Clinical significance of VEGF-A, -C and -D expression in esophageal malignancies

Vascular endothelial growth factors ( VEGF)- A, - C and - D are members of the proangiogenic VEGF family of glycoproteins. VEGF-A is known to be the most important angiogenic factor under physiological and pathological conditions, while VEGF-C and VEGF-D are implicated in the development and sprouting of lymphatic vessels, so called lymphangiogenesis. Local tumor progression, lymph node metastases and hematogenous tumor spread are important prognostic factors for esophageal carcinoma ( EC), one of the most lethal malignancies throughout the world. We found solid evidence in the literature that VEGF expression contributes to tumor angiogenesis, tumor progression and lymph node metastasis in esophageal squamous cell carcinoma ( SCC), and many authors could show a prognostic value for VEGF-assessment. In adenocarcinoma (AC) of the esophagus angiogenic properties are acquired in early stages, particularly in precancerous lesions like Barrett's dysplasia. However, VEGF expression fails to give prognostic information in AC of the esophagus. VEGF-C and VEGF-D were detected in SCC and dysplastic lesions, but not in normal mucosa of the esophagus. VEGF-C expression might be associated with lymphatic tumor invasion, lymph node metastases and advanced disease in esophageal SCC and AC. Therapeutic interference with VEGF signaling may prove to be a promising way of anti-angiogenic co-treatment in esophageal carcinoma. However, concrete clinical data are still pending

Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR) trial [NCT00256139]

BACKGROUND: Chronic psoriasis can negatively affect patients' lives. Assessing the impact of treatment on different aspects of a patient's health-related quality of life (HRQOL) is therefore important and relevant in trials of anti-psoriasis agents. The recombinant humanized IgG(1 )monoclonal antibody efalizumab targets multiple T-cell-dependent steps in the immunopathogenesis of psoriasis. Efalizumab has demonstrated safety and efficacy in several clinical trials, and improves patients' quality of life. Objective: To evaluate the impact of efalizumab on HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis, including a large cohort of High-Need patients for whom at least 2 other systemic therapies were unsuitable because of lack of efficacy, intolerance, or contraindication. METHODS: A total of 793 patients were randomized in a 2:1 ratio to receive efalizumab 1 mg/kg/wk (n = 529) or placebo (n = 264) for 12 weeks. The study population included 526 High-Need patients (342 efalizumab, 184 placebo). The treatment was evaluated by patients using the HRQOL assessment tools Short Form-36 (SF-36) and Dermatology Life Quality Index (DLQI). Other patient-reported assessments included the Psoriasis Symptom Assessment (PSA), a visual analog scale (VAS) for itching, and the Patient's Global Psoriasis Assessment (PGPA). RESULTS: Efalizumab was associated with improvements at Week 12 from baseline in patient-reported outcomes, both in the total study population and in the High-Need cohort. Among all efalizumab-treated patients, the DLQI improved by 5.7 points from baseline to Week 12, relative to an improvement of 2.3 points for placebo patients (P < .001). Corresponding improvements in DLQI in the High-Need cohort were 5.4 points for efalizumab compared to 2.3 for placebo (P < .001). Improvements from baseline on the SF-36, PSA, PGPA, and itching VAS at Week 12 were also significantly greater in efalizumab-treated patients than for placebo. CONCLUSION: A 12-week course of efalizumab improved HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis. The benefits of efalizumab therapy in High-Need patients were similar to those observed in the total study population, indicating that the beneficial impact of efalizumab on QOL is consistent regardless of disease severity, prior therapy, or contraindications to previous therapies

“Thinking about Not-Thinking”: Neural Correlates of Conceptual Processing during Zen Meditation

Recent neuroimaging studies have identified a set of brain regions that are metabolically active during wakeful rest and consistently deactivate in a variety the performance of demanding tasks. This “default network” has been functionally linked to the stream of thoughts occurring automatically in the absence of goal-directed activity and which constitutes an aspect of mental behavior specifically addressed by many meditative practices. Zen meditation, in particular, is traditionally associated with a mental state of full awareness but reduced conceptual content, to be attained via a disciplined regulation of attention and bodily posture. Using fMRI and a simplified meditative condition interspersed with a lexical decision task, we investigated the neural correlates of conceptual processing during meditation in regular Zen practitioners and matched control subjects. While behavioral performance did not differ between groups, Zen practitioners displayed a reduced duration of the neural response linked to conceptual processing in regions of the default network, suggesting that meditative training may foster the ability to control the automatic cascade of semantic associations triggered by a stimulus and, by extension, to voluntarily regulate the flow of spontaneous mentation

Biotic resistance to invasion along an estuarine gradient

Biotic resistance is the ability of native communities to repel the establishment of invasive species. Predation by native species may confer biotic resistance to communities, but the environmental context under which this form of biotic resistance occurs is not well understood. We evaluated several factors that influence the distribution of invasive Asian mussels (Musculista senhousia) in Mission Bay, a southern California estuary containing an extensive eelgrass (Zostera marina) habitat. Asian mussels exhibit a distinct spatial pattern of invasion, with extremely high densities towards the back of Mission Bay (up to 4,000 m−2) in contrast with near-complete absence at sites towards the front of the bay. We established that recruits arrived at sites where adult mussels were absent and found that dense eelgrass does not appear to preclude Asian mussel growth and survival. Mussel survival and growth were high in predator-exclusion plots throughout the bay, but mussel survival was low in the front of the bay when plots were open to predators. Additional experiments revealed that consumption by spiny lobsters (Panulirus interruptus) and a gastropod (Pteropurpura festiva) likely are the primary factors responsible for resistance to Asian mussel invasion. However, biotic resistance was dependent on location within the estuary (for both species) and also on the availability of a hard substratum (for P. festiva). Our findings indicate that biotic resistance in the form of predation may be conferred by higher order predators, but that the strength of resistance may strongly vary across estuarine gradients and depend on the nature of the locally available habitat

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

The "Persuadable Middle" on Same-Sex Marriage: Formative Research to Build Support among Heterosexual College Students

Same-sex marriage is a controversial policy issue that affects the welfare of gay and lesbian couples throughout the USA. Considerable research examines opinions about same-sex marriage; however, studies have not investigated the covariates of the “persuadable middle”— those individuals who are neutral or unsure about their views. This group of people is often the target of same-sex marriage campaigns, yet they have received no empirical attention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89607/1/Woodford et al 2011 Persuadable Middle.pd

Mitochondrial polymorphisms in rat genetic models of hypertension

Hypertension is a complex trait that has been studied extensively for genetic contributions of the nuclear genome. We examined mitochondrial genomes of the hypertensive strains: the Dahl Salt-Sensitive (S) rat, the Spontaneously Hypertensive Rat (SHR), and the Albino Surgery (AS) rat, and the relatively normotensive strains: the Dahl Salt-Resistant (R) rat, the Milan Normotensive Strain (MNS), and the Lewis rat (LEW). These strains were used previously for linkage analysis for blood pressure (BP) in our laboratory. The results provide evidence to suggest that variations in the mitochondrial genome do not account for observed differences in blood pressure between the S and R rats. However, variants were detected among the mitochondrial genomes of the various hypertensive strains, S, SHR, and AS, and also among the normotensive strains R, MNS, and LEW. A total of 115, 114, 106, 106, and 16 variations in mtDNA were observed between the comparisons S versus LEW, S versus MNS, S versus SHR, S versus AS, and SHR versus AS, respectively. Among the 13 genes coding for proteins of the electron transport chain, 8 genes had nonsynonymous variations between S, LEW, MNS, SHR, and AS. The lack of any sequence variants between the mitochondrial genomes of S and R rats provides conclusive evidence that divergence in blood pressure between these two inbred strains is exclusively programmed through their nuclear genomes. The variations detected among the various hypertensive strains provides the basis to construct conplastic strains and further evaluate the effects of these variants on hypertension and associated phenotypes

Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family

The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs) and nucleotides (NTs). This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified. Here, we analyzed this issue using the extensive LacI family of transcriptional factors (TFs). We searched for recognition patterns by introducing a new approach to phylogenetic footprinting, based on the pervasive presence of local regulation in prokaryotic transcriptional networks. We identified a set of specificity correlations –determined by two AAs of the TFs and two NTs in the binding sites– that is conserved throughout a dominant subgroup within the family regardless of the evolutionary distance, and that act as a relatively consistent recognition code. The proposed rules are confirmed with data of previous experimental studies and by events of convergent evolution in the phylogenetic tree. The presence of a code emphasizes the stable structural context of the LacI family, while defining a precise blueprint to reprogram TF specificity with many practical applications.Ministerio de Ciencia e Innovación, Spain (Formación de Profesorado Universitario fellowship)Ministerio de Ciencia e Innovación, Spain (grant BFU2008-03632/BMC)Madrid (Spain : Region) (grant CCG08-CSIC/SAL-3651

Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region

<p>Abstract</p> <p>Background</p> <p>Duffy blood group polymorphisms are important in areas where <it>Plasmodium vivax </it>predominates, because this molecule acts as a receptor for this protozoan. In the present study, Duffy blood group genotyping in <it>P. vivax </it>malaria patients from four different Brazilian endemic areas is reported, exploring significant associations between blood group variants and susceptibility or resistance to malaria.</p> <p>Methods</p> <p>The <it>P. vivax </it>identification was determined by non-genotypic and genotypic screening tests. The Duffy blood group was genotyped by PCR/RFLP in 330 blood donors and 312 malaria patients from four Brazilian Amazon areas. In order to assess the variables significance and to obtain independence among the proportions, the Fisher's exact test was used.</p> <p>Results</p> <p>The data show a high frequency of the <it>FYA/FYB </it>genotype, followed by <it>FYB/FYB, FYA/FYA</it>, <it>FYA/FYB-33 </it>and <it>FYB/FYB-33</it>. Low frequencies were detected for the <it>FYA/FY</it>^<it>X</it>, <it>FYB/FY</it>^<it>X</it>, <it>FYX/FY</it>^{<it>X </it>}and <it>FYB-33/FYB-33 </it>genotypes. Negative Duffy genotype (<it>FYB-33/FYB-33</it>) was found in both groups: individuals infected and non-infected (blood donors). No individual carried the <it>FY</it>^<it>X</it><it>/FYB-33 </it>genotype. Some of the Duffy genotypes frequencies showed significant differences between donors and malaria patients.</p> <p>Conclusion</p> <p>The obtained data suggest that individuals with the <it>FYA/FYB </it>genotype have higher susceptibility to malaria. The presence of the <it>FYB-33 </it>allele may be a selective advantage in the population, reducing the rate of infection by <it>P. vivax </it>in this region. Additional efforts may contribute to better elucidate the physiopathologic differences in this parasite/host relationship in regions endemic for <it>P. vivax </it>malaria, in particular the Brazilian Amazon region.</p

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic