at cadastral level prepared previously by Haryana Space Applications Centre (HARSAC) was used. The degree of forest canopy density is expressed in percentages: i.e. &lt;&thinsp;10% FCD (scrub land), 10–20% (Open Forest-I), 20–40% (Open Forest-II), 40–60% (Moderate Dense), 60–80% (Medium Dense) and &gt;&thinsp;80% (Highly Dense). Forest Canopy Density was based on three indices i.e. Advanced Vegetation Index (AVI), Bare Soil Index (BSI) and Canopy Shadow Index (CSI). Accuracy assessment was done based on ground data and comparison with Coterminous Google Earth imagery and it was found that the devised methodology has achieved overall accuracy of 93% with kappa coefficient of 0.9153. The result shows that maximum forest area in Yamunanagar district is in medium dense FCD category which is approximately 23948.08 acres. This study tells us that 24.2% of the total forest area is under scrub land and open forest which should be focussed for activities in working plan to increase the forest cover. This paper highlights the utility of high resolution satellite data for monitoring and management of forest and improvement in its quality. This attempt provided large scale (1&thinsp;:&thinsp;10,000) maps to the forest managers to better equip them in planning for afforestation, reforestation and rehabilitation of water logged areas, environment management and their future aspect

Integrating Association Mapping, Linkage Mapping, Fine Mapping with RNA Seq Conferring Seedling Vigor Improvement for Successful Crop Establishment in Deep Sown Direct-Seeded Rice

Background: Ongoing large-scale shift towards direct seeded rice (DSR) necessitates a convergence of breeding and genetic approaches for its sustenance and harnessing natural resources and environmental benefits. Improving seedling vigour remains key objective for breeders working with DSR. The present study aims to understand the genetic control of seedling vigour in deep sown DSR. Combined genome-wide association mapping, linkage mapping, fine mapping, RNA-sequencing to identify candidate genes and validation of putative candidate genes were performed in the present study. Results: Significant phenotypic variations were observed among genotypes in both F3:4:5 and BC2F2:3 populations. The mesocotyl length showed significant positive correlation with %germination, root and shoot length. The 881 kb region on chromosome 7 reported to be associated with mesocotyl elongation. RNA-seq data and RT-PCR results identified and validated seven potential candidate genes. The four promising introgression lines free from linkage drag and with longer mesocotyl length, longer root length, semi-dwarf plant height have been identified. Conclusion: The study will provide rice breeders (1) the pre breeding material in the form of anticipated DSR adapted introgression lines possessing useful traits and alleles improving germination under deep sown DSR field conditions (2) the base for the studies involving functional characterization of candidate genes. The development and utilization of improved introgression lines and molecular markers may play an important role in genomics-assisted breeding (GAB) during the pyramiding of valuable genes providing adaptation to rice under DSR. Our results offer a robust and reliable package that can contribute towards enhancing genetic gains in direct seeded rice breeding programs

Understanding the Uptake of Big Data in Health Care: Protocol for a Multinational Mixed-Methods Study

Background: Despite the high potential of big data, their applications in health care face many organizational, social, financial, and regulatory challenges. The societal dimensions of big data are underrepresented in much medical research. Little is known about integrating big data applications in the corporate routines of hospitals and other care providers. Equally little is understood about embedding big data applications in daily work practices and how they lead to actual improvements for health care actors, such as patients, care professionals, care providers, information technology companies, payers, and the society. Objective: This planned study aims to provide an integrated analysis of big data applications, focusing on the interrelations among concrete big data experiments, organizational routines, and relevant systemic and societal dimensions. To understand the similarities and differences between interactions in various contexts, the study covers 12 big data pilot projects in eight European countries, each with its own health care system. Workshops will be held with stakeholders to

Increased Expression of Fatty-Acid and Calcium Metabolism Genes in Failing Human Heart

Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca(2+))-handling in the human heart.RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6).Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+)-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+)-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM.DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes

Cells activated for wound repair have the potential to direct collective invasion of an epithelium.

Mechanisms regulating how groups of cells are signaled to move collectively from their original site and invade surrounding matrix are poorly understood. Here we develop a clinically relevant ex vivo injury invasion model to determine whether cells involved in directing wound healing have invasive function and whether they can act as leader cells to direct movement of a wounded epithelium through a three-dimensional (3D) extracellular matrix (ECM) environment. Similar to cancer invasion, we found that the injured cells invade into the ECM as cords, involving heterotypical cell-cell interactions. Mesenchymal cells with properties of activated repair cells that typically locate to a wound edge are present in leader positions at the front of ZO-1-rich invading cords of cells, where they extend vimentin intermediate filament-enriched protrusions into the 3D ECM. Injury-induced invasion depends on both vimentin cytoskeletal function and MMP-2/9 matrix remodeling, because inhibiting either of these suppressed invasion. Potential push and pull forces at the tips of the invading cords were revealed by time-lapse imaging, which showed cells actively extending and retracting protrusions into the ECM. This 3D injury invasion model can be used to investigate mechanisms of leader cell-directed invasion and understand how mechanisms of wound healing are hijacked to cause disease