Evaluating the Effect of Labeled Benchmarks on Children's Number Line Estimation Performance and Strategy Use.
Some authors argue that age-related improvements in number line estimation (NLE) performance result from changes in strategy use. More specifically, children's strategy use develops from only using the origin of the number line, to using the origin and the endpoint, to eventually also relying on the midpoint of the number line. Recently, Peeters et al. (unpublished) investigated whether the provision of additional unlabeled benchmarks at 25, 50, and 75% of the number line, positively affects third and fifth graders' NLE performance and benchmark-based strategy use. It was found that only the older children benefitted from the presence of these benchmarks at the quartiles of the number line (i.e., 25 and 75%), as they made more use of these benchmarks, leading to more accurate estimates. A possible explanation for this lack of improvement in third graders might be their inability to correctly link the presented benchmarks with their corresponding numerical values. In the present study, we investigated whether labeling these benchmarks with their corresponding numerical values, would have a positive effect on younger children's NLE performance and quartile-based strategy use as well. Third and sixth graders were assigned to one of three conditions: (a) a control condition with an empty number line bounded by 0 at the origin and 1,000 at the endpoint, (b) an unlabeled condition with three additional external benchmarks without numerical labels at 25, 50, and 75% of the number line, and (c) a labeled condition in which these benchmarks were labeled with 250, 500, and 750, respectively. Results indicated that labeling the benchmarks has a positive effect on third graders' NLE performance and quartile-based strategy use, whereas sixth graders already benefited from the mere provision of unlabeled benchmarks. These findings imply that children's benchmark-based strategy use can be stimulated by adding additional externally provided benchmarks on the number line, but that, depending on children's age and familiarity with the number range, these additional external benchmarks might need to be labeled.


RNA sequencing uncovers the key microRNAs potentially contributing to sudden sensorineural hearing loss.
This study aimed to identify miRNAs that may contribute to the pathogenesis of sudden sensorineural hearing loss (SSNHL) by RNA-seq (RNA-sequencing).RNA was extracted from SSNHL patients and healthy volunteers, respectively. Sequencing was performed on HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differential expression analysis of miRNAs between the SSNHL samples and the normal samples was performed using DEseq to identify differentially expressed microRNAs (DEMs). The target genes of the DEMs were predicted using the online tool miRWalk, which were then mapped to DAVID (https://david.ncifcrf.gov/) for functional annotation based on GO database and for pathway enrichment analysis based on KEGG. Finally, a miRNA-target-protein-protein interaction (PPIs) network was constructed using the DEMs and their target genes with interaction.Differential expression analysis reveals 24 DEMs between the SSNHL group and control group. A total of 1083 target genes were predicted. GO functional annotation analysis reveals that the target genes in the top 10 terms are mainly related to the development of salivary glands, neurotransmission, dendritic development, and other processes. KEGG pathway enrichment analysis reveals that the target genes were functionally enriched in pathways arachidonic acid metabolism, complement and coagulation cascades, linoleic acid metabolism, and MAPK signaling pathway. In the miRNA-target-PPI network, hsa-miR-34a/548n/15a/143/23a/210/1255a/18b/ /1180/99b had the most target genes; genes YWHAG, GSK3B, CDC42, NR3C1, LCK, UNC119, SIN3A, and NFKB2, interact with most other genes among all the predicted target genes.Hsa-miR-34a/15a/23a/210/18b/548n/143 is likely to have a role in the pathogenesis of SSNHL.


Psychiatric symptoms in systemic lupus erythematosus: a systematic review.
Systemic lupus erythematosus (SLE) presents with psychiatric symptoms in most patients that often remain undiagnosed and untreated. This study evaluates the prevalence of psychiatric symptoms in SLE on the basis of clinical trials that fulfilled diagnostic criteria specified by the American College of Rheumatology (ACR). Current hypotheses explaining the pathogenesis of psychiatric symptoms of lupus are reviewed to gain new insights into the neuroimmune pathogenesis of other psychiatric disorders. A MEDLINE search of the literature (English language only) from April 1999 to August 2011 was performed using the search terms lupus and psychiatric to identify studies of neuropsychiatric SLE. Of 163 publications, 18 clinical studies were selected that focused on psychiatric symptoms, had a sample size of at least 20, and included patients of any age or gender as long as they fulfilled ACR criteria for neuropsychiatric SLE. The following data were extracted: author name, year of publication, psychiatric diagnostic method, total number of patients with SLE, and percentage of patients with individual psychiatric diagnoses. The point prevalence of psychiatric symptoms was calculated for neuropsychiatric SLE diagnoses in every study included. Psychiatric symptoms are present in the majority of patients with SLE. Depression (in up to 39% of patients) and cognitive dysfunction (up to 80%) are the most common psychiatric manifestations. Genetic and environmental factors (eg, ultraviolet light, retroviruses, and medications) may play a role in the pathogenesis. In addition, the patient's reaction to the illness may result in anxiety (up to 24%) and depression. Currently known biomarkers are nonspecific for neuropsychiatric SLE and indicate inflammation, microglial activation, ischemia, oxidative stress, mitochondrial dysfunction, and blood-brain barrier dysfunction. Identification of lupus-specific biomarkers of psychiatric symptoms is a high priority. Our current diagnostic assessment methods need improvement. Development of evidence-based guidelines is needed to improve diagnosis, prevention, and treatment of disabling psychiatric complications in lupus.


Transcatheter embolization of extensive left gastric artery collaterals presenting with massive upper gastrointestinal bleed.
We report a case of extensive left gastric artery collaterals that were formed in the region of gastric fundus due to splenic artery occlusion and resulted in massive hematemesis. These collaterals were thought to be portosystemic collaterals related to portal hypertension during upper endoscopy study and single-phase venous computed tomography studies. The collaterals were treated by transcatheter endovascular coil embolization. Our case highlights the importance of recognizing and differentiating left gastric artery collaterals from gastric venous varices as a cause of hematemesis since the treatment approach for each condition is totally different. It also introduces the feasibility of percutaneous left gastric artery embolization as a treatment for this condition, without the need for surgical splenectomy and partial gastrectomy which have a higher mortality and morbidity.


Diagnostic Accuracy of the AzBio Speech Recognition in Noise Test.
Purpose The goal of this study was to determine the ability of the AzBio speech recognition in noise (SRN) test to distinguish between groups of participants with and without a self-reported SRN disorder and a self-reported signal-to-noise ratio (SNR) loss. Method Fifty-four native English-speaking young adults with normal pure-tone thresholds (≤ 25 dB HL, 0.25-6.0 kHz) participated. Individuals who reported hearing difficulty in a noisy restaurant (Reference Standard 1) were placed in the SRN disorder group. SNR loss groups were created based on the self-report of the ability to hear Hearing in Noise Test (HINT) sentences in steady-state speech-shaped noise, four-talker babble, and 20-talker babble in a controlled listening environment (Reference Standard 2). Participants with HINT thresholds poorer than or equal to the median were assigned to the SNR loss group. Results The area under the curve from the receiver operating characteristics curves revealed that the AzBio test was not a significant predictor of an SRN disorder, or an SNR loss using the steady-state noise Reference Standard 2 condition. However, the AzBio was a significant predictor of an SNR loss using the four-talker babble and 20-talker babble Reference Standard 2 conditions (p < .05). The AzBio was a significant predictor of an SNR loss when using the average HINT thresholds across the three Reference Standard 2 masker conditions (area under the curve = .79, p = .001). Conclusions The AzBio test was not a significant predictor of a self-reported SRN disorder or a self-reported SNR loss in steady-state noise. However, it was a significant predictor of a self-reported SNR loss in babble noise and the average across all noise conditions. A battery of reference standard tests with a range of maskers in a controlled listening environment is recommended for diagnostic accuracy evaluations of SRN tests.


Changes in the molecular structure of hair in insulin-dependent diabetes.
Low-angle synchrotron X-ray diffraction has revealed clear and consistent changes in the molecular structure of alpha-keratin of hair in insulin-dependent diabetes (IDDM) both for human IDDM subjects and for baboons with streptozocin induced diabetes. These changes in both meridional and equatorial intensity distributions are fully explained by a newly developed hexagonally packed model for keratin which locates the modification produced in hair in IDDM in the labile structure of the matrix at established intermediate filament linkage sites. The nature of the extracellular bonding suggests that the change is endogenous, occurring via the blood during the aggregation of the IFs in the follicle. The reproducibility of these changes indicate that hair may represent an easily accessible tissue for the study of how hyperglycaemia can modify extracellular matrix materials which lead to diabetic complications.


Radiographic measurement of the sagittal plane deformity in patients with osteoporotic spinal fractures evaluation of intrinsic error.
Cobb method has been shown to be the most reliable technique with a reasonable measurement error to determine the kyphosis in fresh fractures of young patients. However, measurement errors may be higher for elderly patients as it may be difficult to determine the landmarks due to osteopenia and the degenerative changes. The aim of this study is to investigate the intrinsic error for different techniques used in evaluation of local sagittal plane deformity caused by OVCF. Lateral X-rays of OVCF patients were randomly selected. Patient group was composed of 28 females and 7 males and the mean age was 62.7 (55-75) years. The kyphosis angle and the vertebral body height were analyzed to reveal the severity of sagittal plane deformity. Kyphotic deformity was measured by using four different techniques; and the vertebral body heights (VBH) were measured at three different points. The mean intra-observer agreement interval for kyphosis angle measurement techniques ranged from +/-7.1 to +/-9.3 degrees while it ranged from +/-4.5 to +/-6.5 mm for VBH measurement techniques. The mean interobserver agreement interval for kyphosis angle ranged from +/-8.2 to +/-11.1 degrees , while it was between +/-4.5 to +/-6.5 mm for vertebral body height measurement techniques. This study revealed that although the intra and interobserver agreement were similar for all techniques, they are still higher than expected. These high intervals for measurement errors should be taken into account when interpreting the results of correction in local sagittal plane deformities of OVCF patients after surgical procedures such as vertebral augmentation techniques.


MINERVA-a platform for visualization and curation of molecular interaction networks.
Our growing knowledge about various molecular mechanisms is becoming increasingly more structured and accessible. Different repositories of molecular interactions and available literature enable construction of focused and high-quality molecular interaction networks. Novel tools for curation and exploration of such networks are needed, in order to foster the development of a systems biology environment. In particular, solutions for visualization, annotation and data cross-linking will facilitate usage of network-encoded knowledge in biomedical research. To this end we developed the MINERVA (Molecular Interaction NEtwoRks VisuAlization) platform, a standalone webservice supporting curation, annotation and visualization of molecular interaction networks in Systems Biology Graphical Notation (SBGN)-compliant format. MINERVA provides automated content annotation and verification for improved quality control. The end users can explore and interact with hosted networks, and provide direct feedback to content curators. MINERVA enables mapping drug targets or overlaying experimental data on the visualized networks. Extensive export functions enable downloading areas of the visualized networks as SBGN-compliant models for efficient reuse of hosted networks. The software is available under Affero GPL 3.0 as a Virtual Machine snapshot, Debian package and Docker instance at http://r3lab.uni.lu/web/minerva-website/. We believe that MINERVA is an important contribution to systems biology community, as its architecture enables set-up of locally or globally accessible SBGN-oriented repositories of molecular interaction networks. Its functionalities allow overlay of multiple information layers, facilitating exploration of content and interpretation of data. Moreover, annotation and verification workflows of MINERVA improve the efficiency of curation of networks, allowing life-science researchers to better engage in development and use of biomedical knowledge repositories.


Risk Factors for Ulcer Recurrence in Diabetic Patients Managed by an Integrated Foot Care Protocol.
The aim of our study was to identify risk factors for the recurrence of diabetic foot ulcers (DFUs) in a selected population of patients in secondary prevention treated, according to International Guidelines, with an integrated foot care protocol by a referral diabetic foot clinic. A retrospective study was performed with the inclusion of selected outpatients with diabetes at higher risk for ulceration with a history of previous ulcer and/or amputation followed in our diabetic foot clinic between January 2015 and December 2021. According to the presence or absence of recurrence, patients were divided into 2 groups: ulcer recurrence and without ulcer recurrence. One hundred twenty-seven (127) patients were included, 47 patients (37%) developed an ulcer recurrence while 80 patients (63%) did not. The mean age was 71.7 years; 65% were male; 97% were affected by type 2 diabetes with a mean duration of 21.1 years, the mean HbA1c was 63 + 21 mmol/mol. Both groups of patients had foot deformities, such as claw and hammertoes; hallux valgus, and prominent metatarsal heads (MTHs). The presence of deformity was significantly associated with ulceration. The group with ulcer recurrence showed a higher rate of prominence MTHs in comparison to a group without ulcer recurrence. The MTHs resulted as the only independent predictor for recurrence. This study shows that the presence of the prominent MTH is a significant risk factor for ulcer recurrence in a selected population of diabetic foot patients treated in the best way with integrated foot care.


Emerging role of carbon monoxide in physiologic and pathophysiologic states.
The discovery of nitric oxide in the 1980s unraveled the novel concept then that an endogenous production of a gaseous substance such as nitric oxide can impart critical physiologic functions in a variety of biological and pathological processes. Interestingly though, we have known for a longer period of time that there exists another gaseous molecule, carbon monoxide (CO), that can be generated endogenously. The heme oxygenase enzyme system generates the majority, if not, all of the endogenous CO. Accumulating data in recent years have lent an intriguing supposition that we need to regard CO beyond the old paradigm that it imparts only toxicity and lethality to organisms. Instead, we need to consider CO, at low physiologic concentration, to play critical physiologic roles in various pathophysiologic states. This forum will review this double-edge sword of CO.


Production and characterization of 60Fe standards for accelerator mass spectrometry.
Accelerator Mass Spectrometry (AMS) is one of the most sensitive analysis techniques to measure long-lived radionuclides, reaching detection limits for isotopic ratios down to 10-15-10-16 in special cases. Its application portfolio covers nearly every field of environmental research, considering processes in the atmosphere, biosphere, hydrosphere, cryosphere, lithosphere and the cosmosphere. Normally, AMS measures the content of isotopes in comparison to a validated standard. However, in some cases like for example 60Fe, well characterized standard materials are difficult to produce due to the extreme rareness of the isotope. We report here on the manufacturing of a set of 60Fe standards, obtained by processing irradiated copper from a beam dump of the high-power proton accelerator (HIPA) at the Paul Scherrer Institute (PSI). The isotopic ratios of the standards have been adjusted via a dilution series of a master solution, isotopic content of which has been characterized by Multi Collector-Inductively Coupled Plasma-Mass Spectrometry (MC-ICP-MS). In total, we produced three samples with isotopic ratios of 1.037(6)·10-8, 1.125(7)·10-10 and 1.234 (7)·10-12, respectively. The latter had already been applied in three pioneering AMS studies investigating the remaining signal of injected matter of nearby super novae explosions in sediment archives.


[Analysis of UPB1 gene mutation in a family affected with beta-ureidopropinoase deficiency].
OBJECTIVE To detect potential mutation in a Chinese family affected with beta-ureidopropinoase deficiency. METHODS Genomic DNA was extracted from peripheral blood samples. All exons and flanking intron regions of the UPB1 gene were amplified by PCR and detected by direct sequencing. RESULTS A homozygous mutation c.977G>A was identified in exon 9 of the UPB1 gene in the proband. Both parents of the proband had heterozygous change of the same site. CONCLUSION The c.977G>A mutation of the UPB1 gene is responsible for the pathogenesis of the disease in the infant.


Optimization of a homogeneous assay for kinase inhibitors in plant extracts.
To identify natural and original kinase inhibitors from plant extracts, we have developed and compared a heterogeneous enzyme-linked immunosorbent assay (ELISA) and a homogeneous time-resolved fluorescence (HTRF, Cisbio International, Bagnols/Cèze, France) assay. Kinase affinity for the ATP substrate was determined in both assays, and the same [ATP]/ATP Km ratio was used in each case to enable the identification of ATP competitive and noncompetitive inhibitors. Assays were then used to screen the same collection of chemical compounds and plant extracts. The intra-assay correlation analysis of each technology showed a very good screening precision in HTRF and an acceptable one in ELISA. When the two methods were compared, a poor correlation was obtained with a higher hit rate in the ELISA. We then performed a detailed study of the ELISA hits and showed that they also presented a strong antioxidant activity, associated with high adsorption into microplate wells, which interfered with the horseradish peroxidase-based detection system. These hits were then flagged as false-positives. We also showed that many plant extracts presented this kind of activity and that this interference could explain the lack of correlation between the assays. These findings suggest that assay design should be carefully adapted to the substances to be screened and that interferences should be extensively considered before any assay development process and comparison studies. In spite of a few interferences, our results showed that a homogeneous-phase assay like the HTRF assay could be more efficiently used for plant extract screening than a heterogeneous-phase assay like ELISA.


SSR180575 (7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide), a peripheral benzodiazepine receptor ligand, promotes neuronal survival and repair.
In the present study, we have investigated the potential neuroprotective effects of a novel peripheral benzodiazepine binding site (PBR) ligand, 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (SSR180575), in models of central and peripheral neurodegeneration in vivo and its effect on steroid concentrations in plasma and nervous tissue. SSR180575 shows high affinity (IC(50), 2.5-3.5 nM) and selectivity for the rat and human PBR and potently inhibits the in vivo binding of [(3)H]alpidem to PBR in the rat brain and spleen after oral or i.p. administration (ID(50), 0.1-0.3 mg/kg). In an experimental model of motoneuron degeneration induced by facial nerve axotomy in the immature rat, SSR180575 given i.p. or orally for 8 days rescued facial motoneurons, increasing their survival by 40 to 72% at 6 and 10 mg/kg p.o. b.i.d. Moreover, in this model, SSR180575 (10 mg/kg p.o. b.i.d.) increased by 87% the number of motoneurons immunoreactive to peripherin, a type III intermediate filament, whose expression is up-regulated during nerve regeneration. SSR180575 also improved functional recovery in acrylamide-induced neuropathy in the rat when given therapeutically at 2.5 to 10 mg/kg/day p.o. Furthermore, SSR180575 (3 mg/kg i.p. b.i.d.) accelerated functional recovery of the blink reflex after local injury of the facial nerve in the rat. SSR180575 increased pregnenolone accumulation in the brain and sciatic nerve (+100% at 3 mg/kg i.p.), suggesting that its neuroprotective effects are steroid-mediated. These results indicate that PBR ligands (e.g., SSR180575) promote neuronal survival and repair in axotomy and neuropathy models and have potential for the treatment of neurodegenerative diseases (e.g., peripheral neuropathies or amyotrophic lateral sclerosis).


Degradation in the degree of polarization in human retinal nerve fiber layer.
Using a fiber-based swept-source (SS) polarization-sensitive optical coherence tomography (PS-OCT) system, we investigate the degree of polarization (DOP) of light backscattered from the retinal nerve fiber layer (RNFL) in normal human subjects. Algorithms for processing data were developed to analyze the deviation in phase retardation and intensity of backscattered light in directions parallel and perpendicular to the nerve fiber axis (fast and slow axes of RNFL). Considering superior, inferior, and nasal quadrants, we observe the strongest degradation in the DOP with increasing RNFL depth in the temporal quadrant. Retinal ganglion cell axons in normal human subjects are known to have the smallest diameter in the temporal quadrant, and the greater degradation observed in the DOP suggests that higher polarimetric noise may be associated with neural structure in the temporal RNFL. The association between depth degradation in the DOP and RNFL structural properties may broaden the utility of PS-OCT as a functional imaging technique.


Pain and internal hypertension in bone lesions.
Internal pressures of bone tumors and tumorous conditions were measured in 20 patients. High pressures were frequently found in patients with painful bone lesions while low pressures were common in patients with no pain. Internal hypertension may be a causative factor of aching bone pain at rest.


The distribution and potential prognostic value of SMAD protein expression in chronic lymphocytic leukemia.
The SMAD proteins are responsible for transducing signals from activated transforming growth factor-beta. This is the first study assessing the expression of SMAD-1/8, SMAD-2/3, SMAD-4, and SMAD-7 in chronic lymphocytic leukemia cells with regard to their clinical significance and potential prognostic value. Overexpression of SMAD-1/8 was observed in 160 chronic lymphocytic leukemia patients compared to 42 healthy volunteers (p = 0.023) and was associated with a more progressive course of the disease (p = 0.016). Moreover, the high expression of SMAD-1/8 correlated with other, well-established prognostic factors, including clinical stage (p = 0.010) and lymphocyte doubling time (p = 0.021). The expression of SMAD-4 was lower in chronic lymphocytic leukemia patients compared with the control group (p = 0.003). Importantly, lower SMAD-4 levels correlated with longer progression-free survival (p = 0.009), progressive course of the disease (p = 0.002), advanced clinical stage (p = 0.0004), elevated beta-2-microglobulin and lactate dehydrogenase levels (p < 0.05), shorter lymphocyte doubling time (p = 0.009), and CD38 antigen expression (p = 0.039). In addition, lower SMAD-4 expression correlated with lower apoptotic index (p = 0.0007) and lower expression of receptors for vascular endothelial growth factors VEGFR-1 and VEGFR-2. A significant association was found between the low expression of inhibitory protein SMAD-7 and both zeta-chain-associated protein kinase 70-negative cells (p = 0.04) and lower apoptotic index (p = 0.004). No differences were observed in SMAD-2/3 expression. In conclusion, our results demonstrate a significant correlation between greater SMAD-1/8 and lower SMAD-4 expression in chronic lymphocytic leukemia cells, as well as more progressive outcome and poor prognosis. These data provide supporting evidence that the expression of SMAD proteins plays an important role in disease development and may be considered as a novel, biologic prognostic factor in this disease.


Biotechnological applications of phage and cell display.
In recent years, the use of surface-display vectors for displaying polypeptides on the surface of bacteriophage and bacteria, combined with in vitro selection technologies, has transformed the way in which we generate and manipulate ligands, such as enzymes, antibodies and peptides. Phage display is based on expressing recombinant proteins or peptides fused to a phage coat protein. Bacterial display is based on expressing recombinant proteins fused to sorting signals that direct their incorporation on the cell surface. In both systems, the genetic information encoding for the displayed molecule is physically linked to its product via the displaying particle. Using these two complementary technologies, we are now able to design repertoires of ligands from scratch and use the power of affinity selection to select those ligands having the desired (biological) properties from a large excess of irrelevant ones. With phage display, tailor-made proteins (fused peptides, antibodies, enzymes, DNA-binding proteins) may be synthesized and selected to acquire the desired catalytic properties or affinity of binding and specificity for in vitro and in vivo diagnosis, for immunotherapy of human disease or for biocatalysis. Bacterial surface display has found a range of applications in the expression of various antigenic determinants, heterologous enzymes, single-chain antibodies, and combinatorial peptide libraries. This review explains the basis of phage and bacterial surface display and discusses the contributions made by these two leading technologies to biotechnological applications. This review focuses mainly on three areas where phage and cell display have had the greatest impact, namely, antibody engineering, enzyme technology and vaccine development.


Quality of Life in Individuals with Erythematotelangiectatic and Papulopustular Rosacea: Findings From a Web-based Survey.
OBJECTIVE: The objective of the study was to evaluate the impact of rosacea on self-perception, emotional, social, and overall well-being and quality of life in individuals with erythematotelangiectatic rosacea (ETR) and papulopustular rosacea (PPR). DESIGN: We distributed a cross-sectional email invitation for participants in the United States to fill out a web-based survey. PARTICIPANTS: We included adults who reported having previously received a diagnosis of erythematotelangiectatic rosacea or papulopustular rosacea. MEASUREMENTS: Questionnaires measured the psychosocial aspects of rosacea, including the Satisfaction With Appearance Scale and modified Satisfaction With Appearance Scale questionnaires, Impact Assessment for Rosacea Facial Redness, Rosacea-Specific Quality-of-Life questionnaire, and RAND 36-Item Short Form Health Survey. The Impact Assessment for Rosacea Facial Bumps or Pimples was administered to the papulopustular rosacea cohort. RESULTS: Six hundred participants enrolled and completed the survey, with most rating their rosacea as mild or moderate (ETR: 95.6%; PPR: 93.7%). In the erythematotelangiectatic rosacea and papulopustular rosacea cohorts, respectively, 45 and 53 percent disagreed/strongly disagreed that they were satisfied with their appearance due to rosacea; 42 and 27 percent agreed/strongly agreed that they "worry how people will react when they see my rosacea"; and 43 and 59 percent agreed/strongly agreed that they feel their rosacea is unattractive to others. Rosacea-Specific Quality-of-Life total and domain scores indicated negative impact of rosacea for both cohorts. Both cohorts reported worse 36-item Short Form Health Survey overall and domain scores than population norms in the United States. CONCLUSION: Rosacea had wide-ranging, negative effects on self-perceptions and emotional, social, and overall well-being as well as rosacea-specific quality of life. Overall, both erythematotelangiectatic rosacea and papulopustular rosacea cohorts reported a substantial negative impact of rosacea on quality of life on a range of instruments.


First experiences with model based iterative reconstructions influence on quantitative plaque volume and intensity measurements in coronary computed tomography angiography.
Investigate the influence of adaptive statistical iterative reconstruction (ASIR) and the model-based IR (Veo) reconstruction algorithm in coronary computed tomography angiography (CCTA) images on quantitative measurements in coronary arteries for plaque volumes and intensities. Three patients had three independent dose reduced CCTA performed and reconstructed with 30% ASIR (CTDIvol at 6.7 mGy), 60% ASIR (CTDIvol 4.3 mGy) and Veo (CTDIvol at 1.9 mGy). Coronary plaque analysis was performed for each measured CCTA volumes, plaque burden and intensities. Plaque volume and plaque burden show a decreasing tendency from ASIR to Veo as median volume for ASIR is 314 mm3 and 337 mm3-252 mm3 for Veo and plaque burden is 42% and 44% for ASIR to 39% for Veo. The lumen and vessel volume decrease slightly from 30% ASIR to 60% ASIR with 498 mm3-391 mm3 for lumen volume and vessel volume from 939 mm3 to 830 mm3. The intensities did not change overall between the different reconstructions for either lumen or plaque. We found a tendency of decreasing plaque volumes and plaque burden but no change in intensities with the use of low dose Veo CCTA (1.9 mGy) compared to dose reduced ASIR CCTA (6.7 mGy & 4.3 mGy), although more studies are warranted.


Staphylococcal protein Ecb impairs complement receptor-1 mediated recognition of opsonized bacteria.
Staphyloccus aureus is a major human pathogen leading frequently to sepsis and soft tissue infections with abscesses. Multiple virulence factors including several immune modulating molecules contribute to its survival in the host. When S. aureus invades the human body, one of the first line defenses is the complement system, which opsonizes the bacteria with C3b and attract neutrophils by release of chemotactic peptides. Neutrophils express Complement receptor-1 [CR1, CD35) that interacts with the C3b-opsonized particles and thereby plays an important role in pathogen recognition by phagocytic cells. In this study we observed that a fraction of S. aureus culture supernatant prevented binding of C3b to neutrophils. This fraction consisted of S. aureus leukocidins and Efb. The C-terminus of Efb is known to bind C3b and shares significant sequence homology to the extracellular complement binding protein [Ecb). Here we show that S. aureus Ecb displays various mechanisms to block bacterial recognition by neutrophils. The presence of Ecb blocked direct interaction between soluble CR1 and C3b and reduced the cofactor activity of CR1 in proteolytic inactivation of C3b. Furthermore, Ecb could dose-dependently prevent recognition of C3b by cell-bound CR1 that lead to impaired phagocytosis of NHS-opsonized S. aureus. Phagocytosis was furthermore reduced in the presence of soluble CR1 [sCR1). These data indicate that the staphylococcal protein Ecb prevents recognition of C3b opsonized bacteria by neutrophil CR1 leading to impaired killing by phagocytosis and thereby contribute to immune evasion of S. aureus.


Molecular mechanism of the blockade of plasma cholesteryl ester transfer protein by its physiological inhibitor apolipoprotein CI.
Genetically engineered mice demonstrated that apolipoprotein (apo) CI is a potent, physiological inhibitor of plasma cholesteryl ester transfer protein (CETP) activity. The goal of this study was to determine the molecular mechanism of the apoCI-mediated blockade of CETP activity. Kinetic analyses revealed that the inhibitory property of apoCI is independent of the amount of active CETP, but it is tightly dependent on the amount of high density lipoproteins (HDL) in the incubation mixtures. The electrostatic charge of HDL, i.e. the main carrier of apoCI in human plasma, is gradually modified with increasing amounts of apoCI, and the neutralization of apoCI lysine residues by acetylation produces a marked reduction in its inhibitory potential. The inhibitory property of full-length apoCI is shared by its C-terminal alpha-helix with significant electrostratic properties, whereas its N-terminal alpha-helix with no CETP inhibitory property has no effect on HDL electronegativity. Finally, binding experiments demonstrated that apoCI and to a lower extent its C-terminal alpha-helix are able to disrupt CETP-lipoprotein complexes in a concentration-dependent manner. It was concluded that the inhibition of CETP activity by apoCI is in direct link with its specific electrostatic properties, and the apoCI-mediated reduction in the binding properties of lipoproteins results in weaker CETP-HDL interactions and fewer cholesteryl ester transfers.


Regional Influences on Nutritional Iodine Status of Pregnant Women in Pakistan.
Pregnant women are particularly vulnerable to iodine deficiency. Considering the rural-urban disparities in nutritional status in Pakistan, this study aimed to assess regional influences on nutritional iodine status of pregnant women in Pakistan. Data were collected from 1246 pregnant women in all trimesters of pregnancy who visited antenatal clinics for routine checkups in five Khyber Pakhtunkhwa province districts. Information concerning iodized salt intake and knowledge of iodine deficiency disorders (IDD) was obtained through an interview questionnaire. Goiter and urinary iodine concentration (UIC) levels were assessed by the palpation method and Sandell-Kolthoff reaction, respectively. Logistic regression analysis was used to quantify associations between residence (rural-urban), pregnancy trimester, and previous pregnancy outcomes with knowledge about IDD, iodized salt intake, presence of goiter, and UIC <150 μg/L. Among study participants, 87.7% had no knowledge about IDD, and only 21.0% were consuming iodized salt. Goiter was present in 25.5% of the women. The median UIC level was 131 μg/L, and 41.3% of study participants had a UIC ≥150 μg/L. There were no significant differences between pregnant women from rural and urban settings in regions with a solid socioeconomic status with respect to knowledge about IDD, iodized salt intake, iodine deficiency, and goiter prevalence. Urban-rural differences were observed only in socioeconomically disadvantaged districts. Only pregnant women living in the Lakki Marwat district had higher odds of having knowledge of IDD and iodized salt intake than those from rural regions. Trimesters of pregnancy and previous pregnancy outcomes had no significant effect on the outcome measures. Relative to a national nutrition survey conducted in Pakistan in 2011, the results from this study indicate that UIC levels remained stable with mild iodine deficiency, whereas rates of goiter and iodized salt intake remained high and low, respectively, especially in rural areas. Rural-urban disparities were observed only in socioeconomically disadvantaged districts, and these disparities limit the effectiveness of the IDD prevention program in rural areas in Pakistan. Thus, implementation of mandatory salt iodization requires improvement, and program effectiveness should be continuously monitored to prevent adverse health effects of iodine deficiency during pregnancy.


Quality of leadership and presenteeism in health professions education and research: a test of a recovery-based process model with cognitive irritation and impaired sleep as mediators.
Presenteeism (PRES) includes working while feeling ill and constrained in performance. Compared with absence from work, PRES generates significantly higher cost estimates. Health problems and PRES are related to leadership quality. Hence, research on corporate health management needs to explore why leadership problems (LP) correspond to more frequent PRES.This study tests recovery after work as an underlying process with cognitive irritation (COGIRR) and sleep problems (SP) as simultaneous mediators and explores three mediation pathways (path one: LP→COGIRR→PRES; path two: LP→SP→PRES; and path three: LP→COGIRR→SP→PRES). Out of 293 employees of a university's school of health professions in German-speaking Switzerland, 211 completed a questionnaire. LP and PRES were found to be positively related (r(211) = .22, p < .01). The tests of mediation yielded no significant results for path one and two, but the third mediation path LP→COGIRR→SP→PRES was positive and differed significantly from zero (B = 0.83, CI95 = 0.33 to 1.69). According to our results, a recovery-based mediation model fits the empirical self-report data best. These results suggest that occupational health interventions should improve leadership quality to promote recovery after work in order to increase health and productivity by reduced PRES.


Weak Hydrogen Bonds Lead to Self-Healable and Bioadhesive Hybrid Polymeric Hydrogels with Mineralization-Active Functions.
Hydrogels with self-healing features that can spontaneously repair themselves upon mechanical damage are increasingly attractive for biomedical applications. Many attempts have been made to develop unique hydrogels possessing this property, as well as stimuli-responsiveness and biocompatibility; however, the hydrogel fabrication strategies often involve specific design of functional monomers that are able to optimally provide reversible physical or chemical interactions. Here, we report that weak hydrogen bonds, provided by oligo(ethylene glycol) methacrylate (OEGMA) and methacrylic acid (MAA), a monomer combination that is commonly used to prepare chemically cross-linking hydrogels, can generate self-healable hydrogels with mechanically resilient and adhesive properties through a facile one-step free radical copolymerization. The hydrogen bonds break and reform, providing an effective energy dissipation mechanism and synergic mechanical reinforcement. The physical properties can be simply tuned by OEGMA/MAA ratio control and reversible pH adjustment. Furthermore, the hydrogel can serve as a robust template for biomineralization to produce hydrogel composite that facilitate cell attachment and proliferations. This work is synthetically simple and dramatically increases the choice of amendable and adhesive hydrogels for industrial and biomedical applications.


A Powdering Technique for Veneering Zirconia and Its Effect on the Flexural Strength of Ceramic Bilayers.
The aim of this study was to assess the powdering technique and its effects on the flexural strength of bilayered zirconia. Bars made of zirconia partially stabilized by yttrium (Y-TZP) received porcelain by the following techniques (n = 10 per group): (1) L: VM9 application; (2) P: powdering technique + VM9 application; (3) C: Y-TZP coloring before sintering + Y-TZP sintering + VM9 application; or (4) CP: Y-TZP coloring before sintering + Y-TZP sintering + powdering technique + VM9 application. The powdering technique consisted of the application of VM9 margin powder followed by sintering. The samples were subjected to a 4-point flexural strength test and contact angle. Data were analyzed by one-way ANOVA and Tukey test (α = 5%). Surface treatments did not affect the flexural strength of bilayered specimens (P = .1264), but contact angle was affected by surface treatments (P < .0001), wherein the association of coloring and powdering (CP) reached higher values of wettability. Powdering did not affect the flexural strength of bilayered specimens, but did increase the Y-TZP wettability.


Spatio-temporal filtering techniques for the detection of disaster-related communication.
Individuals predominantly exchange information with one another through informal, interpersonal channels. During disasters and other disrupted settings, information spread through informal channels regularly outpaces official information provided by public officials and the press. Social scientists have long examined this kind of informal communication in the rumoring literature, but studying rumoring in disrupted settings has posed numerous methodological challenges. Measuring features of informal communication-timing, content, location-with any degree of precision has historically been extremely challenging in small studies and infeasible at large scales. We address this challenge by using online, informal communication from a popular microblogging website and for which we have precise spatial and temporal metadata. While the online environment provides a new means for observing rumoring, the abundance of data poses challenges for parsing hazard-related rumoring from countless other topics in numerous streams of communication. Rumoring about disaster events is typically temporally and spatially constrained to places where that event is salient. Accordingly, we use spatio and temporal subsampling to increase the resolution of our detection techniques. By filtering out data from known sources of error (per rumor theories), we greatly enhance the signal of disaster-related rumoring activity. We use these spatio-temporal filtering techniques to detect rumoring during a variety of disaster events, from high-casualty events in major population centers to minimally destructive events in remote areas. We consistently find three phases of response: anticipatory excitation where warnings and alerts are issued ahead of an event, primary excitation in and around the impacted area, and secondary excitation which frequently brings a convergence of attention from distant locales onto locations impacted by the event. Our results demonstrate the promise of spatio-temporal filtering techniques for "tuning" measurement of hazard-related rumoring to enable observation of rumoring at scales that have long been infeasible.


[Immunotherapy and cancer: towards 2020.]
Immunotherapy is a novel treatment strategy that, even though implemented decades ago, has emerged with important clinical data in the last 10 years and is fulfilling the promise of prolonging survival in several types of cancer by restoring the immune system activity against the tumor. To understand its benefits it is necessary to correctly evaluate the right endpoints and to know and manage the toxicity profile. The two immune-checkpoint receptors that have been most actively studied in the context of clinical cancer immunotherapy are the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and the programmed cell death protein-1 (PD-1), which are both inhibitory receptors and regulate immune responses at different levels and by different mechanisms. Despite the benefits shown by these checkpoint inhibitors in several types of cancer, there are still many patients who do not respond to immunotherapy. This is why research is focused on overcoming resistance and on how to identify molecular and mutational biomarker to fit the right therapy to the right patient.


Phenolic compounds in strawberry (Fragaria x ananassa Duch.) fruits: Composition in 27 cultivars and changes during ripening.
Phenolic compounds in fruits of 27 cultivars of strawberry (Fragaria x ananassa Duch.) grown in Norway were characterised and quantified by HPLC-DAD-MS(n). Total phenolic content, calculated as the sum of the individual compounds, varied 2.3-fold among cultivars, i.e., from 57 to 133mg/100g of fw. There were significant differences among cultivars in concentration of all phenolic compounds. The highest variation between cultivars was found for cinnamoyl glucose (0.6-24.9mg/100g of fw). Concentration of anthocyanins, the most abundant class of phenolic compounds in the majority of the cultivars, varied from 8.5 to 65.9mg/100g of fw. Flavan-3-ols (11-45mg/100g of fw) and ellagitannins (7.7-18.2mg/100g of fw) contributed on average 28% and 14% to total phenolic contents in the strawberry cultivars, respectively. In three cultivars harvested at three stages of ripeness, anthocyanins and cinnamic acid conjugates were the compounds most affected by ripening. The anthocyanin profile for the individual cultivars was only slightly affected by ripening and growing conditions.


TFIID TAF6-TAF9 complex formation involves the HEAT repeat-containing C-terminal domain of TAF6 and is modulated by TAF5 protein.
The general transcription factor TFIID recognizes specifically the core promoter of genes transcribed by eukaryotic RNA polymerase II, nucleating the assembly of the preinitiation complex at the transcription start site. However, the understanding in molecular terms of TFIID assembly and function remains poorly understood. Histone fold motifs have been shown to be extremely important for the heterodimerization of many TFIID subunits. However, these subunits display several evolutionary conserved noncanonical features when compared with histones, including additional regions whose role is unknown. Here we show that the conserved additional C-terminal region of TFIID subunit TAF6 can be divided into two domains: a small middle domain (TAF6M) and a large C-terminal domain (TAF6C). Our crystal structure of the TAF6C domain from Antonospora locustae at 1.9 Å resolution reveals the presence of five conserved HEAT repeats. Based on these data, we designed several mutants that were introduced into full-length human TAF6. Surprisingly, the mutants affect the interaction between TAF6 and TAF9, suggesting that the formation of the complex between these two TFIID subunits do not only depend on their histone fold motifs. In addition, the same mutants affect even more strongly the interaction between TAF6 and TAF9 in the context of a TAF5-TAF6-TAF9 complex. Expression of these mutants in HeLa cells reveals that most of them are unstable, suggesting their poor incorporation within endogenous TFIID. Taken together, our results suggest that the conserved additional domains in histone fold-containing subunits of TFIID and of co-activator SAGA are important for the assembly of these complexes.


Iron-Gold Composites for Biodegradable Implants: In Vitro Investigation on Biodegradation and Biomineralization.
The biocompatibility and biodegradation of iron (Fe) make it a suitable candidate for developing biodegradable metallic implants. However, the degradation rate of Fe in a physiological environment is extremely slow and needs to be enhanced to a rate compatible with tissue growth. Incorporating noble metals improves the Fe degradation rate by forming galvanic couples. This study incorporated gold (Au) into Fe at very low concentrations of 1.25 and 2.37 μg/g to improve the degradation rate. The electrochemical corrosion test of the samples revealed that the Au-containing samples showed a four-time and nine-time faster degradation rate than pure Fe. Furthermore, the immersion test and long-term electrochemical impedance spectroscopy conducted in simulated body fluid (SBF) revealed that the Au-incorporated samples exhibited increased bioactivity and degraded faster than pure Fe. Integrating nanogold into a Fe matrix increased the in situ formation of hydroxyapatite on the sample's surface and did not cause toxicity to L929-murine fibroblast cells. It is suggested that Fe-Au composites with low concentrations of Au can be used to tailor the biodegradation rate and promote the biomineralization of Fe-based implants in the physiological environment.


Localizing and extracting filament distributions from microscopy images.
Detailed quantitative measurements of biological filament networks represent a crucial step in understanding architecture and structure of cells and tissues, which in turn explain important biological events such as wound healing and cancer metastases. Confocal microscope images of biological specimens marked for different structural proteins constitute an important source for observing and measuring meaningful parameters of biological networks. Unfortunately, current efforts at quantitative estimation of architecture and orientation of biological filament networks from microscopy images are predominantly limited to visual estimation and indirect experimental inference. Here we describe a new method for localizing and extracting filament distributions from 2D confocal microscopy images. The method combines a filter-based detection of pixels likely to contain a filament with a constrained reverse diffusion-based approach for localizing the filaments centrelines. We show with qualitative and quantitative experiments, using both simulated and real data, that the new method can provide more accurate centreline estimates of filament in comparison to other approaches currently available. In addition, we show the algorithm is more robust with respect to variations in the initial filter-based filament detection step often used. We demonstrate the application of the method in extracting quantitative parameters from an experiment that seeks to quantify the effects of carbon nanotubes on actin cytoskeleton in live HeLa cells. We show that their presence can disrupt the overall actin cytoskeletal organization in such cells.


Substitution pharmacotherapies for opioid addiction: from methadone to LAAM and buprenorphine.
The efficacy and cost-effectiveness of opioid substitution therapy for the treatment of opioid addiction has been well documented within the methadone maintenance model for over thirty years. However, methadone does not meet the specific treatment needs of all opioid-dependent persons who might benefit from substitution therapy; consequently, a significant proportion of heroin addicts remain untreated. The recent approval of l-alpha-acetylmethadol (LAAM) as a maintenance treatment agent represents the first opioid substitution alternative to methadone. LAAM is a fundamentally different medication than methadone, with unique pharmacological characteristics. Its use requires a different approach to the clinical management of opioid substitution therapy and a different medication delivery strategy. The availability of LAAM has potential important implications for patients, clinics, and the community at large. Full realization of its advantages could move opioid substitution therapy into mainstream medical care and draw into treatment a substantial number of new patients able to benefit from such treatment. Buprenorphine, the other new opioid substitution therapy under development, shares some common advantages with LAAM. Its high safety profile and low physical dependence liability make it uniquely suitable for a subset of addicts as well as an initial treatment of choice in the opioid substitution treatment armamentarium.


Association between untreated caries and age, gender and dental attendance in adults.
The aim of the study was to examine the association between untreated caries on the crown and root of the tooth with the age, gender and dental attendance in a group of adult. Six general practitioners in the Greater Manchester area agreed to take part. Over a 6-week period they collected clinical and personal data on 270 of their adult patients. No association was found between the mean number of coronal surfaces with caries and age; however, there was more root caries in people over 55 yr. More recurrent caries associated with a restoration was diagnosed than primary caries. There were proportionally more female than male regular attenders, and once attendance has been taken into account there were no gender differences for either coronal or root caries. Both coronal and root caries were associated with attendance, with irregular attenders experiencing more. Irregular attenders were three and a half times more likely to have caries on the root surfaces than regular attenders.


Amplification of the CD24 Gene Is an Independent Predictor for Poor Prognosis of Breast Cancer.
CD24 is a glycosyl-phosphatidyl-inositol linked glycoprotein expressed in a broad range of cell types including cancer cells. Although it is overexpressed in nearly 70% of human cancers, copy number variation of the CD24 locus has not been reported for any cancer. Here, we analyzed the genomics, transcriptomics, and clinical data of 1082 breast cancer (BRCA) samples and other cancer samples from the clinically annotated genomic database, The Cancer Genome Atlas (TCGA). The GISTIC2 method was applied to stratify the CD24 copy number, and Cox regression was performed to compare hazard ratio (HR) of CD24 overexpression, amplification and other traditional prognosis features for overall survival (OS). Our data demonstrated that CD24 amplification strongly correlated with its mRNA overexpression as well as TP53 mutant, cancer proliferation and metastasis features. In particular, CD24 amplification was enriched in basal-like subtype samples and associated with poor clinical outcome. Surprisingly, based on the univariate Cox regression analysis, CD24 overexpression (HR = 1.62, P = 0.010) and copy number amplification (HR = 1.79, P = 0.022) was more relevant to OS than TP53 mutant, mutation counts, diagnosis age, and BRCA subtypes. And based on multivariate survival analysis, CD24 amplification remained the most significant and independent predictor for worse OS (HR = 1.88, P = 0.015).


[HPLC Fingerprint Study and Quantitative Determination of Index Components of Pilea aquarum].
To establish an HPLC fingerprint and a quantitative determination method for determination of index components of Pilea aquarum. The HPLC fingerprint of Pilea aquarum were determined on an Agilent Zorbax SB-C18 column (250 mm x 4.6 mm, 5 µm), eluted with mobile phase containing of acetonitrile-0.2% acetic acid in a gradient mode. The temperature of column was 30 °C. The flow rate was 0.8 mL/min and the detection wavelength was set at 330 nm. The chromatograms of 24 batches of Pilea aquarum were compared by the software of Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (version 2004 A). The contents of luteoloside and cosmosiin were also determined simultaneously. The HPLC fingerprint of Pilea aquarum had been established. There were ten common peaks,two chromatographic peaks of which were identified by reference substances. The samples of Pilea aquarum from different habitats can be distinguished from their fingerprints, the contents of luteoloside and cosmosiin varied greatly. This method has desirable precision, stability, repeatability, and can be applied for identification and quality control of Pilea aquarum.


Effects of ethanol applied by electrosmosis on neurons in the lateral and medial vestibular nuclei.
Electrophysiological studies were performed to elucidate the effects of ethanol on neuron activities in the lateral vestibular nucleus (LVN) and medial vestibular nucleus (MVN) of cats using an electrosmotic and microiontophoretic method. The LVN and MVN neurons were classified into two types according to the firing pattern and latency of the first spike with vestibular nerve stimulation: monosynaptic and polysynaptic neurons. Electrosmotic application of ethanol up to 200 nA produced a dose-dependent inhibition of spikes of the LVN monosynaptic neurons with vestibular nerve stimulation and iontophoretically applied glutamate, but no significant alterations of the spikes of the LVN polysynaptic neurons. Acetylcholine-induced firing in the LVN monosynaptic neurons was also inhibited by ethanol. In the MVN, spike generation of the monosynaptic and polysynaptic neurons with vestibular nerve stimulation and iontophoretically applied glutamate remained unaltered with ethanol up to 200 nA. These results indicate that ethanol predominantly inhibits synaptic transmission of the LVN monosynaptic neurons, probably by acting on the postsynaptic cell bodies.


Scientific and regulatory policy committee (SRPC) paper: assessment of circulating hormones in nonclinical toxicity studies III. female reproductive hormones.
Hormonally mediated effects on the female reproductive system may manifest as pathologic changes of endocrine-responsive organs and altered reproductive function. Identification of these effects requires proper assessment, which may include investigative studies to profile female reproductive hormones. Here, we briefly describe normal hormonal patterns across the estrous or menstrual cycle and provide general guidance on measuring female reproductive hormones and characterizing hormonal disturbances in nonclinical toxicity studies. Although species used in standard toxicity studies share basic features of reproductive endocrinology, there are important species differences that affect both study design and interpretation of results. Diagnosing female reproductive hormone disturbances can be complicated by many factors, including estrous/menstrual cyclicity, diurnal variation, and age- and stress-related factors. Thus, female reproductive hormonal measurements should not generally be included in first-tier toxicity studies of standard design with groups of unsynchronized intact female animals. Rather, appropriately designed and statistically powered investigative studies are recommended in order to properly identify ovarian and/or pituitary hormone changes and bridge these effects to mechanistic evaluations and safety assessments. This article is intended to provide general considerations and approaches for these types of targeted studies.


Survival radiology for GPs.
General practitioners in regional and rural areas may be required to interpret emergency imaging of their patients without the immediate assistance of a radiologist. To provide a structured approach to interpretation of X-rays performed as part of routine care of common emergency presentations. X-rays are an important diagnostic tool and should follow a complete history and examination. A structured approach and awareness of potential pitfalls will enable the primary care doctor to confidently interpret plain X-rays in emergency situations.


Effect of remote patient management in peritoneal dialysis on haemodynamic and volume control.
Reduced treatment compliance in patients with peritoneal dialysis facilitates the development of fluid overload and as a result increased blood pressure and vascular stiffness in the long term. We aimed to evaluate blood pressure change and anti-hypertensive needs of patients within 1 year after the changeover to remote monitoring automated peritoneal dialysis (RM-APD) and compare the effect of RM-APD and continuous ambulatory peritoneal dialysis (CAPD) on peripheral and central haemodynamic parameters, volume status of patients and anti-hypertensive drug needs. This was an observational and cross-sectional study. We enrolled 15 patients performing CAPD, 20 patients performing RM-APD, and 38 age, and gender-matched healthy control. We measured pulse wave velocity to assess arterial stiffness, peripheral and central haemodynamic parameters. We measured the volume status of participants via bioimpedance spectroscopy. The mean excess hydration of patients who underwent CAPD were higher than those who performed RM-APD and healthy control (P = .02). We found that mean diastolic blood pressure, heart rate, central systolic and diastolic blood pressure, and central pulse pressure were significantly different between the RM-APD, CAPD and healthy control (P = .02, P = .05, P = .007, P = .05 and P = .005, respectively). Post hoc analysis of these results showed that the differences between the groups were caused by the healthy control group and the patients with underwent CAPD. Daily anti-hypertensive drug count in patients with performing RM-APD was reduced over time (P < .001). The RM-APD provides better control of peripheral blood pressure and decrease of central haemodynamic parameters via controlling the excess body water.


Morphological study on vagal innervation in human atrioventricular valves using histochemical method.
To demonstrate innervation in human atrioventricular valves, we examined the tricuspid and mitral valves of apparently normal autopsied hearts of four men (ages ranging from 50 to 74 years). Whole valve tissues were stained for acetylcholinesterase by a histochemical method. Acetylcholinesterase-positive nerve fibers with a diameter of 2 to 5 microns were distributed widely in the deep atrialis of the atrioventricular valves and partly in the fibrosa. The nerve fibers formed a network or plexus from the base to the anatomical edge of the valves. Meshes of the nerve fiber network were more dense towards the base and at the commissure than either towards the edge or at the body. Thicker nerve fibers, which were interspersed coarsely in the leaflets, were intercalated by special varicose apparatuses at a few sites in their long running course. On the contrary, thinner nerve fibers which were distributed abundantly, ended, as a rule, in small dotor brush-like formations. Approximately half of the chordae tendineae were innervated by the nerve fibers. The mode of vagal innervation suggests that the nerve system may assist valve movement by moderating myocyte contraction in the valve base and change valve structure by sensing a stress in the valves.


Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi.
We identified a gene of the fungal pathogen Candida albicans, designated EFG1, whose high-level expression stimulates pseudohyphal morphogenesis in the yeast Saccharomyces cerevisiae. In a central region the deduced Efg1 protein is highly homologous to the StuA and Phd1/Sok2 proteins that regulate morphogenesis of Aspergillus nidulans and S. cerevisiae, respectively. The core of the conserved region is homologous to the basic helix-loop-helix (bHLH) motif of eukaryotic transcription factors, specifically to the human Myc and Max proteins. Fungal-specific residues in the bHLH domain include the substitution of an invariant glutamate, responsible for target (E-box) specificity, by a threonine residue. During hyphal induction EFG1 transcript levels decline to low levels; downregulation is effected at the level of transcriptional initiation as shown by a EFG1 promoter-LAC4 fusion. A strain carrying one disrupted EFG1 allele and one EFG1 allele under the control of the glucose-repressible PCK1 promoter forms rod-like, pseudohyphal cells, but is unable to form true hyphae on glucose-containing media. Overexpression of EFG1 in C. albicans leads to enhanced filamentous growth in the form of extended pseudohyphae in liquid and on solid media. The results suggest that Efg1p has a dual role as a transcriptional activator and repressor, whose balanced activity is essential for yeast, pseudohyphal and hyphal morphogenesis of C. albicans. Functional analogies between Efg1p and Myc are discussed.


Amoxicillin Increased Functional Pathway Genes and Beta-Lactam Resistance Genes by Pathogens Bloomed in Intestinal Microbiota Using a Simulator of the Human Intestinal Microbial Ecosystem.
Antibiotics are frequently used to treat bacterial infections; however, they affect not only the target pathogen but also commensal gut bacteria. They may cause the dysbiosis of human intestinal microbiota and consequent metabolic alterations, as well as the spreading of antibiotic resistant bacteria and antibiotic resistance genes (ARGs). In vitro experiments by simulator of the human intestinal microbial ecosystem (SHIME) can clarify the direct effects of antibiotics on different regions of the human intestinal microbiota, allowing complex human microbiota to be stably maintained in the absence of host cells. However, there are very few articles added the antibiotics into this in vitro model to observe the effects of antibiotics on the human intestinal microbiota. To date, no studies have focused on the correlations between the bloomed pathogens caused by amoxicillin (AMX) exposure and increased functional pathway genes as well as ARGs. This study investigated the influence of 600 mg day-1 AMX on human intestinal microbiota using SHIME. The impact of AMX on the composition and function of the human intestinal microbiota was revealed by 16S rRNA gene sequencing and high-throughput quantitative PCR. The results suggested that: (i) AMX treatment has tremendous influence on the overall taxonomic composition of the gut microbiota by increasing the relative abundance of Klebsiella [linear discriminant analysis (LDA) score = 5.26] and Bacteroides uniformis (LDA score = 4.75), as well as taxonomic diversity (Simpson, P = 0.067, T-test; Shannon, P = 0.061, T-test), and decreasing the members of Parabacteroides (LDA score = 4.18), Bifidobacterium (LDA score = 4.06), and Phascolarctobacterium (LDA score = 3.95); (ii) AMX exposure significantly enhanced the functional pathway genes and beta-lactam resistance genes, and the bloomed pathogens were strongly correlated with the metabolic and immune system diseases gene numbers (R = 0.98, P < 0.001) or bl2_len and bl2be_shv2 abundance (R = 0.94, P < 0.001); (iii) the changes caused by AMX were "SHIME-compartment" different with more significant alteration in ascending colon, and the effects were permanent, which could not be restored after 2-week AMX discontinuance. Overall results demonstrated negative side-effects of AMX, which should be considered for AMX prescription.


[Aberrometry of a new artificial implanted lenses model with changeable refractive surface].
There was made an aberrometry of new IOL with changeable refractive surface. Different power of silicon oil inside the lens become changes in it refractive power. So, in this way we made three types of IOL refractive power: 17,5 D; 20 D; 22 D. The quality of experimental optical system may be comparative with optical system that made by ReSTOR IOL implantation in human eye. HOA and LOA, that generated by the new IOL, had no or small influence to the quality of optical system.


Ploidy of bovine nuclear transfer blastocysts reconstructed using in vitro produced blastomere donors.
The higher rate of embryonic loss in nuclear transfer compared to in vitro produced embryos may be due to chromosome abnormalities that occur during preimplantation in vitro development. Because little is known about ploidy errors in nuclear transfer embryos, this was examined using embryos reconstructed from in vitro produced embryo donors. In vitro matured oocytes were enucleated and then activated using calcium ionophore A23187 followed by 6-dimethylaminopurine (6-DMAP). Subsequently, embryos were reconstructed using blastomeres from day 4-5 in vitro produced donors. The embryos were cultured until day 7 at which time blastocyst nuclei were extracted and chromosome abnormalities were evaluated by fluorescent in situ hybridization using two probes that bind to the subcentromeric regions on chromosomes 6 and 7. In 16 nuclear transfer blastocysts generated from 5 donor embryos, 53.8 +/- 20.2 (mean % +/- SD) nuclei/embryo were examined. Of these 16, 7 embryos (43.8%) were potentially abnormal because in these, 1.1%, 1.4%, 5.3%, 7.5%, 26.3%, 30.4%, and 66.2% % of the nuclei had a chromosome composition deviating from the diploid condition, indicating a wide degree of variation between embryos. These errors comprised mainly triploid (8.2 +/- 10.3 [0-26.3]: % +/- SD [range]) and tetraploid (10.6 +/- 19.9 [0-54.9]) nuclei with other ploidy combinations accounting for only 0.9 +/- 2.1 [0-2.1]% of deviant nuclei. The proportion of completely normal nuclear transfer embryos was no less than those produced by in vitro fertilization but the distribution of chromosome abnormalities was different (p = 0.0002). In conclusion, nuclear transfer embryos reconstructed using blastomere cells can produce over 50% blastocysts with a diploid chromosome complement. However, the contribution of chromosome abnormalities to embryonic loss in the remaining embryos deserves further investigation.


Electrophysiologic properties of a narrow isthmus in rabbit atrial tissue: cycle length dependent effect of quinidine.
The modulation of quinidine's effect by pacing cycle lengths was assessed over an isthmus of atrial myocardium, simulating the Wolff-Parkinson-White syndrome. Isolated rabbit atria were dissected so that two tissue blocks, A and B, were linked by an isthmus, 1 mm in width. Effective refractory period in the tissue blocks and over the isthmus was measured at cycle lengths of 1,000, 600, and 400 ms, and the minimum cycle length to sustain 1:1 conduction over the isthmus was measured before treatment, during quinidine superfusion (4 mg/L), and after washout. Longitudinal velocity over the isthmus was also measured. The increment in the effective refractory period in the tissue blocks by quinidine appeared to be similar, about 10% at three pacing cycle lengths (p > 0.05). However, the increment of the effective refractory period over the isthmus was modulated by pacing cycle lengths: greater increase at shorter cycle lengths (p < 0.001). Quinidine prolonged the minimum cycle length over the isthmus by 44 +/- 17%. Regression analysis showed that after quinidine there was a correlationship between conduction velocity and refractoriness over the isthmus (R = 0.85, p < 0.001). Intracellular implements showed stable action potentials, confirming the integrity of the preparation. We conclude that (i) quinidine preferentially prolongs refractoriness over the isthmus and (ii) quinidine's effect on refractoriness over the isthmus is cycle length dependent.


Bacterial cell growth is arrested by violet and blue, but not yellow light excitation during fluorescence microscopy.
Fluorescence microscopy is a powerful tool in cell biology, especially for the study of dynamic processes. Intensive irradiation of bacteria with UV, blue and violet light has been shown to be able to kill cells, but very little information is available on the effect of blue or violet light during live-cell imaging. We show here that in the model bacterium Bacillus subtilis chromosome segregation and cell growth are rapidly halted by standard violet (405 nm) and blue light (CFP) (445-457 nm) excitation, whereas they are largely unaffected by green light (YFP). The stress sigma factor σB and the blue-light receptor YtvA are not involved in growth arrest. Using synchronized B. subtilis cells, we show that the use of blue light for fluorescence microscopy likely induces non-specific toxic effects, rather than a specific cell cycle arrest. Escherichia coli and Caulobacter crescentus cells also stop to grow after 15 one-second exposures to blue light (CFP), but continue growth when imaged under similar conditions in the YFP channel. In the case of E. coli, YFP excitation slows growth relative to white light excitation, whereas CFP excitation leads to cell death in a majority of cells. Thus, even mild violet/blue light excitation interferes with bacterial growth. Analyzing the dose-dependent effects of violet light in B. subtilis, we show that short exposures to low-intensity violet light allow for continued cell growth, while longer exposures do not. Our experiments show that care must be taken in the design of live-cell imaging experiments in that violet or blue excitation effects must be closely controlled during and after imaging. Violet excitation during sptPALM or other imaging studies involving photoactivation has a threshold, below which little effects can be seen, but above which a sharp transition into cell death occurs. YFP imaging proves to be better suited for time-lapse studies, especially when cell cycle or cell growth parameters are to be examined.


Interleukin 17 Cytokine Profiles in Patients with Cystic Echinococcosis in Babylon Province, Iraq.
Cystic Echinococcosis (CE) is the silent chronic Helminthes zoonotic infection caused by the larval stage in intermediate hosts of the dog tapeworm Echicoccous granulosus, which belongs to the Taeniidae family and genus Echinococcu ssp. According to the study of CE, the hospitalization and surgeries of patients indicated the high prevalence of the disease in Iraq.This study aimed to determine some immunological parameters in patients infected with Echinococcus granulose. The study of 53 patients infected with CE showed that in 40 (75.4 %), 5 (9.4%), 4 (7.5%), and 2 (3.7 %) cases the liver, abdominal cavity, kidney, and lungs were involved. In terms of age, most and least number of the patients were within the age ranges of30-40 (n=15, 28.3 %) and60-70 years old (n=7, 13.2 %), respectively. Moreover, 37(56.9%) and 16(43%) of them were female and male, respectively. The enzyme-linked immunosorbent assay (ELISA) was used to measure the level of the Interleukin family among patients. There was a significant increase in the serum level concentration of IL17A and IL17B in patients with hydatid disease, compared to the control group. The changes in different age groups also showed statistically significant differences among them (P≤0.05). The outcome of this study indicated that CE is endemic in Babylon province, Iraq. The ELISA technique is a reliable and efficient test for the early diagnosis and monitoring of human hydatid disease. Moreover, it was found that the liver was the most common site of human hydatid cyst.


The influence of maternal nicotine exposure on neonatal lung metabolism. Protective effect of ascorbic acid.
The aim of the present study was to establish whether ascorbic acid supplementation (1 mg/kg/body mass/day) during pregnancy and lactation will prevent the effect of maternal nicotine exposure (1 mg/kg/body weight/day) on neonatal lung carbohydrate, DNA and protein metabolism. The data show that the adult lung ascorbic acid content was reduced by 76% after exposure to nicotine. In contrast, maternal nicotine exposure during pregnancy and lactation has no effect on neonatal lung ascorbic acid content. However, ascorbic acid supplementation during pregnancy and lactation prevented the adverse effects of maternal nicotine exposure on neonatal lung carbohydrate, DNA and protein metabolism.


Prohibiting Students from Asking Questions during Exams: A Guideline for Promoting Fairness and Preserving Score Validity.
Many medical and professional programs implement policies that prohibit students from asking questions during examinations. The reasoning behind these policies remains unclear to some, as there is a lack of literature addressing this topic. The purpose of this article is to present the rationale behind such policies and to discuss why these policies may help promote fairness and preserve score validity.


Liver involvement in hereditary hemorrhagic telangiectasia: CT and clinical findings do not correlate in symptomatic patients.
The purpose of our study was to report the multiphasic CT findings in patients with symptomatic liver involvement by hereditary hemorrhagic telangiectasia (HHT) and to correlate the CT findings with the type of clinical presentation. Patients with symptomatic HHT liver disease have diffuse hepatic telangiectases, a dilated common hepatic artery, and a high incidence of biliary abnormalities. Multiphasic CT is useful in diagnosing liver involvement due to HHT; however, no strong correlation was seen between CT findings and the clinical subtype of HHT liver disease.


Variations in the Peritrophic Matrix Composition of Heparan Sulphate from the Tsetse Fly, Glossina morsitans morsitans.
Tsetse flies are the principal insect vectors of African trypanosomes-sleeping sickness in humans and Nagana in cattle. One of the tsetse fly species, Glossina morsitans morsitans, is host to the parasite, Trypanosoma brucei, a major cause of African trypanosomiasis. Precise details of the life cycle have yet to be established, but the parasite life cycle involves crossing the insect peritrophic matrix (PM). The PM consists of the polysaccharide chitin, several hundred proteins, and both glycosamino- and galactosaminoglycan (GAG) polysaccharides. Owing to the technical challenges of detecting small amounts of GAG polysaccharides, their conclusive identification and composition have not been possible until now. Following removal of PMs from the insects and the application of heparinases (bacterial lyase enzymes that are specific for heparan sulphate (HS) GAG polysaccharides), dot blots with a HS-specific antibody showed heparan sulphate proteoglycans (HSPGs) to be present, consistent with Glossina morsitans morsitans genome analysis, as well as the likely expression of the HSPGs syndecan and perlecan. Exhaustive HS digestion with heparinases, fluorescent labeling of the resulting disaccharides with BODIPY fluorophore, and separation by strong anion exchange chromatography then demonstrated the presence of HS for the first time and provided the disaccharide composition. There were no significant differences in the type of disaccharide species present between genders or between ages (24 vs. 48 h post emergence), although the HS from female flies was more heavily sulphated overall. Significant differences, which may relate to differences in infection between genders or ages, were evident, however, in overall levels of 2-O-sulphation between sexes and, for females, between 24 and 48 h post-emergence, implying a change in expression or activity for the 2-O-sulphotransferase enzyme. The presence of significant quantities of disaccharides containing the monosaccharide GlcNAc6S contrasts with previous findings in Drosophila melanogaster and suggests subtle differences in HS fine structure between species of the Diptera.


Recovery of renal function after administration of adipose-tissue-derived stromal vascular fraction in rat model of acute kidney injury induced by ischemia/reperfusion injury.
Acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) injury is a major challenge in critical care medicine. The purpose of this study is to determine the therapeutic effects of the adipose-tissue-derived stromal vascular fraction (SVF) and the optimal route for SVF delivery in a rat model of AKI induced by I/R injury. Fifty male Sprague-Dawley rats were randomly divided into five groups (10 animals per group): sham, nephrectomy control, I/R injury control, renal arterial SVF infusion and subcapsular SVF injection. To induce AKI by I/R injury, the left renal artery was clamped with a nontraumatic vascular clamp for 40 min, and the right kidney was removed. Rats receiving renal arterial infusion of SVF had a significantly reduced increase in serum creatinine compared with the I/R injury control group at 4 days after I/R injury. The glomerular filtration rate of the renal arterial SVF infusion group was maintained at a level similar to that of the sham and nephrectomy control groups at 14 days after I/R injury. Masson's trichrome staining showed significantly less fibrosis in the renal arterial SVF infusion group compared with that in the I/R injury control group in the outer stripe (P < 0.001). TUNEL labeling showed significantly decreased apoptosis in both the renal arterial SVF infusion and subcapsular SVF injection groups compared with the I/R injury control group in the outer stripe (P < 0.001). Thus, renal function is effectively rescued from AKI induced by I/R injury through the renal arterial administration of SVF in a rat model.


A systematic study of the competitive sorption of per- and polyfluoroalkyl substances (PFAS) on colloidal activated carbon.
Treatment of environmental media contaminated with per- and polyfluoroalkyl substances (PFAS) is crucial to mitigate mounting health risks associated with exposure. Colloidal activated carbon (CAC) has shown promise in treating contaminated soils, but understanding the interaction among PFAS during sorption is necessary for optimal remediation. This study investigated the extent to which PFAS of varying chain lengths and functional groups compete for sorption to CAC. Batch tests were conducted with natural soil and spiked water, using CAC at 0.2% w/w to remove seven PFAS with individual starting concentrations up to 0.05 mmol L-1. PFAS sorption to CAC was evaluated in three systems: a composite mixture of all studied compounds, a binary-solute system, and a single-solute system. The sorption experiments exhibited strong PFAS affinity to CAC, with removal rates between 41% and 100%, and solid/liquid partition coefficients (Kd) between 10 and 104 L kg-1. Differences were noticed among the various spiking mixtures, based on perfluorocarbon chain length, functional group, and the starting PFAS concentrations. Competition effects were detected when PFAS were in a multi-solute system, with an average 10% drop in removal, which can evidently become more relevant at higher concentrations, due to the observed non-linearity of the sorption process. The PFAS most vulnerable to competition effects in multi-solute systems were the short-chain perfluoropentanoic acid (PFPeA) and perfluorobutane sulfonic acid (PFBS), with an up to 25% reduction in removal. In bi-solute systems, perfluorooctane sulfonamide (FOSA) dominated over its ionisable counterparts, i.e. perfluorooctane sulfonic acid (PFOS) and perfluorononanoic acid (PFNA), indicating the importance of hydrophobic effects or layer formation in the sorption process. These results underscore the importance of considering competition in PFAS sorption processes when designing and implementing remediation techniques for PFAS-contaminated media.


Prevalence of Key Modifiable Cardiovascular Risk Factors among Urban Adolescents: The CRO-PALS Study.
The occurrence of chronic diseases in youth has become a serious global issue requiring early prevention. Due to the specific environment in large cities, urban youth are especially exposed to risky lifestyle patterns. This survey aimed to determine the prevalence of key modifiable cardiovascular risk factors in the adolescent population of the Croatian capital Zagreb. A clustered two-stage random sample design was employed to select a representative group of 903 adolescents (girls n = 444; boys n = 459; age 15.6 ± 0.4) starting their secondary education. Participants were invited to fulfil an electronic questionnaire meant to collect data on daily physical activity, screen time and tobacco use. In addition, anthropometric and blood pressure measurements were taken by medically trained personnel. Data that were not originally categorical were dichotomized based on internationally accepted cut-off values for each risk factor, summarized for females and males, and presented as percentages and 95% confidence intervals. The outcomes suggest that that more than one half did not meet the recommended daily physical activity (girls 59.4%; boys 45.5%), while about one quarter exceeded 2 hours of screen time per day and had high blood pressure (girls 26.6% and 21.6%; boys 27.0% and 27.0%, respectively). Moreover, the results indicated nearly one fifth of adolescents had excess weight (girls 16.1%; boys 22.2%) and a similar proportion smoked tobacco (girls 20.8%; boys 17.0%). Local and regional health stakeholders should make additional efforts to promote healthy lifestyles in urban teenagers. Special emphasis should be placed on promoting physical activity.


Statins inhibit beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes via a Rac1-dependent mechanism.
3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) inhibit myocyte hypertrophy in vitro and ameliorate the progression of cardiac remodeling in vivo, possibly because of inhibition of the small GTPase Rac1. The role of Rac1 in mediating myocyte apoptosis is not known. beta-Adrenergic receptor (betaAR)-stimulated myocyte apoptosis is mediated via activation of c-Jun NH2-terminal kinase (JNK), leading to activation of the mitochondrial death pathway. We hypothesized that betaAR-stimulated apoptosis in adult rat ventricular myocyte (ARVMs) is mediated by Rac1 and inhibited by statins. betaAR stimulation increased apoptosis, as assessed by transferase-mediated nick-end labeling, from 5+/-1% to 24+/-2%. betaAR stimulation also increased Rac1 activity. Adenoviral overexpression of a dominant-negative mutant of Rac1 inhibited betaAR-stimulated apoptosis, JNK activation, cytochrome C release, and caspase-3 activation. Cerivastatin likewise inhibited the betaAR-stimulated activation of Rac1, decreased betaAR-stimulated apoptosis to 11+/-2%, and inhibited JNK activation, cytochrome C release, and caspase-3 activation. betaAR stimulation causes Rac1 activation, which is required for myocyte apoptosis and leads to activation of JNK and the mitochondrial death pathway. Cerivastatin inhibits betaAR-stimulated activation of Rac1 and thereby inhibits JNK-dependent activation of the mitochondrial death pathway and apoptosis. The beneficial effects of statins on the myocardium may be mediated in part via inhibition of Rac1-dependent myocyte apoptosis.


Shotgun proteomics and network analysis between plasma membrane and extracellular matrix proteins from rat olfactory ensheathing cells.
Olfactory ensheathing cells (OECs) are a special type of glial cells that have characteristics of both astrocytes and Schwann cells. Evidence suggests that the regenerative capacity of OECs is induced by soluble, secreted factors that influence their microenvironment. These factors may regulate OECs self-renewal and/or induce their capacity to augment spinal cord regeneration. Profiling of plasma membrane and extracellular matrix through a high-throughput expression proteomics approach was undertaken to identify plasma membrane and extracellular matrix proteins of OECs under serum-free conditions. 1D-shotgun proteomics followed with gene ontology (GO) analysis was used to screen proteins from primary culture rat OECs. Four hundred and seventy nonredundant plasma membrane proteins and 168 extracellular matrix proteins were identified, the majority of which were never before reported to be produced by OECs. Furthermore, plasma membrane and extracellular proteins were classified based on their protein-protein interaction predicted by STRING quantitatively integrates interaction data. The proteomic profiling of the OECs plasma membrane proteins and their connection with the secretome in serum-free culture conditions provides new insights into the nature of their in vivo microenvironmental niche. Proteomic analysis for the discovery of clinical biomarkers of OECs mechanism warrants further study.


An ecosystem services approach to pesticide risk assessment and risk management of non-target terrestrial plants: recommendations from a SETAC Europe workshop.
The registration of plant protection products (PPPs) in the EU is under Regulation 1107/2009, which recommends a tiered approach to assessing the risk to non-target terrestrial plants (NTTPs). However, little information is provided on how to perform and implement higher tier studies or how to use them to refine the risk assessments. Therefore, a stakeholder workshop was organized to consolidate current knowledge and expertise to aid the further development of testing and assessment procedures for NTTPs. This brief communication highlights the agreed recommendations of the workshop, which relate to the three main themes, i.e. specific protection goals, risk assessment and mitigation. The participants of the workshop adopted the European Food Safety Authority (EFSA) approach of using an ecosystem services framework for identifying specific protection goals. First, delivery and protection of ecosystem services were discussed for in-crop, in-field and off-crop, and off-field areas. Second, lower and higher tier risk assessment methods, including modelling approaches, were evaluated. Third, options for risk mitigation of spray drift and run-off were discussed and evaluated. Several important knowledge gaps were identified, and specific data collation and literature-based tasks were actioned to begin to address them. A full workshop report is planned for the fall of 2014.


Relapsing and remitting scapular winging in a pediatric patient.
Scapular winging (scapula alata) is a condition in which the scapula is rotated or displaced away from the body. The nature of this rotation or displacement can vary depending on the origin. There are many different causes of scapular winging including neurogenic, structural, muscular, and bursal (Frontera, Silver, Essentials of Physical Medicine and Rehabilitation. Philadelphia, Hanley and Belfus, 2002, pp 99-102). Structural causes are not frequently at the top of a clinician's differential diagnosis, but they must always be considered. We review the case of a teenage boy who developed intermittent scapular winging after tackling his brother in a backyard football game. His symptoms resolved and recurred over a period of 9 mos. Approximately 1 yr after the initial episode of winging, during a recurrence of his symptoms, a repeat shoulder x-ray was ordered. This study revealed a previously undetected osteochondroma. The patient subsequently underwent resection of the inferior angle of his right scapula and had complete resolution of his symptoms.


The consequences of backcountry surface disposal of human waste in an alpine, temperate forest and arid environment.
Surface disposal of human waste by the smear method, a suggested but heretofore unexamined technique, was tested in three environments and examined for reductions in fecal mass and fecal indicator bacteria. Substantial reduction in fecal mass was observed after six and fourteen weeks of exposure in all environments, but extensive reduction in fecal indicator bacteria was observed in only the arid and alpine environments. Although surface smears appear favorable to cathole techniques in terms of indicator bacteria reduction, the application of this method is limited by several other factors common to backcountry sanitation situations. It is therefore likely that surface disposal would only be applicable in very remote, low use, alpine and arid settings where lack of soil development precludes the use of catholes and carry-out techniques are otherwise impractical.


Additional interventions to enhance the effectiveness of individual placement and support: a rapid evidence assessment.
Topic. Additional interventions used to enhance the effectiveness of individual placement and support (IPS). Aim. To establish whether additional interventions improve the vocational outcomes of IPS alone for people with severe mental illness. Method. A rapid evidence assessment of the literature was conducted for studies where behavioural or psychological interventions have been used to supplement standard IPS. Published and unpublished empirical studies of IPS with additional interventions were considered for inclusion. Conclusions. Six published studies were found which compared IPS alone to IPS plus a supplementary intervention. Of these, three used skills training and three used cognitive remediation. The contribution of each discrete intervention is difficult to establish. Some evidence suggests that work-related social skills and cognitive training are effective adjuncts, but this is an area where large RCTs are required to yield conclusive evidence.


Anger expression and blood pressure in adolescents.
The clinical significance of childhood hypertension is important as elevated pressures during childhood are found to follow a progressively increasing track into adulthood. Little work has been done to examine the relationship of emotions and emotional behavioral factors to the development of hypertension in children. Using the Roy Adaptation Model as a guide, this study investigated the relationship of anger expression and blood pressure (BP) among adolescents 16-18 years of age. Participants were 63 urban high school seniors. Measurements included the Anger Expression Inventory, a Demographic Questionnaire, and measures of systolic and diastolic blood pressure. Analysis revealed significant positive relationships between anger expression with blood pressure, and a significant inverse relationship between blood pressure and the control of anger for girls. No significant relationships between anger expression and blood pressure were noted for boys. The majority of students (53%) were found to have high normal or hypertensive blood pressure readings, putting them at increased cardiovascular risk.


Role of cytokine signaling during nervous system development.
Cytokines are signaling proteins that were first characterized as components of the immune response, but have been found to have pleiotropic effects in diverse aspects of body function in health and disease. They are secreted by numerous cells and are used extensively in intercellular communications to produce different activities, including intricate processes engaged in the ontogenetic development of the brain. This review discusses factors involved in brain growth regulation and recent findings exploring cytokine signaling pathways during development of the central nervous system. In view of existing data suggesting roles for neurotropic cytokines in promoting brain growth and repair, these molecules and their signaling pathways might become targets for therapeutic intervention in neurodegenerative processes due to diseases, toxicity, or trauma.


[Lipid metabolism in man--new knowledge on molecular level gives hope for better therapy].
Application of the techniques of molecular biology to the study of cholesterol and lipoprotein metabolism in recent years has led to a dramatic increase in our knowledge of this field. This brief review provides a general outline of normal lipoprotein and cholesterol metabolism; some recent advances in research are discussed, and the molecular defects present in hypobetalipoproteinaemia, familial apo B-100 deficiency, type III hyperlipoproteinaemia, and familial hypercholesterolaemia are described and their clinical relevance is discussed. New aspects are presented of the finely tuned regulation of cholesterol synthesis, and its importance in treatment of hypercholesterolaemia is discussed, as is its possible involvement in oncogen expression.


Histidine-Rich Protein Accelerates the Biomineralization of Zeolitic Imidazolate Frameworks for In Vivo Protein Delivery.
Biomineralization of metal-organic frameworks (MOFs) provides a powerful approach for intracellular protein delivery, enabling the study of biological function and therapeutic potential of proteins. However, the potency of this approach is largely challenged by the low efficiency of current strategies for interfacing proteins with MOFs for biomineralization and intracellular delivery. Here, we report a versatile and convenient biomineralization strategy for the rapid encapsulation and enhanced delivery of proteins using MOFs, accelerated by histidine-rich proteins. We demonstrate that the histidine-rich green fluorescent protein (H39GFP) can accelerate the biomineralization of MOFs by promoting the coordination between proteins and metal ions, leading to enhanced protein delivery efficiency up to 15-fold. Moreover, we show that the delivery of H39GFP-fused cytotoxic ribonuclease and bacterial-derived RAS protease can effectively inhibit tumor cell growth. The strategy of promoting the biomineralization of MOFs via histidine-rich proteins for enhanced intracellular delivery could be expanded to other biomacromolecules, advancing their therapeutic potential and the biomedical scope of MOFs.


Using Best Practices to Extract, Organize, and Reuse Embedded Decision Support Content Knowledge Rules from Mature Clinical Systems.
Clinical decision support (CDS) knowledge, embedded over time in mature medical systems, presents an interesting and complex opportunity for information organization, maintenance, and reuse. To have a holistic view of all decision support requires an in-depth understanding of each clinical system as well as expert knowledge of the latest evidence. This approach to clinical decision support presents an opportunity to unify and externalize the knowledge within rules-based decision support. Driven by an institutional need to prioritize decision support content for migration to new clinical systems, the Center for Knowledge Management and Health Information Technology teams applied their unique expertise to extract content from individual systems, organize it through a single extensible schema, and present it for discovery and reuse through a newly created Clinical Support Knowledge Acquisition and Archival Tool (CS-KAAT). CS-KAAT can build and maintain the underlying knowledge infrastructure needed by clinical systems.


Role of oxidized low-density lipoprotein in renal disease.
Accelerated atherosclerosis is often observed in patients with chronic renal failure. In the present review we summarize and discuss the recent literature on the pathogenic role of low-density lipoproteins modified by oxidative processes in atherosclerosis and the possible role in renal diseases. Pathogenetically, the oxidation of low-density lipoproteins is considered to be a key event in the development of atherosclerosis, in part by causing enhanced uptake of lipids by macrophages. In addition, oxidation of low-density lipoproteins exerts cytotoxic, proinflammatory and immunogenic properties, all of which could potentially contribute to the development and progression of atherosclerosis.