Optimisation of b-values for the accurate estimation of the apparent diffusion coefficient (ADC) in whole-body diffusion-weighted MRI in patients with metastatic melanoma.

OBJECTIVE: To establish optimised diffusion weightings ('b-values') for acquisition of whole-body diffusion-weighted MRI (WB-DWI) for estimation of the apparent diffusion coefficient (ADC) in patients with metastatic melanoma (MM). Existing recommendations for WB-DWI have not been optimised for the tumour properties in MM; therefore, evaluation of acquisition parameters is essential before embarking on larger studies. METHODS: Retrospective clinical data and phantom experiments were used. Clinical data comprised 125 lesions from 14 examinations in 11 patients with multifocal MM, imaged before and/or after treatment with immunotherapy at a single institution. ADC estimates from these data were applied to a model to estimate the optimum b-value. A large non-diffusing phantom was used to assess eddy current-induced geometric distortion. RESULTS: Considering all tumour sites from pre- and post-treatment examinations together, metastases exhibited a large range of mean ADC values, [0.67-1.49] × 10-3 mm2/s, and the optimum high b-value (bhigh) for ADC estimation was 1100 (10th-90th percentile: 740-1790) s/mm2. At higher b-values, geometric distortion increased, and longer echo times were required, leading to reduced signal. CONCLUSIONS: Theoretical optimisation gave an optimum bhigh of 1100 (10th-90th percentile: 740-1790) s/mm2 for ADC estimation in MM, with the large range of optimum b-values reflecting the wide range of ADC values in these tumours. Geometric distortion and minimum echo time increase at higher b-values and are not included in the theoretical optimisation; bhigh in the range 750-1100 s/mm2 should be adopted to maintain acceptable image quality but performance should be evaluated for a specific scanner. KEY POINTS: • Theoretical optimisation gave an optimum high b-value of 1100 (10th-90th percentile: 740-1790) s/mm2 for ADC estimation in metastatic melanoma. • Considering geometric distortion and minimum echo time (TE), a b-value in the range 750-1100 s/mm2 is recommended. • Sites should evaluate the performance of specific scanners to assess the effect of geometric distortion and minimum TE

The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

Multimodal MRI characteristics of the glioblastoma infiltration beyond contrast enhancement

Our inability to identify the invasive margin of glioblastomas hampers attempts to achieve local control. Diffusion tensor imaging (DTI) has been implemented clinically to delineate the margin of the tumor infiltration, its derived anisotropic (q) values can extend beyond the contrast-enhanced area and correlates closely with the tumor. However, its correlation with tumor infiltration shown on multivoxel proton magnetic resonance spectroscopy1 (MRS) and perfusion magnetic resonance imaging (MRI) should be investigated. In this study, we aimed to show tissue characteristics of the q-defined peritumoral invasion on MRS and perfusion MRI. Patients with a primary glioblastoma were included (n = 51). Four regions of interest were analyzed; the contrast-enhanced lesion, peritumoral abnormal q region, peritumoral normal q region, and contralateral normal-appearing white matter. MRS, including choline (Cho)/creatinine (Cr), Cho/N-acetyl-aspartate (NAA) and NAA/Cr ratios, and the relative cerebral blood volume (rCBV) were analyzed. Our results showed an increase in the Cho/NAA (p = 0.0346) and Cho/Cr (p = 0.0219) ratios in the peritumoral abnormal q region, suggestive of tumor invasion. The rCBV was marginally elevated (p = 0.0798). Furthermore, the size of the abnormal q regions was correlated with survival; patients with larger abnormal q regions showed better progression-free survival (median 287 versus 53 days, p = 0.001) and overall survival (median 464 versus 274 days, p = 0.006) than those with smaller peritumoral abnormal q regions of interest. These results support how the DTI q abnormal area identifies tumor activity beyond the contrast-enhanced area, especially correlating with MRS

A specific case in the classification of woods by FTIR and chemometric: discrimination of Fagales from Malpighiales

Fourier transform infrared (FTIR) spectroscopic data was used to classify wood samples from nine species within the Fagales and Malpighiales using a range of multivariate statistical methods. Taxonomic classification of the family Fagaceae and Betulaceae from Angiosperm Phylogenetic System Classification (APG II System) was successfully performed using supervised pattern recognition techniques. A methodology for wood sample discrimination was developed using both sapwood and heartwood samples. Ten and eight biomarkers emerged from the dataset to discriminate order and family, respectively. In the species studied FTIR in combination with multivariate analysis highlighted significant chemical differences in hemicelluloses, cellulose and guaiacyl (lignin) and shows promise as a suitable approach for wood sample classification

Changes in glycemic control from 1996 to 2006 among adults with type 2 diabetes: a longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>Our objectives were to examine temporal changes in HbA1c and lipid levels over a 10-year period and to identify predictors of metabolic control in a longitudinal patient cohort.</p> <p>Methods</p> <p>We identified all adults within our hospital network with T2DM who had HbA1c's measured in both 1996 and 2006 (longitudinal cohort). For patients with no data in 2006, we used hospital and social security records to distinguish patients lost to follow-up from those who died after 1996. We compared characteristics of the 3 baseline cohorts (longitudinal, lost to f/u, died) and examined metabolic trends in the longitudinal cohort.</p> <p>Results</p> <p>Of the 4944 patients with HbA1c measured in 1996, 1772 (36%) had an HbA1c measured in 2006, 1296 (26%) were lost to follow-up, and 1876 (38%) had died by 2006. In the longitudinal cohort, mean HbA1c decreased by 0.4 ± 1.8% over the ten-year span (from 8.2% ± 1.7% to 7.8% ± 1.4%) and mean total cholesterol decreased by 49.3 (± 46.5) mg/dL. In a multivariate model, independent predictors of HbA1c decline included older age (OR 1.41 per decade, 95% CI: 1.3-1.6, p < 0.001), baseline HbA1c (OR 2.9 per 1% increment, 2.6 - 3.2, p < 0.001), and speaking English (OR 2.1, 1.4-3.1, p < 0.001).</p> <p>Conclusions</p> <p>Despite having had diabetes for an additional 10 years, patients in our longitudinal cohort had better glycemic and cholesterol control in 2006 than 1996. Greatest improvements occurred in patients with the highest levels in the baseline year.</p

Purification and functional characterisation of rhiminopeptidase A, a novel aminopeptidase from the venom of Bitis gabonica rhinoceros

This study describes the discovery and characterisation of a novel aminopeptidase A from the venom of B. g. rhinoceros and highlights its potential biological importance. Similar to mammalian aminopeptidases, rhiminopeptidase A might be capable of playing roles in altering the blood pressure and brain function of victims. Furthermore, it could have additional effects on the biological functions of other host proteins by cleaving their N-terminal amino acids. This study points towards the importance of complete analysis of individual components of snake venom in order to develop effective therapies for snake bites

Anaerobic Carbon Monoxide Dehydrogenase Diversity in the Homoacetogenic Hindgut Microbial Communities of Lower Termites and the Wood Roach

Anaerobic carbon monoxide dehydrogenase (CODH) is a key enzyme in the Wood-Ljungdahl (acetyl-CoA) pathway for acetogenesis performed by homoacetogenic bacteria. Acetate generated by gut bacteria via the acetyl-CoA pathway provides considerable nutrition to wood-feeding dictyopteran insects making CODH important to the obligate mutualism occurring between termites and their hindgut microbiota. To investigate CODH diversity in insect gut communities, we developed the first degenerate primers designed to amplify cooS genes, which encode the catalytic (β) subunit of anaerobic CODH enzyme complexes. These primers target over 68 million combinations of potential forward and reverse cooS primer-binding sequences. We used the primers to identify cooS genes in bacterial isolates from the hindgut of a phylogenetically lower termite and to sample cooS diversity present in a variety of insect hindgut microbial communities including those of three phylogenetically-lower termites, Zootermopsis nevadensis, Reticulitermes hesperus, and Incisitermes minor, a wood-feeding cockroach, Cryptocercus punctulatus, and an omnivorous cockroach, Periplaneta americana. In total, we sequenced and analyzed 151 different cooS genes. These genes encode proteins that group within one of three highly divergent CODH phylogenetic clades. Each insect gut community contained CODH variants from all three of these clades. The patterns of CODH diversity in these communities likely reflect differences in enzyme or physiological function, and suggest that a diversity of microbial species participate in homoacetogenesis in these communities

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

PCR Primers for Metazoan Mitochondrial 12S Ribosomal DNA Sequences

Background: Assessment of the biodiversity of communities of small organisms is most readily done using PCR-based analysis of environmental samples consisting of mixtures of individuals. Known as metagenetics, this approach has transformed understanding of microbial communities and is beginning to be applied to metazoans as well. Unlike microbial studies, where analysis of the 16S ribosomal DNA sequence is standard, the best gene for metazoan metagenetics is less clear. In this study we designed a set of PCR primers for the mitochondrial 12S ribosomal DNA sequence based on 64 complete mitochondrial genomes and then tested their efficacy. Methodology/Principal Findings: A total of the 64 complete mitochondrial genome sequences representing all metazoan classes available in GenBank were downloaded using the NCBI Taxonomy Browser. Alignment of sequences was performed for the excised mitochondrial 12S ribosomal DNA sequences, and conserved regions were identified for all 64 mitochondrial genomes. These regions were used to design a primer pair that flanks a more variable region in the gene. Then all of the complete metazoan mitochondrial genomes available in NCBI’s Organelle Genome Resources database were used to determine the percentage of taxa that would likely be amplified using these primers. Results suggest that these primers will amplify target sequences for many metazoans. Conclusions/Significance: Newly designed 12S ribosomal DNA primers have considerable potential for metazoa

The transition experience of rural older persons with advanced cancer and their families: a grounded theory study

BACKGROUND: Transitions often occur suddenly and can be traumatic to both patients with advanced disease and their families. The purpose of this study was to explore the transition experience of older rural persons with advanced cancer and their families from the perspective of palliative home care patients, bereaved family caregivers, and health care professionals. The specific aims were to: (1) describe the experience of significant transitions experienced by older rural persons who were receiving palliative home care and their families and (2) develop a substantive theory of transitions in this population. METHODS: Using a grounded theory approach, 27 open-ended individual audio-taped interviews were conducted with six older rural persons with advanced cancer and 10 bereaved family caregivers. Four focus group interviews were conducted with 12 palliative care health care professionals. All interviews were transcribed verbatim, coded, and analyzed using Charmaz\u27s constructivist grounded theory approach. RESULTS: Within a rural context of isolation, lack of information and limited accessibility to services, and values of individuality and community connectedness, older rural palliative patients and their families experienced multiple complex transitions in environment, roles/relationships, activities of daily living, and physical and mental health. Transitions disrupted the lives of palliative patients and their caregivers, resulting in distress and uncertainty. Rural palliative patients and their families adapted to transitions through the processes of Navigating Unknown Waters . This tentative theory includes processes of coming to terms with their situation, connecting, and redefining normal. Timely communication, provision of information and support networks facilitated the processes. CONCLUSION: The emerging theory provides a foundation for future research. Significant transitions identified in this study may serve as a focus for improving delivery of palliative and end of life care in rural areas. Improved understanding of the transitions experienced by advanced cancer palliative care patients and their families, as well as the psychological processes involved in adapting to the transitions, will help health care providers address the unique needs of this vulnerable population