Dual-energy computed tomography with advanced postimage acquisition data processing: improved determination of urinary stone composition.

INTRODUCTION: The characterization of urinary calculi using noninvasive methods has the potential to affect clinical management. CT remains the gold standard for diagnosis of urinary calculi, but has not reliably differentiated varying stone compositions. Dual-energy CT (DECT) has emerged as a technology to improve CT characterization of anatomic structures. This study aims to assess the ability of DECT to accurately discriminate between different types of urinary calculi in an in vitro model using novel postimage acquisition data processing techniques. METHODS: Fifty urinary calculi were assessed, of which 44 had >or=60% composition of one component. DECT was performed utilizing 64-slice multidetector CT. The attenuation profiles of the lower-energy (DECT-Low) and higher-energy (DECT-High) datasets were used to investigate whether differences could be seen between different stone compositions. RESULTS: Postimage acquisition processing allowed for identification of the main different chemical compositions of urinary calculi: brushite, calcium oxalate-calcium phosphate, struvite, cystine, and uric acid. Statistical analysis demonstrated that this processing identified all stone compositions without obvious graphical overlap. CONCLUSION: Dual-energy multidetector CT with postprocessing techniques allows for accurate discrimination among the main different subtypes of urinary calculi in an in vitro model. The ability to better detect stone composition may have implications in determining the optimum clinical treatment modality for urinary calculi from noninvasive, preprocedure radiological assessment.

Quantifiable biomarkers of normal aging in the Japanese medaka fish (Oryzias latipes).

BACKGROUND: Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes), a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research. PRINCIPAL FINDINGS: The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old), mature adults (16 months old), and adults that had survived beyond the median lifespan (24 months). Livers of 24-month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated β-galactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain. SIGNIFICANCE: The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors.

Magnetic Resonance Imaging Biomarkers of Renal Structure and Function

The kidney's major role in filtration depends on its high blood flow, concentrating mechanisms, and biochemical activation. The kidney's greatest strengths also lead to vulnerability for drug-induced nephrotoxicity and other renal injuries. The current standard to diagnose renal injuries is with a percutaneous renal biopsy, which can be biased and insufficient. In one particular case, biopsy of a kidney with renal cell carcinoma can actually initiate metastasis. Tools that are sensitive and specific to detect renal disease early are essential, especially noninvasive diagnostic imaging. While other imaging modalities (ultrasound and x-ray/CT) have their unique advantages and disadvantages, MRI has superb soft tissue contrast without ionizing radiation. More importantly, there is a richness of contrast mechanisms in MRI that has yet to be explored and applied to study renal disease.

The focus of this work is to advance preclinical imaging tools to study the structure and function of the renal system. Studies were conducted in normal and disease models to understand general renal physiology as well as pathophysiology. This dissertation is separated into two parts--the first is the identification of renal architecture with ex vivo MRI; the second is the characterization of renal dynamics and function with in vivo MRI. High resolution ex vivo imaging provided several opportunities including: 1) identification of fine renal structures, 2) implementation of different contrast mechanisms with several pulse sequences and reconstruction methods, 3) development of image-processing tools to extract regions and structures, and 4) understanding of the nephron structures that create MR contrast and that are important for renal physiology. The ex vivo studies allowed for understanding and translation to in vivo studies. While the structure of this dissertation is organized by individual projects, the goal is singular: to develop magnetic resonance imaging biomarkers for renal system.

The work presented here includes three ex vivo studies and two in vivo studies:

1) Magnetic resonance histology of age-related nephropathy in sprague dawley.

2) Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice.

3) Susceptibility tensor imaging of the kidney and its microstructural underpinnings.

4) 4D MRI of renal function in the developing mouse.

5) 4D MRI of polycystic kidneys in rapamycin treated Glis3-deficient mice.

Genetic Studies Identify Critical Biomarkers and Refine the Classification of Malignant Gliomas

Gliomagenesis is driven by a complex network of genetic alterations and while the glioma genome has been a focus of investigation for many years; critical gaps in our knowledge of this disease remain. The identification of novel molecular biomarkers remains a focus of the greater cancer community as a method to improve the consistency and accuracy of pathological diagnosis. In addition, novel molecular biomarkers are drastically needed for the identification of targets that may ultimately result in novel therapeutics aimed at improving glioma treatment. Through the identification of new biomarkers, laboratories will focus future studies on the molecular mechanisms that underlie glioma development. Here, we report a series of genomic analyses identifying novel molecular biomarkers in multiple histopathological subtypes of glioma and refine the classification of malignant gliomas. We have completed a large scale analysis of the WHO grade II-III astrocytoma exome and report frequent mutations in the chromatin modifier, alpha thalassemia mental retardation x-linked (ATRX), isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), and mutations in tumor protein 53 (TP53) as the most frequent genetic mutations in low grade astrocytomas. Furthermore, by analyzing the status of recurrently mutated genes in 363 brain tumors, we establish that highly recurrent gene mutational signatures are an effective tool in stratifying homogeneous patient populations into distinct groups with varying outcomes, thereby capable of predicting prognosis. Next, we have established mutations in the promoter of telomerase reverse transcriptase (TERT) as a frequent genetic event in gliomas and in tissues with low rates of self renewal. We identify TERT promoter mutations as the most frequently mutated gene in primary glioblastoma. Additionally, we show that TERT promoter mutations in combination with IDH1 and IDH2 mutations are able to delineate distinct clinical tumor cohorts and are capable of predicting median overall survival more effectively than standard histopathological diagnosis alone. Taken together, these data advance our understanding of the genetic alterations that underlie the transformation of glial cells into neoplasms and we provide novel genetic biomarkers and multi – gene mutational signatures that can be utilized to refine the classification of malignant gliomas and provide opportunity for improved diagnosis.

The effect of a urinary incontinence self-management program for older women in South Korea: A pilot study

© 2015 Chinese Nursing Association.Background Although self-management approaches have shown strong evidence of positive outcomes for urinary incontinence prevention and management, few programs have been developed for Korean rural communities. Objectives This pilot study aimed to develop, implement, and evaluate a urinary incontinence self-management program for community-dwelling women aged 55 and older with urinary incontinence in rural South Korea. Methods This study used a one-group pre- post-test design to measure the effects of the intervention using standardized urinary incontinence symptom, knowledge, and attitude measures. Seventeen community-dwelling older women completed weekly 90-min group sessions for 5 weeks. Descriptive statistics and paired t-tests and were used to analyze data. Results The mean of the overall interference on daily life from urine leakage (pre-test: M = 5.76 ± 2.68, post-test: M = 2.29 ± 1.93, t = -4.609, p < 0.001) and the sum of International Consultation on Incontinence Questionnaire scores (pre-test: M = 11.59 ± 3.00, post-test: M = 5.29 ± 3.02, t = -5.881, p < 0.001) indicated significant improvement after the intervention. Improvement was also noted on the mean knowledge (pre-test: M = 19.07 ± 3.34, post-test: M = 23.15 ± 2.60, t = 7.550, p < 0.001) and attitude scores (pre-test: M = 2.64 ± 0.19, post-test: M = 3.08 ± 0.41, t = 5.150, p < 0.001). Weekly assignments were completed 82.4% of the time. Participants showed a high satisfaction level (M = 26.82 ± 1.74, range 22-28) with the group program. Conclusions Implementation of a urinary incontinence self-management program was accompanied by improved outcomes for Korean older women living in rural communities who have scarce resources for urinary incontinence management and treatment. Urinary incontinence self-management education approaches have potential for widespread implementation in nursing practice.

Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma.

The early detection of hepatocellular carcinoma (HCC) presents a challenge because of the lack of specific biomarkers. Serum/plasma microRNAs (miRNAs) can discriminate HCC patients from controls. We aimed to identify and evaluate HCC-associated plasma miRNAs originating from the liver as early biomarkers for detecting HCC. In this multicenter three-phase study, we first performed screening using both plasma (HCC before and after liver transplantation or liver hepatectomy) and tissue samples (HCC, para-carcinoma and cirrhotic tissues). Then, we evaluated the diagnostic potential of the miRNAs in two case-control studies (training and validation sets). Finally, we used two prospective cohorts to test the potential of the identified miRNAs for the early detection of HCC. During the screening phase, we identified ten miRNAs, eight of which (miR-20a-5p, miR-25-3p, miR-30a-5p, miR-92a-3p, miR-132-3p, miR-185-5p, miR-320a and miR-324-3p) were significantly overexpressed in the HBV-positive HCC patients compared with the HBV-positive cancer-free controls in both the training and validation sets, with a sensitivity of 0.866 and specificity of 0.646. Furthermore, we assessed the potential for early HCC detection of these eight newly identified miRNAs and three previously reported miRNAs (miR-192-5p, miR-21-5p and miR-375) in two prospective cohorts. Our meta-analysis revealed that four miRNAs (miR-20a-5p, miR-320a, miR-324-3p and miR-375) could be used as preclinical biomarkers (pmeta  < 0.05) for HCC. The expression profile of the eight-miRNA panel can be used to discriminate HCC patients from cancer-free controls, and the four-miRNA panel (alone or combined with AFP) could be a blood-based early detection biomarker for HCC screening.

Biomarkers of PTA

© Springer Science+Business Media New York 2015.Prognostic biomarkers may indicate the likelihood of disease development and speed of progression or may serve as predictive indicators of responsiveness to treatment. Joint injuries, particularly severe injuries, may result in post-traumatic osteoarthritis (PTOA), and pre- and post-injury prognostic biomarkers are needed to enhance primary and secondary prevention approaches for PTOA. Several macromolecules from joint structures found in serum, urine, and synovial fluid are promising biochemical markers for monitoring joint metabolism and health before and after joint injury. The use of metabolic profiling (analysis of small molecules) as a predictive tool for osteoarthritis (OA) has increased in the past decade. Although there is some question as to whether PTOA and idiopathic OA are comparable conditions, there is some evidence to suggest that components of their pathogenesis are similar. Potentially, biomarkers important to the high-risk PTOA profile translate to idiopathic OA. Further work is needed to confirm the utility of macromolecules and metabolites as biomarkers for PTOA, particularly focusing on those strongly correlated to clinical efficacy measures important to the patient (e.g., symptoms, physical function, and quality of life) and the causal pathway of PTOA.

Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.

BACKGROUND AND OBJECTIVES: Pain symptoms are common among Iraq/Afghanistan-era veterans, many of whom continue to experience persistent pain symptoms despite multiple pharmacological interventions. Preclinical data suggest that neurosteroids such as allopregnanolone demonstrate pronounced analgesic properties, and thus represent logical biomarker candidates and therapeutic targets for pain. Allopregnanolone is also a positive GABAA receptor modulator with anxiolytic, anticonvulsant, and neuroprotective actions in rodent models. We previously reported inverse associations between serum allopregnanolone levels and self-reported pain symptom severity in a pilot study of 82 male veterans. METHODS: The current study investigates allopregnanolone levels in a larger cohort of 485 male Iraq/Afghanistan-era veterans to attempt to replicate these initial findings. Pain symptoms were assessed by items from the Symptom Checklist-90-R (SCL-90-R) querying headache, chest pain, muscle soreness, and low back pain over the past 7 days. Allopregnanolone levels were quantified by gas chromatography/mass spectrometry. RESULTS: Associations between pain ratings and allopregnanolone levels were examined with Poisson regression analyses, controlling for age and smoking. Bivariate nonparametric Mann–Whitney analyses examining allopregnanolone levels across high and low levels of pain were also conducted. Allopregnanolone levels were inversely associated with muscle soreness [P = 0.0028], chest pain [P = 0.032], and aggregate total pain (sum of all four pain items) [P = 0.0001]. In the bivariate analyses, allopregnanolone levels were lower in the group reporting high levels of muscle soreness [P = 0.001]. CONCLUSIONS: These findings are generally consistent with our prior pilot study and suggest that allopregnanolone may function as an endogenous analgesic. Thus, exogenous supplementation with allopregnanolone could have therapeutic potential. The characterization of neurosteroid profiles may also have biomarker utility.