[(18)F] fluoromisonidazole and [(18)F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study

BACKGROUND: Experimental and clinical evidence suggest that hypoxia in solid tumours reduces their sensitivity to conventional treatment modalities modulating response to ionizing radiation or chemotherapeutic agents. The aim of the present study was to show the feasibility of determining radiotherapeutically relevant hypoxia and early tumour response by ([(18)F] Fluoromisonidazole (FMISO) and [(18)F]-2-fluoro-2'-deoxyglucose (FDG) PET. METHODS: Eight patients with non-small-cell lung cancer underwent PET scans. Tumour tissue oxygenation was measured with FMISO PET, whereas tumour glucose metabolism was measured with FDG PET. All PET studies were carried out with an ECAT EXACT 922/47(® )scanner with an axial field of view of 16.2 cm. FMISO PET consisted of one static scan of the relevant region, performed 180 min after intravenous administration of the tracer. The acquisition and reconstruction parameters were as follows: 30 min emission scanning and 4 min transmission scanning with 68-Ge/68-Ga rod sources. The patients were treated with chemotherapy, consisting of 2 cycles of gemcitabine (1200 mg/m(2)) and vinorelbine (30 mg/m(2)) followed by concurrent radio- (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine (300–500 mg/m(2)) every two weeks. FMISO PET and FDG PET were performed in all patients 3 days before and 14 days after finishing chemotherapy. RESULTS: FMISO PET allowed for the qualitative and quantitative definition of hypoxic sub-areas which may correspond to a localization of local recurrences. In addition, changes in FMISO and FDG PET measure the early response to therapy, and in this way, may predict freedom from disease, as well as overall survival. CONCLUSION: These preliminary results warrant validation in larger trials. If confirmed, several novel treatment strategies may be considered, including the early use of PET to evaluate the effectiveness of the selected therapy

Evolution of laparoscopic left lateral sectionectomy without the Pringle maneuver: through resection of benign and malignant tumors to living liver donation

BACKGROUND: Laparoscopic left lateral sectionectomy (LLS) has gained popularity in its use for benign and malignant tumors. This report describes the evolution of the authors' experience using laparoscopic LLS for different indications including living liver donation. METHODS: Between January 2004 and January 2009, 37 consecutive patients underwent laparoscopic LLS for benign, primary, and metastatic liver diseases, and for one case of living liver donation. Resection of malignant tumors was indicated for 19 (51%) of the 37 patients. RESULTS: All but three patients (deceased due to metastatic cancer disease) are alive and well after a median follow-up period of 20 months (range, 8-46 months). Liver cell adenomas (72%) were the main indication among benign tumors, and colorectal liver metastases (84%) were the first indication of malignancy. One case of live liver donation was performed. Whereas 16 patients (43%) had undergone a previous abdominal surgery, 3 patients (8%) had LLS combined with bowel resection. The median operation time was of 195 min (range, 115-300 min), and the median blood loss was of 50 ml (range, 0-500 ml). Mild to severe steatosis was noted in 7 patients (19%) and aspecific portal inflammation in 11 patients (30%). A median free margin of 5 mm (range, 5-27 mm) was achieved for all cancer patients. The overall recurrence rate for colorectal liver metastases was of 44% (7 patients), but none recurred at the surgical margin. No conversion to laparotomy was recorded, and the overall morbidity rate was 8.1% (1 grade 1 and 2 grade 2 complications). The median hospital stay was 6 days (range, 2-10 days). CONCLUSIONS: Laparoscopic LLS without portal clamping can be performed safely for cases of benign and malignant liver disease with minimal blood loss and overall morbidity, free resection margins, and a favorable outcome. As the ultimate step of the learning curve, laparoscopic LLS could be routinely proposed, potentially increasing the donor pool for living-related liver transplantation

The association of 25-hydroxyvitamin D3 and D2 with behavioural problems in childhood

Background Higher serum concentrations of 25-hydroxyvitamin D (25(OH)D), an indicator of vitamin D synthesis and intake, have been associated with better mental health and cognitive function. Concentrations of 1,25-dihydroxyvitamin D3 (the active vitamin D3 metabolite) have been associated with openness and extrovert behaviour, but 25(OH)D concentrations have not been associated with behavioural problems in humans. Methods We investigated the prospective association between the different forms of 25(OH)D - 25(OH)D3 and 25(OH)D2– and childhood behavioural problems in Avon Longitudinal Study of Parents and Children (ALSPAC). Serum 25(OH)D3 and 25(OH)D2 concentrations were assessed at mean age 9.9 years. Incident behavioural problems were assessed with Strengths and Difficulties Questionnaire (SDQ; emotional symptoms, conduct problems, hyperactivity-inattention problems, peer relationship problems and pro-social behaviour subscales and total difficulties score) at mean age 11.7. Sample sizes varied between 2413-2666 depending on the outcome. Results Higher 25(OH)D3 concentrations were weakly associated with lower risk of prosocial problems (fully adjusted odds ratio: OR (95% confidence interval: CI) 0.85 (0.74, 0.98)). Serum 25(OH)D3 or 25(OH)D2 concentrations were not associated with other subscales of SDQ or total difficulties score after adjusting for concfounders and other measured analytes related to vitamin D. Conclusions Our findings do not support the hypothesis that 25-hydroxyvitamin D status in childhood has important influences on behavioural traits in humans

Maize (Zea mays L.) Genome Diversity as Revealed by RNA-Sequencing

Maize is rich in genetic and phenotypic diversity. Understanding the sequence, structural, and expression variation that contributes to phenotypic diversity would facilitate more efficient varietal improvement. RNA based sequencing (RNA-seq) is a powerful approach for transcriptional analysis, assessing sequence variation, and identifying novel transcript sequences, particularly in large, complex, repetitive genomes such as maize. In this study, we sequenced RNA from whole seedlings of 21 maize inbred lines representing diverse North American and exotic germplasm. Single nucleotide polymorphism (SNP) detection identified 351,710 polymorphic loci distributed throughout the genome covering 22,830 annotated genes. Tight clustering of two distinct heterotic groups and exotic lines was evident using these SNPs as genetic markers. Transcript abundance analysis revealed minimal variation in the total number of genes expressed across these 21 lines (57.1% to 66.0%). However, the transcribed gene set among the 21 lines varied, with 48.7% expressed in all of the lines, 27.9% expressed in one to 20 lines, and 23.4% expressed in none of the lines. De novo assembly of RNA-seq reads that did not map to the reference B73 genome sequence revealed 1,321 high confidence novel transcripts, of which, 564 loci were present in all 21 lines, including B73, and 757 loci were restricted to a subset of the lines. RT-PCR validation demonstrated 87.5% concordance with the computational prediction of these expressed novel transcripts. Intriguingly, 145 of the novel de novo assembled loci were present in lines from only one of the two heterotic groups consistent with the hypothesis that, in addition to sequence polymorphisms and transcript abundance, transcript presence/absence variation is present and, thereby, may be a mechanism contributing to the genetic basis of heterosis

A case-series study to explore the efficacy of foot orthoses in treating first metatarsophalangeal joint pain

Background: First metatarsophalangeal (MTP) joint pain is a common foot complaint which is often considered to be a consequence of altered mechanics. Foot orthoses are often prescribed to reduce 1 stMTP joint pain with the aim of altering dorsiflexion at propulsion. This study explores changes in 1 stMTP joint pain and kinematics following the use of foot orthoses.Methods: The effect of modified, pre-fabricated foot orthoses (X-line ®) were evaluated in thirty-two patients with 1 stMTP joint pain of mechanical origin. The primary outcome was pain measured at baseline and 24 weeks using the pain subscale of the foot function index (FFI). In a small sub-group of patients (n = 9), the relationship between pain and kinematic variables was explored with and without their orthoses, using an electromagnetic motion tracking (EMT) system.Results: A significant reduction in pain was observed between baseline (median = 48 mm) and the 24 week endpoint (median = 14.50 mm, z = -4.88, p < 0.001). In the sub-group analysis, we found no relationship between pain reduction and 1 stMTP joint motion, and no significant differences were found between the 1 stMTP joint maximum dorsiflexion or ankle/subtalar complex maximum eversion, with and without the orthoses.Conclusions: This observational study demonstrated a significant decrease in 1 stMTP joint pain associated with the use of foot orthoses. Change in pain was not shown to be associated with 1 stMTP joint dorsiflexion nor with altered ankle/subtalar complex eversion. Further research into the effect of foot orthoses on foot function is indicated. © 2010 Welsh et al; licensee BioMed Central Ltd

Heterogeneity within the Asian American community

BACKGROUND: Educational interventions are grounded on scientific data and assumptions about the community to be served. While the Pan Asian community is composed of multiple, ethnic subgroups, it is often treated as a single group for which one health promotion program will be applicable for all of its cultural subgroups. Compounding this stereotypical view of the Pan Asian community, there is sparse data about the cultural subgroups' similarities and dissimilarities. The Asian Grocery Store based cancer education program evaluation data provided an opportunity to compare data collected under identical circumstances from members of six Asian American cultural groups. METHODS: A convenience sample of 1,202 Asian American women evaluated the cultural alignment of a cancer education program, completing baseline and follow-up surveys that included questions about their breast cancer knowledge, attitudes, and screening behaviors. Participants took part in a brief education program that facilitated adherence to recommended screening guidelines. RESULTS: Unique recruitment methods were needed to attract participants from each ethnic group. Impressions gained from the aggregate data revealed different insights than the disaggregate data. Statistically significant variations existed among the subgroups' breast cancer knowledge, attitudes, and screening behaviors that could contribute to health disparities among the subgroups and within the aggregate Pan Asian community. CONCLUSION: Health promotion efforts of providers, educators, and policy makers can be enhanced if cultural differences are identified and taken into account when developing strategies to reduce health disparities and promote health equity

Alzheimer's disease - input of vitamin D with mEmantine assay (AD-IDEA trial): study protocol for a randomized controlled trial

BACKGROUND: Current treatments for Alzheimer\u27s disease and related disorders (ADRD) are symptomatic and can only temporarily slow down ADRD. Future possibilities of care rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline. The aim of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol) with the effect of a placebo on the change of cognitive performance in patients suffering from moderate ADRD and receiving memantine. METHODS: The AD-IDEA Trial is a unicentre, double-blind, randomized, placebo-controlled, intent-to-treat, superiority trial. Patients aged 60 years and older presenting with moderate ADRD (i.e., Mini-Mental State Examination [MMSE] score between 10-20), hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD] < 30 ng/mL), normocalcemia (i.e., serum calcium < 2.65 mmol/L) and receiving no antidementia treatment at time of inclusion are being recruited. All participants receive memantine 20 mg once daily -titrated in 5 mg increments over 4 weeks- and each one is randomized to one of the two treatment options: either cholecalciferol (one 100,000 IU drinking vial every 4 weeks) or placebo (administered at the same pace). One hundred and twenty participants are being recruited and treatment continues for 24 weeks. Primary outcome measure is change in cognitive performance using Alzheimer\u27s Disease Assessment Scale-cognition score. Secondary outcomes are changes in other cognitive scores (MMSE, Frontal Assessment Battery, Trail Making Test parts A and B), change in functional performance (Activities of Daily Living scale, and 4-item Instrumental Activities of Daily Living scale), posture and gait (Timed Up & Go, Five Time Sit-to-Stand, spatio-temporal analysis of walking), as well as the between-groups comparison of compliance to treatment and tolerance. These outcomes are assessed at baseline, 12 and 24 weeks, together with the serum concentrations of 25OHD, calcium and parathyroid hormone. DISCUSSION: The combination of memantine plus vitamin D may represent a new multi-target therapeutic class for the treatment of ADRD. The AD-IDEA Trial seeks to provide evidence on its efficacy in limiting cognitive and functional declines in ADRD. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01409694

Single nucleotide polymorphism discovery in elite north american potato germplasm

BACKGROUND: Current breeding approaches in potato rely almost entirely on phenotypic evaluations; molecular markers, with the exception of a few linked to disease resistance traits, are not widely used. Large-scale sequence datasets generated primarily through Sanger Expressed Sequence Tag projects are available from a limited number of potato cultivars and access to next generation sequencing technologies permits rapid generation of sequence data for additional cultivars. When coupled with the advent of high throughput genotyping methods, an opportunity now exists for potato breeders to incorporate considerably more genotypic data into their decision-making. RESULTS: To identify a large number of Single Nucleotide Polymorphisms (SNPs) in elite potato germplasm, we sequenced normalized cDNA prepared from three commercial potato cultivars: 'Atlantic', 'Premier Russet' and 'Snowden'. For each cultivar, we generated 2 Gb of sequence which was assembled into a representative transcriptome of (~)28-29 Mb for each cultivar. Using the Maq SNP filter that filters read depth, density, and quality, 575,340 SNPs were identified within these three cultivars. In parallel, 2,358 SNPs were identified within existing Sanger sequences for three additional cultivars, 'Bintje', 'Kennebec', and 'Shepody'. Using a stringent set of filters in conjunction with the potato reference genome, we identified 69,011 high confidence SNPs from these six cultivars for use in genotyping with the Infinium platform. Ninety-six of these SNPs were used with a BeadXpress assay to assess allelic diversity in a germplasm panel of 248 lines; 82 of the SNPs proved sufficiently informative for subsequent analyses. Within diverse North American germplasm, the chip processing market class was most distinct, clearly separated from all other market classes. The round white and russet market classes both include fresh market and processing cultivars. Nevertheless, the russet and round white market classes are more distant from each other than processing are from fresh market types within these two groups. CONCLUSIONS: The genotype data generated in this study, albeit limited in number, has revealed distinct relationships among the market classes of potato. The SNPs identified in this study will enable high-throughput genotyping of germplasm and populations, which in turn will enable more efficient marker-assisted breeding efforts in potato