Batch analysis of microplastics in water using multi-angle static light scattering and chemometric methods.
Size and concentration are two important parameters for the analysis of microplastics (MPs) in water. The analytical tools reported so far extract this information in a single-particle analysis mode, dramatically increasing the analysis time. Here, we present a combination of multi-angle static light scattering technique, called "Goniophotometry", with chemometric multivariate data processing for the batch analysis of size and concentration of MPs in water. Nine different sizes of polystyrene (PS) MPs with diameters between 500 nm and 20 μm are investigated in two different scenarios with uniform (monodisperse) and non-uniform (polydisperse) size distribution of MPs, respectively. It is shown that Principal Component Analysis (PCA) can reveal the existing relationship between the scattering data of mono- and polydisperse samples according to the size distribution of MPs in mixtures. Therefore, a Linear Discriminant Analysis (LDA) model is constructed based on the PCA of scattering data of PS monodisperse samples and is subsequently employed to classify the size of MPs not only in unknown mono- and polydisperse PS samples, but also for other types of MPs such as Polyethylene (PE) and Polymethylmethacrylate (PMMA). When the size of MPs is classified, their concentration is measured using a simple linear fit. Finally, a Linear Least Square (LLS) model is used to evaluate the reproducibility of the measurements.


Detection of Pedestrians in Reverse Camera Using Multimodal Convolutional Neural Networks.
In recent years, the application of artificial intelligence (AI) in the automotive industry has led to the development of intelligent systems focused on road safety, aiming to improve protection for drivers and pedestrians worldwide to reduce the number of accidents yearly. One of the most critical functions of these systems is pedestrian detection, as it is crucial for the safety of everyone involved in road traffic. However, pedestrian detection goes beyond the front of the vehicle; it is also essential to consider the vehicle's rear since pedestrian collisions occur when the car is in reverse drive. To contribute to the solution of this problem, this research proposes a model based on convolutional neural networks (CNN) using a proposed one-dimensional architecture and the Inception V3 architecture to fuse the information from the backup camera and the distance measured by the ultrasonic sensors, to detect pedestrians when the vehicle is reversing. In addition, specific data collection was performed to build a database for the research. The proposed model showed outstanding results with 99.85% accuracy and 99.86% correct classification performance, demonstrating that it is possible to achieve the goal of pedestrian detection using CNN by fusing two types of data.


Distribution of salicylic acid in human stratum corneum following topical application in vivo: a comparison of six different formulations.
Distribution of salicylic acid in human stratum corneum from treatment of six different formulations was assessed by quantitation of drug content in sequentially tape-stripped stratum corneum after a single 2-h dose was applied unoccluded to skin on the ventral forearm of four female subjects. The profile and total amounts of stratum corneum removed in 20 tape-strips varied among different types of formulations. With or without normalization by the total stratum corneum weights removed, the extent of drug delivery to the stratum corneum decreased in the following order: SA (5%) > > SAC (10%), Duofilm (16.7%) > TSSS (2%) > SAO (10%), Salic (2.5%), the percentage in parentheses indicating the salicylic acid concentration in each formulation. The greatest topical bioavailability was observed for the alcoholic solution containing glycerol (SA). The 10% collodion formulation (SAC) was found to deliver an amount of salicylic acid into the stratum corneum 2-fold greater than 10% ointment formulation (SAO). Use of absorption ointment (TSSS) also increased the uptake of salicylic acid into the stratum corneum in comparison with formulations based on simple ointment (SAO) and oil in water (o/w) cream (Salic). The partitioning of salicylic acid from collodion formulations (SAC and Duofilm) appeared to be concentration-independent. The results of this study indicate that topical bioavailability of salicylic acid in the stratum corneum varies substantially among different formulations.


[Peripheral nervous system and grounds for the neural insult in leprosy].
The mechanism of interaction between Mycobacterium leprae and neural cells has not been elucidated so far. No satisfactory interpretation exists as to the bacterium tropism to the peripheral nervous system in particular. The present study is a review of the micro-physiology of the extracellular apparatus attached to Schwann cells, as well as on the description of morphological units probably involved in the process of the binding to the bacterial wall.


Retinol-Binding Protein-Dependent Cholesterol Uptake Regulates Macrophage Foam Cell Formation and Promotes Atherosclerosis.
Retinol-binding protein 4 (RBP4) is an adipokine that plays decisive roles in glucose metabolism and insulin sensitivity. Elevated circulating RBP4 levels were reported to be associated with increased risk for cardiovascular disease, but the precise role of RBP4 in atherosclerotic diseases and its mechanisms of action remain elusive. Serum RBP4 levels of 1683 participants from South China were evaluated and the occurrence of major adverse cardiovascular events was followed up for 5 years. Apolipoprotein E-deficient mice infected with RBP4-overexpressing/silencing adenovirus, J774A.1 macrophages, and primary peritoneal macrophages from RBP4 transgenic mice were used for investigating the function of RBP4 in foam cell formation. Prospective cohort studies revealed that baseline serum RBP4 level was an independent predictor for incidence of adverse cardiovascular events after adjustment for traditional risk factors. Increased RBP4 expression was observed in atherosclerotic lesions of aortic specimens from both humans and apolipoprotein E-deficient mice, and RBP4 was localized to areas rich in macrophage foam cells. RBP4 inhibition attenuated whereas overexpression accelerated atherosclerosis progression in apolipoprotein E-deficient mice. Both treatment with exogenous recombinant RBP4 and overexpression of RBP4 gene promoted macrophage-derived foam cell formation through the activation of scavenger-receptor CD36-mediated cholesterol uptake, and RBP4 transcriptionally upregulated CD36 expression in a manner dependent on jun N-terminal kinase and signal transducer and activator of transcription 1. The tyrosine kinase c-Src was identified as the upstream regulator of jun N-terminal kinase-signal transducer and activator of transcription 1-mediated CD36-dependent cholesterol uptake, and RBP4 challenge was found to alter the membrane distribution of c-Src and cause c-Src to partition into lipid-raft membrane subdomains, where the kinase was activated. Lastly, Toll-like receptor 4, but not retinol or stimulated by retinoic acid 6, mediated the inductive effects of RBP4 in macrophages. Inclusion of RBP4 levels in traditional models enhances the predictive ability for the incidence of atherosclerotic events. RBP4 promotes atherogenesis by inducing macrophage-derived foam cell formation.


Chronic α-hydroxyisocaproic acid treatment improves muscle recovery after immobilization-induced atrophy.
Muscle disuse atrophy is observed routinely in patients recovering from traumatic injury and can be either generalized resulting from extended bed rest or localized resulting from single-limb immobilization. The present study addressed the hypothesis that a diet containing 5% α-hydroxyisocaproic acid (α-HICA), a leucine (Leu) metabolite, will slow the loss and/or improve recovery of muscle mass in response to disuse. Adult 14-wk-old male Wistar rats were provided a control diet or an isonitrogenous isocaloric diet containing either 5% α-HICA or Leu. Disuse atrophy was produced by unilateral hindlimb immobilization ("casting") for 7 days and the contralateral muscle used as control. Rats were also casted for 7 days and permitted to recover for 7 or 14 days. Casting decreased gastrocnemius mass, which was associated with both a reduction in protein synthesis and S6K1 phosphorylation as well as enhanced proteasome activity and increased atrogin-1 and MuRF1 mRNA. Although neither α-HICA nor Leu prevented the casting-induced muscle atrophy, the decreased muscle protein synthesis was not observed in α-HICA-treated rats. Neither α-HICA nor Leu altered the increased proteasome activity and atrogene expression observed with immobilization. After 14 days of recovery, muscle mass had returned to control values only in the rats fed α-HICA, and this was associated with a sustained increase in protein synthesis and phosphorylation of S6K1 and 4E-BP1 of previously immobilized muscle. Proteasome activity and atrogene mRNA content were at control levels after 14 days and not affected by either treatment. These data suggest that whereas α-HICA does not slow the loss of muscle produced by disuse, it does speed recovery at least in part by maintaining an increased rate of protein synthesis.


Simultaneous hydrogen production and pollutant removal from olive mill wastewaters using electrohydrolysis process.
Management of olive mill wastewaters is one of the most challenging environmental issue in Mediterranean countries due to its high organic load, color, presence of phenolic compounds and need for high energy cost. Performance of electrohydrolysis (EH) process in terms of removal of organic compounds, detoxification and discoloration of olive mill wastewater (OMW) with simultaneous energy production in the hydrogen gas form has been investigated using aluminum electrodes. Different reaction times and electric potential gradients have been tested in order to determine the most effective conditions for removal of pollutants. The optimum reaction time and current were determined as 8 h and 8 V, respectively. Under these conditions, removal efficiencies for tCOD, suspended solids, color and phenol were obtained as 73%, 84%, 91% and 75%, respectively. At the end of the operating period of 8 h, 1037 ml hydrogen gas was obtained. The results show that electrohydrolysis process can be used as an alternative solution for the management of OMW and the process can be upgraded with a better reactor design or combined with different treatment processes to achieve a better effluent quality to meet discharge standards.


Evaluation of two-dimensional and three-dimensional ultrasound in the assessment of thyroid volume of the Indo-Pacific bottlenose dolphin (Tursiops aduncus).
The assessment of thyroid volume plays an indispensable role in the diagnosis and management of different thyroid diseases. The present study evaluates the accuracy of dolphin thyroid volume measurement as determined by four two-dimensional (2D) ultrasound methods (A-D), with a standard of reference using three-dimensional (3D) ultrasound. The measurement accuracy for different recognized thyroid configuration is also evaluated. Inter- and intraoperator variability of the measurement methods was determined. Thyroid ultrasound examinations were conducted in 16 apparently healthy Indo-Pacific bottlenose dolphins (Tursiops aduncus) with 2D and 3D ultrasound under identical scanning conditions. All 2D ultrasound measurement methods yielded high accuracies (79.9-81.3%) when compared with the 3D ultrasound measurement, and had high measurement reproducibility (77.6-86.2%) and repeatability (78.1-99.7%). For 2D ultrasound measurements, Methods A and B were more accurate and reliable than Methods C and D, regardless of thyroid configuration. Ultrasound is useful in the measurement of thyroid volume in bottlenose dolphins. For the first time, a reliable ultrasound scanning protocol for measuring dolphin thyroid volume was developed, which provides a means to establish a normative reference for the diagnosis of thyroid pathologies and to monitor the thyroid volume during the course of treatment in living dolphins. Key words: 3D ultrasound, Indo-Pacific bottlenose dolphin, thyroid volume measurement, Tursiops aduncus.


Temperature sensitivity of poly(ADP-ribose) synthetase in intact cells.
The response of cells to various poly(ADP-ribose) synthetase inhibitors may vary with the cell type and inhibitor type. We have observed that most cells show an inhibition of growth, at least transiently, when exposed to synthetase inhibitors. For one cell type, there is, in contrast, a stimulation of proliferation. These results suggest that the synthetase plays different roles in different cell types or, the inhibitors also affect other cell processes that are variably represented in the different cell types. Because of these difficulties we have sought alternative methods of modulating poly(ADP-ribose) synthetase activity in intact cells. A method of inactivating the synthetase by heat shock is described and the consequences of this inactivation for the repair of single strand breaks in DNA is presented. Additionally, a method for elevating the synthetase in intact cells is given.


An Integrative Approach to Inform Optimal Administration of OX40 Agonist Antibodies in Patients with Advanced Solid Tumors.
The success of checkpoint blockade has led to a significant increase in the development of a broad range of immunomodulatory molecules for the treatment of cancer, including agonists against T-cell costimulatory receptors, such as OX40. Unlike checkpoint blockade, where complete and sustained receptor saturation may be required for maximal activity, the optimal dosing regimen and receptor occupancy for agonist agents is less well understood and requires further study. We integrated both preclinical and clinical biomarker data sets centered on dose, exposure, receptor occupancy, receptor engagement, and downstream pharmacodynamic changes to model the optimal dose and schedule for the OX40 agonist antibody BMS-986178 alone and in combination with checkpoint blockade. Administration of the ligand-blocking anti-mouse surrogate antibody OX40.23 or BMS-986178 as monotherapy or in combination with checkpoint blockade led to increased peripheral CD4+ and CD8+ T-cell activation in tumor-bearing mice and patients with solid tumors, respectively. OX40 receptor occupancy between 20% and 50% both in vitro and in vivo was associated with maximal enhancement of T-cell effector function by anti-OX40 treatment, whereas a receptor occupancy > 40% led to a profound loss in OX40 receptor expression, with clear implications for availability for repeat dosing. Our results highlight the value of an integrated translational approach applied during early clinical development to aggregate preclinical and clinical data in an effort to define the optimal dose and schedule for T-cell agonists in the clinic.


Parallel regulation of constitutive NO synthase and renin at JGA of rat kidney under various stimuli.
Four chronic experiments were performed to assess changes in the activity and gene expression of type I nitric oxide synthase (NOS) at the macula densa (MD) and of renin expression and immunoreactivity (IR) at the juxtaglomerular apparatus (JGA) of rat kidney, as follows: 1) two-kidney, one-clip Goldblatt hypertension (2K1C, for 3 and 40 days; sham operation for controls), 2) furosemide treatment (150 mg/kg-1.day-1 ip for 5 days), 3) chronic low-salt diet (0.02%) vs. high-salt diet (3%; both for 11 days), and 4) chronic blockade of NOS by nitro-L-arginine methyl ester (L-NAME, 40 mg.kg-1.day-1 for 2 mo). NOS and renin gene expression, NOS enzyme activity and renin IR were semiquantitatively evaluated with histochemical methods (NADPH diaphorase, in situ hybridization, immunohistochemistry). In 2K1C, marked increases were induced in NOS and renin in the ischemic vs. contralateral kidneys both after 3 and 40 days, respectively (P < 0.05). Related to controls, significant increases in the ischemic kidney were encountered after 3 and 40 days, whereas contralateral suppression of NOS and renin was found only after 40 days. Furosemide treatment resulted in a marked increase of both NOS and renin levels compared with controls (P < 0.05). Salt restriction induced a significant elevation of NOS levels compared with salt loading (P < 0.05), whereas only minor changes were evident in renin levels. L-NAME treatment resulted in a moderate reduction of NOS activity (not significant), whereas renin levels were markedly reduced (P < 0.05). These results show that NOS activity and gene expression are inversely related to chronic changes in renal perfusion, salt balance, and salt transport at the distal tubule in parallel with the known response of renin to these changes. Inhibition of NOS decreases renin levels at the JGA. The histochemical findings support previous concepts that MD-derived NO is involved in the control of renin synthesis.


How do aeration mode and influent carbon/nitrogen ratio affect pollutant removal, gas emission, functional genes and bacterial community in subsurface wastewater infiltration systems?
This study investigated the influences of aeration mode and influent carbon/nitrogen ratio on matrix oxygen concentration, pollutant removal, greenhouse gas emission, functional gene abundances and bacterial community in subsurface wastewater infiltration systems (SWISs). Intermittent or continuous aeration enhanced oxygen supply at 0.6 m depth in the matrix, which improved organics removal, nitrogen removal, the abundances of bacterial 16S rRNA, amoA, nxrA, narG, napA, nirK, nirS, norB, nosZ genes, bacterial community Alpha diversity, the relative abundances of Actinobacteria at 0.6 m depth, the relative abundances of Chloroflexi, Gemmatimonadetes, Bacteroidetes and Firmicutes at 0.9 and 1.2 m depth and reduced CH4 and N2O conversion efficiencies, the abundance of mcrA gene with carbon/nitrogen ratio of 12 and 16 compared with non-aeration. Increased carbon/nitrogen ratio resulted in higher TN removal efficiencies and lower CH4 and N2O conversion efficiencies in aeration SWISs than those in non-aeration SWIS. Intermittent aeration SWIS obtained high removal efficiencies of 83.2, 85.4 and 90.8% for TN, NH4+ -N and COD and low conversion efficiency of 0.21 and 0.65% for N2O and CH4 with optimal carbon/nitrogen ratio of 12. However, high TN (82.6%), NH4+ -N (84.9%) and COD (92.2%) removal efficiencies and low CH4 (0.67%) and N2O (0.23%) conversion efficiencies were achieved in continuous aeration SWIS with carbon/nitrogen ratio of 16.


Limb hemodynamics after aortic aneurysm resection.
Preoperative ankle/arm indices were determined in 104 lower extremities from 53 patients who underwent prosthetic graft placement for abdominal aortic aneurysms. Sixty-nine percent of the limbs (group 1) had a normal index; 31% of the limbs (group 2) had indices indicative of arterial occlusive disease. Early postoperative ankle/arm indices were determined in 87 limbs (57 in group 1 and 30 in group 2). Twelve group 1 limbs exhibited a postoperative decrease in the index. In group 2, four of the five decreases were seen when the distal anastomosis was placed above the inguinal ligament, while all 17 group 2 limbs in which the index increased had the distal anastomoses performed at the common femoral level. In 1.8% of the group 1 limbs and 6.7% of the group 2 limbs, a subsequent arterial procedure below the inguinal ligament was required. An additional 1.8% of group 1 limbs and 6.7% of group 2 limbs had undergone a distal arterial procedure prior to aneurysm resection.


A biodistribution study of two differently shaped plant virus nanoparticles reveals new peculiar traits.
Self-assembling plant virus nanoparticles (pVNPs) have started to be explored as nanometre-sized objects for biomedical applications, such as vaccine or drug delivery and imaging. Plant VNPs may be ideal tools in terms of biocompatibility and biodegradability endowed with a wide diversity of symmetries and dimensions, easy chemical/biological engineering, and rapid production in plants. Recently, we defined that icosahedral Tomato bushy stunt virus (TBSV) and filamentous Potato virus X (PVX) are neither toxic nor teratogenic. We report here the results of an interdisciplinary study aimed to define for the first time the biodistribution of unlabelled, unpegylated, underivatized TBSV and PVX by proved detecting antibodies. These data add new insights on the in vivo behaviour of these nano-objects and demonstrate that the pVNPs under scrutiny are each intrinsically endowed with peculiar properties foreshadowing different applications in molecular medicine.


Global molecular changes in a tibial compression induced ACL rupture model of post-traumatic osteoarthritis.
Joint injury causes post-traumatic osteoarthritis (PTOA). About ∼50% of patients rupturing their anterior cruciate ligament (ACL) will develop PTOA within 1-2 decades of the injury, yet the mechanisms responsible for the development of PTOA after joint injury are not well understood. In this study, we examined whole joint gene expression by RNA sequencing (RNAseq) at 1 day, 1-, 6-, and 12 weeks post injury, in a non-invasive tibial compression (TC) overload mouse model of PTOA that mimics ACL rupture in humans. We identified 1446 genes differentially regulated between injured and contralateral joints. This includes known regulators of osteoarthritis such as MMP3, FN1, and COMP, and several new genes including Suco, Sorcs2, and Medag. We also identified 18 long noncoding RNAs that are differentially expressed in the injured joints. By comparing our data to gene expression data generated using the surgical destabilization of the medial meniscus (DMM) PTOA model, we identified several common genes and shared mechanisms. Our study highlights several differences between these two models and suggests that the TC model may be a more rapidly progressing model of PTOA. This study provides the first account of gene expression changes associated with PTOA development and progression in a TC model. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 35:474-485, 2017.


Disease-free probability after the first primary ductal carcinoma in situ of the breast: a comparison between African-American and White-American women.
Compelling evidence about the differences in the biology and behavior of invasive breast cancer between African-American (AA) and White-American (WA) women motivate inquiry into comparing the clinicopathology of non-invasive breast cancer (ductal carcinoma in situ, DCIS). AA and WA women diagnosed with their first primary DCIS between 1990 and 1999 were identified from the institutional tumor registry. Data on method of presentation, treatment, and patient characteristics were retrieved from electronic medical records. Patients were followed up through the medical records until the diagnosis of a subsequent cancer or the last day of contact with the institution. A total of 100 (29.6%) AAs and 236 (70.4%) WAs with the mean age of 60 (SD ± 13) and 57 (SD ± 12), respectively, contributed to this study. DCIS was detected during routine screening mammography for 81% (n = 81) of AAs and 88.4% (n = 206) of WAs (P = 0.073). Differences in the distributions of grade, margin status, necrosis, or treatment modalities were not statistically significant between AAs and WAs. Analysis of competing risks Cox proportional hazard multivariate modeling yielded a significant 8-year cumulative risk of a second cancer for AAs but only in the ipsilateral breast (HR = 3.96, 95% CI 1.42-11.04, P = 0.01). Despite comparable clinical presentation and treatment, 8 years after the initial treatment, AAs experienced a higher risk of second breast cancer in ipsilateral but not in the contralateral breast. The observed excess risk of a second cancer in the ipsilateral breast may suggest of intrinsic differences in the biology of cancer.


Conserved expression of the Arabidopsis ACT1 and ACT 3 actin subclass in organ primordia and mature pollen.
We have proposed that ancient and divergent classes of plant actin genes have been preserved throughout vascular plant evolution, because they have distinct patterns of gene regulation. The hypothesis was explored for ACT1 and ACT3, which represent one of the six ancient subclasses in the Arabidopsis actin gene family. Comparison of ACT1 and ACT3 cDNA and genomic sequences revealed highly divergent flaking and intron sequences, whereas they encoded nearly identical proteins. Quantification of their level of divergence suggests that they have not shared a common ancestor for 30 to 60 million years. Gene-specific RNA gel blot hybridization and reverse transcriptase-polymerase chain reaction analyses demonstrated that the distribution of ACT1 and ACT3 mRNAs was very similar: both preferentially accumulated at high levels in mature pollen and at very low levels in the other major organs. The 5' flanking regions of both genes, including the promoter, leader exon and intron, and the first 19 condons, were fused to the beta-glucuronidase (GUS) reporter gene. The expression of these reporter fusions was examined in a large number of transgenic Arabidopsis plants. Histochemical assays demonstrated that both ACT1-GUS and ACT3-GUS constructs were expressed preferentially in pollen, pollen tubes, and in all organ primordia, including those in roots shoots, and the inflorescence. Comparison of the 5' flanking regions of ACT1 and ACT3 revealed a number of short conserved sequences, which may direct their common transcriptional and post-transcriptional regulation. The expression patterns observed were distinct from those of any other other Arabidopsis actin subclass. The conservation of their expression pattern and amino acid sequences suggests that this actin subclass plays a distinct and required role in the plant cytoskeleton.


The Role of Phylogenetically Conserved Elements in Shaping Patterns of Human Genomic Diversity.
Evolutionary genetic studies have shown a positive correlation between levels of nucleotide diversity and either rates of recombination or genetic distance to genes. Both positive-directional and purifying selection have been offered as the source of these correlations via genetic hitchhiking and background selection, respectively. Phylogenetically conserved elements (CEs) are short (∼100 bp), widely distributed (comprising ∼5% of genome), sequences that are often found far from genes. While the function of many CEs is unknown, CEs also are associated with reduced diversity at linked sites. Using high coverage (>80×) whole genome data from two human populations, the Yoruba and the CEU, we perform fine scale evaluations of diversity, rates of recombination, and linkage to genes. We find that the local rate of recombination has a stronger effect on levels of diversity than linkage to genes, and that these effects of recombination persist even in regions far from genes. Our whole genome modeling demonstrates that, rather than recombination or GC-biased gene conversion, selection on sites within or linked to CEs better explains the observed genomic diversity patterns. A major implication is that very few sites in the human genome are predicted to be free of the effects of selection. These sites, which we refer to as the human "neutralome," comprise only 1.2% of the autosomes and 5.1% of the X chromosome. Demographic analysis of the neutralome reveals larger population sizes and lower rates of growth for ancestral human populations than inferred by previous analyses.


Anti-obesity Effect of Fermented Persimmon Extracts via Activation of AMP-Activated Protein Kinase.
There is significant cultivation of persimmon (Diospyros kaki) in East Asia, a plant whose fruit has abundant nutrients, including vitamins, polyphenols, and dietary fiber. Persimmon dietary supplements can benefit health by amelioration of diabetes, cardiovascular disease, and obesity. There are also persimmon-based beverages produced via fermentation, such as wines and vinegars, and increasing consumption of these products in East Asia. Although there is great interest in functional foods, the health effects of fermented persimmon extract (FPE) are completely unknown. We examined the effects of FPE on the metabolic parameters of mice fed a high-fat diet (HFD). Our results indicated that FPE supplementation led to an approx. 15% reduction of body weight, reduced abdominal and liver fat, and reduced serum levels of triglycerides, total cholesterol, and glucose. FPE also blocked the differentiation of murine 3T3-L1 pre-adipocyte cells into mature adipocytes. We suggest that gallic acid is a major bioactive component of FPE, and that AMP-activated protein kinase mediates the beneficial effects of FPE and gallic acid.


The effect of motility and cell-surface polymers on bacterial attachment.
Recently it was shown that motility of Vibrio alginolyticus facilitated cell attachment to glass surfaces. In the present study the same relationship between motility and cell attachment was confirmed for Alcaligenes and Alteromonas spp. These findings clearly answer a long-standing question: does motility facilitate attachment? However, they are contradictory to a general view on cell attachment that the energy barrier due to electrostatic repulsion between negatively charged bacterial cells and a glass surface is much greater than both the thermal kinetic energy of the bacterial cell and the bacterial swimming energy. It is shown that the energy barrier becomes far less than that usually estimated when bacterial cells are rich in polymers at their surfaces. This finding reasonably explains the dependence of bacterial attachment rate on cell motility and demands reconsideration of the mechanism of bacterial attachment.


Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent.
The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis (CF) patients. P. aeruginosa colonizes the CF lungs by forming biofilm structures in the alveoli. In the biofilm mode of growth the bacteria are highly tolerant to otherwise lethal doses of antibiotics and are protected from bactericidal activity of polymorphonuclear leukocytes (PMNs). P. aeruginosa controls the expression of many of its virulence factors by means of a cell-cell communication system termed quorum sensing (QS). In the present report it is demonstrated that biofilm bacteria in which QS is blocked either by mutation or by administration of QS inhibitory drugs are sensitive to treatment with tobramycin and H2O2, and are readily phagocytosed by PMNs, in contrast to bacteria with functional QS systems. In contrast to the wild-type, QS-deficient biofilms led to an immediate respiratory-burst activation of the PMNs in vitro. In vivo QS-deficient mutants provoked a higher degree of inflammation. It is suggested that quorum signals and QS-inhibitory drugs play direct and opposite roles in this process. Consequently, the faster and highly efficient clearance of QS-deficient bacteria in vivo is probably a two-sided phenomenon: down regulation of virulence and activation of the innate immune system. These data also suggest that a combination of the action of PMNs and QS inhibitors along with conventional antibiotics would eliminate the biofilm-forming bacteria before a chronic infection is established.


Use of cytokines in infection.
Infectious disease remains an ever-growing health concern worldwide due to increasing antibiotic-resistant microbial strains, immune-compromised populations, international traffic and globalisation, and bioterrorism. There exists an urgent need to develop novel prophylactic and therapeutic strategies. In addition to classic antibiotic therapeutics, immune-modulatory molecules such as cytokines or their inhibitors represent a promising form of antimicrobial therapeutics or immune adjuvant used for the purpose of vaccination. These molecules, in the form of either recombinant protein or transgene, exert their antimicrobial effect by enhancing infectious agent-specific immune activation or memory development, or by dampening undesired inflammatory and immune responses resulting from infection and host defence mechanisms. In the last two decades, a number of cytokine therapy-based experimental and clinical trials have been conducted, and some of these efforts have led to the routine clinical use of cytokines. For instance, although IFNs have been used to treat hepatitis C with great success, many other cytokines are yet to be fully evaluated for their antimicrobial potential. This review discusses the biology and therapeutic potential of selected immune modulatory cytokines and their inhibitors, including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IFN-gamma, IL-12 and TNF.


A rich and bountiful harvest: Key discoveries in plant cell biology.
The field of plant cell biology has a rich history of discovery, going back to Robert Hooke's discovery of cells themselves. The development of microscopes and preparation techniques has allowed for the visualization of subcellular structures, and the use of protein biochemistry, genetics, and molecular biology has enabled the identification of proteins and mechanisms that regulate key cellular processes. In this review, seven senior plant cell biologists reflect on the development of this research field in the past decades, including the foundational contributions that their teams have made to our rich, current insights into cell biology. Topics covered include signaling and cell morphogenesis, membrane trafficking, cytokinesis, cytoskeletal regulation, and cell wall biology. In addition, these scientists illustrate the pathways to discovery in this exciting research field.


Building a smart surface with converse temperature-dependent wettability based on poly(acrylamide-co-acrylonitrile).
A smart surface with converse temperature-dependent (CTD) wettability was fabricated from an upper critical solution temperature-type (UCST-type) poly(acrylamide-co-acrylonitrile) (P(AAm-co-AN)) copolymer. The obtained surface exhibits a remarkable and reversible hydrophobic-hydrophilic transition depending on temperature with a high response rate. The static water contact angle of the surface decreases from 103° ± 2° to 60° ± 1° as the temperature increases from 30 °C to 80 °C. Further, the wettability of the UCST-type surface shows a positive linear relationship between wettability and temperature. This study for the first time provides an UCST-type smart surface with wettability that decreases by over 35° as the temperature increases by only 20 °C.


Stigma doesn't discriminate: physical and mental health and stigma in Canadian military personnel and Canadian civilians.
Illness-related stigma has been identified as an important public health concern. Past research suggests there is a disproportionate risk of mental-health stigma in the military, but this same finding has not yet been established for physical-health stigma. The current study aimed to assess the independent contribution of mental and physical health on both enacted stigma (discriminatory behaviour) and felt stigma (feelings of embarrassment) and to determine whether these associations were stronger for military personnel than civilians. Data were obtained from the 2002 Canadian Community Health Survey - Mental Health and Well-being and its corresponding Canadian Forces Supplement. Logistic regressions were used to examine a potential interaction between population (military [N = 1900] versus civilian [N = 2960]), mental health, and physical health in predicting both enacted and felt stigma, with adjustments made for socio-demographic information, mental health characteristics, and disability. Mental health did not predict enacted or felt stigma as a main effect nor in an interaction. There was a strong link between physical health and enacted and felt stigma, where worse physical health was associated with an increased likelihood of experiencing both facets of stigma. The link between physical health and enacted stigma was significantly stronger for military personnel than for civilians. Physical health stigma appears to be present for both civilians and military personnel, but more so for military personnel. Elements of military culture (e.g., the way care is sought, culture of toughness, strict fitness requirements) as well as the physical demands of the job could be potential predictors of group differences.


[Chlamydiosis of urogenitary tract in humans].
Chlamydiae are bacteria commonly found in the environment of human life and they cause many diseases. Chlamydial infections are common among men and women, although they are more often diagnosed in women and they are frequently asymptomatic, due to the biology of chlamydiae. Incorrectly diagnosed and untreated, they cause many complications which can lead to infertility in both, men and women. This work presents the diseases caused by chlamydiae of the urogenitary tract, including environmental chlamydiae, so far in Polish literature rarely presented, which extends the panel responsible for chlamydial genital tract disease, particularly in women. A major problem is that the knowledge of the immune mechanisms that occur in the case of infection with these bacteria, especially in view of prevention of these infection, mainly in the context of creation of the vaccine. Also important fact from the knowledge of immunity in chlamydiosis is base for diagnosis of these infection.


Nuclear import of the varicella-zoster virus latency-associated protein ORF63 in primary neurons requires expression of the lytic protein ORF61 and occurs in a proteasome-dependent manner.
Varicella-zoster virus (VZV) open reading frame (ORF) 63 protein (ORF63p) is one of six VZV ORFs shown to be transcribed and translated in latently infected human dorsal root ganglia. ORF63p accumulates exclusively in the cytoplasm of latently infected sensory neurons, whereas it is both nuclear and cytoplasmic during lytic infection and following reactivation from latency. Here, we demonstrate that infection of primary guinea pig enteric neurons (EN) with an adenovirus expressing ORF63p results in the exclusive cytoplasmic localization of the protein reminiscent of its distribution during latent VZV infection in humans. We show that the addition of the simian virus 40 large-T-antigen nuclear localization signal (NLS) results in the nuclear import of ORF63p in EN and that the ORF63p endogenous NLSs are functional in EN when fused to a heterologous protein. These data suggest that the cytoplasmic localization of ORF63p in EN results from the masking of the NLSs, thus blocking nuclear import. However, the coexpression of ORF61p, a strictly lytic VZV protein, and ORF63p in EN results in the nuclear import of ORF63p in a proteasome-dependent manner, and both ORF63p NLSs are required for this event. We propose that the cytoplasmic localization of ORF63p in neurons results from NLS masking and that the expression of ORF61p removes this block, allowing nuclear import to proceed.


Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat.
Vitamin A deficiency leads to focal metaplasia of numerous epithelial tissues with altered differentiation from columnar (in general) to stratified squamous cells. This process can be reversed with vitamin A repletion. Previously, we described a system of retinoic acid (RA) synthesis in the cycling rat uterus consisting of cellular retinol binding protein (Crbp), epithelial retinol dehydrogenase (eRoldh), retinal dehydrogenase 2 (Aldh1a2), and cellular retinoic acid binding protein type II (Crabp2). Western blot analysis, RT-PCR, and immunohistochemistry were performed to test whether this retinoic acid synthesis system was also present in other vitamin A sensitive tissues. We found that combinations of Crbp, eRoldh, Aldh1a2 or Aldh1a3, and Crabp2 were present in all vitamin A sensitive tissues examined. In the ureter, while eRoldh was present, another short chain alcohol dehydrogenase reductase (possibly Roldh 1, 2, or 3) was in higher concentration in the transitional epithelia. In several tissues, Crbp, Aldh1a2, and/or Aldh1a3 localized to mesenchyme and/or epithelial cells, while eRoldh and Crabp2 were expressed only in epithelial cells. This suggests that mesenchymal-epithelial interactions may be as important in the adult as they are during development and that local synthesis of RA is important in maintenance of these tissues.


Case-control study on renal cell cancer and occupational exposure to trichloroethylene. Part I: Exposure assessment.
A method for a semi-quantitative retrospective assessment of exposure to trichloroethylene (TCE) was implemented for a case-control study conducted in the Arve valley (France), an area with a widely developed screw-cutting industry, where teams of occupational physicians have collected a large quantity of well-documented measurements. A task-exposure matrix was developed to link the main working circumstances in a screw-cutting workshop to corresponding TCE-exposure levels: a 'basic level' was assigned to each task, standing for usual working procedures; exposure circumstances, such as duration or distance from the TCE source, were introduced as corrective factors. In parallel, a detailed occupational questionnaire was designed, setting subjects' descriptions of their successive jobs and working circumstances against levels assessed in the matrix. Possible exposure to TCE, plus some other occupational compounds (other solvents, oils, some metals, asbestos, welding fumes and ionizing radiations), were assessed for any job in all job histories. An average level of exposure to TCE, related to an 8 h usual working day, was attributed to each job period in turn, which was then categorized into six classes: 0; 1-35; 35-50; 50-75; 75-100; and >100 p.p.m. A total of 402 study subjects described their occupational life (average 3.7 jobs/subject, from 1924 to 2003). About 19% of the 1486 job periods described were assessed as being exposed to TCE; of these, 72.2% involved levels<35 p.p.m., 13.2% involved levels>50 p.p.m. and 5.4% above the French occupational exposure limit of 75 p.p.m. (TWA 8 h). A total of 41 job periods included exposure with peaks. Compared with levels encountered in other studies, the more severely exposed part of our study population seemed more exposed than most other populations previously studied, owing to vapor degreasing practices.


Serum amyloid A and haptoglobin concentrations and liver fat percentage in lactating dairy cows with abomasal displacement.
There has been increased interest in measuring the serum concentration of acute phase reactants such as serum amyloid A [SAA] and haptoglobin [haptoglobin] in periparturient cattle in order to provide a method for detecting the presence of inflammation or bacterial infection. To determine whether [SAA] and [haptoglobin] are increased in cows with displaced abomasum as compared with healthy dairy cows. Fifty-four adult dairy cows in early lactation that had left displaced abomasum (LDA, n = 34), right displaced abomasum or abomasal volvulus (RDA/AV, n = 11), or were healthy on physical examination (control, n = 9). Inflammatory diseases or bacterial infections such as mastitis, metritis, or pneumonia were not clinically apparent in any animal. Jugular venous blood was obtained from all cows and analyzed. Liver samples were obtained by biopsy in cattle with abomasal displacement. [SAA] and [haptoglobin] concentrations were increased in cows with LDA or RDA/AV as compared with healthy controls. Cows with displaced abomasum had mild to moderate hepatic lipidosis, based on liver fat percentages of 9.3 +/- 5.3% (mean +/- SD, LDA) and 10.8 +/- 7.7% (RDA/AV). [SAA] and [haptoglobin] were most strongly associated with liver fat percentage, r(s) = +0.55 (P < .0001) and r(s) = +0.42 (P = .0041), respectively. An increase in [SAA] or [haptoglobin] in postparturient dairy cows with LDA or RDA/AV is not specific for inflammation or bacterial infection. An increase in [SAA] or [haptoglobin] may indicate the presence of hepatic lipidosis in cattle with abomasal displacement.


The prevalence of lower urinary tract symptoms (LUTS) and overactive bladder (OAB) by racial/ethnic group and age: results from OAB-POLL.
To estimate the prevalence of LUTS and OAB in a large, ethnically diverse US study. This cross-sectional, population-representative survey was conducted via the Internet in the US among 10,000 men and women aged 18-70 (2,000 African-Americans [AA], 2,000 Hispanics, 6,000 whites). The LUTS tool assessed how often participants experienced LUTS during the past 4 weeks on a five-point Likert scale. OAB was defined by the presence of urinary urgency ≥ "sometimes" or ≥ "often," and/or the presence of urgency urinary incontinence (UUI). Descriptive statistics were used to evaluate group differences. Logistic regression analyses were conducted to examine the impact of racial/ethnic group on OAB. Response rate, 56.7%. Prevalent LUTS included terminal dribble and nocturia across gender, post-micturition leaking (men), and stress incontinence (women). Prevalence of OAB ≥ "sometimes" and ≥ "often" were 17% and 8% in men and 30% and 20% in women--with significantly higher rates among AA men and women. A similar trend was found for UUI among men (AA, 10%; Hispanic and whites, 6%), while AA and white women had higher prevalence of UUI (19%) as compared to Hispanic women (16%). In logistic regression analyses, AA and Hispanic men and women were significantly more likely than whites to have OAB despite having lower prevalence of self-reported comorbid conditions and risk factors. LUTS and OAB are highly prevalent in both men and women and increase with advancing age. Further, racial/ethnic group is a robust predictor of OAB in men and women.


[Intestine infections, inflammation and autoimmunity. Trigger and effector mechanisms of autoimmune disease development as an outcome of intestinal infections].
Problem of interconnection of intestine infections, inflammatory intestine diseases and autoimmune illnesses in this article is examined from the position of their trigger and effector mechanisms. Among trigger mechanisms special attention is given to mechanisms by which the presence of pathogenic microbial causative agent in the organism is transformed into an autoimmune process. The phenomenon of antigen mimicry, carriage of superantigens by pathogenic agents, the role of cell apoptosis are accentuated. Autoimmune diseases are examined in the same way as genetically determined phenomenon with designation of main genes, polymorphism of which is involved in the development of this pathology. Among effector reactions accompanying the development of autoimmune process againstthe background of intestine infections the role of B1 lymphocytes, Th17 and Th1 are analyzed in more detail. Special attention is given to pathogenetic and protective role of natural killers which is recognized as relatively understudied.


Structure-based design and classifications of small molecules regulating the circadian rhythm period.
Circadian rhythm is an important mechanism that controls behavior and biochemical events based on 24 h rhythmicity. Ample evidence indicates disturbance of this mechanism is associated with different diseases such as cancer, mood disorders, and familial delayed phase sleep disorder. Therefore, drug discovery studies have been initiated using high throughput screening. Recently the crystal structures of core clock proteins (CLOCK/BMAL1, Cryptochromes (CRY), Periods), responsible for generating circadian rhythm, have been solved. Availability of structures makes amenable core clock proteins to design molecules regulating their activity by using in silico approaches. In addition to that, the implementation of classification features of molecules based on their toxicity and activity will improve the accuracy of the drug discovery process. Here, we identified 171 molecules that target functional domains of a core clock protein, CRY1, using structure-based drug design methods. We experimentally determined that 115 molecules were nontoxic, and 21 molecules significantly lengthened the period of circadian rhythm in U2OS cells. We then performed a machine learning study to classify these molecules for identifying features that make them toxic and lengthen the circadian period. Decision tree classifiers (DTC) identified 13 molecular descriptors, which predict the toxicity of molecules with a mean accuracy of 79.53% using tenfold cross-validation. Gradient boosting classifiers (XGBC) identified 10 molecular descriptors that predict and increase in the circadian period length with a mean accuracy of 86.56% with tenfold cross-validation. Our results suggested that these features can be used in QSAR studies to design novel nontoxic molecules that exhibit period lengthening activity.


Urethroscopy and laser lithotripsy for the diagnosis and treatment of obstructive urolithiasis in goats and pot-bellied pigs.
To explore the use of urethral endoscopy and laser lithotripsy in the diagnosis and management of urolithiasis in goats and pot-bellied pigs. Prospective clinical study. 16 male goats and 6 male pot-bellied pigs with dysuria. Abdominal ultrasonography and urethral endoscopy were performed on all 22 animals. Endoscopic-guided holmium:yttrium-aluminum-garnet laser lithotripsy was performed in 3 goats and 2 pot-bellied pigs. Urolithiasis was identified in 15 goats and 5 pot-bellied pigs. Primary urinary bladder paralysis and cystitis were identified in the remaining pot-bellied pig and goat. Mean bladder diameters of obstructed small- and large-breed goats were 7 and 9.5 cm, respectively. The mean bladder diameter of obstructed pot-bellied pigs was 9.5 cm. Five of 20 animals with obstructive urolithiasis had severe urethral necrosis or stricture formation at the time of urethroscopy. All of these animals were euthanatized within 6 months because of persistent dysuria. When used, laser lithotripsy successfully fractured the distally located obstructing stones in the 3 goats and 2 pot-bellied pigs. Urethral endoscopy is useful for evaluating urethral patency in goats and pot-bellied pigs. Examination of the urethral mucosa following relief of urethral obstructions aids in the assessment of the long-term prognosis for urethral stricture. Urethral endoscopy also expands the therapeutic options for management of urolithiasis by providing a route for conducting laser lithotripsy. Laser lithotripsy proved to be safe and effective for clearing distally located calculi refractory to removal by traditional urethral flushing. Lithotripsy application is restricted to calculi lodged in the urethra.


Does active commuting improve psychological wellbeing? Longitudinal evidence from eighteen waves of the British Household Panel Survey.
The aim of this study is to explore the relationship between active travel and psychological wellbeing. This study used data on 17,985 adult commuters in eighteen waves of the British Household Panel Survey (1991/2-2008/9). Fixed effects regression models were used to investigate how (i.) travel mode choice, (ii.) commuting time, and (iii.) switching to active travel impacted on overall psychological wellbeing and how (iv.) travel mode choice impacted on specific psychological symptoms included in the General Health Questionnaire. After accounting for changes in individual-level socioeconomic characteristics and potential confounding variables relating to work, residence and health, significant associations were observed between overall psychological wellbeing (on a 36-point Likert scale) and (i.) active travel (0.185, 95% CI: 0.048 to 0.321) and public transport (0.195, 95% CI: 0.035 to 0.355) when compared to car travel, (ii.) time spent (per 10minute change) walking (0.083, 95% CI: 0.003 to 0.163) and driving (-0.033, 95% CI: -0.064 to -0.001), and (iii.) switching from car travel to active travel (0.479, 95% CI: 0.199 to 0.758). Active travel was also associated with reductions in the odds of experiencing two specific psychological symptoms when compared to car travel. The positive psychological wellbeing effects identified in this study should be considered in cost-benefit assessments of interventions seeking to promote active travel.


SnapShot: Target-directed miRNA degradation.
MicroRNAs (miRNAs) guide Argonaute (AGO) proteins to bind and repress target RNAs. However, some unusual targets trigger destruction of the miRNA, a phenomenon known as target-directed miRNA degradation (TDMD). This Snapshot depicts our current understanding of how TDMD occurs and highlights established functions of TDMD in viruses and model organisms. To view this SnapShot, open or download the PDF.


Superior Plasmonic Photodetectors Based on Au@MoS2 Core-Shell Heterostructures.
Integrating plasmonic materials into semiconductor media provides a promising approach for applications such as photosensing and solar energy conversion. The resulting structures introduce enhanced light-matter interactions, additional charge trap states, and efficient charge-transfer pathways for light-harvesting devices, especially when an intimate interface is built between the plasmonic nanostructure and semiconductor. Herein, we report the development of plasmonic photodetectors using Au@MoS2 heterostructures-an Au nanoparticle core that is encapsulated by a CVD-grown multilayer MoS2 shell, which perfectly realizes the intimate and direct interfacing of Au and MoS2. We explored their favorable applications in different types of photosensing devices. The first involves the development of a large-area interdigitated field-effect phototransistor, which shows a photoresponsivity ∼10 times higher than that of planar MoS2 transistors. The other type of device geometry is a Si-supported Au@MoS2 heterojunction gateless photodiode. We demonstrated its superior photoresponse and recovery ability, with a photoresponsivity as high as 22.3 A/W, which is beyond the most distinguished values of previously reported similar gateless photodetectors. The improvement of photosensing performance can be a combined result of multiple factors, including enhanced light absorption, creation of more trap states, and, possibly, the formation of interfacial charge-transfer transition, benefiting from the intimate connection of Au and MoS2.


Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury.
Epoxyeicosatrienoic acids (EETs) contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II)-induced hypertension. EET-B was administered in drinking water for 14 days (10 mg/kg/d) and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.


[Diagnostic difficulties in secondary tumors of the heart].
The authors describe case reports of 2 patients who died from malignant pulmonary neoplasms. In one case, tumor metastasized to the left ventricle myocardium, in the other one, pulmonary tumor invaded the interatrial septum. Clinically, coronary heart disease symptoms with acute manifestations prevailed in both the cases. Based on an analysis of the authors' clinicomorphological findings and reported data a number of the clinical signs were distinguished, enabling one to suspect the presence of secondary heart tumors in cancer patients.


Prognostic impact of S100A9 overexpression in non-small cell lung cancer.
S100 proteins have been implicated in the progression and metastasis of several cancers. Among the S100 family, S100A9 is reportedly expressed in non-small cell lung cancer (NSCLC), though the clinical significance and prognostic value of S100A9 expression in NSCLC remains unclear. The aim of the present study was to examine the relationship between S100A9 expression and prognosis in NSCLC patients. S100A9 expression was evaluated by immunohistochemical staining. Seventy patients with NSCLC who had undergone lung resection were enrolled in the study. Overexpression of S100A9 was observed in 38 (54.3%) patients. Kaplan-Meier analysis showed that, following surgery, patients overexpressing S100A9 had a significantly lower 5-year overall survival rate than patients with weak or no expression of S100A9 (P=0.005). This finding was also observed in pathological stage IA patients (P=0.03). Multivariate Cox regression analysis revealed overexpression of S100A9 to be an independent factor predictive of poor disease outcome (hazard ratio, 0.3; 95% confidence interval, 0.1-0.8; P=0.02). Our results suggest that overexpression of S100A9 is associated with a poor prognosis among NSCLC patients and could serve as a marker identifying patients who are at high risk, even at an early pathological stage.


Sources of delayed provision of neurosurgical care in a rural kenyan setting.
Delay to neurosurgical care can result in significant morbidity and mortality. In this study, we aim to identify and quantify the sources of delay to neurosurgical consultation and care at a rural setting in Kenya. A mixed-methods, cross-sectional analysis of all patients admitted to the neurosurgical department at Kijabe Hospital (KH) was conducted: A retrospective analysis of admissions from October 1 to December 31, 2013 and a prospective analysis from June 2 to June 20, 2014. Sources of delay were categorized and quantified. The Kruskal-Wallis test was used to identify an overall significant difference among diagnoses. The Mann-Whitney U test was used for pairwise comparisons within groups; the Bonferroni correction was applied to the alpha level of significance (0.05) according to the number of comparisons conducted. IBM SPSS version 22.0 (SPSS, Chicago, IL) was used for statistical analyses. A total of 332 admissions were reviewed (237 retrospective, 95 prospective). The majority was pediatric admissions (median age: 3 months). Hydrocephalus (35%) and neural tube defects (NTDs; 27%) were most common. At least one source of delay was identified in 192 cases (58%); 39 (12%) were affected by multiple sources. Delay in primary care (PCPs), in isolation or combined with other sources, comprised 137 of total (71%); misdiagnosis or incorrect management comprised 46 (34%) of these. Finances contributed to delays in 25 of 95 prospective cases. At a median delay of 49 and 200.5 days, the diagnoses of hydrocephalus and tumors were associated with a significantly longer delay compared with NTDs (P < 0.001). A substantial proportion of patients experienced delays in procuring pediatric neurosurgical care. Improvement in PCP knowledge base, implementation of a triage and referral process, and development of community-based funding strategies can potentially reduce these delays.


[The medical dissertation--no definitive model. Results of a survey about obtaining a doctorate contradict frequently stated opinions].
The relevance of medical dissertations is controversial in Germany. The "Wissenschaftsrat" (Science Council) of Germany even made the radical proposal of abolishing medical dissertations, in their present form, in the recently published "Guidelines on writing a thesis". Using a questionnaire with 22 items all students submitting their dissertations within one year at the Medical School in Hannover were asked to participate in a survey about the dissertation, supervision, time spent on it and publishing the results. The answers were evaluated statistically by explorative data analysis. A total of 232 questionnaires were evaluated, which is equivalent to a response rate of 87% (47% were women). A majority of 69% had prepared their thesis in a clinical institution. The supervision during various phases of the dissertation was graded as good. Altogether 90% thought that it had been personally worth-while. In 57% of cases the data of the dissertation had already been published and in 39 % of these cases the author of the dissertation was listed as first author of the publication. In agreement with former studies in German universities an overwhelming majority of 90% of respondents graded dissertations as a significant part of their medical studies, although requiring much additional time. They would recommend such a research phase to younger students as highly valuable. These results are in contrast to many repeatedly made statements.


Validating computer-generated measures of linguistic style matching and accommodation in patient-clinician communication.
To explore the validity of computer-analyzed linguistic style matching (LSM) in patient-clinician communication. Using 330 transcribed HIV patient encounters, we quantified word use with Linguistic Inquiry and Word Count (LIWC), a dictionary-based text analysis software. We measured LSM by calculating the degree to which clinicians matched patients in the use of LIWC "function words" (e.g., articles, pronouns). We tested associations of different LSM metrics with patients' perceptions that their clinicians spoke similiarly to them. We developed 3 measures of LSM: 1) at the whole-visit level; (2) at the turn-by-turn level; and (3) using a "rolling-window" approach, measuring matching between clusters of 8 turns per conversant. None of these measures was associated with patient-rated speech similarity. However, we found that increasing trajectories of LSM, from beginning to end of the visit, were associated with higher patient-rated speech similarity (β 0.35, CI 0.06, 0.64), compared to unchanging trajectories. Our findings point to the potential value of clinicians' adapting their communication style to match their patients, over the course of the visit. With further validation, computer-based linguistic analyses may prove an efficient tool for generating data on communication patterns and providing feedback to clinicians in real time.


Sensitivity to Excluding Treatments in Network Meta-analysis.
Network meta-analysis of randomized controlled trials is increasingly used to combine both direct evidence comparing treatments within trials and indirect evidence comparing treatments across different trials. When the outcome is binary, the commonly used contrast-based network meta-analysis methods focus on relative treatment effects such as odds ratios comparing two treatments. As shown in a recent report, when using contrast-based network meta-analysis, the impact of excluding a treatment in the network can be substantial, suggesting a methodological limitation. In addition, relative treatment effects are sometimes not sufficient for patients to make decisions. For example, it can be challenging for patients to trade off efficacy and safety for two drugs if they only know the relative effects, not the absolute effects. A recently proposed arm-based network meta-analysis, based on a missing-data framework, provides an alternative approach. It focuses on estimating population-averaged treatment-specific absolute effects. This article examines the influence of treatment exclusion empirically using 14 published network meta-analyses, for both arm- and contrast-based approaches. The difference between these two approaches is substantial, and it is almost entirely due to single-arm trials. When a treatment is removed from a contrast-based network meta-analysis, it is necessary to exclude other treatments in two-arm studies that investigated the excluded treatment; such exclusions are not necessary in arm-based network meta-analysis, leading to substantial gain in performance.


Development of histaminergic pathways in brain as influenced by maternal alcoholism.
The development of histaminergic pathways has been studied in the rat brain specially as influenced by maternal alcoholism. Maternal ethanol consumption during pregnancy results in an increase in the cerebral histamine levels of the fetus. An increase in the brain histamine levels is also observed in the newborn rats suckling on the ethanol-fed mothers compared to the corresponding controls. Brain histamine levels are highest towards latter part of the pregnancy and lowest in the adult brains, whereas the brain histidine decarboxylase activity is lowest in the fetal brains and highest in the adult brains. Maternal alcoholism either during gestation or during lactation did not significantly affect histidine decarboxylase activity in the fetal and neonatal brains. Acute administration of ethanol or acetaldehyde after 20 minutes resulted in significant increase in the brain histamine levels. This increase in the brain histamine levels seems to be a direct result of brain histamine release due to ethanol or acetaldehyde metabolism in the body. The effect of ethanol on brain histamine levels may have important implications inview of the fact that both histamine and ethanol influence diuresis, EEG activity, and thermoregulation in the body.


Pressure controlled clamp using shape memory alloy for minimal vessel invasion in blood flow occlusion.
Vessel damage after clamping may affect the success of surgical operations. A new pressure controlled clamp (SMA clamp) was designed using super elastic property of shape memory alloy (SMA) to realize atraumatic vessel occlusion. The ability and biological effect of the SMA clamp to control pressure was investigated in vivo. The loading-displacement curves of the SMA clamps (experimental group) and conventional clamp (control group) by occlusion of pig carotid arteries were evaluated using a clamping-pressure analyzing system. To investigate macroscopically and histologically the vessel damage of the SMA and conventional clamps, pig carotid arteries were stained with Evan's blue and its histological sections were stained with Elastica Massion after clamping for fifteen minutes. Constant value was shown in the loading-displacement curve of SMA clamp. In the control group, damaged area stained with Evan's blue in the vessel wall showed enlargement with the pressure increasing. Less areas in experimental groups are observed than that in the control group. Histological section in the experimental group showed no obvious except a slight compressive damage in the tunica intima. In the control group, vessel wall showed irreversible damages. This experiment indicated that the SMA clamp, which has a unique mechanical property, can be used without vessels damage. This pressure controlled clamp can be a selection in clinical apparatus to improve surgical safety.


Characterization of spectral-domain OCT with autocorrelation interference response for axial resolution performance.
We present a class of novel system characterization methods for spectral-domain optical coherence tomography (SD-OCT) particularly on getting optimized axial resolution performance. Our schemes uniquely utilize the autocorrelation interference response, also known as the self-interference product, which is generated by the optical fields from the imaging sample in automatic interferences. In our methods, an autocorrelation-inducing calibration sample was prepared which was made by sandwiching glass plates. OCT images of the calibration sample were captured by an SD-OCT system under testing. And the image data were processed to find various system characteristics based on the unique properties of autocorrelation interferograms, free of dispersion- and polarization-involved modulations. First, we could analyze the sampling characteristic of the SD-OCT's spectrometer for spectral calibration that enables accurate linear-k resampling of detected spectral fringes. Second, we could obtain the systematic polarization properties for quantifying their impact on the achieved axial resolutions. We found that our methods based on the autocorrelation response provide an easy way of self-characterization and self-validation that is useful in optimizing and maintaining axial resolution performances. It was found very attractive that a variety of system characteristics can be obtained in a single-shot measurement without any increased system complexity.


[Radical cystectomy in patients with pathological non-muscle invasive bladder cancer].
Carcinoma of bladder is the most common malignancy in the urinary system in China. Most patients with this disease had non-muscle invasive bladder cancer (NMIBC) at the time of diagnosis. Radical cystectomy was indicated for patients with high risk or refractory NMIBC. We aimed to investigate the overall survival and disease-specific survival and related influence factors in patients undergoing radical cystectomy for pathological non-muscle invasive bladder cancer. From Jan. 2006 to Dec. 2012, a total of 164 patients with pathological non-muscle invasive bladder cancer underwent radical cystectomy in Peking University First Hospital. Clinical data were retrospectively collected.Incidence of lymph node metastasis and disease recurrence were calculated. The risk factors of disease recurrence were analyzed. Kaplan-Meier plots were used to estimate the overall survival and cancer-specific survival. Multivariate Cox regression analysis was used to evaluate the prognostic factors for survival. Of all the patients included, 159 had T1 disease, and 5 had CIS only. The median follow-up duration was 46.5 months (range: 7-99 months). Fourteen patients were lost during the follow-up. Lymph node metastasis was noted in 6 patients (3.7%), 4 patients had N1 disease, one patient had N2 disease, and one patient had N3 disease. Disease recurrence occurred in 16 patients (9.8%).The most common recurrence sites were the liver, bones, and lungs. The 5-year overall survival and disease-specific survival for all the patients were 85% and 91%, respectively. The patients who underwent pelvic lymph node dissection showed a better prognosis in terms of disease-specific survival than those without (P=0.012). Patients with recurrence harbored a significant poorer survival (P<0.001). According to univariate Cox regression analysis, whether lymph node dissection was performed was an independent risk factor of disease recurrence (P=0.050, OR=2.695, 95%CI 0.999-7.271). In COX regression model, age (P=0.008, OR=1.071, 95%CI 1.018-1.126) and whether lymph node dissection was performed (P=0.011, OR=3.385, 95%CI 1.329-8.621) were related to disease-specific survival. Patients with pathological non-muscle invasive bladder cancer underwent early radical cystectomy have a favorable prognosis, and bilateral pelvic lymph node dissection is essential for this procedure as it gains a survival benefit for the patients.


NEN in a dish: A patient-derived organoid biobank illuminates potential novel therapeutic opportunities for neuroendocrine neoplasms.
Neuroendocrine neoplasms are rare cancers with limited treatment options and preclinical models. In this issue of Cancer Cell, Dayton et al. establish a patient-derived tumor organoid biobank encompassing pulmonary low-grade neuroendocrine tumors (LNETs) and high-grade neuroendocrine carcinomas (LCNECs), identifying novel biomarker-dependent therapeutic vulnerabilities using niche perturbation and drug response assays.


Severity and outcomes of Pneumocystis pneumonia in patients newly diagnosed with HIV infection: an observational cohort study.
It is unclear whether patients who are unaware of their HIV infection have different severity or outcomes of Pneumocystis pneumonia (PCP) compared to patients who have been previously diagnosed with HIV. In this retrospective observational cohort study of consecutive HIV-infected patients with microscopically diagnosed PCP at San Francisco General Hospital between 1997 and 2006, 121 of 522 patients (23%) were unaware of their HIV infection prior to their diagnosis of PCP. The proportion of patients with concurrently diagnosed HIV and PCP each year remained unchanged during the study period. Patients with newly diagnosed HIV had a significantly higher alveolar-arterial oxygen gradient at presentation (median 51 vs 45 mm Hg, p =0.03), but there were no differences in mortality, frequency of mechanical ventilation, or admission to intensive care compared to patients with previously diagnosed HIV infection. In multivariate analysis, patients who reported a sexual risk factor for HIV infection were more likely to be newly diagnosed with HIV than patients who reported injection drug use as their only HIV risk factor (odds ratio = 3.14, 95% CI 1.59-6.18, p=0.001). This study demonstrates a continued need for HIV education and earlier HIV testing, particularly in patients with high-risk sexual behavior.


[Effect of anti-HLA antibodies on the electrophoretic mobility of erythrocytes].
The authors studied the influence of anti-HLA antibodies on electrophoretic mobility of erythrocytes. A total of 25 samples of erythrocytes and 30 samples of anti-HLA sera of varying specificity were used. It has been established that electrophoretic mobility of erythrocytes, sensitized by anti-HLA antibodies, is lowered that permitted validation of the possibility of using the method of analytical cellular electrophoresis for identification of antigens and antibodies of the HLA system. It has been proved that practically all I class HLA antigens identified in the present work are expressed on erythrocytes .


Standardized mortality ratios.
Mortality rates are increasingly used to compare the performance of hospitals and of units within hospitals. Different approaches have been taken to develop 'standardized' measures which adjust for the 'expected' mortality based on key characteristics of the population being treated. This article discusses the original motivation for looking at hospitals in this way in the UK, describes two recent incidents in which such measures were a critical element in decision making and reviews some of the strengths and weaknesses of the approaches. The current practice on the use of standardized mortality ratios is described.


Robust features for the automatic identification of autism spectrum disorder in children.
It is commonly reported that children with autism spectrum disorder (ASD) exhibit hyper-reactivity or hypo-reactivity to sensory stimuli. Electroencephalography (EEG) is commonly used to study neural sensory reactivity, suggesting that statistical analysis of EEG recordings is a potential means of automatic classification of the disorder. EEG recordings taken from children, however, are frequently contaminated with large amounts of noise, making analysis difficult. In this paper, we present a method for the automatic extraction of noise-robust EEG features, which serve to quantify neural sensory reactivity. We show the efficacy of a system for the classification of ASD using these features. An oddball paradigm was used to elicit event-related potentials from a group of 19 ASD children and 30 typically developing children. EEG recordings were taken and robust features were extracted. A support vector machine, logistic regression, and a naive Bayes classifier were used to classify the children as having ASD or being typically developing. A classification accuracy of 79% was achieved, making our method competitive with other automatic diagnosis methods based on EEG. Additionally, we found that classification performance is reduced if eye blink artifacts are removed during preprocessing. This study shows that robust EEG features that quantify neural sensory reactivity are useful for the classification of ASD. We showed that noise-robust features are crucial for our analysis, and observe that traditional preprocessing methods may lead to poor classification performance in the face of a large amount of noise. Further exploration of alternative preprocessing methods is warranted.


Music and Medicine: being in the moment.
This article was migrated. The article was marked as recommended. This article reviews the relationship between music and medicine, informed by our own personal experiences, and by leading scholars who have opened up music and medicine for critical reflection. Performing music, we suggest, is a state of being, in the moment, with fellow musicians and audience members. This establishes bidirectional communication, which can transport both parties to better places. Medicine is, likewise, an act of being with patients, whether or not performing a technical act (a clinical procedure, for example) is part of the interaction. Subjective, non-verbal, dimensions of the interaction engage both parties' senses. Good doctors, like good musicians, tune in to patients at a personal level. The limited research that has examined the relationship between music and medicine shows that music can help students develop auditory skills. Of potentially greater interest is the existential contribution music could make to medical education. We suggest that this could help students and doctors reflect on their experiences of being in the world, and how shared experience can relieve suffering.


Fetal hemoglobin gene activation in a phase II study of 5,6-dihydro-5-azacytidine for bronchogenic carcinoma.
5-Azacytidine and several of its analogues are known to inhibit DNA methylation, alter gene expression, and inhibit cell growth. We report a Phase II study in which we investigated the antineoplastic activity of 5,6-dihydro-5-azacytidine and its induction of fetal hemoglobin synthesis when given by a 5-day continuous i.v. infusion of 1650 mg/m2/day that was repeated every 21 days. Fetal hemoglobin was measured in all patients; increased synthesis was found in 13 of the 17, in the absence of clinically significant anemia. Of the four patients who did not develop increased fetal hemoglobin, three had only one cycle of therapy. Fourteen patients with bronchogenic carcinoma were treated, and ten were evaluable for disease response. Five patients had disease stability of 2 or more mo, and five progressed on treatment. Three additional patients with mesothelioma were treated, and the two who were evaluable for disease response had stabilization of their disease. Fifteen of the 17 patients who received 5,6-dihydro-5-azacytidine developed a pleuritic-type chest pain, 12 had abnormal electrocardiograms, and four developed positive anti-nuclear antibodies. No significant hemopoietic, hepatic, or renal toxicities were observed. This study demonstrates that 5,6-dihydro-5-azacytidine in the dose and schedule used has no significant therapeutic activity in the treatment of lung cancer but does possess an unusual spectrum of clinical toxicities as well as the property of inducing fetal hemoglobin synthesis.


Lipid synthesis in the presence of nitrogenous compounds in Chlorella pyrenoidosa.
Acetate was incorporated by Chlorella pyrenoidosa into nonvolatile water-soluble compounds (amino acids, organic acids and carbohydrates) with pH optimum between 4 and 5. Incorporation into lipid was maximal at pH 7.5. The proportion of incorporated acetate in lipid was not significantly affected by acetate concentration and chlorophyll concentration in the ranges tested. Illumination of Chlorella during acetate metabolism increased the synthesis of lipid with concomitant decrease in the synthesis of water-soluble compounds. Nitrate and ammonium ions had essentially no effect on acetate metabolism. Inhibition by nitrite was greater on the synthesis of lipid. Illumination reversed the gross inhibition by nitrite, but altered the distribution of incorporated label in favor of the water-soluble compounds.


Promoting meaningful use of health information technology in Israel: ministry of health vision.
The Ministry of Health (MOH) of Israel has overall responsibility for the healthcare system. In recent years the MOH has developed strong capabilities in the areas of technology assessment and prioritization of new technologies. Israel completed the transition to computerized medical records a decade ago in most care settings; however, the processes in Israel was spontaneous, without government control and standards settings, therefore large variations among systems and among organizations were created. Currently, the main challenge is to convert the information scattered in different systems, to organized, visible information and to make it available to various levels in health management. The MOH's solution is of implementing a selected information system from a specific vendor, at all the hospitals and all HMO's clinics, in order to achieve interoperability. The sys-tem will enable access to the patient's medical record history from any location.


An Open Trial of Behavioral Activation in Veterans With Major Depressive Disorder or Posttraumatic Stress Disorder in Primary Care.
Integrated behavioral health programs provide brief evaluations and interventions to patients with psychiatric symptoms in primary care. These programs seek to decrease stigma and improve access to mental health services. Several psychotherapeutic interventions are available to providers, each with its own strengths and weaknesses. One treatment with particular promise is behavioral activation treatment for depression (BATD) due to its potential clinical efficacy, transdiagnostic potential, and ease of dissemination and implementation in primary care settings. The objective of this study was to investigate the efficacy of BATD across 2 DSM-5 diagnoses: major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Participants were recruited from October 2014 to December 2017. Thirty-one participants were referred from primary care and consented to receive a 12-session trial of BATD. Participants endorsed criteria consistent with a principal diagnosis of either MDD (n = 20) or PTSD (n = 11). Self-report measures were completed at baseline and immediately posttreatment to monitor treatment progress in symptoms of PTSD and MDD. Twelve of the 31 participants completed all 12 sessions of BATD, although over 70% completed at least 4 sessions. Participants demonstrated significant symptom improvement across symptoms of MDD and PTSD (all P < .004). No disorder group differences were evidenced for symptom reduction, treatment completion, or treatment satisfaction. The present study provides support for the efficacy of BATD for patients with MDD and PTSD. These findings may have implications for the dissemination and implementation efforts for psychotherapies in integrated primary care settings. ClinicalTrials.gov identifier: NCT01947647.


The role of nitric oxide in the hypothalamic control of LHRH and oxytocin release, sexual behavior and aging of the LHRH and oxytocin neurons.
Nitric oxide (NO) affects reproductive processes both at the level of the brain and reproductive tract and this review is focused on its role as an essential regulator of the hypothalamic control of reproduction. The data gathered indicate that glutamate stimulates noradrenergic neurons which subsequently activate NO-ergic cells via alpha1-adrenergic receptors. The released NO diffuses into luteinizing hormone-releasing hormone (LHRH) terminals where it triggers LHRH secretion by activation of guanylyl cyclase and cyclooxygenase. The NO released by estrogen-stimulated NO-ergic ventromedial neurons plays a crucial role in the regulation of sexual behavior. Furthermore, an increased expression of inducible nitric oxide synthase in the LHRH and oxytocin neurons underlies the destructive action of NO on the aging of the hypothalamic neuroendocrine pathways. Within the hypothalamo-hypophyseal system, NO exerts an inhibitory effect in the control of oxytocin secretion. This action seems to employ an indirect mechanism by which NO may modulate the release of GABA. This review provides an overview of the role of NO in hypothalamic control of LHRH and oxytocin release, aging of the LHRH and oxytocin neurons and sexual behavior.


[Mechanism of sudden death in female pseudohermaphroditism].
Sudden death in female pseudohermaphroditism is described. Hemorrhage into hyperplastic adrenals leads to acute adrenal failure and is the immediate cause of death.


Photocatalytic synthesis of gold nanoparticles using TiO2 nanorods: a mechanistic investigation.
Herein, we investigate the mechanism of photocatalytic synthesis of noble metal nanoparticles by reductive photoelectrons generated from semiconductors. To slow down the reaction rate for real-time mechanistic study, oleic acid-capped TiO2 nanorods served as photocatalysts, and chloroauric acid dissolved in oleylamine acted as the gold precursor. Based on the experimental results from the in situ absorption spectrum and corresponding TEM image, we could clarify the photoreduction mechanism: the TiO2 nanorods generate electrons under UV irradiation and provide catalytic centers for the nucleation of gold nanoparticles. Subsequently, the seeded growth of Au nanoparticles is mainly assisted by TiO2 nanorods with continuous reduction of the gold precursor. Interestingly, the separation of Au nanoparticles from TiO2 nanorods could be clearly observed. This proposed reaction mechanism may provide a convenient understanding of the photocatalytic synthesis of noble metal nanoparticles by semiconductors.


Development of resistance to glucocorticoid hormones during rat thymus cell differentiation: proteins associated with emergence of the resistant state.
Two-dimensional gel electrophoresis was used to detect [35S]methionine-labeled newly synthesized proteins from both glucocorticoid-sensitive and -resistant thymus cells. Normal thymic lymphocytes were taken for the sensitive population; the resistant population was composed of medullary thymocytes obtained from rats treated with dexamethasone (10 mg per kg body weight per day) for 3 days. When the proteins from glucocorticoid-sensitive cells are compared to those from resistant cells, the majority of the congruent to 1000 proteins were similar; however, 18 proteins were different. There were 13 proteins that increase in the resistant state and 5 that decrease. One major change is the appearance of a new protein with a molecular weight of about 36,000 in resistant rat thymocytes. This protein is in the same position on the gels as is a protein found in corticosteroid-resistant P1798 mouse lymphosarcoma cells but not in the corticosteroid-sensitive cells. Control experiments indicate that the protein differences are neither components of fibrous tissue associated with the cells nor components of blood. Changes in the synthesis of a common set of proteins that are characteristic of the hormone-resistant state suggest that the presence of one or more of these proteins may confer resistance. The appearance of a single protein in two distinctly different cell types suggests it as the most likely candidate. This coincidence further suggests that tumor cells become resistant by selection of those cells that can express the same gene product as do those normal cells as they undergo immunological commitment.


Array comparative genomic hybridization as a clinical diagnostic tool in syndromic and nonsyndromic congenital heart disease.
Congenital heart diseases (CHDs) are often associated with other congenital anomalies, dysmorphic features, and developmental delay, and only a few cases of chromosomal abnormalities are detected by conventional cytogenetic techniques. The microarray comparative genomic hybridization (CGH) analysis allows the identification of submicroscopic genomic rearrangements. During the past 3 y, 55 of 330 patients referred for array CGH had CHD of unknown etiology plus at least one additional indication of abnormal chromosomal phenotype. High-resolution 1 × 244 K or 4 × 180 K Agilent arrays were used in this study (average resolution 7-13 kb). Copy-number variations were detected in 37 of 55 patients, and in 29 of 37 patients there were genes that have been associated with CHD. All 37 patients had at least one additional phenotypic abnormality: 30 of 37 had one or more other congenital anomalies, 23 of 37 had dysmorphic features, 16 of 37 had intellectual disability, 13 of 37 had abnormal magnetic resonance imaging, 10 of 37 had hypotonia, and 7 of 37 had seizures. In 9 of 55 patients, unexpected genomic rearrangements in relation to their phenotype were identified. In patients with CHD and at least one additional indication of abnormal chromosomal phenotype, array CGH analysis could detect possible submicroscopic chromosomal abnormalities and provide proper genetic counseling.


Choice of models for the analysis and forecasting of hospital beds.
There is growing concern that current health care services are not sustainable. The compartmental flow model provides the opportunity for improved decision-making about bed occupancy decisions, particularly those of a strategic nature. This modelling can be applied to complement infrastructure and workforce-planning methods. Discussion about appropriateness of the level of model complexity, the degree of fit and the ability to use compartmental flow models for generalization and forecasting has been lacking. The authors investigated model selection and assessment in relation to hospital bed compartment flow models. A compartment model for a range of scenarios was created. The training and test data related to the 1998 and 1999 calendar years, respectively. The majority of scenarios tested were based upon commonly used periods that describe periods of time. The goodness-of-fit achieved by optimisation was measured against the training and test data. Model fit improved with increasing complexity as expected. The analysis of model fit against the test data showed that increasing model complexity did result in over-fitting, and better prediction was achieved with a relatively simple model. In terms of generalisation, the seasonal models performed best. Single day census type models, which have been used by Millard and his colleagues, were also generated. The performance of these models was similar, but inferior to that of the models generated from a full year of training data. The additional data make the models better able to capture the variation across the year in activity.


Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities.
Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher vulnerability to affective disorders in a dose-dependent manner.


The largest bilateral gemination of permanent maxillary central incisors: Report of a case.
Gemination is defined as an attempt to make two teeth from one enamel organ. Bilateral presentation of this phenomenon is very rare, with prevalence of 0.01% to 0.04% in the primary, and 0.05% in the permanent dentition. This paper describes a rare case of huge bilateral gemination of permanent maxillary central incisors in a nine-year-old Iranian boy with poor aesthetic. The patient did not have history of anomaly in his primary dentition and in his family either. This type of dental anomaly can cause clinical problems in the form of malocclusion, poor aesthetic, and impaction of adjacent teeth, caries, and periodontal destruction. Key words:Gemination, central incisor, bilateral.


Localization of Foramen Ovale According to Bone Landmarks of the Splanchnocranium: Help for Transforaminal Surgical Approach to Trigeminal Neuralgia.
Trigeminal neuralgia is a painful condition, usually treated through surgical procedures focusing on the foramen ovale (FO). A detailed localization of FO relative to reference landmarks is therefore crucial to avoid possible complications.The present study aims at assessing the position of FO according to the surrounding bone structures: 100 CT-scans of patients, equally divided between sexes, aged between 18 and 86 years were examined. From each subject, the 3D models of FO and the maxillary bones, the zygomatic bones and the zygomatic process of the temporal bones were segmented through ITK-SNAP software. The distance between the center of the FO and subnasale, zygion, and the upper edge of the zygomatic bone at the origin of the frontal process were measured on 3D models. On CT-scans three cranial measurements were taken as well (distance between anterior and posterior nasal spine, upper facial height and bizygomatic breadth).Statistically significant differences in the three distances according to side and sex were assessed through two-way ANCOVA test, using the three cranial measurements (ANS-PNS, NP, ZZ) as covariates (P < 0.05).Distances between the centre of FO and subnasale, zygion and the upper edge of the zygomatic bone were on average 82.3 ± 3.4 mm, 41.9 ± 2.6 mm and 48.8 ± 3.5 mm in males, 77.3 ± 3.9 mm, 38.2 ± 2.5 mm and 45.5 ± 3.1 mm in females, with a significant difference according to sex (P < 0.05).Results provide innovative data for the localization of FO and will be useful for the management of transforaminal procedures in case of trigeminal neuralgia.


Electron tunneling pathways in proteins: influences on the transfer rate.
A strategy for calculating the tunneling matrix element dependence on the medium intervening between donor and acceptor in specific proteins is described. The scheme is based on prior studies of small molecules and is general enough to allow inclusion of through bond and through space contributions to the electronic tunneling interaction. This strategy should allow the prediction of relative electron transfer rates in a number of proteins. It will therefore serve as a design tool and will be explicitly testable, in contrast with calculations on single molecules. As an example, the method is applied to ruthenated myoglobin and the tunneling matrix elements are estimated. Quantitative improvements of the model are described and effects due to motion of the bridging protein are discussed. The method should be of use for designing target proteins having tailored electron transfer rates for production with site directed mutagenesis. The relevance of the technique to understanding certain photosynthetic reaction center electron transfer rates is discussed.


Innovative MRI Techniques in Neuroimaging Approaches for Cerebrovascular Diseases and Vascular Cognitive Impairment.
Cognitive impairment and dementia are recognized as major threats to public health. Many studies have shown the important role played by challenges to the cerebral vasculature and the neurovascular unit. To investigate the structural and functional characteristics of the brain, MRI has proven an invaluable tool for visualizing the internal organs of patients and analyzing the parameters related to neuronal activation and blood flow in vivo. Different strategies of imaging can be combined to obtain various parameters: (i) measures of cortical and subcortical structures (cortical thickness, subcortical structures volume); (ii) evaluation of microstructural characteristics of the white matter (fractional anisotropy, mean diffusivity); (iii) neuronal activation and synchronicity to identify functional networks across different regions (functional connectivity between specific regions, graph measures of specific nodes); and (iv) structure of the cerebral vasculature and its efficacy in irrorating the brain (main vessel diameter, cerebral perfusion). The high amount of data obtainable from multi-modal sources calls for methods of advanced analysis, like machine-learning algorithms that allow the discrimination of the most informative features, to comprehensively characterize the cerebrovascular network into specific and sensitive biomarkers. By using the same techniques of human imaging in pre-clinical research, we can also investigate the mechanisms underlying the pathophysiological alterations identified in patients by imaging, with the chance of looking for molecular mechanisms to recover the pathology or hamper its progression.