Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

Background: To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. Methods: Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [ 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age. Results: Four fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. Conclusion: During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome

Comparison of DNA histograms by standard flow cytometry and image cytometry on sections in Barrett's adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare DNA histograms obtained by standard flow cytometry (FC) and high fidelity image cytometry on sections (ICS) in normal gastrointestinal mucosa and Barrett's adenocarcinoma (BAC).</p> <p>Methods</p> <p>Archival formalin-fixed paraffin-embedded tissue blocks of 10 normal controls from 10 subjects and 42 BAC tissues from 17 patients were examined. DNA FC was performed using standard techniques and ICS was carried out by Automated Cellular Imaging System (ACIS). DNA ploidy histograms were classified into diploid with peak DNA index (DI) at 0.9–1.1, and aneuploid with peak DI > 1.1. DI values of aneuploid peaks were determined. Additionally, for DNA ICS, heterogeneity index (HI) representing DNA content heterogeneity, and histograms containing cells with DI > G2 were also identified.</p> <p>Results</p> <p>All control samples were diploid by both FC and ICS analyses. In BAC, FC showed diploid peaks in 29%, diploid peaks with additional aneuploid or tetraploid peaks in 57%, and 14% of the samples, respectively. In contrast, ICS showed aneuploid peaks in all the cases with peak DI > 1.25; 37 cases had peak DI between 1.25 and 2.25; and 5 cases had peak DI > 2.25. HI values (mean ± SD) were 11.3 ± 1.1 in controls and 32.4 ± 8.5 in BAC (p < 0.05). Controls had no G2 exceeding cells. However, 19/37 (51%) of the cases with primary peak DI < 2.25 had cells exceeding 9N.</p> <p>Conclusion</p> <p>ICS detects DNA aneuploidy in all BAC samples while FC missed the diagnosis of aneuploidy in 29%. In addition, ICS provides more information on HI and G2 exceeding rates.</p

Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients

BACKGROUND: Molecular markers and the rich biological information they contain have great potential for cancer diagnosis, prognostication and therapy prediction. So far, however, they have not superseded routine histopathology and staging criteria, partly because the few studies performed on molecular subtyping have had little validation and limited clinical characterization. METHODS: We obtained gene expression and clinical data for 412 breast cancers obtained from population-based cohorts of patients from Stockholm and Uppsala, Sweden. Using the intrinsic set of approximately 500 genes derived in the Norway/Stanford breast cancer data, we validated the existence of five molecular subtypes – basal-like, ERBB2, luminal A/B and normal-like – and characterized these subtypes extensively with the use of conventional clinical variables. RESULTS: We found an overall 77.5% concordance between the centroid prediction of the Swedish cohort by using the Norway/Stanford signature and the k-means clustering performed internally within the Swedish cohort. The highest rate of discordant assignments occurred between the luminal A and luminal B subtypes and between the luminal B and ERBB2 subtypes. The subtypes varied significantly in terms of grade (p < 0.001), p53 mutation (p < 0.001) and genomic instability (p = 0.01), but surprisingly there was little difference in lymph-node metastasis (p = 0.31). Furthermore, current users of hormone-replacement therapy were strikingly over-represented in the normal-like subgroup (p < 0.001). Separate analyses of the patients who received endocrine therapy and those who did not receive any adjuvant therapy supported the previous hypothesis that the basal-like subtype responded to adjuvant treatment, whereas the ERBB2 and luminal B subtypes were poor responders. CONCLUSION: We found that the intrinsic molecular subtypes of breast cancer are broadly present in a diverse collection of patients from a population-based cohort in Sweden. The intrinsic gene set, originally selected to reveal stable tumor characteristics, was shown to have a strong correlation with progression-related properties such as grade, p53 mutation and genomic instability

Impact of RNA degradation on gene expression profiling

<p>Abstract</p> <p>Background</p> <p>Gene expression profiling is a highly sensitive technique which is used for profiling tumor samples for medical prognosis. RNA quality and degradation influence the analysis results of gene expression profiles. The impact of this influence on the profiles and its medical impact is not fully understood. As patient samples are very valuable for clinical studies, it is necessary to establish criteria for the RNA quality to be able to use these samples in later analysis.</p> <p>Methods</p> <p>To investigate the effects of RNA integrity on gene expression profiling, whole genome expression arrays were used. We used tumor biopsies from patients diagnosed with locally advanced rectal cancer. To simulate degradation, the isolated total RNA of all patients was subjected to heat-induced degradation in a time-dependent manner. Expression profiling was then performed and data were analyzed bioinformatically to assess the differences.</p> <p>Results</p> <p>The differences introduced by RNA degradation were largely outweighed by the biological differences between the patients. Only a relatively small number of probes (275 out of 41,000) show a significant effect due to degradation. The genes that show the strongest effect due to RNA degradation were, especially, those with short mRNAs and probe positions near the 5' end.</p> <p>Conclusions</p> <p>Degraded RNA from tumor samples (RIN > 5) can still be used to perform gene expression analysis. A much higher biological variance between patients is observed compared to the effect that is imposed by degradation of RNA. Nevertheless there are genes, very short ones and those with the probe binding side close to the 5' end that should be excluded from gene expression analysis when working with degraded RNA. These results are limited to the Agilent 44 k microarray platform and should be carefully interpreted when transferring to other settings.</p

PuLSE:Quality control and quantification of peptide sequences explored by phage display libraries

The design of highly diverse phage display libraries is based on assumption that DNA bases are incorporated at similar rates within the randomized sequence. As library complexity increases and expected copy numbers of unique sequences decrease, the exploration of library space becomes sparser and the presence of truly random sequences becomes critical. We present the program PuLSE (Phage Library Sequence Evaluation) as a tool for assessing randomness and therefore diversity of phage display libraries. PuLSE runs on a collection of sequence reads in the fastq file format and generates tables profiling the library in terms of unique DNA sequence counts and positions, translated peptide sequences, and normalized 'expected' occurrences from base to residue codon frequencies. The output allows at-a-glance quantitative quality control of a phage library in terms of sequence coverage both at the DNA base and translated protein residue level, which has been missing from toolsets and literature. The open source program PuLSE is available in two formats, a C++ source code package for compilation and integration into existing bioinformatics pipelines and precompiled binaries for ease of use

The effect of cartilage and bone density of mushroom-shaped, photooxidized, osteochondral transplants: an experimental study on graft performance in sheep using transplants originating from different species

BACKGROUND: Differences in overall performance of osteochondral photooxidized grafts were studied in accordance of their species origin and a new, more rigorous cleansing procedure using alcohol during preparation. METHODS: Photooxidized mushroom-shaped grafts of bovine, ovine, human and equine origin were implanted in the femoral condyles of 32 sheep (condyles: n = 64). No viable chondrocytes were present at the time of implantation. Grafts were evaluated at 6 months using plastic embedded sections of non-decalcified bone and cartilage specimens. Graft incorporation, the formation of cyst-like lesions at the base of the cartilage junction as well as cartilage morphology was studied qualitatively, semi-quantitatively using a score system and quantitatively by performing histomorphometrical measurements of percentage of bone and fibrous tissue of the original defects. For statistical analysis a factorial analysis of variance (ANOVA- test) was applied. RESULTS: Differences of graft performance were found according to species origin and cleansing process during graft preparation. According to the score system cartilage surface integrity was best for equine grafts, as well as dislocation or mechanical stability. The equine grafts showed the highest percentage for bone and lowest for fibrous tissue, resp. cystic lesions. The new, more rigorous cleansing process decreased cartilage persistence and overall graft performance. CONCLUSION: Performance of grafts from equine origin was better compared to bovine, ovine and human grafts. The exact reason for this difference was not proven in the current study, but could be related to differences in density of cartilage and subchondral bone between species

Effect of garlic on cardiovascular disorders: a review

Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic

The case for using personally relevant and emotionally stimulating gambling messages as a gambling harm-minimisation strategy

Emotions typically exert powerful, enduring, and often predictable influences over decision-making. However, emotion-based decision-making is seen as a mediator of impulsive and reckless gambling behaviour, where emotion may be seen as the antithesis of controlled and rational decision-making, a proposition supported by recent neuroimaging evidence. The present paper argues that the same emotional mechanisms can be used to influence a gambler to cease gambling, by focusing their emotional decision-making on positive external and personally relevant factors, such as familial impact or longer term financial factors. Emotionally stimulating messages may also have the advantage of capturing attention above and beyond traditionally responsible gambling messaging. This is important given the highly emotionally aroused states often experienced by both gamblers and problem gamblers, where attentional activation thresholds for external stimuli such as messages may be increased

Cerebral cortical thickness in chronic pain due to knee osteoarthritis: the effect of pain duration and pain densitization

Objective This study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis. Methods Whole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1± 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7± 7.4, 17 females). Results Cortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (p<0.05, age-controlled, FDR corrected). Pain sensitivity was unrelated to cortical thickness. Patients showed lower cortical thickness in the right anterior insula (p<0.001, uncorrected) with no changes surviving multiple test correction. Conclusion With increasing number of years of suffering from chronic arthritis pain we found increasing cortical thinning in extended cerebral cortical regions beyond recognised pain-processing areas. While the mechanisms of cortical thinning remain to be elucidated, we show that pain progression indexed by central sensitization does not play a major role

Antimicrobial and cell-penetrating peptides induce lipid vesicle fusion by folding and aggregation

According to their distinct biological functions, membrane-active peptides are generally classified as antimicrobial (AMP), cell-penetrating (CPP), or fusion peptides (FP). The former two classes are known to have some structural and physicochemical similarities, but fusogenic peptides tend to have rather different features and sequences. Nevertheless, we found that many CPPs and some AMPs exhibit a pronounced fusogenic activity, as measured by a lipid mixing assay with vesicles composed of typical eukaryotic lipids. Compared to the HIV fusion peptide (FP23) as a representative standard, all designer-made peptides showed much higher lipid-mixing activities (MSI-103, MAP, transportan, penetratin, Pep1). Native sequences, on the other hand, were less fusogenic (magainin 2, PGLa, gramicidin S), and pre-aggregated ones were inactive (alamethicin, SAP). The peptide structures were characterized by circular dichroism before and after interacting with the lipid vesicles. A striking correlation between the extent of conformational change and the respective fusion activities was found for the series of peptides investigated here. At the same time, the CD data show that lipid mixing can be triggered by any type of conformation acquired upon binding, whether α-helical, β-stranded, or other. These observations suggest that lipid vesicle fusion can simply be driven by the energy released upon membrane binding, peptide folding, and possibly further aggregation. This comparative study of AMPs, CPPs, and FPs emphasizes the multifunctional aspects of membrane-active peptides, and it suggests that the origin of a peptide (native sequence or designer-made) may be more relevant to define its functional range than any given name