title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Bacterial flagella are firmly anchored. | There are mutants of Salmonella enterica (with mutations in fliF and fliL) that shed flagella when they are swimming in a viscous medium or on the surface of soft agar. Filaments with hooks and the distal rod segment FlgG are recovered. We tried to extract flagellar filaments from such cells by pulling on them with an optical trap but failed, even when we used forces large enough to straighten the filaments. Thus, flagella are firmly anchored. | 18,849,436 |
Volatilization and precipitation of tellurium by aerobic, tellurite-resistant marine microbes. | Microbial resistance to tellurite, an oxyanion of tellurium, is widespread in the biosphere, but the geochemical significance of this trait is poorly understood. As some tellurite resistance markers appear to mediate the formation of volatile tellurides, the potential contribution of tellurite-resistant microbial strains to trace element volatilization in salt marsh sediments was evaluated. Microbial strains were isolated aerobically on the basis of tellurite resistance and subsequently examined for their capacity to volatilize tellurium in pure cultures. The tellurite-resistant strains recovered were either yeasts related to marine isolates of Rhodotorula spp. or gram-positive bacteria related to marine strains within the family Bacillaceae based on rRNA gene sequence comparisons. Most strains produced volatile tellurides, primarily dimethyltelluride, though there was a wide range of the types and amounts of species produced. For example, the Rhodotorula spp. produced the greatest quantities and highest diversity of volatile tellurium compounds. All strains also produced methylated sulfur compounds, primarily dimethyldisulfide. Intracellular tellurium precipitates were a major product of tellurite metabolism in all strains tested, with nearly complete recovery of the tellurite initially provided to cultures as a precipitate. Different strains appeared to produce different shapes and sizes of tellurium containing nanostructures. These studies suggest that aerobic marine yeast and Bacillus spp. may play a greater role in trace element biogeochemistry than has been previously assumed, though additional work is needed to further define and quantify their specific contributions. | 18,849,455 |
Differential expression in Phanerochaete chrysosporium of membrane-associated proteins relevant to lignin degradation. | Fungal lignin-degrading systems likely include membrane-associated proteins that participate in diverse processes such as uptake and oxidation of lignin fragments, production of ligninolytic secondary metabolites, and defense of the mycelium against ligninolytic oxidants. Little is known about the nature or regulation of these membrane-associated components. We grew the white rot basidiomycete Phanerochaete chrysosporium on cellulose or glucose as the carbon source and monitored the mineralization of a (14)C-labeled synthetic lignin by these cultures to assess their ligninolytic competence. The results showed that the cellulose-grown cultures were ligninolytic, whereas the glucose-grown ones were not. We isolated microsomal membrane fractions from both types of culture and analyzed tryptic digests of their proteins by shotgun liquid chromatography-tandem mass spectrometry. Comparison of the results against the predicted P. chrysosporium proteome showed that a catalase (Joint Genome Institute P. chrysosporium protein identification number [I.D.] 124398), an alcohol oxidase (126879), two transporters (137220 and 132234), and two cytochrome P450s (5011 and 8912) were upregulated under ligninolytic conditions. Quantitative reverse transcription-PCR assays showed that RNA transcripts encoding all of these proteins were also more abundant in ligninolytic cultures. Catalase 124398, alcohol oxidase 126879, and transporter 137220 were found in a proteomic analysis of partially purified plasma membranes from ligninolytic P. chrysosporium and are therefore most likely associated with the outer envelope of the fungus. | 18,849,459 |
Noncontact ultrasound therapy for adjunctive treatment of nonhealing wounds: retrospective analysis. | The optimal adjunctive therapy for wounds that fail to heal despite conventional wound care has not been established. Clinical evidence suggests improved healing in wounds treated with noncontact ultrasound therapy (NCUT). Although existing evidence supports the use of NCUT for enhanced wound healing, the total number of participants studied remains modest. This study was conducted to assess the impact of adjunctive NCUT on the healing of wounds that fail to progress to healing with conventional wound care alone. A retrospective review of charts for 76 patients who had received outpatient wound care at a single center between January 2005 and December 2006 and who were treated with NCUT as an adjunct to conventional wound care was conducted. All wound care interventions used during the study period were assessed. The primary effectiveness endpoint was the percentage of change in wound area from the start of NCUT to the end of NCUT. Noncontact ultrasound was administered for a mean of 5.1 minutes per session for a mean of 2.3 times per week. The median duration of therapy was 4.3 weeks. The median wound area was reduced by 79% from the start of NCUT to the end of NCUT (from 2.5 to 0.6 cm(2)). The proportion of participants with greater than 75% granulation tissue increased from 32% before NCUT to 46% after NCUT. The single-arm, retrospective design did not allow for comparative assessments of the efficacies of noncontact ultrasound and other wound care interventions. The use of adjunctive NCUT appears to improve healing in wounds that fail to heal with conventional wound care alone. | 18,849,480 |
Deleterious role of TLR3 during hyperoxia-induced acute lung injury. | Acute respiratory distress syndrome (ARDS) manifests clinically as a consequence of septic and/or traumatic injury in the lung. Oxygen therapy remains a major therapeutic intervention in ARDS, but this can contribute further to lung damage. Patients with ARDS are highly susceptible to viral infection and it may be due to altered Toll-like receptor (TLR) expression. To evaluate the role of TLR3 in ARDS. TLR3 expression and signaling was determined in airway epithelial cells after in vitro hyperoxia challenge. Using a murine model of hyperoxia-induced lung injury, the role of TLR3 was determined using either TLR3-gene deficient mice or a specific neutralizing antibody directed to TLR3. Increased TLR3 expression was observed in airway epithelial cells from patients with ARDS. Further, hyperoxic conditions alone were a major stimulus for increased TLR3 expression and activation in cultured human epithelial cells. Interestingly, TLR3(-/-) mice exhibited less acute lung injury, activation of apoptotic cascades, and extracellular matrix deposition after 5 days of 80% oxygen compared with wild-type (TLR3(+/+)) mice under the same conditions. Administration of a monoclonal anti-TLR3 antibody to TLR3(+/+) mice exposed to hyperoxic conditions likewise protected these mice from lung injury and inflammation. The potential for redundancy in function as well as cross-talk between distinct TLRs may indeed contribute to whether the inflammatory cascade can be effectively disrupted once signaling has been initiated. Together, these data show that TLR3 has a major role in the development of ARDS-like pathology in the absence of a viral pathogen. | 18,849,495 |
High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling. | Phosphate (Pi) is an essential nutrient to living organisms. Recent surveys indicate that the intake of Pi has increased steadily. Our previous studies have indicated that elevated Pi activates the Akt signaling pathway. An increased knowledge of the response of lung cancer tissue to high dietary Pi may provide an important link between diet and lung tumorigenesis. The current study was performed to elucidate the potential effects of high dietary Pi on lung cancer development. Experiments were performed on 5-week-old male K-ras(LA1) lung cancer model mice and 6-week-old male urethane-induced lung cancer model mice. Mice were fed a diet containing 0.5% Pi (normal Pi) and 1.0% Pi (high Pi) for 4 weeks. At the end of the experiment, all mice were killed. Lung cancer development was evaluated by diverse methods. A diet high in Pi increased lung tumor progression and growth compared with normal diet. High dietary Pi increased the sodium-dependent inorganic phosphate transporter-2b protein levels in the lungs. High dietary consumption of Pi stimulated pulmonary Akt activity while suppressing the protein levels of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 as well as Akt binding partner carboxyl-terminal modulator protein, resulting in facilitated cap-dependent protein translation. In addition, high dietary Pi significantly stimulated cell proliferation in the lungs of K-ras(LA1) mice. Our results showed that high dietary Pi promoted tumorigenesis and altered Akt signaling, thus suggesting that careful regulation of dietary Pi may be critical for lung cancer prevention as well as treatment. | 18,849,498 |
Gradual loss of homelikeness in exhaustion disorder. | Our aim with the present study was to explore the lived experiences of the process leading to exhaustion. Within a hermeneutic phenomenological perspective, semistructured interviews were conducted with eleven individuals on sick leave because of exhaustion disorder. The findings were interpreted as a process of five stages of losing one's homelikeness in the body and in the familiar world: (a) the body calling for attention, (b) loss of self-recognition, (c) uncanniness, (d) fighting for survival, and (e) existential breakdown. Findings help us to identify early signs of exhaustion disorder and highlight the need for treatments that focus on bodily experiences and habitual stress-related patterns. Helping the patient to regain homelikeness is an important treatment goal. | 18,849,512 |
Contradictions and misperceptions: an exploration of injecting practice, cleanliness, risk, and partnership in the lives of women drug users. | We report the findings of an in-depth interview study conducted with 45 women injecting drug users in Britain. Women described experiences of injecting themselves and being injected by others, including instances of bodily harm and pain. Cleanliness when injecting was an issue of particular importance. An interesting division ("line of decency") occurred between opinions on sharing needles versus sharing injecting equipment. Partnership dynamics were important and partners sometimes had a pervasive influence on women's drug use and injecting practices. Narratives of risk showed that some women understood the risk of blood-borne viruses and outlined practical risk-prevention strategies. Some women did not perceive themselves to be at particular risk. Moral opinions were voiced about the risk behavior of others. Notions of risk were highly contextual and depended on a woman's immediate injecting situation. This article reports the inherent complexity resident in women drug users' decisions surrounding their injecting behavior. | 18,849,514 |
Multidisciplinary, interdisciplinary, or dysfunctional? Team working in mixed-methods research. | Combining qualitative and quantitative methods in a single study-otherwise known as mixed-methods research-is common. In health research these projects can be delivered by research teams. A typical scenario, for example, involves medical sociologists delivering qualitative components and researchers from medicine or health economics delivering quantitative components. We undertook semistructured interviews with 20 researchers who had worked on mixed-methods studies in health services research to explore the facilitators of and barriers to exploiting the potential of this approach. Team working emerged as a key issue, with three models of team working apparent: multidisciplinary, interdisciplinary, and dysfunctional. Interdisciplinary research was associated with integration of data or findings from the qualitative and quantitative components in both the final reports and the peer-reviewed publications. Methodological respect between team members and a principal investigator who valued integration emerged as essential to achieving integrated research outcomes. | 18,849,518 |
Schizophrenia patients lack normal positive correlation between age and brain response during verbal learning. | To investigate the differences in the relationship of age to brain function among individuals with schizophrenia and a healthy comparison group. The authors hypothesized that the correlation with age would be more strongly negative among schizophrenia patients, particularly in the frontal cortex. Cross-sectional measures of functional MRI (fMRI) brain response were correlated with age in both groups. Participants came to university research facilities for testing. The authors analyzed data from 30 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia or schizoaffective disorder ranging in age from 25 to 68 years and 14 healthy comparison participants ranging in age from 21 to 70 years. Brain response during word pair learning was measured with fMRI in each voxel of the brain. This measure was correlated with age within each group and the correlations were compared across groups in regions of interest determined a priori and based on a whole-brain analysis. In exploratory analyses, the authors examined the interaction of task performance with age and study group. The correlations between age and brain response were more positive in the healthy group than in the schizophrenia group in several regions, including right lateral prefrontal cortex and clusters in midline precuneus and right superior temporal gyrus. Interactions with task performance suggest that age effects on brain function relate differently to cognitive output in patients and comparison participants. There is no strong evidence that functional brain response during learning changes significantly with age among schizophrenia patients, in contrast to findings of positive associations with age among healthy individuals. | 18,849,533 |
Timing of Egf treatment differentially affects Tgf-beta2 induced cranial suture closure. | Premature suture obliteration results in an inability of cranial and facial bones to grow, with craniofacial dysmorphology requiring surgical correction as a consequence. Understanding signaling pathways associated with suture morphogenesis might enable non-invasive treatment of patients with fused sutures. Tgf-beta 2 induces premature suture fusion associated with increased cell proliferation both in vitro and in vivo. Tgf-beta 2 and Egf signal transduction pathways use some signaling proteins in common to regulate proliferation and differentiation, leading to speculation that these two pathways converge to regulate normal suture development. It was therefore hypothesized that Egf could induce suture fusion, and that Tgf-beta 2-induced suture closure occurred via an Egf-dependent pathway. A well-established fetal calvarial organ culture system was used to expose developing E19.5 fetal rat coronal sutures to Egf, Tgf-beta 2 and SC-120, a blocker of Egf receptor activity. Co-culture experiments examined the effect of Egf on Tgf-beta 2-induced suture closure when Egf was given either prior to or after Tgf-beta 2 treatment. Histomorphometric measurement of suture width was done on sagittal sections through coronal sutures harvested after 5 days in culture. Western blotting using phospho-antibodies against Egf receptors was used to confirm Egf receptor activity. Suture width increased with increasing concentrations of Egf, demonstrating that Egf-induced cell activity alone was not sufficient to cause premature suture obliteration. Egf administered prior to Tgf-beta 2 treatment rescued sutures from Tgf-beta 2-induced suture obliteration, demonstrating that pre-exposure of cells to this powerful mitogen prevented their response to signals induced by Tgf-beta 2. However, Egf added after Tgf-beta 2 treatment had no effect on Tgf-beta 2-induced suture closure. Blocking Egf activity after Tgf-beta 2 treatment rescued sutures from Tgf-beta 2-induced obliteration, indicating that Tgf-beta 2 required Egf activity to induce suture obliteration. Appropriate timing of signal generation by Egf and Tgf-beta 2 is critical for normal suture development and maintenance of suture patency. | 18,849,541 |
Regulatory agency consideration of pharmacogenomics. | This article discusses the current ambiguous state of federal regulatory agency control over pharmacogenomic testing, a subset of genetic testing that combines information about genetic variability with pharmacology in order to improve drug recommendations. An analysis of the common three terms used to evaluate regulation of pharmacogenomic testing: research validity, clinical validity, and clinical utility, followed by a case study involving U. S. Food and Drug Administration (FDA) regulation of laboratory developed tests, illustrates the present gap in pharmacogenomic oversight. The existing agency overlap in regulating pharmacogenomic testing leads to unclear or even contradictory authoritative advice. | 18,849,547 |
Characteristics of thiamin and its relevance to the management of heart failure. | Heart failure (HF) is a major public health problem in the United States that puts a significant burden on both patients and the healthcare system. The prevalence of malnutrition in HF patients is well-known and correlates with a dramatic decline in quality of life and disease progression, and is associated with high morbidity and mortality rates. The implication of HF on micronutrient status is underrecognized in the quest to offer "best practice" medical, device, and surgical interventions to this population. The micronutrient thiamin is of particular interest in the management of HF for several reasons: (a) HF is a disease of the elderly whose micronutrient status is in need of attention; (b) HF patients tend to have inadequate nutrient intake, which has been associated with thiamin deficiency; (c) thiamin deficiency (wet beriberi) impairs cardiac performance and can mimic the signs and symptoms of HF thereby potentially exacerbating the underlying disease; (d) use of loop diuretics to manage fluid and sodium imbalances associated with HF may cause the hyperexcretion of thiamin, thereby increasing the risk of deficiency; and (e) the prevention of thiamin deficiency should be a routine component in the overall management of this disease. | 18,849,553 |
Degradation of sphingoid long-chain base 1-phosphates (LCB-1Ps): functional characterization and expression of AtDPL1 encoding LCB-1P lyase involved in the dehydration stress response in Arabidopsis. | Sphingoid long-chain base (LCB) 1-phosphates are degradated by LCB 1-phosphate lyase to C(16) fatty aldehydes and phosphoethanolamine. Here, we confirmed that the At1g27980 gene product, AtDPL1, is a functional LCB-1-phosphate lyase. Expression of green fluorescent protein fusion products in suspension-cultured Arabidopsis cells showed that AtDPL1 is located to the endoplasmic reticulum. The rates of fresh weight decreases of dpl1-1 and dpl1-2 mutants were significantly slower than those of the wild-type plants. This ability to limit their transpiration reflected the leaf temperature of the mutant plants more than that of wild-type plants, suggesting that AtDPL1 plays a role in dehydration stress. | 18,849,574 |
Proapoptotic protein Siva binds to the muscle protein telethonin in cardiomyocytes during coxsackieviral infection. | Coxsackievirus B3 (CVB3) is known to cause a variety of human diseases including acute and chronic myocarditis as well as dilated cardiomyopathy (DCM). However, the mechanisms by which CVB3 causes diseases are not well understood. Studies identifying protein-protein interactions during CVB3 infection are useful in delineating the pathogenesis of acute or chronic myocarditis. Screening a human heart cDNA library revealed a yet unknown interaction partner of the proapoptotic protein Siva. We demonstrate that Siva specifically interacts with the heart and skeletal muscle protein telethonin. The expression of Siva is increased in heart tissue of CVB3-infected mice and the proteins colocalize in cardiomyocytes. telethonin might be involved in CVB3-mediated cell damage and in the resulting cardiac dysfunction due to the interaction with Siva. We suggest a molecular mechanism through which coxsackieviral infection contributes to the pathogenesis of chronic myocarditis and in particular of acquired forms of DCM. | 18,849,585 |
New mouse models for recessive retinitis pigmentosa caused by mutations in the Pde6a gene. | The heterotetrameric phosphodiesterase (PDE) 6 complex, made up of alpha, beta and two gamma subunits, regulates intracellular cGMP levels by hydrolyzing cGMP in response to light activation of G protein coupled receptors in cones and rods, making it an essential component of the visual phototransduction cascade [Zhang, X. and Cote, R.H. (2005) cGMP signaling in vertebrate retinal photoreceptor cells. Front. Biosci., 10, 1191-1204.]. Using a genetic positional candidate cloning strategy, we have identified missense mutations within the catalytic domain of the Pde6a gene in two mouse models from an ethyl nitrosourea chemical mutagenesis screen. In these first small rodent models of PDE6A, significantly different biochemical outcomes and rates of degeneration of murine photoreceptor cells were observed, indicating allelic variation and previously unrecognized structure-function relationships. In addition, these new models reveal that the mutations not only affect the function of the PDE6A protein itself, but also the level of PDE6B within the retina. Finally, we show that the variation of the disease phenotype by background modifier genes may be dependent upon the particular disease allele present. | 18,849,587 |
Analysis of polymorphisms in olive pollen allergy: IL13, IL4RA, IL5 and ADRB2 genes. | Previous results demonstrated that sensitization to specific olive pollen allergens could be related with a different clinical pattern (asthma and/or rhinitis), and that specific patterns of sensitization are regulated by different HLA class II antigens. The authors analyze the possible implication of 7 genetic polymorphisms described as asthma susceptibility genes: IL13 (C-1112T and R130Q), IL4RA (I50V, Q551R), IL5 (C-746T) and ADRB2 (Q27E and R16G) in specific olive pollen allergic sensitization. The authors genotyped seven polymorphisms of the IL13, IL4RA, IL5 and ADRB2 genes in 146 patients allergic to olive pollen with seasonal rhinitis/asthma and 50 controls using the polymerase chain reaction-restriction fragment length polymorphism and real-time polymerase chain reaction techniques. Two polymorphisms of IL13 were associated with allergy to olive pollen: the TT genotype of IL13 C-1112T was decreased (odds ratio, OR = 0.35, p = 0.006) whereas the RQ heterozygous genotype of IL13 R130Q increased in patients allergic to olive pollen (OR = 3.12, p = 0.009). The combined analysis of two IL4RA single nucleotide polymorphisms (SNPs) (I50V and Q551R) showed an association with asthma: IL4RA V50/Q551 was associated with risk (OR = 2.48, p = 0.007) whereas the IL4RA V50R551 haplotype was associated with protection (OR = 0.31, p = 0.003). The IL13 polymorphisms under study were associated with specific allergy to olive pollen: the IL13 C-1112T polymorphism as a protective factor and the IL13 R130Q polymorphism as a risk factor. Interestingly, although single polymorphisms of IL4RA are not associated with any phenotype analyzed, the interaction between IL4RA I50V/Q551R was strongly associated with the asthma phenotype. IL13 and IL4RA could be relevant markers for allergy to olive pollen and asthma development. | 18,849,614 |
The molecular interactions between filtered proteins and proximal tubular cells in proteinuria. | Proteinuria is associated with progressive chronic kidney disease and poor cardiovascular outcomes. Exposure of proximal tubular epithelial cells to excess proteins leads to the development of proteinuric nephropathy with tubular atrophy, interstitial inflammation and scarring. Numerous signalling pathways are activated in proximal tubular epithelial cells under proteinuric conditions resulting in gene transcription, altered growth and the secretion of inflammatory and profibrotic mediators. Megalin, the proximal tubular scavenger receptor for filtered macromolecules, has intrinsic signalling functions and may also link albumin to growth factor receptor signalling via regulated intramembrane proteolysis. It now seems that endocytosis is not always a prerequisite for albumin-evoked alterations in proximal tubular cell phenotype. Recent evidence shows the presence of other potential receptors for proteins, such as the neonatal Fc receptor and CD36, in the proximal tubular epithelium. | 18,849,618 |
Values for macular perimetry using the MP-1 microperimeter in normal subjects. | To establish values for the fixation pattern and macular sensitivity to light in healthy subjects using the MP-1 microperimeter (Nideck Technologies, Vigonza, Italy). A prospective study of 37 healthy subjects (age: 19-71 years), approved by the institutional review board. Full-threshold microperimetry of the central 12 degrees of the retina (the macula) was performed prospectively, utilizing 16 points with the MP-1. The fixation stability was simultaneously recorded during microperimetry testing. The relationship between the fixation pattern and light sensitivity with age was calculated using linear regression analysis. Microperimetry was performed on 66 eyes. Total mean sensitivity was 18.33 dB (range: 13.0-19 dB). Mean macular sensitivities at 2 degrees , 4 degrees and 6 degrees as measured by the MP-1 were 18.4+/-2.0, 18.2+/-2.3 and 18.2+/-2.1 dB, respectively. The linear regression analysis revealed a 0.019240, 0.0248 and 0.0285 dB per year age-related decline in mean macular sensitivity at 2 degrees, 4 degrees and 6 degrees from the center of the macula, respectively. The total mean fixation stability values within 2 degrees and 4 degrees were 86 and 96%, respectively. The linear regression analysis also revealed a 0.344% and 0.122% per year decline in age-related fixation stability within 2 degrees and 4 degrees , respectively. There were no statistically significant differences between the median retinal sensitivity or fixation stability values for sex or race in the study. The MP-1 may be a reliable tool to measure macular sensitivity. Among normal healthy subjects, there was a linear decline in light sensitivity with increasing age. | 18,849,636 |
Long-term survival and prognostic indicators in small (<or=2 cm) pancreatic cancer. | In a matched analysis, we investigated clinical, histopathological, and survival characteristics of small (<or=2 cm) pancreatic cancer (PaC) as compared to large PaC. From the Mayo pathology database, we identified 41 consecutive patients with small PaC and 94 matched controls with margin-negative PaC >2 cm. Two experienced pathologists, who were blinded to survival data, independently reviewed tumor stage and differentiation. Kaplan-Meier survival analysis and Cox proportional hazards models were applied for data analyses. In patients with localized disease (stages I and II), survival was similar in small and large PaC but survival was significantly better in small PaC with regional nodal metastasis (stage III) as compared to similar stage large PaC (5-year survival 44 vs. 7%, median survival 58 vs.18 months, p < 0.001). Well-differentiated small and large PaC had similar median survival (76 vs. 74 months, p = NS). In multivariate analysis, tumor differentiation, not tumor size, was the only independent factor predicting survival in PaC (risk ratio, RR, for moderate vs. well- differentiated: 2.6, 95% confidence interval, CI, 1.5-4.5, and RR for poorly differentiated vs. well-differentiated: 5.0, 95% CI 2.4-10.1). Tumor differentiation may be a better predictor of survival in resectable PaC than tumor stage. | 18,849,640 |
Application of a global proteomic approach to archival precursor lesions: deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancer precursors. | Pancreatic cancer is an almost uniformly fatal disease, and early detection is a critical determinant of improved survival. A variety of noninvasive precursor lesions of pancreatic adenocarcinoma have been identified, which provide a unique opportunity for intervention prior to onset of invasive cancer. Biomarker discovery in precursor lesions has been hampered by the ready availability of fresh specimens, and limited yields of proteins suitable for large scale screening. We utilized Liquid Tissue, a novel technique for protein extraction from archival formalin-fixed material, and mass spectrometry to conduct a global proteomic analysis of an intraductal papillary mucinous neoplasm (IPMN). Tissue microarrays comprised of 38 IPMNs were used for validation of candidate proteins. The proteomic analysis of the IPMN Liquid Tissue lysate resulted in identification of 1,534 peptides corresponding to 523 unique proteins. A subset of 25 proteins was identified that had previously been reported as upregulated in pancreatic cancer. Immunohistochemical analysis for two of these, deleted in malignant brain tumors 1 (DMBT1) and tissue transglutaminase 2 (TGM2), confirmed their overexpression in IPMNs. Global proteomics analysis using the Liquid Tissue workflow is a feasible approach for unbiased biomarker discovery in limited archival material, particularly applicable to precursor lesions of cancer. | 18,849,643 |
Next generation of human vaccines: what does the future hold? | The World Vaccine Congress was held in Arlington, VA April 21st-24th, 2008. Tevi Troy, the deputy secretary of the US Department of Health and Human Services, set the tone of the meeting during his keynote address. He discussed the government's plan to deliver a strategic outlook and follow a road map for vaccine development. He also emphasized the importance of ongoing cooperation between industry and the government's many departments. In an electrifying keynote address Gregory Poland, Professor of Medicine and Infectious Diseases at the Mayo Clinic in Rochester, MN discussed the role of recent advancements in the fields of Immunology, Genetics, Molecular Biology, Bioinformatics and the completion of the Human Genome Project. Poland described the recent emergence of the field of Vaccinomics and laid out his vision for an era of personalized medicine. Next-generation vaccine approaches targeting cervical cancer, meningitis, childhood diarrhea and renal cell carcinoma were presented by leaders in the field. Preclinical and early-stage clinical successes of vaccines against Malaria, TB and Ebola were discussed along with a road map for HIV, TB and Malaria vaccine development. The importance of collaborations among government departments, academic institutions, industries and philanthropic foundations was a common theme stressed throughout the conference. | 18,849,649 |
Subtype-selective conopeptides targeted to nicotinic receptors: Concerted discovery and biomedical applications. | Conus peptides that are selectively targeted to different molecular isoforms of nicotinic acetylcholine receptors (nAChRs) have been identified and characterized; several have recently been shown to have significant biomedical potential. An emerging strategy for the discovery from animal biodiversity of subtype-specific ligands for ion channel families is described in this review. Characterization of the gene family encoding a set of related ligands is required for discovery using a molecular genetics approach; when discovery is guided by a knowledge of the phylogeny of the biodiverse animal lineage being used as a source of ligands, a rational, efficient scan of the library of putative ligands becomes feasible. Together, these constitute an approach to uncover subtype-specific ligands, called "concerted discovery"; this was applied to the alpha-conotoxins, a family of Conus peptides generally targeted to nAChRs. Subtype-specific alpha-conotoxins were developed that target two groups of nAChRs, alpha(6)* and alpha(9)*. alpha-conotoxin MII has become the defining ligand for identifying the alpha(6)* nAChR subtype. A synthetic analog, MII [E11A], further subdivides alpha(6)* nAChRs into those that contain an alpha(4) subunit and those that do not. Importantly, these two subtypes are differentially affected by nigrostriatal damage, findings of likely relevance to the pathopysiology of Parkinson's disease. In contrast, alpha-conotoxins that target alpha(9) nAChR subtypes have potential as analgesics for the treatment of neuropathic pain that develops after nerve injury. The discovery of alpha-conotoxin RgIA enabled the identification of a novel role for alpha(9)* nAChRs. Use of alpha(9)* nAChR antagonists is associated with reversal of inflammation caused by the nerve injury. Thus, subtype-specific alpha-conotoxins targeted to particular nAChR isoforms are not only useful for understanding the physiological role of these receptors, but can have important diagnostic and therapeutic applications as well. | 18,849,660 |
Fourth Annual Warren K. Sinclair Keynote Address: the use and misuse of radiation in medicine. | Among the many diagnostic and therapeutic uses of ionizing radiation in medicine, the potential for misuse is greatest in diagnostic imaging, particularly with computed tomography. While several technical adjustments may be made to produce a dose that is as low as reasonably achievable, appropriate utilization of these tests is a more difficult issue to address. The risks of ionizing radiation, taking into account the patient's age, sex, and body part to be examined, must be balanced with the potential benefit that comes with medical imaging. Fortunately, the benefits outweigh the risks in most clinical scenarios, particularly in patients without a confirmed diagnosis. However, the repetitive imaging of patients with known clinical conditions to assess for interval change may pose the greatest opportunity to curb over-utilization of imaging tests that may be harmful. The medical community at large must be educated in the effects of ionizing radiation. Moreover, practitioners must be inspired to differentiate imaging tests for primary diagnosis from those performed in follow-up of known pathology in common diagnostic algorithms. This metamorphosis must extend from the most senior health care administrator to the most junior healthcare professional and must include those who are charged with acquiring the necessary imaging tests. In addition, imaging professionals must avail themselves of the numerous technical advances that allow a reduction in the dose of ionizing radiation that is associated with common imaging procedures. And, dose monitoring must be performed on many levels, including the dose to an individual patient undergoing a specific imaging test. | 18,849,681 |
Update on linear non-threshold dose-response model and implications for diagnostic radiology procedures. | Cancer risk estimates are used in the setting of radiation protection standards by international and national organizations, and for this purpose need to be developed for low doses of radiation. The approach has involved extrapolation from cancer mortality and incidence values at higher doses to predict the low-dose estimates. Such an extrapolation has generally involved the use of the linear non-threshold (LNT) theory. Recent reports from the National Research Council (BEIR VII) and the International Commission on Radiological Protection (ICRP) have considered the appropriateness of the use of LNT for the purposes of radiation protection standard setting. The overall conclusion from both committees was that current scientific evidence remains consistent with the LNT hypothesis, while appreciating that this might not rule out the possibility that other extrapolation models might well be valid but require further evaluation and additional research to establish their validity. The dose and dose-rate effectiveness factor (DDREF) is used for adjustment in the extrapolation from high to low doses and from high to low dose rates. The BEIR VII committee proposed a new Bayesian approach for estimating DDREF and concluded that a value of 1.5 best fit the data. This is a departure from the previously used value of 2, which is still proposed by ICRP in its most recent recommendations. The current cancer risk estimation process as utilized by ICRP and BEIR VII is used here to assess the potential risks from annual whole-body computed tomography (CT) screens using information and an approach published by Brenner and Ellington. The major conclusion is that potential radiation risks need to be considered along with the pros and cons of the detection limits of the procedure and the impact of false positives. | 18,849,687 |
Research involving human subjects. | This paper will discuss the history of human subjects in research and the subsequent regulations and requirements that now govern human subject research. Also presented are the requirements and definitions of the oversight bodies which govern human use research in the United States. | 18,849,688 |
Digital radiography: image quality and radiation dose. | Digital radiography devices, rapidly replacing analog screen-film detectors, are now common in diagnostic radiological imaging, where implementation has been accelerated by the commodity status of electronic imaging and display systems. The shift from narrow latitude, fixed-speed screen-film detectors to wide latitude, variable-speed digital detectors has created a flexible imaging system that can easily result in overexposures to the patient without the knowledge of the operator, thus potentially increasing the radiation burden of the patient population from radiographic examinations. In addition, image processing can be inappropriately applied causing inconsistent or artifactual appearance of anatomy, which can lead to misdiagnosis. On the other hand, many advantages can be obtained from the variable-speed digital detector, such as an ability to lower dose in many examinations, image post-processing for disease-specific conditions, display flexibility to change the appearance of the image and aid the physician in making a differential diagnosis, and easy access to digital images. An understanding of digital radiography is necessary to minimize the possibility of overexposures and inconsistent results, and to achieve the principle of as low as reasonably achievable (ALARA) for the safe and effective care of all patients. Thus many issues must be considered for optimal implementation of digital radiography, as reviewed in this article. | 18,849,693 |
Technical advances of interventional fluoroscopy and flat panel image receptor. | In the past decade, various radiation reducing devices and control circuits have been implemented on fluoroscopic imaging equipment. Because of the potential for lengthy fluoroscopic procedures in interventional cardiovascular angiography, these devices and control circuits have been developed for the cardiac catheterization laboratories and interventional angiography suites. Additionally, fluoroscopic systems equipped with image intensifiers have benefited from technological advances in x-ray tube, x-ray generator, and spectral shaping filter technologies. The high heat capacity x-ray tube, the medium frequency inverter generator with high performance switching capability, and the patient dose reduction spectral shaping filter had already been implemented on the image intensified fluoroscopy systems. These three underlying technologies together with the automatic dose rate and image quality (ADRIQ) control logic allow patients undergoing cardiovascular angiography procedures to benefit from "lower patient dose" with "high image quality." While photoconductor (or phosphor plate) x-ray detectors and signal capture thin film transistor (TFT) and charge coupled device (CCD) arrays are analog in nature, the advent of the flat panel image receptor allowed for fluoroscopy procedures to become more streamlined. With the analog-to-digital converter built into the data lines, the flat panel image receptor appears to become a digital device. While the transition from image intensified fluoroscopy systems to flat panel image receptor fluoroscopy systems is part of the on-going "digitization of imaging," the value of a flat panel image receptor may have to be evaluated with respect to patient dose, image quality, and clinical application capabilities. The advantage of flat panel image receptors has yet to be fully explored. For instance, the flat panel image receptor has its disadvantages as compared to the image intensifiers; the cost of the equipment is probably the most obvious. On the other hand, due to its wide dynamic range and linearity, lowering of patient dose beyond current practice could be achieved through the calibration process of the flat panel input dose rate being set to, for example, one half or less of current values. In this article various radiation saving devices and control circuits are briefly described. This includes various types of fluoroscopic systems designed to strive for reduction of patient exposure with the application of spectral shaping filters. The main thrust is to understand the ADRIQ control logic, through equipment testing, as it relates to clinical applications, and to show how this ADRIQ control logic "ties" those three technological advancements together to provide low radiation dose to the patient with high quality fluoroscopic images. Finally, rotational angiography with computed tomography (CT) and three dimensional (3-D) images utilizing flat panel technology will be reviewed as they pertain to diagnostic imaging in cardiovascular disease. | 18,849,699 |
Dose to normal tissues outside the radiation therapy patient's treated volume: a review of different radiation therapy techniques. | Radiation therapy treatment planning and delivery capabilities have changed dramatically since the introduction of three-dimensional treatment planning and are continuing to change relatively rapidly in response to the implementation of new advanced technologies. Three-dimensional conformal radiation therapy (3DCRT) is now firmly in place as the standard of practice in clinics around the world. Medical accelerator manufacturers have employed advanced computer technology to produce treatment planning/delivery systems capable of precise shaping of dose distributions via computer-controlled multileaf collimator (MLC) systems, by which the beam fluence is varied optimally to achieve the desired dose distribution. This mode of conformal therapy is referred to as intensity modulated radiation therapy (IMRT), and is capable of generating dose distributions (including concave isodose volumes) that closely conform the prescription dose to the target volume and/or avoid specific sensitive normal structures. The increasing use of IMRT has focused attention on the need to better account for the intra- and inter-fraction spatial uncertainties in the dose delivery process. This has helped spur the development of treatment machines with integrated planar and volumetric advanced imaging capabilities, providing a new treatment modality referred to as image-guided IMRT (IG-IMRT), or simply image-guided radiation therapy (IGRT). In addition, there is a growing interest in replacing x rays with protons because of the physical characteristics of the depth dose curve, which peaks at the end of particle range, and eventually with even heavier charged particles to take advantage of the greater density of energy deposition close to the Bragg peak and hence larger relative biological effectiveness (RBE). Three-dimensional CRT, IMRT and proton beam therapy all provide improved target coverage and lower doses to surrounding normal tissues as compared to the previously used two-dimensional radiation therapy techniques. However, this is achieved at the expense of a greater volume of normal tissue in the irradiated volume receiving some dose and a higher whole body dose (or peripheral dose) to distant normal tissues. The higher whole body dose is a result of the increased x-ray leakage radiation to the patient due to the longer beam-on times associated with IMRT, and also from neutron leakage radiation associated with high energy x-ray beams (>10 MV) and proton beams. Dose distributions for the various CRT techniques and the current status of available data for normal tissues, and whole body dose are reviewed. | 18,849,701 |
A robotic manipulator for handling TLD badges. | A prototype system for automatic handling of Harshaw/Bicron (now ThermoFisher Scientific) thermoluminescent dosimetry (TLD) badges, which is based on a robotic arm, was designed and built. The robot performs the loading and unloading of the TLD cards in the badges and transports them between the loading/unloading station and magazine stations. For quality assurance, a sticker containing the worker's details printed in barcode format was added to the badge. Automatic on-line identification is performed for checking the correlation between the badge and the TLD card number. | 18,849,713 |
An evidence-based protocol for nurse retention. | Registered nurse turnover can drastically affect the quality of patient care while costing more than 1 billion dollars. The ongoing nursing shortage makes it hard to replace nurses, necessitating a novel approach to reduce nurse turnover. The authors discuss an evidence-based protocol that improves organizational commitment among nurses as a way to retain nurses through facilitating autonomy, improving communication, and offering recognition and rewards to nursing staff. | 18,849,749 |
The prevalence of metabolic syndrome in an employed population and the impact on health and productivity. | To investigate the prevalence of metabolic syndrome in an employed population and its association with health risks, health perception, illness days, work limitation (presenteeism), and short-term disability (STD). Five thousand five hundred twelve employees of a financial services company responded to an on-site health risk appraisal which included measured waist circumference and biometric results. The metabolic syndrome criteria were based on the 2005 AHA/NHLBI scientific statement on the diagnosis and management of metabolic syndrome. Perceived health, illness days, and presenteeism were self-reported; STD days were obtained from claims data. In this employee population (61% women, average age 41 years), 22.6% met the criteria for metabolic syndrome and were more likely to report more health risks, poorer health perception, and more absent days due to illness. There was no clear association with presenteeism or STD incidence. However, as the number of metabolic risk factors increased, there was an increase in STD incidence, decrease in health perception, and increase in illness days. No association was found with number of metabolic risk factors and presenteeism. Metabolic syndrome was associated with poor perceived health, increased illness days, and an increased trend of STD incidence. Worksite health promotion programs could be useful in helping employees and employers to identify metabolic syndrome risks and take steps to reduce risk and potential productivity losses. | 18,849,759 |
NACCHO helps local health departments adapt to the ever-changing field of environmental health. | The National Association of County and City Health Officials (NACCHO) is the national organization representing local health departments. NACCHO supports efforts that protect and improve the health of all people and all communities by promoting national policy, developing resources and programs, seeking health equity, and supporting effective local public health practice and systems. | 18,849,783 |
Injuries from roadside improvised explosive devices. | After the invasion of Iraq in April 2003, coalition forces have remained in the country in a bid to maintain stability and support the local security forces. The improvised explosive device (IED) has been widely used by the insurgents and is the leading cause of death and injury among Coalition troops in the region. From January 2006, data were prospectively collected on 100 consecutive casualties who were either injured or killed in hostile action. Mechanism of injury, new Injury Severity Score (NISS), The International Classification of Disease-9th edition diagnosis, anatomic pattern of wounding, and operative management were recorded in a trauma registry. The weapon incident reports were analyzed to ascertain the type of IED employed. Of the 100 casualties injured in hostile action, 53 casualties were injured by IEDs in 23 incidents (mean 2.3 casualties per incident). Twenty-one of 23 (91.3%) of the IEDs employed were explosive formed projectile (EFP) type. Twelve casualties (22.6%) were either killed or died of wounds. Median NISS score of survivors was 3 (range, 1-50). All fatalities sustained unsurvivable injuries with a NISS score of 75. Primary blast injuries were seen in only 2 (3.8%) and thermal injuries in 8 casualties (15.1%). Twenty (48.7%) of survivors underwent surgery by British surgeons in the field hospital. At 18 months follow, all but one of the United Kingdom Service personnel had returned to military employment. The injury profile seen with EFP-IEDs does not follow the traditional pattern of injuries seen with conventional high explosives. Primary blast injuries were uncommon despite all casualties being in close proximity to the explosion. When the EFP-IED is detonated, the EFP produced results in catastrophic injuries to casualties caught in its path, but causes relatively minor injuries to personnel sited adjacent to its trajectory. Improvements in vehicle protection may prevent the EFP from entering the passenger compartments and thereby reduce fatalities. | 18,849,810 |
Nutrition consumption of female combat recruits in army basic training. | The Karakal is an existing light infantry unit consisting of both female and male fighters (predominantly female). This was the first Israel Defense Forces study to assess and to evaluate the dietary intake among male and female recruit fighters in comparison to nonfighters from preinduction through Army Basic Training (ABT). One company of Karakal recruits plus a control group of female medics were assessed for dietary intake at three time points: day of recruitment, 2 months into ABT, and at the end of 4 months ABT, using validated Food Frequency Questionnaires. Means of dietary intake were presented and compared with the Military Dietary Reference Intakes (MDRI). This study included 92 Karakal females (KF), 33 Karakal males (KM), and 48 control females (CF) aged 18-19 yr. Mean energy and calcium intakes at preinduction for KF were 90% and 71% of MDRI, respectively. These values were significantly lower than CF values (108% and 88%). Both groups of females consumed 57% of vitamin D. The KM intakes were similarly deficient. At preinduction, deficiencies were greater among recruits who first volunteered for 1 yr of national service (NS). During ABT, average dietary intakes decreased in all groups. Values for KF and CF were as follows: energy intake = 80% and 71%, respectively; Ca = 61% and 49%, respectively; Zn = 71% and 57%, respectively; and vitamin D = 34% and 24%, respectively. The diet of all groups met the MDRI requirements for protein, vitamin B6, and vitamin B12. Karakal fighters' food consumption during ABT did not meet most MDRI nutrient requirements. Females entering the army directly from a home environment began with a nutritional status that met MDRI requirements, unlike those inducted after 1 yr of NS away from home. Deficiencies need further investigation as they may have a negative impact on soldiers' health and physical performance. | 18,849,866 |
Overuse injuries in female infantry recruits during low-intensity basic training. | The purpose of this prospective study was to investigate the epidemiology of overuse injuries and to identify common risk factors for stress fractures among female and male recruits in a new light infantry basic training designed to minimize the incidence of overuse injuries. Study subjects were male and female recruits in the 16-wk light infantry basic training. A control group of noncombat female medics whose military service did not include demanding physical activities was recruited to assess the female recruits' preinduction physical preparedness. Pretraining survey of all participants' medical and sports participation histories was conducted. Anthropometric measurements were performed. Subjects were followed every 3 wk for overuse injuries. Stress fractures were diagnosed by radiography or scintigraphy. Ninety-nine female recruits, 36 male recruits, and 55 controls participated. Although 31% of the controls reported regular preinduction sports participation, less than 25% of both male and female recruits did. Stress fractures incidence was 0% among males and controls but 12% among female recruits (P = 0.03). The mean body mass index of female recruits with stress fractures was 19.2 +/- 2.6 versus 22.5 +/- 3.3 kg x m of female recruits without stress fractures (P = 0.02, odds ratio = 1.397, 95% confidence interval = 1.065-1.833). No statistically significant difference was found between female and male military trainees in the incidence of other overuse injuries, but there was a statistical trend (P = 0.07) for more back pain among females. Lower body mass index was the only variable identified as a risk factor for stress fractures among female recruits in the present study. It does not explain the markedly different response of female and male recruits' bones to the low demand training. There may be an intrinsic difference between male and female bone resistance to fatigue. | 18,849,872 |
Chronic morphine application is protective against cell death in primary human neurons. | Morphine addiction has become a long-time, serious medical and social problem. To understand the cellular mechanisms of morphine application and addiction, the effects of chronic morphine treatments were examined in primary cultured human neurons. Our results show that, surprisingly, morphine protects cultured human neurons against serum deprivation and staurosporine induced cytotoxicity. Morphine downregulates proapoptotic factor Bax levels in cultured human neurons. In addition, heat shock protein 70 is also involved in morphine protection. Our data suggest that chronic morphine application may be beneficial to stimulate cell survival. | 18,849,879 |
A review on quality of life and depression in obsessive-compulsive disorder. | Quality of life (QoL) is increasingly recognized as a pivotal outcome parameter in research on obsessive-compulsive disorder (OCD). While the concept remains somewhat ill-defined, there is now little dispute that the patients' personal goals deserve foremost consideration during the course of treatment as the primary aim of treatment should be relief from individual despair, which is related but by no means synonymous to symptom reduction. Studies using generic (ie, illness-unspecific) instruments have confirmed poor QoL in OCD patients across a wide range of domains, especially with respect to social, work role functioning, and mental health aspects. Scores are sometimes as low as those obtained by patients with schizophrenia. Depression and obsessions are the symptom clusters that most strongly contribute to low QoL. Findings from a novel survey of 105 OCD participants point to multiple daily life problems, poor work status, and tense social networks in these patients. In order to achieve therapeutic success and improve QoL, functional problems at work and comorbid disorders such as secondary depression and physical impairments should be targeted. While successful treatment sometimes positively impacts well-being, in some studies symptom decline did not translate into improved QoL. | 18,849,907 |
Subclinical obsessive-compulsive disorder in children and adolescents: additional results from a "high-risk" study. | The concept of subclinical obsessive-compulsive disorder is explored using data from a "high-risk" study of offspring of persons with (OCD) and offspring of controls. Offspring with OCD were compared to those with subclinical OCD, and those without either condition. Subclinical OCD is defined as the presence of obsessions and/or compulsions without functional impairment. Adults with OCD and their offspring 7-18 years of age were recruited through a tertiary care center psychiatric outpatient clinic, while controls (and their children) were recruited via advertisement. Parents and offspring were assessed using structured interviews and validated questionnaires at baseline and follow-up interviews. Offspring from both proband groups were pooled to create three subject groups: group 1, offspring with neither condition (n=43); group 2, offspring with subclinical OCD (n=24); and group 3, offspring with full OCD (n=11). Offspring with subclinical OCD held the middle ground for most comparisons. They were more symptomatic than offspring without either condition (group 1), but less symptomatic than subjects with OCD (group 3). Across the board, comparisons of diagnoses, Child Behavior Checklist (CBCL) results; Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey results; and Leyton Obsessional Inventory (LOI) results were associated with subject group at baseline and follow-up. In post-hoc comparisons, subjects with subclinical OCD had fewer comorbid anxiety disorders and lower CBCL internalizing scale scores at follow-up. Parents of children with OCD had higher LOI symptom and severity scores than parents in those of groups 1 or 2. The findings suggest that subclinical OCD holds the middle ground between full-blown OCD and having neither condition in terms of obsessive-compulsive symptoms and severity, tics, associated mood/anxiety disorders, and general functioning. At least in persons at risk for OCD, the presence of subclinical OCD may herald the onset of OCD, though in others may be an independent condition that does not lead to full OCD. | 18,849,913 |
Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. | Systems for protein degradation are essential for tight control of the inflammatory immune response. Autophagy, a bulk degradation system that delivers cytoplasmic constituents into autolysosomes, controls degradation of long-lived proteins, insoluble protein aggregates and invading microbes, and is suggested to be involved in the regulation of inflammation. However, the mechanism underlying the regulation of inflammatory response by autophagy is poorly understood. Here we show that Atg16L1 (autophagy-related 16-like 1), which is implicated in Crohn's disease, regulates endotoxin-induced inflammasome activation in mice. Atg16L1-deficiency disrupts the recruitment of the Atg12-Atg5 conjugate to the isolation membrane, resulting in a loss of microtubule-associated protein 1 light chain 3 (LC3) conjugation to phosphatidylethanolamine. Consequently, both autophagosome formation and degradation of long-lived proteins are severely impaired in Atg16L1-deficient cells. Following stimulation with lipopolysaccharide, a ligand for Toll-like receptor 4 (refs 8, 9), Atg16L1-deficient macrophages produce high amounts of the inflammatory cytokines IL-1beta and IL-18. In lipopolysaccharide-stimulated macrophages, Atg16L1-deficiency causes Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF)-dependent activation of caspase-1, leading to increased production of IL-1beta. Mice lacking Atg16L1 in haematopoietic cells are highly susceptible to dextran sulphate sodium-induced acute colitis, which is alleviated by injection of anti-IL-1beta and IL-18 antibodies, indicating the importance of Atg16L1 in the suppression of intestinal inflammation. These results demonstrate that Atg16L1 is an essential component of the autophagic machinery responsible for control of the endotoxin-induced inflammatory immune response. | 18,849,965 |
Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. | The clinical success of multitargeted kinase inhibitors has stimulated efforts to identify promiscuous drugs with optimal selectivity profiles. It remains unclear to what extent such drugs can be rationally designed, particularly for combinations of targets that are structurally divergent. Here we report the systematic discovery of molecules that potently inhibit both tyrosine kinases and phosphatidylinositol-3-OH kinases, two protein families that are among the most intensely pursued cancer drug targets. Through iterative chemical synthesis, X-ray crystallography and kinome-level biochemical profiling, we identified compounds that inhibit a spectrum of new target combinations in these two families. Crystal structures revealed that the dual selectivity of these molecules is controlled by a hydrophobic pocket conserved in both enzyme classes and accessible through a rotatable bond in the drug skeleton. We show that one compound, PP121, blocks the proliferation of tumor cells by direct inhibition of oncogenic tyrosine kinases and phosphatidylinositol-3-OH kinases. These molecules demonstrate the feasibility of accessing a chemical space that intersects two families of oncogenes. | 18,849,971 |
Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. | Ectopic expression of defined sets of genetic factors can reprogram somatic cells to induced pluripotent stem (iPS) cells that closely resemble embryonic stem (ES) cells. The low efficiency with which iPS cells are derived hinders studies on the molecular mechanism of reprogramming, and integration of viral transgenes, in particular the oncogenes c-Myc and Klf4, may handicap this method for human therapeutic applications. Here we report that valproic acid (VPA), a histone deacetylase inhibitor, enables reprogramming of primary human fibroblasts with only two factors, Oct4 and Sox2, without the need for the oncogenes c-Myc or Klf4. The two factor-induced human iPS cells resemble human ES cells in pluripotency, global gene expression profiles and epigenetic states. These results support the possibility of reprogramming through purely chemical means, which would make therapeutic use of reprogrammed cells safer and more practical. | 18,849,973 |
Millisecond-scale differences in neural activity in auditory cortex can drive decisions. | Neurons in the auditory cortex can lock to the fine timing of acoustic stimuli with millisecond precision, but it is not known whether this precise spike timing can be used to guide decisions. We used chronically implanted microelectrode pairs to stimulate neurons in the rat auditory cortex directly and found that rats can exploit differences in the timing of cortical activity that are as short as 3 ms to guide decisions. | 18,849,984 |
A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs. | We used conditional knockout strategies in mice to determine the developmental events and gene expression program regulated by the LIM-homeodomain factor Islet1 in developing sensory neurons. Early development of the trigeminal and dorsal root ganglia was grossly normal in the absence of Islet1. From E12.5 onward, however, Isl1 mutant embryos showed a loss of the nociceptive markers TrkA and Runx1 and a near absence of cutaneous innervation. Proprioceptive neurons characterized by the expression of TrkC, Runx3 and Etv1 were relatively spared. Microarray analysis of Isl1 mutant ganglia revealed prolonged expression of developmental regulators that are normally restricted to early sensory neurogenesis and ectopic expression of transcription factors that are normally found in the CNS, but not in sensory ganglia. Later excision of Isl1 did not reactivate early genes, but resulted in decreased expression of transcripts related to specific sensory functions. Together these results establish a central role for Islet1 in the transition from sensory neurogenesis to subtype specification. | 18,849,985 |
Hypoxic silencing of tumor suppressor RUNX3 by histone modification in gastric cancer cells. | RUNX3 is a tumor suppressor that is silenced in cancer following hypermethylation of its promoter. The effects of hypoxia in tumor suppressor gene (TSG) transcription are largely unknown. Here, we investigated hypoxia-induced silencing mechanisms of RUNX3. The expression of RUNX3 was downregulated in response to hypoxia in human gastric cancer cells at the transcriptional level. This downregulation was abolished following treatment with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) and cytosine methylation inhibitor 5-aza-2-deoxycytidine (5-Aza), suggesting that an epigenetic regulatory mechanism may be involved in RUNX3 silencing by hypoxia. DNA methylation PCR and bisulfite-sequencing data revealed that hypoxia did not affect the methylation of RUNX3 promoter. A chromatin immunoprecipitation (ChIP) assay revealed increased histone H3-lysine 9 dimethylation and decreased H3 acetylation in the RUNX3 promoter following hypoxia. Hypoxia resulted in the upregulation of G9a histone methyltransferase (HMT) and HDAC1; additionally, overexpression of G9a and HDAC1 attenuated RUNX3 expression. The overexpression of G9a and HDAC1, but not their mutants, inhibited the nuclear localization and expression of RUNX3. Diminished mRNA expression and nuclear localization of RUNX3 during hypoxia was abolished by siRNA-mediated knockdown of G9a and HDAC1. This study suggests that hypoxia silences RUNX3 by epigenetic histone regulation during the progression of gastric cancer. | 18,850,007 |
Immunogenic disparities of 11 minor histocompatibility antigens (mHAs) in HLA-matched unrelated allogeneic hematopoietic SCT. | We determined the alleles of 11 mHAs and investigated the association of immunogenic mHA mismatches between a donor and a recipient with a course of allogeneic hematopoietic SCT (allo-HSCT) from 10/10 alleles HLA-matched unrelated donors in 92 recipients after myeloablative conditioning between 2004 and 2006. The frequency analysis of mHA alleles, genotypes and phenotypes accompanied by appropriate restriction HLA Ags allowed for an estimation of the probability of immunogenic mismatches, which was the highest for HA-1, HA-8 and HY. GVH-directed disparity of mHAs with broad tissue distribution, especially of the sex-related HY Ag, influenced the results of allo-HSCT from HLA-matched unrelated donors by not only increasing the probability of chronic GVHD (cGVHD) but also by decreasing the relapse rate. | 18,850,018 |
Daclizumab as useful treatment in refractory acute GVHD: a paediatric experience. | GVHD remains a serious complication after allogeneic SCT. We describe 13 paediatric patients treated with daclizumab for refractory acute GVHD (aGVHD). After 30 days of daclizumab administration, all patients with cutaneous aGVHD reached complete response. Among patients with gastrointestinal disease, 50 and 30% had complete and partial response, respectively, whereas 11 and 55% of patients with hepatic aGVHD achieved CR and PR, respectively. Overall, complete (46%) and partial (46%) responses were demonstrated in 92% of our patients, whereas the remaining patients (8%) were nonresponders. No life-threatening infectious episodes were recorded within 100 days from transplant in this selected group of paediatric patients. Overall 46% of patients were alive at a median of 461 days from SCT, but 50% of them developed chronic GVHD. In our experience, daclizumab proved to be a useful and safe treatment for refractory and steroid-resistant/dependent aGVHD, in particular for cutaneous and low-moderate intestinal involvement. | 18,850,021 |
Lethal limb ischaemia in leukaemia. Case report and review of the literature. | Several disturbances of the coagulation system are associated with malignancies of the hematopoietic system. The primary mechanisms of these are disseminated intravascular coagulation and hyperviscosity. As such, bleeding or thrombotic events are often encountered and, occasionally, they may even be the inaugural symptom of leukaemia. The lack of a diagnostic tool that would enable a rapid diagnosis of a hematopoietic malignancy, which may present initially as, for example, a coagulation disorder (arterial or venous thrombotic event and/or haemorrhage), can have dramatic consequences. The treatment of choice for this clinical condition is chemotherapy associated with leukopheresis with the aim of obtaining a rapid cytoreduction. We report here a case relevant to this situation and attempt to assess current knowledge on the ethiopathogenesis and treatment of coagulation abnormalities in leukaemia. Our report highlights the imperative need for immediate haematological diagnosis despite the non-specific presentation. | 18,850,069 |
Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are associated with increased superoxide. | The mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases the incidence of human cardiovascular disease are not known. We investigated the degree to which cardiovascular disease develops in mice following subchronic TCDD exposure. Adult male C57BL/6 mice were dosed with vehicle or 300 ng TCDD/kg by oral gavage three times per week for 60 days. Blood pressure was recorded by radiotelemetry and aortic endothelial function was assessed by acetylcholine-induced vasorelaxation. Mean arterial pressure of TCDD-exposed mice was increased significantly by day 4 and between days 7-10, 25-35, and 45-60 with two periods of normalization on days 11-24 and days 36-39. Consistent with a prolonged period of systemic hypertension, heart weight was increased and was associated with concentric left ventricular hypertrophy. Significant increases in superoxide production also were observed in the kidney, heart, and aorta of TCDD-exposed mice. Furthermore, increased aortic superoxide resulted in endothelial dysfunction as demonstrated by significant impairment of acetylcholine-induced vasorelaxation in TCDD-exposed mice, which was restored by tempol, a superoxide dismutase (SOD) mimetic. Our model is the first to definitely demonstrate that sustained AhR activation by TCDD increases blood pressure and induces cardiac hypertrophy, which may be mediated, in part, by increased superoxide. | 18,850,075 |
Sex identification in female crayfish is bimodal. | Sex identification has been studied in several species of crustacean decapods but only seldom was the role of multimodality investigated in a systematic fashion. Here, we analyse the effect of single/combined chemical and visual stimuli on the ability of the crayfish Procambarus clarkii to identify the sex of a conspecific during mating interactions. Our results show that crayfish respond to the offered stimuli depending on their sex. While males rely on olfaction alone for sex identification, females require the combination of olfaction and vision to do so. In the latter, chemical and visual stimuli act as non-redundant signal components that possibly enhance the female ability to discriminate potential mates in the crowded social context experienced during mating period. This is one of the few clear examples in invertebrates of non-redundancy in a bimodal communication system. | 18,850,080 |
A novel patatin-like protein from cotton plant, GhPat1, is co-expressed with GhLox1 during Xanthomonas campestris-mediated hypersensitive cell death. | In cotton plant, Xanthomonas-induced hypersensitive response (HR) is accompanied by a lipid peroxidation process involving a 9-lipoxygenase (LOX), GhLox1. Initiation of this oxidative metabolism implies the release of the LOX substrates, or polyunsaturated fatty acids. Since patatin-like proteins (PLPs) are likely candidates for mediating the latter step, we searched for genes encoding such enzymes, identified and cloned one of them that we named GhPat1. Biochemical and molecular studies showed that GhPat1 expression was up-regulated during the incompatible interaction, prior to the onset of the corresponding galactolipase activity and cell death symptoms in tissues. Protein sequence analysis and modelling also revealed that GhPat1 catalytic amino acids and fold were conserved across plant PLPs. Based on these results and our previous work (Jalloul et al. in Plant J 32:1-12, 2002), a role for GhPat1, in synergy with GhLox1, during HR-specific lipid peroxidation is discussed. | 18,850,102 |
Genetic variation in ABC G5/G8 and NPC1L1 impact cholesterol response to plant sterols in hypercholesterolemic men. | ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies. | 18,850,127 |
Adverse effects of vitamin E by induction of drug metabolism. | Observational studies with healthy persons demonstrated an inverse association of vitamin E with the risk of coronary heart disease or cancer, the outcome of large-scale clinical trials conducted to prove a benefit of vitamin E in the recurrence and/or progression of such disease, however, was disappointing. Vitamin E did not provide benefits to patients with cardiovascular diseases, cancer, diabetes or hypertension. Even harmful events and worsening of pre-existing diseases were reported, which are hard to explain. Since vitamin E is metabolized along the same routes as xenobiotics and induces drug-metabolizing enzymes in rodents, it is hypothesized that a supplementation with high dosages of vitamin E may also lead to an induction of the drug-metabolizing system in patients that depend on drug therapy. Compromising essential therapy might therefore outweigh any benefit of vitamin E in patients. It is recommended to work out at which threshold the drug-metabolizing system can be induced in humans before new trials with high dosages of vitamin E are started. | 18,850,180 |
Effect of genistein on cholesterol metabolism-related genes in a colon cancer cell line. | The major soy-derived isoflavones such as genistein has been demonstrated to possess anticarcinogenic activity in animal model systems. The present study was designed to investigate the effects of isoflavone genistein exposure at concentrations ranging from 0.01 to 50 muM on the LDL receptor and HMG-CoA reductase gene expression in the estrogen receptor positive DLD-1 human colon cancer cell line. LDL receptor and HMG-CoA reductase gene expressions were evaluated by reverse transcription followed by real-time PCR. Genistein induced an increase of LDL receptor gene expression and later decrease of HMG-CoA reductase mRNA expression in DLD-1 cells. These findings provide direct evidence on the role of genistein in regulating LDL receptor and HMG-CoA reductase gene expression in colon cancer. | 18,850,198 |
Nutrition, sirtuins and aging. | Beyond our inherited genetic make-up environmental factors are central for health and disease and finally determine our life span. Amongst the environmental factors nutrition plays a prominent role in affecting a variety of degenerative processes that are linked to aging. The exponential increase of non-insulin-dependent diabetes mellitus in industrialized nations as a consequence of a long-lasting caloric supernutrition is an expression of this environmental challenge that also affects aging processes. The most consistent effects along the environmental factors that slow down aging - from simple organisms to rodents and primates - have been observed for caloric restriction. In the yeast Saccharomyces cerevisiae, the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, sirtuins (silencing information regulators) have been identified to mediate as "molecular sensors" the effects of caloric restriction on aging processes. Sirtuins are NAD(+)-dependent deacetylases that are activated when e.g. cell energy status is low and the NAD(+) over NADH ratio is high. As a consequence transcription rates of a variety of genes including that of the apoptosis inducing p(53) gene are reduced. Moreover, in C. elegans, sirtuins were shown to interact with proteins of the insulin/IGF-1 signaling cascade of which several members are known to extend life span of the nematodes when mutated. Downstream targets of this pathway include genes that encode antioxidative enzymes such as Superoxide dismutase (SOD) whose transcription is activated when receptor activation by insulin/IGF is low or when sirtuins are active and the ability of cells to resist oxidative damage appears to determine their life span. Amongst dietary factors that activate sirtuins are certain polyphenols such as quercetin and resveratrol. Whereas their ability to affect life span has been demonstrated in simple organisms, their efficacy in mammals awaits proof of principle. | 18,850,202 |
Harnessing Nutrigenomics: Development of web-based communication, databases, resources, and tools. | Nutrient - gene interactions are responsible for maintaining health and preventing or delaying disease. Unbalanced diets for a given genotype lead to chronic diseases such as obesity, diabetes, cardiovascular, and are likely to contribute to increased severity and/or early-onset of many age-related diseases. Many nutrition and many genetic studies still fail to properly include both variables in the design, execution, and analyses of human, laboratory animal, or cell culture experiments. The complexity ofnutrient-gene interactions has led to the realization that strategic international alliances are needed to improve the completeness of nutrigenomic studies - a task beyond the capabilities of a single laboratory team. Eighty-eight researchers from 22 countries recently outlined the issues and challenges for harnessing the nutritional genomics for public and personal health. The next step in the process of forming productive international alliances is the development of a virtual center for organizing collaborations and communications that foster resources sharing, best practices improvements, and creation of databases. We describe here plans and initial efforts of creating the Nutrigenomics Information Portal, a web-based resource for the international nutrigenomics society. This portal aims at becoming the prime source ofinformation and interaction for nutrigenomics scientists through a collaborative effort. | 18,850,216 |
Genes involved in obesity: Adipocytes, brain and microflora. | The incidence of obesity and related metabolic disorders such as cardiovascular diseases and type 2 diabetes, are reaching worldwide epidemic proportions. It results from an imbalance between caloric intake and energy expenditure leading to excess energy storage, mostly due to genetic and environmental factors such as diet, food components and/or way of life. It is known since long that this balance is maintained to equilibrium by multiple mechanisms allowing the brain to sense the nutritional status of the body and adapt behavioral and metabolic responses to changes in fuel availability. In this review, we summarize selected aspects of the regulation of energy homeostasis, prevalently highlighting the complex relationships existing between the white adipose tissue, the central nervous system, the endogenous microbiota, and nutrition. We first describe how both the formation and functionality of adipose cells are strongly modulated by the diet before summarizing where and how the central nervous system integrates peripheral signals from the adipose tissue and/or the gastro-intestinal tract. Finally, after a short description of the intestinal commensal flora, rangingfrom its composition to its importance in immune surveillance, we enlarge the discussion on how nutrition modified this perfectly well-balanced ecosystem. | 18,850,214 |
The Znt4 mutation inlethal milk mice affects intestinal zinc homeostasis through the expression of other Zn transporters. | The lethal milk mouse syndrome is caused by a point mutation in the zinc transporter gene ZnT4 resulting in defective zinc secretion in the milk of homozygous mutant dams. Pups of any genotype fed solely on lm milk die within the first two weeks of neonatal life, displaying zinc deficiency symptoms. Homozygous mutant pups survive when foster nursed by wild type dams and show signs of mild zinc deficiency in adulthood. To further investigate the role of ZnT4 in zinc secretion in the intestinal epithelium, we have studied the expression by real time quantitative PCR of mutant ZnT4 and of other zinc transporters of the Zip and ZnT families, in the jejunum of homozygous lm mice and of the isogenic wild type strain C57BL/ 6J. We report in this paper that expression of the mutant ZnT4 mRNA, carrying a premature translational termination codon (ZnT4/lm), is almost absent in tissues from lm mice, probably as a result of degradation by the Nonsense Mediated mRNA Decay (NMD) Pathway. In the jejunum of mutant mice, we also observed decreased expression of the uptake zinc transporter Zip4, paralleled by increased levels of both metallothionein genes MTI and MTII. Zinc supplementation of lm mice in the drinking water did not result in further decrease of Zip4 expression, but led to full induction of MT mRNAs. These results lead us to conclude that, although in the enterocytes of lm mice the absence of the zinc secretion activity mediated by ZnT4 results in increased intracellular zinc concentration, other zinc efflux activities are able to maintain the level of zinc ions below the threshold necessary for full induction of metallothioneins. | 18,850,221 |
Caffeic acid phenethyl ester inhibits invasion and expression of matrix metalloproteinase in SK-Hep1 human hepatocellular carcinoma cells by targeting nuclear factor kappa B. | Numerous studies have shown that the levels of matrix metalloproteinase (MMP)-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. This study investigated the effects of caffeic acid phenethyl ester (CAPE), a chemopreventive phytochemical derived from honeybee propolis, on the invasive phenotype of SK-Hep1 human hepatocellular carcinoma cells (SK-Hep1 cells). CAPE effectively suppressed SK-Hep1 cell invasion in a dose-dependent manner. The constitutive expression of MMP-2 and MMP-9 in SK-Hep1 cells was almost completely abolished by treatment with 12.5 muM CAPE. CAPE also significantly inhibited nuclear factor kappa B (NF-kappaB) DNA-binding activity in SK-Hep1 cells. These results taken together suggest that CAPE exerts antimetastatic potential through inhibition of MMP-2 and MMP-9 expression, possibly by targeting NF-kappaB in hepatocellular carcinoma. | 18,850,224 |
Extracts of Rehmanniae radix, Ginseng radix and Scutellariae radix improve glucose-stimulated insulin secretion and beta-cell proliferation through IRS2 induction. | Recent studies have revealed that beta-cell dysfunction is an important factor in developing type 2 diabetes. beta-cell dysfunction is related to impairment of the insulin/IGF-1 signaling cascade through insulin receptor substrate-2 (IRS2). The induction of IRS2 in beta-cells plays an important role in potentiating beta-cell function and mass. In this study, we investigated whether herbs used for treating diabetes in Chinese medicine-Galla rhois, Rehmanniae radix, Machilus bark, Ginseng radix, Polygonatum radix, and Scutellariae radix-improved IRS2 induction in rat islets, glucose-stimulated insulin secretion and beta-cell survival. R. radix, Ginseng radix and S. radix significantly enhanced glucose-stimulated insulin secretion compared to the control, i.e., by 49, 67 and 58%, respectively. These herbs induced the expression of IRS2, pancreas duodenum homeobox-1 (PDX-1), and glucokinase. The increased level of glucokinase could explain the enhancement of glucose-stimulated insulin secretion with these extracts. Increased PDX-1 expression was associated with beta-cell proliferation, which was consistent with the cell viability assay. In conclusion, R. radix, Ginseng radix and S. radix had an insulinotropic action similar to that of exendin-4. | 18,850,229 |
Severe tricuspid valve stenosis secondary to pacemaker leads presenting as ascites and liver dysfunction: a complex problem requiring a multidisciplinary therapeutic approach. | Tricuspid stenosis secondary to ventricular pacemaker leads is uncommon. We present a unique case of iatrogenic tricuspid stenosis secondary to fusion of the valve leaflets to transvenous implanted pacing leads. This occurred in an adult with childhood repaired Tetralogy of Fallot and high grade surgical heart block following multiple pacemaker procedures. The case was complicated by superior vena cava (SVC) and innominate vein stenosis secondary to implanted pacing leads, severe tricuspid valve (TV) stenosis, perforation of the heart by one of the implanted transvenous ventricular pacing leads, prolapse of the transvenous atrial pacing lead into the right ventricle, and unusual coronary sinus anatomy. We describe a multidisciplinary approach to management. | 18,850,261 |
United States-Mexico border crossing: experiences and risk perceptions of undocumented male immigrants. | Undocumented immigrants crossing the US-Mexico border face many hazards as they attempt to enter the United States, including heat and cold injury, dehydration, and wild animal encounters. In the Tucson sector of the US-Mexico border, there are over 100 deaths a year from heat-related injuries alone. Public awareness campaigns have been undertaken to disseminate information on the dangers inherent in crossing. Little is known, however, about the ways in which undocumented immigrants actually receive information regarding the risks of crossing the border, how such information impacts their preparation for crossing or how the journey itself effects their motivation to cross again in the future. A qualitative descriptive method was used to describe and analyze information from adult males who had attempted to illegally cross the US-Mexico Border and had recently been returned to Mexico. Semi-structured interviews were conducted, and responses were classified into several broad themes. Interviews were conducted and analyzed iteratively until thematic saturation was achieved. The responses validated the established risks as being commonplace. A total of eight (8) male undocumented immigrants participated in the interviews. Individuals sought information prior to crossing from the media, their families and friends, and acquaintances in border towns. They did not appear to value any particular information source over any other. New areas of risk were identified, such as traveling with others who might have new or existing medical problems. There was also substantial concern for the family unit as both a source of inspiration and motivation. The family emerged as an additional at-risk unit due to the destabilization and financial strain of having one of its members leave to attempt to immigrate to the US for work. While many planned to cross again, the majority of the men in our sample had no intention of seeking permanent residence in the US, instead planning to work and then return to their families in Mexico. This preliminary study found that individuals crossing the US-Mexico border appear willing to put themselves and their families at substantial perceived risk in order to seek economic opportunity. Future public awareness campaigns may choose to shift focus solely from the individual risk of the crossing to the additional risks to family and community. | 18,850,270 |
Spatial succession modeling of biological communities: a multi-model approach. | Strong spatial correlation may exist in the spatial succession of biological communities, and the spatial succession can be mathematically described. It was confirmed by our study on spatial succession of both plant and arthropod communities along a linear transect of natural grassland. Both auto-correlation and cross-correlation analyses revealed that the succession of plant and arthropod communities exhibited a significant spatial correlation, and the spatial correlation for plant community succession was stronger than arthropod community succession. Theoretically it should be reasonable to infer a site's community composition from the last site in the linear transect. An artificial neural network for state space modeling (ANNSSM) was developed in present study. An algorithm (i.e., Importance Detection Method (IDM)) for determining the relative importance of input variables was proposed. The relative importance for plant families Gramineae, Compositae and Leguminosae, and arthropod orders Homoptera, Diptera and Orthoptera, were detected and analyzed using IDM. ANNSSM performed better than multivariate linear regression and ordinary differential equation, while ordinary differential equation exhibited the worst performance in the simulation and prediction of spatial succession of biological communities. A state transition probability model (STPM) was proposed to simulate the state transition process of biological communities. STPM performed better than multinomial logistic regression in the state transition modeling. We suggested a novel multi-model framework, i.e., the joint use of ANNSSM and STPM, to predict the spatial succession of biological communities. In this framework, ANNSSM and STPM can be separately used to simulate the continuous and discrete dynamics. | 18,850,283 |
Analysis of mosses and topsoils for detecting sources of heavy metal pollution: multivariate and enrichment factor analysis. | In order to assess the contribution of emission sources to the pollution of areas remote from industrial facilities, a combined approach of enrichment factor analysis and multivariate statistics was used for detecting the origin of heavy metal pollution in the Zlatibor ecosystem, in Serbia. Samples of moss (Pleurozium schreberi, Hylocomium splendens, Scleropodium purum, Hypnum cupressiforme and Thuidum delicatulum) and of topsoil (0-5 cm) were collected in 2005. The concentrations of seven heavy metals (Cd, Cr, Cu, Mn, Ni, Pb and Zn) were determined in moss and soil samples by atomic absorption spectrometry. The results obtained by enrichment factor analysis and two multivariate statistical methods, principal component analysis and cluster analysis, enabled discrimination of the lithologic and anthropogenic sources of heavy metals in the mosses. Enrichment factors, calculated to evaluate the contribution to the metal content in moss from anthropogenic sources, revealed pollution of the investigated area by Cd and Pb, originating from long-range transport and fossil fuel burning. | 18,850,291 |
Determination of toxic inorganic elements pollution in ground waters of Kahuta Industrial Triangle Islamabad, Pakistan using inductively coupled plasma mass spectrometry. | The present study deals with the ground water quality assessment in Kahuta Industrial Triangle Islamabad, Pakistan. The objective of the study was to assess ground water quality against the drinking water standards for various toxic inorganic elements. Representative groundwater samples were collected and analyzed in the Water Quality Laboratory of Pakistan Council of Research in Water Resources (PCRWR) at Islamabad, Pakistan. The samples were run on ICP-MS (Inductively coupled plasma mass spectrometry), which has the capability to separate and quantify 70 elements at a time. One of the finding of study is that ICP-MS is a very good tool to analyze broad range of toxic inorganic elements to the level of parts per billion (ppb). World Health Organization drinking water standards shows that these toxic inorganic elements such as heavy metals even at this concentration level (ppb) are injurious to human health. This analysis indicated pollution of various toxic elements including Selenium. Vertical leachate through industrial waste septic tanks is identified as major cause of groundwater pollution in the Industrial Triangle. Monitoring of the septic tanks and groundwater quality in study area is suggested along with remedial measures. | 18,850,292 |
Effect of hypotensive challenge on systemic hemodynamics and cerebral blood flow in persons with tetraplegia. | Individuals with tetraplegia have impaired central control of sympathetic vascular modulation and blood pressure (BP); how this impairment affects cerebral blood flow (CBF) is unclear. To determine if persons with tetraplegia maintain CBF similarly to able-bodied controls after a hypotensive challenge. Seven individuals with chronic tetraplegia and seven age-matched, non-SCI control subjects underwent a hypotensive challenge consisting of angiotensin-converting enzyme (ACE) inhibition (1.25 mg enalaprilat) and 45 degrees head-up tilt (HUT). Heart rate (HR), low frequency systolic BP variability (LFsbp), brachial mean arterial pressure (MAP) and middle cerebral artery CBF were measured before and after the challenge. Group differences for the baseline (BL) to post-challenge response were determined by repeated measures ANOVA. HR did not differ between the groups in response to the hypotensive challenge. LFsbp response was significantly reduced in the tetra compared to the control group (-38 +/- 51 vs. 72 +/- 93%, respectively). MAP did not differ between the groups at BL but was significantly lower in the tetra compared to the control group post-challenge (55 +/- 13 vs. 71 +/- 9 mmHg, respectively); the percent change in MAP was significantly greater in the tetra than in the control group (-29 +/- 14.1 vs. -13 +/- 9%, respectively). However, CBF did not differ between the groups at baseline or post-challenge; the percent change in CBF post-challenge was not different between the tetra and control groups (-29 +/- 13.2 vs. -23 +/- 10.3%, respectively). Despite impaired sympathetic vasomotor and BP control, CBF in persons with tetraplegia was comparable to that of control subjects during a hypotensive challenge. | 18,850,311 |
3-pentanol: a new attractant present in volatile emissions from the ambrosia beetle, Megaplatypus mutatus. | Megaplatypus mutatus (=Platypus mutatus) (Coleoptera: Platypodidae) is an ambrosia beetle that is native to South America. It attacks only standing live trees and causes severe stem breakage and death in commercial poplar (Populus) plantations. Previous work showed that male M. mutatus emits a sex pheromone composed mainly of (+)-sulcatol and sulcatone. We collected male volatile emissions during the hours of maximum emergence by using a specific polar microextraction phase; analyzed the extract by GC-MS; and tested the biological activity of selected compounds in the extract with a walking behavioral assay. Female M. mutatus emerged primarily between 7 and 11 h. In the chemical analyses of volatiles, a third compound, 3-pentanol, was identified in a small percentage of samples. Walking behavioral bioassays with video image analysis showed that at the doses tested, 3-pentanol elicited an attractive response from females. | 18,850,328 |
Working memory performance following paediatric traumatic brain injury. | The present study investigated working memory ability in children who sustained moderate-to-severe traumatic brain injuries in relation to pre-injury, injury-related and developmental factors. It was hypothesized that there would be a correlation between performance- and rater-based working memory measures; factors predictive of working memory impairment would include earlier age at injury, more severe injury, longer time since injury and poorer overall cognitive functioning; and working memory performance would be significantly impaired when compared to normative populations. Working memory was assessed in 62 children using a traditional performance measure (digit span backward) and parent report (Behaviour Rating Inventory of Executive Function (BRIEF)). Contrary to prediction, there was no statistical association between performance- and rater-based measures of working memory. Regression analyses revealed injury severity, time-since-injury, overall cognitive ability and attention span were predictive of working memory performance. As a group, working memory was impaired relative to normative samples on both measures. Performance- and rater-based working memory measures, while not significantly correlated, are both sensitive to acquired cognitive dysfunction following paediatric traumatic brain injury. Demographic and clinical factors may be used to predict cognitive outcomes, educate caregivers and design clinical interventions. | 18,850,343 |
Effect of modified constraint-induced movement therapy on lower extremity hemiplegia due to a higher-motor area lesion. | Modified CIT (mCIT) was performed in a stroke patient with a lesion in the left medial frontal region including the supplementary motor area (SMA), which is part of the higher-motor area, and whose primary symptom was motor ignition difficulty observed at the start of voluntary movement of the right leg. mCIT was performed from awakening to bedtime (not including bath time) with his non-affected limb fixed with a knee splint while he was in the hospital ward. Two days (the total time he wore the appliance was 19.5 hours) after the intervention was introduced, voluntary movement of the right leg occurred, and functional improvement was observed. These findings are speculated to be related to the facts that the unilateral SMA strongly contributes to movement of the ipsilateral limb and that the plasticity of the SMA, which is a higher-motor area, is greater than that of primary areas. It is probable that different regions of the brain have different plasticity, resulting in differences in the process of functional recovery and the level of recovery. | 18,850,348 |
Aquasomes--a nanoparticulate approach for the delivery of antigen. | The development of compound that enhances immune responses to recombinant or synthetic epitopes is of considerable importance in vaccine research. Of the many different types of immunopotentiating compounds that have been researched, aquasomes are of considerable promise, because of their potency and adjuvanticity. Aquasomes were prepared by self-assembling of hydroxyapatite by co-precipitation method and thereafter preliminary coated with polyhydroxyl oligomers (cellobiose and trehalose) and subsequently adsorbed with bovine serum albumin (BSA) as a model antigen. The prepared systems were characterized for size, shape, antigen-loading efficiency, in vitro antigen stability, and in vivo performance. BSA-immobilized aquasomes were around 200 nm in diameter and spherical in shape and had approximately 20-30% BSA-loading efficiency. The immunological activity of the formulated aquasomes was compared with plain BSA and better results were observed. Studies also indicated that aquasome formulations could elicit combined T-helper 1 (Th1) and Th2 immune response. | 18,850,363 |
Lung tissue storage: optimizing conditions for future use in molecular research. | The quality of tissue studied impacts greatly on oligonucleotide microarray results, emphasizing the importance of harvesting techniques. The analyzed RNA extracted from human lung samples preserved via 4 different storage conditions (RNAlater, phosphate-buffered saline, TRIzol, liquid nitrogen). RNA was assessed by denaturing gel electrophoresis, Agilent bioanalysis, real-time polymerase chain reaction (PCR), and Test3 Affymetrix chip hybridization. Results revealed better quality RNA from RNAlater samples on gel electrophoresis and bioanalysis. RNAlater samples also showed greater yield (r18s via PCR P < .05) and resulted in better Test3 chips hybridization (p < .05), suggesting RNAlater was superior at preserving lung tissue nucleic acid. | 18,850,373 |
The role of religiosity, religious norms, subjective norms, and bodily integrity in signing an organ donor card. | This article examines the influence of religiosity, religious norms, subjective norms, and bodily integrity (the extent to which people think the body should remain unaltered after death) on intent to donate organs postmortem. A total of 4,426 participants from 6 universities completed surveys for this study. The results indicate that religiosity and religious norms had a nonsignificant effect on willingness to donate. In addition, attitudes toward donation had a weak positive relationship on intent to donate, whereas subjective norms exerted a modest positive relationship on intent to donate. Finally, the results reveal a strong direct and indirect effect of bodily integrity on intent to donate. | 18,850,391 |
Effects of risk-focused and recommendation-focused mental imagery on occupational risk communication. | This study examined the impact of mental imagery instructions in a National Institute for Occupational Safety and Health (NIOSH) safety document conveying risk and safety information to farmers. A sample of 314 farmers recruited from a large Southeastern state fair was randomly assigned to conditions in a 2 x 2 design. Participants received a NIOSH safety document about skid steer loader safety in which 2 types of mental imagery instructions were manipulated: (a) risk-focused (imagery vs. control) and (b) recommendation-focused (imagery vs. control). Results indicate that risk-focused imagery influenced perceptions of susceptibility to workplace accidents, whereas recommendation-focused imagery influenced attitudes toward engaging in safety behaviors, intentions to share safety information with others, and perceptions of the safety message. Further analyses indicated that ease of imagery partially mediated the relationship between the imagery manipulations and these outcomes. Other potential mechanisms for these effects are discussed. | 18,850,394 |
Formal semantics of guarded task structures for clinical practice guidelines. | In many of the clinical practice guidelines, the process of delivering health care is only implicitly or vaguely defined. An explicit model of the medical tasks involved in this process is needed before active clinical decision support for the patient encounter can be provided. We propose task diagrams as a structured, but semi-formal intermediate step in the process of enacting a clinical practice guideline. This allows for the application-independent representation of the content of a guideline enabled for clinical decision support. Developed as a semi-formal modelling language, task diagrams require a precise semantics. We define a formal counterpart of task diagrams named guarded task structures and provide a formal semantics for what it means to act according to such a structure. | 18,850,401 |
Bariatric surgery in paediatrics--when and how? | Morbid obesity and its rapidly increasing prevalence has became a serious health, social and economic problem not only in Europe, but in other developed countries in the Western world. It is well recognized that conservative treatment usually fails in morbidly obese patients in the long-term. In severely obese patients, the only long-term effective treatment of their obesity and obesity related co-morbidities, such as type 2 diabetes mellitus, is bariatric surgery. However, there is neither consensus on how to treat morbidly obese adolescents (including bariatric surgery), nor existing specific child/adolescent guidelines on this topic. This article presents an overview of existing views on bariatric surgery in adolescents as well as some treatment results achieved with bariatric surgery. | 18,850,407 |
Sticks and stones may break my bones: work-related orthopaedic injuries sustained during obstetrics and gynaecology training. | Backache is a common cause of morbidity among doctors and 50% of the obstetricians and gynaecologists suffering from this attribute it to work practice and posture. Occupational injuries remain poorly studied among obstetricians and gynaecologists and we have therefore tried to assess the extent and demographics of work-related injuries sustained during training by sending an eight-item questionnaire to 418 Registrar grade trainees in the London area. A low 23.2% response rate (97/418) was obtained, despite second questionnaires being sent to initial non-responders. Out of the 97 responders, 28 (28.7%) had suffered injuries at work at least once throughout their career. There was female preponderance in those reporting injuries, with a female to male ratio of 3:1. Of the 28 positive responders, 11 were UK graduates, 7 EU and the remaining 10 from Colombia, West Indies, India and Sudan. The mean age was 32.5 +/- 4.2 years, with 21 of the 28 (75%) being senior trainees (post-MRCOG). The injuries reported were: forearm (4); wrist (7); thumb (3); hands (1) shoulder and neck (9), ankle (1) and lower back (6). Of these, 18 sought medical help and received treatment for these injuries, which included long-term physiotherapy, although no-one required surgery. Eight were forced to take time off work, with a cumulative total of 80 days; one had to prolong her training by 3 months. Seven trainees sustained their injuries (e.g. ligamentous strain of wrist and scaphoid fracture) while performing caesarean sections, while forceps deliveries were the cause of six occupational injuries (e.g. ligamentous strain of sacroiliac joint). Work-related injuries can have adverse effects on training and workforce. Awareness of correct surgical techniques and adoption of ergonomic posture when performing procedures may help to minimise the risk of a work-related injury. | 18,850,418 |
Exposure to ultrafine particles in asphalt work. | An epidemiologic study has demonstrated that asphalt workers show increased loss of lung function and an increase of biomarkers of inflammation over the asphalt paving season. The aim of this study was to investigate which possible agent(s) causes the inflammatory reaction, with emphasis on ultrafine particles. The workers' exposure to total dust, polycyclic aromatic hydrocarbons, and NO(2) was determined by personal sampling. Exposure to ultrafine particles was measured by means of particle counters and scanning mobility particle sizer mounted on a van following the paving machine. The fractions of organic and elemental carbon were determined. Asphalt paving workers were exposed to ultrafine particles with medium concentration of about 3.4 x 10(4)/cm(3). Ultrafine particles at the paving site originated mainly from asphalt paving activities and traffic exhaust; most seemed to originate from asphalt fumes. Oil mist exceeded occupational limits on some occasions. Diesel particulate matter was measured as elemental carbon, which was low, around 3 microg/m(3). NO(2) and total dust did not exceed limits. Asphalt pavers were exposed to relatively high concentrations of ultrafine particles throughout their working day, with possible adverse health effects. | 18,850,455 |
Spatial variability of ambient nitrogen dioxide and sulfur dioxide in Sarnia, "Chemical Valley," Ontario, Canada. | This study aimed at developing models to predict nitrogen dioxide (NO(2)) and sulfur dioxide (SO(2)) concentrations in Sarnia, "Chemical Valley", Ontario, Canada, and model the intra-urban variation of ambient NO(2) and SO(2) in the city for a community health study. NO(2) and SO(2) samples were monitored with Ogawa passive samplers at 39 locations across the city for 2 wk during the fall of 2005. The final land use regression models were constructed to generate independent variables that might best predict NO(2) and SO(2) concentrations. The coefficients of determinations for the final NO(2) and SO(2) models were .79 and .66, respectively. The explanatory variables in the final NO(2) model were: proximity to the industrial core, industrial areas within 1600 m, highways within 400 m, and dwelling counts within 2400 m. The variables in the final SO(2) model were: proximity to the industrial core, industrial areas within 1200 m, and major roads within 100 m. The spatial variations captured in these analyses are being used to estimate ambient pollution concentrations for a large health study. | 18,850,457 |
Transgenic mice expressing cyan fluorescent protein as a reporter strain to detect the effects of rotenone toxicity on retinal ganglion cells. | This is the first study using a reporter transgenic model to investigate the effects of an environmental toxin on the retina. Rotenone is a widely used pesticide that inhibits mitochondrial complex I and produces neurotoxicity. Previous studies demonstrated the time course and dose response of rotenone toxicity on retinal ganglion cells (RGC). However, previous analyses of rotenone-induced retinotoxicity provided little detail of the optic nerve axons and cellular pathology. These limitations were successfully surmounted by using a transgenic mouse line shown to express cyan fluorescent protein (CFP) in neurons, including RGC, under regulatory elements of the human the thy1.1 promoter (thy-CFP). Data showed that CFP expression is limited to RGC and their processes in the retina of thy-CFP mice. Eyes exposed to the pesticide rotenone displayed marked alterations in RGC morphology, inner plexiform layer, optic disc, and optic nerves. After 24 h, the number of CFP-labeled RGC was reduced 50%. Correlated with a loss of RGC bodies was an approximate 50% reduction in CFP fluorescence intensity at the optic disc. The findings showed that rotenone-induced degeneration of RGC and their processes can be visualized with exquisite detail in thy-CFP mice, and that this approach may provide a novel and effective way to monitor the association between environmental toxins and neurodegeneration in living animals. | 18,850,458 |
Exposure assessment and risk of gastrointestinal illness among surfers. | Surfing is a unique recreational activity with the possibility of elevated risk for contracting gastrointestinal (GI) illness through ingestion of contaminated water. No prior studies have assessed exposure from ingestion among surfing populations. This study estimated the magnitude and frequency of incidental water ingestion using a Web-based survey and integrated exposure distributions with enterococci distributions to predict the probability of GI illness at six Oregon beaches. The mean exposure magnitude and frequency were 170 ml of water ingested per day and 77 days spent surfing per year, respectively. The mean number of enterococci ingested ranged from approximately 11 to 86 colony-forming units (CFU) per day. Exposure-response analyses were conducted using an ingested dose model and two epidemiological models. Risk was characterized using joint probability curves (JPC). At the most contaminated beach, the annualized ingested dose model estimated a mean 9% probability of a 50% probability of GI illness, similar to the results of the first epidemiological model (mean 6% probability of a 50% probability of GI illness). The second epidemiological model predicted a 23% probability of exceeding an exposure equivalent to the U.S. Environmental Protection Agency (EPA) maximum acceptable GI illness rate (19 cases/1000 swimmers). While the annual risk of GI illness for Oregon surfers is not high, data showed that surfers ingest more water compared to swimmers and divers and need to be considered in regulatory and public health efforts, especially in more contaminated waters. Our approach to characterize risk among surfers is novel and informative to officials responsible for advisory programs. It also highlights the need for further research on microbial dose-response relationships to meet the needs of quantitative microbial risk assessments (QMRA). | 18,850,460 |
Pareidolias in obsessive-compulsive disorder: neglected symptoms that may respond to serotonin reuptake inhibitors. | Obsessive-compulsive disorder (OCD) is a multifaceted and treatable condition. We describe a patient with OCD whose main complaint was the experience of pareidolias (i.e., 'images seen out of shapes'), a symptom that responded to treatment with a serotonin reuptake inhibitor. Single case report. Mrs A, a 38-year-old married white woman with a history of OCD, reported visualizing faces of witches and gorillas out of floor tiles. She would see these figures without making any effort, and despite the intense discomfort associated with it, was unable to dismiss the images. Her symptoms responded to a therapeutic trial with clomipramine. Patients presenting typical pareidolias need to be probed for underlying OCD. This approach may have material impact on treatment decisions, with good response of the aforementioned condition to serotonin reuptake inhibitors. | 18,850,462 |
Evaluation of glucose homeostasis in transfusion-dependent thalassemic patients. | Diabetes is an important problem encountered in thalassemic patients. The severity and type of glucose disturbances vary greatly in different studies. Also the pathogenesis seems to be complex; either insulin deficiency or insulin resistance may mediate the glucose disturbances. In a group of thalassemic patients glucose homeostasis was evaluated. Diabetes prevalence was 1.8%. Forty patients were investigated both with an oral glucose tolerance test and first-phase insulin response. Three patients had impaired fasting glucose, 1 patient had impaired glucose tolerance, and 2 patients had hyperinsulinism. Nineteen of 40 patients who were tested had low first-phase insulin response (47.5%) with below 10th centile. Age, BMI, height SDS, age at diagnosis, age at first blood transfusion, number of blood transfusions in a year, percentage of elevated liver enzyme, and hemoglobin and ferritin levels were not different between patients with low first-phase insulin response to patients with normal first-phase insulin response. Four patients are HCV infected, and only 1 of them had low first-phase insulin response. The study group showed a high rate of impairement in insulin secretion by first-phase insulin response to glucose overload, despite the low rate of insulin resistance. Defect of insulin secretion in thalassemic patients may develop earlier than insulin resistance, and then be accompanied by insulin resistance. Increasing insulin resistance with age and the occurrence of additional factors could lead to detoriation of glucose metabolism. | 18,850,475 |
Vaginal clear cell adenocarcinoma with early pulmonary metastasis in a child. | Although a few cases of vaginal clear cell adenocarcinoma (CCAC) have been reported in the ages under 14, they have presented in a much more aggressive form than the CCAC cases in higher ages and parenchymal pulmonary metastasis are known to occur following the primary tumor. This is a case report of a primary vaginal CCAC in an 8.6-year-old girl with no history of DES exposure who presented with vaginal bleeding and abdominal pain and the imaging signs of pulmonary metastasis at the presentation. Diagnostic imaging modalities should be considered for any child complaining of vaginal bleeding, due to limitation of vaginal examination. Chest X-ray is recommended at the time of diagnosis of CCAC and at follow-up sessions for early diagnosis of pulmonary metastasis. | 18,850,481 |
Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. | Physical and psychological stressors not only enhance activity of the hypothalamo-pituitary-adrenocortical axis, but also cause oxidative damage by inducing an imbalance between the in vivo pro-oxidant and antioxidant status. The involvement of adrenal steroid stress hormones in oxidative damage associated with these stressors has not been extensively investigated. Therefore, this study was designed to probe any direct role of glucocorticoids on induction of oxidative processes by comparing the effects of low, intermediate and high doses of exogenously administered corticosterone, without other applied stressors, on a wide range of key components of the antioxidant defence system. The data presented here indicate a substantial decline in antioxidant defences by actions of corticosterone, evidenced by coordinate decreases in the activities in the brain, liver and heart of free-radical scavenging enzymes superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and glutathione reductase (GR), as well as the non-enzymatic antioxidants glutathione (GSH) and serum urate. Also, lipid peroxidation and protein carbonyl contents, oxidative stress markers, were found to be significantly increased in brain, liver and heart. The compromised in vivo antioxidant status was strikingly analogous to the deleterious effects of restraint stress, indicating a direct effect of stress hormones on induction of oxidative damage during physical or psychological stress. A dose-dependent decrease of SOD and CAT, and increase in protein oxidation was observed between the high (40 mg/kg) and low (10 mg/kg) doses of corticosterone. The findings have fundamental implications for oxidative stress as a major pathological mechanism in the maladaptation to chronic stress. Thus, the study suggests that stress hormones have a causal role in impacting oxidative processes induced during the adaptive response. This may hold important implications for pharmacological interventions targeting cellular antioxidants as a promising strategy for protecting against oxidative insults in various psychiatric and non-psychiatric conditions induced by physical or psychological stress. | 18,850,490 |
Urinary cortisol responses to unusual events in captive chimpanzees (Pan troglodytes). | This study investigated the urinary cortisol stress response to one known stressor (anaesthesia) and three unusual events hypothesized to result in increases in cortisol (confinement to one half of an enclosure for several days due to a hurricane, an enrichment exercise, and a change in group composition) in young chimpanzees (Pan troglodytes). Although a cortisol stress response to a variety of laboratory experiences has been documented in captive animals, it is unclear whether other types of atypical events are stressful, including those that are not necessarily negative. Cortisol was measured in 519 urine samples collected from 20 awake, unrestrained chimpanzees; individuals were compared against their own baseline values. A significant increase in urinary cortisol concentration was found as a result of the stress of anaesthesia, but no significant change in urinary cortisol resulted from the three other potential stressors. A lack of a urinary cortisol response to these events may indicate that the events were not actually stressful for the chimpanzees, but may have resulted from the limited temporal resolution of measuring cortisol excretion as an indicator of integrated secretion, or from changes in rates of agonistic behaviors. | 18,850,493 |
[A challenge in spite of acceptance - how mothers of newborn babies with a "cleft" experience the transition from the hospital back home]. | There is almost no empirical data about how mothers of newborn babies with a cleft lip and/or palate manage the transition from the hospital to home. This qualitative study therefore focuses on the experiences of mothers of newborn babies with a cleft lip and palate. Two problem-oriented interviews were conducted with five women. Using a qualitative content analysis, one main category and four sub-categories were defined. The main category called "receive the right kind of help" shows that the women depended on different types of support, concerning various topics from the diagnosis to everyday family life. This is reflected in the sub-categories: a) it is the way it is, b) sudden disappearance of the child, c) time-consuming and difficult nutrition and d) master everyday family-life. These sub-categories display the experiences of mothers of newborn babies with a cleft lip and palate during the transition from hospital to home and point to the big challenge of these mothers in transition. Most important is that health professionals seek to better understand mothers' experiences in this important phase in order to optimize both the support in hospital and outpatient facilities. | 18,850,534 |
[Nurses' perspective on interprofessional communication on an intensive care unit]. | The aim of this qualitative study was to explore experience in nurses' interdisciplinary/interprofessional communication on an intensive care unit. The structure of communication and influencing factors were shown and interpreted from the perspective of the nurses. Nurses working on an internal medical intensive care unit at a teaching facility in central Germany were questioned by means of semi-structured interviews. One main result was that for nurses the culture of communication in the investigation unit was characterized primarily by hierarchical structures imposed by the physicians. This dominance was identified in all nursing activities resulting in a considerable adverse effect on the flow of information concerning the patient between nurses and physicians. Especially within the context of daily rounds nurses were confronted with barriers to participate actively with their knowledge and professional competence in the process of decision-making. The problems described are well known in everyday nursing practice and have been dealt with in the English research literature. However, this study's aim is to present and summarize the gained insights and to transfer them in a practice-oriented way into a selected field of work. Possible solutions for the problems of inter-professional communication are suggested in subsequent work steps in order to optimize patient care. | 18,850,538 |
Oxidative stress intensity in lens and aqueous depending on age-related cataract type and brunescense. | Cataract formation represents a serious problem in the elderly, and has a large impact on healthcare budget. The oxidative stress form and intensity might determine the cataract type and pigmentation, making efforts in the cataract prevention challenge more complex. This is a retrospective cross-sectional review of 80 samples of aqueous humor and lens corticonuclear blocks. Aqueous samples were analyzed by the method of antioxidant activity estimation (%iMDA), while lipid peroxides (LP) and total sulfhydryl groups (TSH) were determined in lenses. Mixed and brunescent cataracts have statistically significant lower values of antioxidative %iMDA and TSH (p<0.001 for both parameters) and higher values of lipid peroxidation (p<0.001). No correlation between LP and TSH with maturity of cortical cataract was found, but there was a significant correlation with the %iMDA (p<0.05). The role of the oxidative stress in cataractogenesis could not be the same for all cataract types. High level of lipid peroxides in pigmented cataracts may point to the different nature of pigment source than proteins solely, whereas lipid peroxidation and SH groups consumption in cortical cataractogenesis might be of less importance. | 18,850,540 |
Amniotic membrane transplantation: indications and results. | To describe amniotic membrane transplantation indications and results at the authors' institution. In this study, chart review of 108 patients who underwent amniotic membrane transplantation between January 2002 and April 2006 was performed. The survival rate of corneal integrity was compared, using Kaplan-Meier survival analysis, as a measure of success rate. The mean age of the patients was 55.2+/-20.1 (6-87 years, 75 female, 51 male). The patients underwent amniotic membrane transplantation for six different diagnoses: nontraumatic corneal perforation (32 eyes, Group 1), persistent epithelial defect (29 eyes, Group 2), aphakic/pseudophakic bullous keratopathy (18 eyes, Group 3), infectious ulcer resistant to treatment (14 eyes, Group 4), necrotizing keratitis secondary to endophthalmitis (10 eyes, Group 5), and caustic injury (5 eyes, Group 6). The mean survival of corneal integrity was similar in all groups (p=0.156). Amniotic membrane transplantation is a successful adjunctive method in achieving corneal epithelization in the study indications. | 18,850,543 |
Post-trabeculectomy choroidal detachment: not an adverse prognostic sign for either visual acuity or surgical success. | To report the incidence of choroidal detachment (CD) following trabeculectomy and to evaluate its effect on long-term surgical success and best-corrected visual acuity (BCVA). A total of 253 eyes of 198 subjects who underwent trabeculectomy between 1993 and 2003 with at least 1 year follow-up were reviewed retrospectively. Twenty-eight eyes of 28 subjects which developed CD postoperatively were classified as Group 1 and the remaining 225 eyes of 170 subjects as Group 2. The risk factors for the development of CD and the influence of CD on BCVA and on the success of trabeculectomy were analyzed and compared between the two groups. In Group 1, preoperative BCVA was significantly lower and cup to disc ratio and the frequency of pseudoexfoliative glaucoma were higher with respect to the control group (p=0.009, p=0.01, p=0.02). The correlations between the development of CD and postoperative findings such as shallowing of the anterior chamber, hypotony, hypotonic maculopathy, hyphema, and fibrin reaction in the anterior chamber were statistically significant.CD was not associated with a significant reduction of BCVA. Intraocular pressures at postoperative first day, sixth month, and first year were lower in Group 1. The success of trabeculectomy and the average number of medications used were not significantly different between the two groups. CD following trabeculectomy occurred in 11% of our patients. CD was not associated with either a significant drop in BCVA or an adverse influence on long-term IOP control. | 18,850,557 |
Intravenous diclofenac as prophylactic treatment for verteporfin-associated low back pain. | The authors report on the therapeutic effect of intravenous diclofenac on verteporfin associated low back pain (LBP), which is the most frequent adverse effect of photodynamic therapy (PDT) for macular degeneration. The authors studied 818 patients who received PDT with verteporfin for choroidal neovascularization. Systemic blood pressures were recorded in all study participants half an hour before PDT treatment. All patients who experienced LBP during verteporfin infusion were asked to grade their pain as mild (1), moderate (2), severe (3), or unbearable (4). Thirty-three patients had LBP during their first verteporfin infusion. Of these, 11 subjects (1.34% of all) reported increased pain scores (level 2 to 4) and received intravenous diclofenac ahead of their next PDT. Patients with LBP during verteporfin infusion had significantly higher systolic blood pressures than uncomplicated cases (180 mmHg vs 155 mmHg, p=0.01). Treatment with intravenous diclofenac short before PDT significantly reduced the patients' mean pain score by 1.8 levels (p=0.0001). In this study, intravenous application of diclofenac short before verteporfin infusion effectively prevented verteporfin associated LBP in patients with systemic hypertension. | 18,850,562 |
Effective treatment with topical cyclosporine of a child with steroid-dependent interstitial keratitis. | To report a case of steroid-dependent idiopathic interstitial keratitis in a child successfullytreated with topical cyclosporine 2% drops. Case report. The authors describe a case of a 6-year-old boy with a history of recurrent idiopathic bilateral interstitial keratitis. The patient had recurrent episodes of corneal inflammation that became more frequent and severe during the follow-up, and caused severe corneal opacities and visual loss. Long-term treatment with topical corticosteroid was required to avoid corneal scarring that eventually caused secondary elevation of intraocular pressure. Topical cyclosporine 2% was therefore introduced as a steroid sparing agent totreat the keratitis. The treatment was continued for 1 year and the patient achieved a complete remission of corneal inflammation with resolution of corneal scarring and normalization of intraocular pressure. In this child with recurrent episodes of interstitial keratitis, topical cyclosporine 2% has been shown to be a safe and effective alternative for treating corneal inflammation. | 18,850,565 |
Japanese medaka Hox paralog group 2: insights into the evolution of Hox PG2 gene composition and expression in the Osteichthyes. | Hox paralog group 2 (PG2) genes function to specify the development of the hindbrain and pharyngeal arch-derived structures in the Osteichthyes. In this article, we describe the cDNA cloning and embryonic expression analysis of Japanese medaka (Oryzias latipes) Hox PG2 genes. We show that there are only two functional canonical Hox genes, hoxa2a and b2a, and that a previously identified hoxa2b gene is a transcribed pseudogene, psihoxa2b. The functional genes, hoxa2a and b2a, were expressed in developing rhombomeres and pharyngeal arches in a manner that was relatively well conserved compared with zebrafish (Danio rerio) but differed significantly from orthologous striped bass (Morone saxatilis) and Nile tilapia (Oreochromis niloticus) genes, which, we suggest, may be owing to effects of post-genome duplication loss of a Hox PG2 gene in the medaka and zebrafish lineages. psihoxa2b was expressed at readily detectable levels in several noncanonical Hox expression domains, including the ventral aspect of the neural tube, the pectoral fin buds and caudal-most region of the embryonic trunk, indicative that regulatory control elements needed for spatio-temporal expression have diverged from their ancestral counterparts. Comparative expression analyses showed medaka hoxa2a and b2a expression in the 2nd pharyngeal arch (PA2) beyond the onset of chondrogenesis, which, according to previous hypotheses, suggests these genes function redundantly as selector genes of PA2 identity. We conclude that Hox PG2 gene composition and expression have diverged significantly during osteichthyan evolution and that this divergence in teleosts may be related to lineage-dependent differential gene loss following an actinopterygian-specific whole genome duplication. | 18,850,588 |
Fetal death persists through recurrent pregnancies in mice following Ljungan virus infection. | Laboratory mice infected with Ljungan virus (LV) early in pregnancy suffer from perinatal death. Here we investigate the persistence of that effect through the outcome of consecutive pregnancies in LV-infected mice. CD-1 mice were infected while pregnant and their adult female offspring were followed in parallel with uninfected control mice during repeated pregnancies. Three mating attempts resulted in two or three pregnancies per dam. The outcome of the last pregnancy was carefully monitored. Both the dams infected as adults and their adult female offspring suffered perinatal deaths during the last pregnancy which occurred approximately 6 months after the original LV exposure and acute infection. The non-infected control animals experienced no perinatal death. Perinatal death persists across recurrent pregnancies in this mouse model of LV infection, both in animals infected as adults and in females exposed to the virus in utero. This implies that LV persists in mice long after initial infection, and is maintained in a quiescent state but can remain pathogenic in later pregnancies. | 18,850,589 |
3- Instead of 4-helix formation in a de novo designed protein in solution revealed by small-angle X-ray scattering. | De novo design and chemical synthesis of proteins and their mimics are central approaches for understanding protein folding and accessing proteins with novel functions. We have previously described carbohydrates as templates for the assembly of artificial proteins, so-called carboproteins. Here, we describe the preparation and structural studies of three alpha-helical bundle carboproteins, which were assembled from three different carbohydrate templates and one amphiphilic hexadecapeptide sequence. This heptad repeat peptide sequence has been reported to lead to 4-alpha-helix formation. The low resolution solution structures of the three carboproteins were analyzed by means of small-angle X-ray scattering (SAXS) and synchrotron radiation circular dichroism (SRCD). The ab initio SAXS data analysis revealed that all three carboproteins adopted an unexpected 3+1-helix folding topology in solution, while the free peptide formed a 3-helix bundle. This finding is consistent with the calculated alpha-helicities based on the SRCD data, which are 72 and 68 % for two of the carboproteins. The choice of template did not affect the overall folding topology (that is for the 3+1 helix bundle) the template did have a noticeable impact on the solution structure. This was particularly evident when comparing 4-helix carboprotein monomers with the 2x2-helix carboprotein dimer as the latter adopted a more compact conformation. Furthermore, the clear conformational differences observed between the two 4-helix (3+1) carboproteins based on D-altropyranoside and D-galactopyranoside support the notion that folding is affected by the template, and subtle variations in template distance-geometry design may be exploited to control the solution fold. In addition, the SRCD data show that template assembly significantly increases thermostability. | 18,850,602 |
Cobalt- and nickel-catalyzed regio- and stereoselective reductive coupling of alkynes, allenes, and alkenes with alkenes. | Transition-metal-catalyzed coupling of two different C-C pi components through a metallacycle intermediate is a highly atom economical method to construct C-C bonds in organic synthesis. The metal-catalyzed coupling of an alkene and alkyne generally gives an Alder-ene or reductive coupling product. In this article, we focus on the cobalt- and nickel-catalyzed reductive coupling of alkynes, allenes, and alkenes with alkenes. These reductive coupling reactions provide convenient methods for the synthesis of various alkenes, dienes, functionalized alkanes, lactones, lactams, and cyclic alcohols in a highly regio- and stereoselective manner. A chemselective formation of metallacyclopentene intermediate from the two different C-C pi components and a low-valence metal species plays a key role for the high regio- and stereoselectivity of the catalytic reaction. | 18,850,608 |
Acceleration effect of an allylic hydroxy group on ring-closing enyne metathesis of terminal alkynes: scope, application, and mechanistic insights. | An interesting acceleration effect of an allylic hydroxy group on ring-closing enyne metathesis has been found. Ring-closing enyne metathesis of terminal alkynes possessing an allylic hydroxy group proceeded smoothly without the ethylene atmosphere generally necessary to promote the reaction. The synthesis of (+)-isofagomine with the aid of this efficient reaction has been demonstrated. Mechanistic studies of the acceleration effect were also carried out. Results of NMR studies suggested that the reaction proceeded via an "ene-then-yne" pathway. Kinetic studies indicated switching of the rate-determining step as a consequence of the presence of an allylic hydroxy group. These results suggest acceleration of the reentry step of Ru-carbene species by the allylic hydroxy group. | 18,850,614 |
Interaction proteomics of the HMGA chromatin architectural factors. | The high mobility group A (HMGA) chromatin architectural transcription factors are a group of proteins involved in development and neoplastic transformation. They take part in an articulated interaction network, both with DNA and other nuclear proteins, organizing multimolecular complexes at chromatin level. Here, we report the development of a novel in vitro strategy for the identification of HMGA molecular partners based on the combination of an RP-HPLC prefractionation procedure, 2-DE gels, blot-overlay and MS. To demonstrate that our approach could be a reliable screening method we confirmed a representative number of interactions in vitro by GST pull-down and far-Western and in vivo by co-affinity purification. This approach allowed us to enlarge the HMGA molecular network confirming their involvement also in non-transcriptional-related processes such as RNA processing and DNA repair. | 18,850,631 |
Evaluation of carrier ampholyte-based capillary electrophoresis for separation of peptides and peptide mimetics. | Carrier ampholyte-based capillary electrophoresis (CABCE) has recently been introduced as an alternative to CE (CZE) in the classical buffers. In this study, isoelectric BGEs were obtained by fractionation of Servalyt pH 4-9 carrier ampholytes to cuts of typical width of 0.2 pH unit. CABCE feasibility was examined on a series of insect oostatic peptides, i.e. proline-rich di- to decapeptides, and phosphinic pseudopeptides--tetrapeptide mimetics synthesized as a mixture of four diastereomers having the -P(O)(OH)-CH(2)- moiety embedded into the peptide backbone. With identical selectivity, the separation efficiency of CABCE proved to be as good as classical CE for the insect oostatic peptides and better for diastereomers of the phosphinic pseudopeptides. In addition, despite the numerous species present in the narrow pH cuts of carrier ampholytes, CABCE seems to be free of system zones that could hamper the analysis. Peak symmetry was good for moderately to low mobile peptides, whereas some peak distortion due to electromigration dispersion, was observed for short peptides of rather high mobility. | 18,850,645 |
Stacking enhanced determination of steroids by CE. | This study outlines a simple method for pH-mediated stacking of natural and synthetic steroids facilitated with carboxymethyl-beta-CD. Sample stacking (10 kV, 60 s) is accomplished with 23 mM carboxymethyl-beta-CD in 50 mM 3-[cyclohexylamino]-1-propanesulfonic acid buffered at pH 10. Following stacking, steroidal compounds are separated in less than 5 min with a running buffer of 13 mM hydroxypropyl-beta-CD, 30 mM SDS in 200 mM phosphate buffered at pH 2.5. Using a 60 s electrokinetic injection, the limits of detection of estradiol, ethynyl estradiol, estrone, hydroxyprogesterone, progesterone, and 11-ketotestosterone range from 2 to 14 nM. For all steroids, the within-day and day-to-day reproducibility in migration time is < or =1 and < or =2% RSD, respectively. The within-day and day-to-day reproducibility in peak area is < or =9 and < or =22% RSD, respectively. The method is applied to fish plasma and holds potential to profile multiple steroids in a single biological sample. | 18,850,649 |
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