Differences in intrinsic aerobic capacity alters sensitivity to ischemia-reperfusion injury but not cardioprotective capacity by ischemic preconditioning in rats.
Aerobic capacity is a strong predictor of cardiovascular mortality. Whether aerobic capacity influences myocardial ischemia and reperfusion (IR) injury is unknown. To investigate the impact of intrinsic differences in aerobic capacity and the cardioprotective potential on IR injury. We studied hearts from rats developed by selective breeding for high (HCR) or low (LCR) capacity for treadmill running. The rats were randomized to: (1) control, (2) local ischemic preconditioning (IPC) or (3) remote ischemic preconditioning (RIC) followed by 30 minutes of ischemia and 120 minutes of reperfusion in an isolated perfused heart model. The primary endpoint was infarct size. Secondary endpoints included uptake of labelled glucose, content of selected mitochondrial proteins in skeletal and cardiac muscle, and activation of AMP-activated kinase (AMPK). At baseline, running distance was 203±7 m in LCR vs 1905±51 m in HCR rats (p<0.01). Infarct size was significantly lower in LCR than in HCR controls (49±5% vs 68±5%, p = 0.04). IPC reduced infarct size by 47% in LCR (p<0.01) and by 31% in HCR rats (p = 0.01). RIC did not modulate infarct size (LCR: 52±5, p>0.99; HCR: 69±6%, p>0.99, respectively). Phosphorylaion of AMPK did not differ between LCR and HCR controls. IPC did not modulate cardiac phosphorylation of AMPK. Glucose uptake during reperfusion was similar in LCR and HCR rats. IPC increased glucose uptake during reperfusion in LCR animals (p = 0.02). Mitochondrial protein content in skeletal muscle was lower in LCR than in HCR (0.77±0.10 arbitrary units (AU) vs 1.09±0.07 AU, p = 0.02), but not in cardiac muscle. Aerobic capacity is associated with altered myocardial sensitivity to IR injury, but the cardioprotective effect of IPC is not. Glucose uptake, AMPK activation immediately prior to ischemia and basal mitochondrial protein content in the heart seem to be of minor importance as underlying mechanisms for the cardioprotective effects.


Removal of Kirschner wire that migrated from the pelvic bone into the right ventricle of the heart.
A sixty-year-old man was admitted due to chest pain. He had a history of pelvic bone fracture fixation with Kirschner wire about 20 years earlier. On examination, we detected a Kirschner wire that had migrated into the right ventricle. Without cardiopulmonary bypass, we removed the migrating Kirschner wire via median sternotomy. The patient recovered without complications and was discharged on the 5th postoperative day.


Automated extraction of odontocete whistle contours.
Many odontocetes produce frequency modulated tonal calls known as whistles. The ability to automatically determine time × frequency tracks corresponding to these vocalizations has numerous applications including species description, identification, and density estimation. This work develops and compares two algorithms on a common corpus of nearly one hour of data collected in the Southern California Bight and at Palmyra Atoll. The corpus contains over 3000 whistles from bottlenose dolphins, long- and short-beaked common dolphins, spinner dolphins, and melon-headed whales that have been annotated by a human, and released to the Moby Sound archive. Both algorithms use a common signal processing front end to determine time × frequency peaks from a spectrogram. In the first method, a particle filter performs Bayesian filtering, estimating the contour from the noisy spectral peaks. The second method uses an adaptive polynomial prediction to connect peaks into a graph, merging graphs when they cross. Whistle contours are extracted from graphs using information from both sides of crossings. The particle filter was able to retrieve 71.5% (recall) of the human annotated tonals with 60.8% of the detections being valid (precision). The graph algorithm's recall rate was 80.0% with a precision of 76.9%.


Structure of human aldose reductase holoenzyme in complex with statil: an approach to structure-based inhibitor design of the enzyme.
Aldose reductase, a monomeric NADPH-dependent oxidoreductase, catalyzes the reduction of a wide variety of aldehydes and ketones to their corresponding alcohols. The X-ray structure of human aldose reductase holoenzyme in complex with statil was determined at a resolution of 2.1 A. The carboxylate group of statil interacted with the conserved anion binding site located between the nicotinamide ring of the coenzyme and active site residues Tyr48, His110, and Trp111. Statil's hydrophobic phthalazinyl ring was bound in an adjacent pocket lined by residues Trp20, Phe122, and Trp219, with the bromo-fluorobenzyl group penetrating the "specificity" pocket. The interactions between the inhibitor's bromo-fluorobenzyl group and the enzyme include the stacking against the side-chain of Trp111 as well as hydrogen bonding to residues Leu300 and Thr113. Based on the model of the ternary complex, the program GRID was used in an attempt to design novel potential inhibitors of human aldose reductase with enhanced binding energies of the complex. Molecular modeling calculations suggested that the replacement of the fluorine atom of statil with a carboxylate functional group may enhance the binding energies of the complex by 33%.


Surfboard Related Orbital and Periocular Injury.
The objective of this study is to present the complexity of surfboard related orbital and periocular injuries and to discuss the different prevention aspects of such injuries. A retrospective review was performed on surfing related orbital and periocular injuries cases in a single tertiary medical center over a period of 10 years. Six patients at a mean age of 34 (range 20-50) years were evaluated. All were amateur surfers. Five patients had an orbital fracture, 3 had a full thickness eyelid laceration, 3 had lacrimal drainage system damage and 3 had intraocular findings related to trauma, but no perforation of the globe was observed. Two patients had complete optic nerve avulsion or transection, 1 of them had extraocular muscle transection. Five patients underwent surgery and 2 required an additional surgical intervention. At the end of follow-up, 3 patients had an unrepairable lacrimal drainage damage, 2 had a malposition of an eyelid, 2 eyes remained blind, 1 patient had a hypoglobus, and 1 had hypoesthesia in distribution of infraorbital nerve. Surfboard related orbital injuries may cause a severe orbital injury, which may debilitate and disable a previously active and healthy group of young people. Hence, protective gear wear should be more vigorously encouraged as already been done in other sports.


Antimicrobial Stewardship for Respiratory Pathogens in Swine.
The aim of this study was to set up antimicrobial stewardship for swine respiratory pathogens following the recommendation from the European Medicine Agency. The obtained antimicrobial susceptibility pattern recommended using antimicrobial stewardship for each clinical case instead of treatment guidelines focused on pathogens. Thus, the bacteria are isolated and the MIC values, the clinical interpretation for each antimicrobial (susceptible or resistant), additional information about the distance between the MIC obtained and the clinical breakpoint, and set up for each drug, are represented in the report provided for veterinarians. A graph from green (susceptible) to red (resistant) is enclosed for each antimicrobial and microorganism in the report. The greener, the more susceptible is the strain, and the redder, the less susceptible is the strain for each particular antimicrobial. This information could help veterinarians to select the most suitable antimicrobial from first, second, or last option antimicrobials. Thus, veterinarians should choose the antimicrobial, inside each option, with the best antimicrobial susceptibility pattern that corresponds with the greener status in the report. The information provided in the report could be useful for all clinical cases, caused by a certain bacterium within the same pig production system, if an epidemiological link could be established.


Simultaneous but independent activation of adenylate cyclase and glycosylphosphatidylinositol-phospholipase C under stress conditions in Trypanosoma brucei.
Previous observations suggested a concomitant relationship between the release of the variant surface glycoprotein (VSG) and the activation of adenylate cyclase in the bloodstream form of the parasitic protozoan Trypanosoma brucei. In order to evaluate this hypothesis, adenylate cyclase activity was measured in live trypanosomes subjected to different treatments known to induce the shedding of the VSG coat, namely low pH and trypsin digestion. In both cases adenylate cyclase activation occurred in parallel with the release of the VSG. The latter was found to be mediated by the glycosylphosphatidylinositol-specific phospholipase C that cleaves the glycosylphosphatidylinositol anchor of the protein (VSG lipase). Furthermore, both adenylate cyclase and VSG release were activated by the incubation of trypanosomes with specific inhibitors of protein kinase C, suggesting a repressive role for protein kinase C on both VSG lipase and adenylate cyclase activities. Significantly, in mutant trypanosomes lacking VSG lipase, adenylate cyclase was activated under conditions where VSG release did not occur. Moreover,VSG release was also found to occur in the absence of activation of the cyclase, as observed in the presence of low concentration of the thiol modifying reagent p-chloromercuriphenylsulfonic acid. These observations provide the first demonstration that release of the VSG in response to cellular stress is mediated by the VSG lipase and that while both release of the VSG and activation of adenylate cyclase occur in response to the same stimuli they are not obligatorily coupled.


Mitochondrial dysfunction, oxidative stress, and major depressive disorder.
There is controversy about depression being a physical illness, in part because a reproducible, sensitive, and specific biologic marker is not available. However, there is evidence that mitochondrial dysfunction and oxidative stress may be associated with abnormal brain function and mood disorders, such as depression. This paper reviews selected human and animal studies providing evidence that intracellular mitochondrial metabolic dysfunction in specific brain regions is associated with major depressive disorder. This supports the hypothesis that chronic mitochondrial dysfunction in specific tissues may be associated with depression. Evaluation of mitochondrial dysfunction in specific tissues may broaden the perspective of depression beyond theories about neurotransmitters or receptor sites, and may explain the persistent signs and symptoms of depression.


iTRAQ-Based Proteomics Analysis of Rat Cerebral Cortex Exposed to Valproic Acid before Delivery.
Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social and communication difficulties. Valproic acid (VPA) injection during pregnancy elicits autism-like behavior in the offspring, making it a classic animal model of ASD. However, the mechanisms involved have not yet been determined. In this study, we used iTRAQ (isobaric tags for relative and absolute quantification) proteomics analysis of the cerebral cortex of a VPA rat model (VPA group) and controls (CON group). The results showed that 79 differentially expressed proteins (DEPs) were identified between the VPA group and the CON group. Based on bioinformatics analysis, the DEPs were mainly enriched at synapses, especially glutamatergic synapses and GABAergic synapses. Some DEPs were involved in energy metabolism, thyroid hormone synthesis pathway, and Na+-K+-ATPase. Cytoskeleton and endoplasmic reticulum (ER) stress-related proteins were also involved. Some DEPs matched either the ASD gene database or previous reports on cerebral cortical transcriptome studies in VPA rat models. Dysregulation of these DEPs in the cerebral cortex of VPA rats may be responsible for autism-like behavior in rats. We also found that some DEPs were associated with neuropsychiatric disorders, implying that these diseases share common signaling pathways and mechanisms. Moreover, increased expression of DEPs was associated with energy metabolism in the cerebral cortex of VPA rats, implying that ASD may be a distinct type of mitochondrial dysfunction that requires further investigation.


Single-Cell Transcriptome Comparison of Bladder Cancer Reveals Its Ecosystem.
Bladder carcinoma (BLCA) is a highly heterogeneous disease, and the underlying biological behavior is still poorly understood. Here, single-cell RNA sequencing was performed on four clinical samples of different grades from three patients, and 26,792 cell transcriptomes were obtained revealing different tumor ecosystems. We found that N-glycan biosynthesis pathway was activated in high-grade tumor, but TNF-related pathway was activated in cystitis glandularis. The tumor microenvironment (TME) of different samples showed great heterogeneity. Notably, cystitis glandularis was dominated by T cells, low-grade and high-grade tumors by macrophages, while TME in patient with high-grade relapse by stromal cells. Our research provides single-cell transcriptome profiles of cystitis glandularis and BLCA in different clinical states, and the biological program revealed by single-cell data can be used as biomarkers related to clinical prognosis in independent cohorts.


The Effect of Resident Participation on Appendectomy Operative Times.
To assess the association between level of resident autonomy and operative times for appendectomies. A single center retrospective analysis of electronic medical record data of patients who underwent an appendectomy from 1/1/2017 to 12/31/2018. Medical record numbers s were matched with cases entered in the ACGME Resident Case Log system. Cases were stratified by resident role ("First Assistant," "Surgeon Junior," "Surgeon Chief," or "Teaching Assistant") and operative times were compared to cases without resident participation using student's t test. Maine Medical Center, Department of Surgery, Portland, Maine. Inclusion criteria: ≥5 years old, underwent appendectomy at a tertiary medical center during the study duration, and either had corresponding Case-log data or had no resident involvement. Patients who underwent appendectomy as part of a larger procedure were excluded. Six hundred eighty-eight patients met inclusion criteria, with residents participating in 574 (83.5%) cases. Overall mean operating time was 51 ± 21.5 minutes. Attending physicians without resident participation had the shortest OR times (43 ± 19.1 minutes). There was no difference in operating time between chief resident involvement and attending physicians without resident participation (45 ± 21; p = 0.43). Cases with residents involved as "First Assistant" (53 ± 18.6 minutes; p = 0.04) "Surgeon Junior" (52 ± 24.0 minutes; p < 0.001), or "Teaching Assistant" (57 ± 21.6 minutes; p < 0.001) were found to have longer operating times as compared to attending physicians operating without a resident. Operative times for appendectomies are impacted by resident role. Chief residents' operative times approach that of attendings when operating as Surgeon Chief, however they are significantly longer when operating as Teaching Assistant. Involvement of junior residents in any role lengthen operating times. This suggests that surgical education influences operating room efficiency.


Fibroblast growth factor receptor 3 protein expression in urothelial carcinoma of the urinary bladder, exhibiting no association with low-grade and/or non-invasive lesions.
Activating mutations of fibroblast growth factor receptor 3 (FGFR3), found in autosomal dominant human skeletal dysplasia, were reported to be involved in tumorigenesis and correlate with low-grade and superficial lesions of urothelial carcinoma. FGFR3 protein expression was immunohistochemically investigated in 126 cases of urothelial carcinoma of the urinary bladder to evaluate the role of this receptor in tumor behavior. p53 expression and the proliferating activity of tumor cells, assessed by Ki-67 expression, were also analyzed in parallel. Cytoplasmic and/or membrane immunostaining for FGFR3 was observed in 62 (49.2%) cases, including 20 (15.9%) cases of intense staining and 42 (33.3%) of moderate staining. p53 expression and Ki-67 labeling index (LI) were significantly correlated with high tumor grade (p=0.0093 and <0.0001, respectively) and invasion (p=0.0041 and <0.0001, respectively). Although there were two groups of interesting cases: low-grade and non-invasive tumors negative for p53 but positive for FGFR3, and high-grade and invasive tumors positive for p53 but negative for FGFR3, no statistically significant relationship was found between FGFR3 expression and tumor grade, invasion, p53 expression or Ki-67 LI. These results suggest that FGFR3 protein expression in bladder cancer is unlikely to affect tumor behavior as a unique single factor.


Association of the protein D and protein E forms of rat CRISP1 with epididymal sperm.
Cysteine-rich secretory protein 1 (CRISP1) is a secretory glycoprotein produced by the rat epididymal epithelium in two forms, referred to as proteins D and E. CRISP1 has been implicated in sperm-egg fusion and has been shown to suppress capacitation in rat sperm. Several studies have suggested that CRISP1 associates transiently with the sperm surface, whereas others have shown that at least a portion of CRISP1 persists on the surface. In the present study, we demonstrate that protein D associates transiently with the sperm surface in a concentration-dependent manner, exhibiting saturable binding to both caput and cauda sperm in a concentration range that is consistent with its capacitation-inhibiting activity. In contrast, protein E persists on the sperm surface after all exogenous protein D has been dissociated. Comparison of caput and cauda sperm reveal that protein E becomes bound to the sperm in the cauda epididymidis. We show that protein E associates with caput sperm, which do not normally have it on their surfaces, in vitro in a time- and temperature-dependent manner. These studies demonstrate that most CRISP1 interacts with sperm transiently, possibly with a specific receptor on the sperm surface, consistent with its action in suppressing capacitation during epididymal storage of sperm. These studies also confirm a tightly bound population of protein E that could act in the female tract.


Antagonism of oestrogen action in human breast and endometrial cells in vitro: potential novel antitumour agents.
There is a need to find novel oestrogen receptor (ER) ligands that antagonize oestrogen action in the reproductive tissues and would therefore have therapeutic potential in oestrogen-dependent tumours. We tested novel ER ligands in both breast and endometrial cells to profile agonism/antagonism in these oestrogen target reproductive tissues. Novel analogues of the ER antagonist ICI 182,780 were synthesized and tested for their ability to inhibit gene expression dependent on oestrogen response elements (ERE) in human breast (MCF-7) and endometrial (Ishikawa) cell lines. This activity was correlated with inhibition of oestrogen-induced cell proliferation and ER binding. The sulphide analogue (compound 1) and sulphone analogue (compound 2) had no intrinsic ERE-dependent agonism in either breast cancer or endometrial cells in culture. All three compounds dose-dependently inhibited ERE-mediated oestrogen agonism. Moreover, these ER ligands inhibited oestrogen-stimulated proliferation of breast cancer and endometrial cells. ICI 182,780, compound 1 and compound 2 were all able to bind both isoforms of the ER (ER alpha and ER beta). In endometrial cells, the relative binding to ER beta correlated with the ERE-dependent antioestrogenic effect of these ligands, suggesting that in this tissue this receptor is the predominant isoform that determines antioestrogenic activity. The ability of these analogues of ICI 182,780 to inhibit oestrogen-stimulated transcriptional activity and cell proliferation suggests that these agents, in particular the sulphone analogue, have therapeutic potential in the treatment of breast cancer without exhibiting the unwanted oestrogenic effects in the endometrium.


Warthin tumor--morphological study of the stromal compartment.
Warthin tumor is the second most common benign tumors of the parotid gland, after pleomorphic adenoma. Our study was performed on 21 cases with Warthin tumor diagnosed between 2005-2010, which were analyzed clinically, histologically and immunohistochemically, using anti-CD20 and anti-CD45RO antibodies. The analysis of age distribution within the investigated cases indicated that Warthin tumor incidence is increasing in the seventh decade of life, most patients being male (M/F 5/2). Histopathological, the analysis report of stroma÷parenchyma in 14 cases revealed a balanced distribution of the two components, in four cases, the epithelial component was predominant and in three cases, the stromal component was predominant. Immunohistochemical study for the two specific lymphocyte proliferation markers indicated positivity for both epithelial component and stroma. Cell layout of CD45RO and CD20cy at the level of lymphoid stroma had a similar pattern with normal or reactive lymph nodes.


Aerobic vaginitis - An underdiagnosed cause of vaginal discharge - Narrative review.
The concept of vaginal dysbiosis was for long considered synonymous with bacterial vaginosis (BV), which is characterized by a homogenous non-inflammatory vaginal discharge. The inflammatory variant of vaginal dysbiosis, called aerobic vaginitis (AV), has remained unknown to a large part of the global dermatology and venereology community, gynaecologists and reproductive tract infection specialists with consequential under diagnosis. AV significantly differs from BV, in clinical presentation, diagnostic criteria and management. The deleterious impact of untreated AV on pregnancy merits discussion. Understanding AV is also crucial for better comprehension of desquamative inflammatory vaginitis (DIV), the most severe form of the same entity. We review the condition's epidemiology, risk factors and suspected aetiology, symptoms and signs, and the latest evidence-backed approach to diagnosis and treatment. The ideal diagnostic approach and treatment for AV/DIV are yet to be established. The currently recommended diagnostic approach for AV/DIV merits an overhaul by incorporating changes to render it feasible for resource-constraint countries. The diagnostic criteria lack a uniform applicability in different physiological groups of women and cannot be used in postpartum or postmenopausal states at the same cut-off levels. Similarly, treatment guidelines merit a relook, and customization, given the equivocality of options suggested by different investigators.


Virtual bronchoscopy. Relationships of virtual reality endobronchial simulations to actual bronchoscopic findings.
Advances in computer technology have permitted development of virtual reality images of the tracheobronchial tree using data sets derived from helical CT of the chest. To determine the relevance of these images to actual bronchoscopic findings, we compared "virtual bronchoscopy" images with videotaped bronchoscopy results in 20 patients who had undergone both helical chest CT and fiberoptic bronchoscopy during clinical evaluation of their thoracic problems. Suboptimal endobronchial simulations in ten patients identified important, readily-addressed technical requirements for this imaging procedure. In the ten patients with technically suitable renderings of the airway, virtual bronchoscopy simulations accurately demonstrated endobronchial obstructions by tumor in five, airway distortion and/or ectasia in four, and accessory bronchi in another. These preliminary observations suggest that virtual bronchoscopy simulations accurately represent major endobronchial anatomic findings. This technique may have a role in prebronchoscopy planning, endoscopy training, and/or endobronchial therapy, and merits further study.


Apolipoprotein B exhibits phospholipase A1 and phospholipase A2 activities.
Low density lipoproteins (LDL) as well as isolated apolipoprotein B (ApoB) have been shown to exhibit phospholipase A2 (PLA2) activity toward phospholipids containing an oxidized or short fatty acyl chain at position 2. Some of these studies employed the fluorescent analogue of phosphatidyl choline (PC), C6-NBD-PC, containing NBD-caproic acid (C6-NBD-FA) at position 2 as a substrate, representative of short fatty acyl chains. The release of NBD-caproic acid from position 2 is attributed to PLA2-catalysed hydrolysis. However, this fatty acid can be released also by other enzymatic pathways. In the present study we examined, and ruled out, other enzymatic pathways which may be responsible for the hydrolysis of fatty acids from position 2 of phospholipids. On the other hand, we found that LDL as well as isolated ApoB hydrolyse C6-NBD-FA from both carbon 1 and carbon 2 of these phospholipids, thus exhibiting independent and simultaneous activities of phospholipase A1 and phospholipase A2.


Effect of biologic mediators on ciprofloxacin accumulation by gingival fibroblasts.
Human gingival fibroblasts actively accumulate fluoroquinolone antimicrobials. Because fibroblasts are prevalent in gingiva, they may help sustain therapeutic fluoroquinolone levels at that site. The purpose of this study was to determine whether mediators associated with infection or injury can enhance ciprofloxacin accumulation by gingival fibroblasts. Quiescent fibroblast monolayers were treated for 1, 6, or 24 hours with several concentrations of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, platelet-derived growth factor (PDGF)-BB, fibroblast growth factor (FGF)-2, or insulin-like growth factor (IGF)-1. Transport was assayed by measuring cell-associated fluoroquinolone fluorescence. All mediators significantly enhanced ciprofloxacin transport in a dose dependent manner (P < 0.05; ANOVA). Except for TNF, this enhancement was associated with a decrease in the Km of ciprofloxacin transport. Maximal enhancement was observed with 10 ng/ml PDGF or FGF and 30 ng/ml TNF, TGF, or IGF. Brief (1 hour) treatment with TNF or FGF upregulated ciprofloxacin accumulation by a maximum of 13% to 14%, whereas TGF, PDGF, and IGF enhanced this process by 19% to 24%. All of the mediators enhanced ciprofloxacin accumulation by a maximum of 19% to 24% after 6 hours and 30% to 38% after 24 hours. The accumulation of other fluoroquinolones (e.g., gatifloxacin) was also slightly enhanced. Gingival fibroblasts treated with cytokines or growth factors accumulate significantly more ciprofloxacin than untreated controls. This provides a mechanism by which ciprofloxacin could be preferentially distributed to gingival wound or inflammatory sites, yielding local therapeutic levels that are more sustained than in serum.


Hydrodynamics of thermal granular convection.
A hydrodynamic theory is formulated for buoyancy-driven ("thermal") granular convection, recently predicted in molecular dynamic simulations and observed in experiment. The limit of a dilute flow is considered. The problem is fully described by three scaled parameters. The convection occurs via a supercritical bifurcation, the inelasticity of the collisions being the control parameter. The character of hydrodynamic modes of the system is discussed. The theory is expected to be valid for small Knudsen numbers and nearly elastic grain collisions.


A physical interaction between the cell death protein Fas and the tyrosine kinase p59fynT.
The Fas antigen (Apo1/CD95) is a transmembrane protein belonging to the nerve growth factor receptor family. It is expressed on a variety of cells, including activated T lymphocytes. Ligation of Fas with its natural ligand or with anti-Fas antibodies often results in the apoptotic death of the cell, making Fas an important mediator of down-regulating immune responses. The signal transduction pathways utilized by Fas are currently unknown, although tyrosine kinase activity has recently been strongly implicated. Here, we report that the tyrosine kinase p59fyn physically associates with Fas in Fas-sensitive cells. In addition, we show that activated T lymphocytes from fyn knockout mice exhibit elevated lifespans and reduced apoptosis in vitro compared to their normal counterparts. Furthermore, activated T lymphocytes from the fyn-deficient mice are less sensitive to killing by both anti-Fas antibody and Fas-ligand cytotoxic T cells. These results suggest that p59fyn plays an important role in Fas signal transduction.


Effect of polymerized orosomucoid on some strains of influenza virus.
1. Polymers of orosomucoid were produced in two molecular shapes, filamentous (;chain') and spherical (;ball'), by heating the sodium salt of the monomer in either water or high concentrations of sodium chloride. An ;intermediate' state containing both shapes in various proportions was found in preparations obtained by polymerizing orosomucoid in intermediate concentrations of sodium chloride. 2. The filamentous form of polymer was found to inhibit strongly the haemagglutination of some (;sensitive') strains but not of other (;insensitive') strains of influenza virus; the ;intermediate' form feebly inhibited haemagglutination by ;sensitive' strains. 3. The filamentous form agglutinated both ;sensitive' and ;insensitive' strains of virus; the other forms of polymer did not. It also inhibited multiplication of both ;sensitive' and ;insensitive' strains when inoculated into embryonated and de-embryonated eggs. 4. The ;intermediate' and spherical forms of the polymer had no effect on the virus multiplication. 5. Polymers of orosomucoid from which neuraminic acid had been split off had no detectable effect on influenza viruses.


Directional distribution of radiation around an accident at a uranium fuel factory in Tokai-mura, 1999.
A beta-ray survey was carried out on concrete walls of the boundary and buildings after a criticality accident at a factory of JCO Co. Ltd. at Tokai-mura. A remarkable distribution of beta counts was observed on the walls depending on the complex internal and external structures of buildings surrounding a precipitation vessel containing uranium 23 days after the accident. The directional distribution function, based on the beta counts on the walls, was consistent with data concerning the neutron dose rate measured in several directions during the accident, suggesting an anisotropic neutron distribution to the residential area.


Legionella pneumophila pneumonia successfully treated with intravenous ciprofloxacin.
A 69-year-old man developed a cough and fever during treatment with corticosteroid (p.o. and external use) for erythroderma. Chest X-ray films revealed a consolidation shadow in the right upper lung field. Initial treatment with sulbactam sodium/ampicillin followed by imipenem/cilastatin was not effective. A urinary antigen test for Legionella was positive, making for a diagnosis of Legionella pneumonia. Intravenous treatment with ciprofloxacin (CPFX) was remarkably effective. His symptoms, chest X-ray and laboratory data rapidly improved after its initiation. Our findings strongly suggest that intravenous treatment with fluoroquinolones including CPFX should also be a first choice for Legionella pneumonia in Japan.


Chromatin proteins and RNA are associated with DNA during all phases of mitosis.
Mitosis brings about major changes to chromosome and nuclear structure. We used recently developed proximity ligation assay-based techniques to investigate the association with DNA of chromatin-associated proteins and RNAs in Drosophila embryos during mitosis. All groups of tested proteins, histone-modifying and chromatin-remodeling proteins and methylated histones remained in close proximity to DNA during all phases of mitosis. We also found that RNA transcripts are associated with DNA during all stages of mitosis. Reduction of H3K27me3 levels or elimination of RNAs had no effect on the association of the components of PcG and TrxG complexes to DNA. Using a combination of proximity ligation assay-based techniques and super-resolution microscopy, we found that the number of protein-DNA and RNA-DNA foci undergoes significant reduction during mitosis, suggesting that mitosis may be accompanied by structural re-arrangement or compaction of specific chromatin domains.


Emodin Derivatives as Multi-Target-Directed Ligands Inhibiting Monoamine Oxidase and Antagonizing Vasopressin V1A Receptors.
The brain neurotransmitter level is associated with the pathology of various neurodegenerative diseases, and age-dependent increase in the blood level of vasopressin, human brain monoamine oxidase (hMAO) level, oxidative stress, and imbalance in aminergic signaling are common disease-modifying factors leading to various neurodegenerative disorders. Based on the reports of emodin in hMAO inhibition and antagonist effect on the vasopressin V1A receptor, in this study we synthesized six emodin derivatives and evaluated their effects on MAO activity and G protein-coupled receptors. Among them, 4-hydroxyemodin and 5-hydroxyemodin were potent inhibitors of hMAO, and 2-hydroxyemodin and 5-hydroxyemodin were good V1AR antagonists. In silico molecular docking simulation revealed that the hydroxyl group at C2, C4, and C5 of the respective compounds interacted with prime residues, which corroborates the in vitro effect. Likewise, these three derivatives were predicted to have good drug-like properties. Overall, our study demonstrates that the hydroxyl derivatives of emodin are multi-target-directed ligands that may act as leads for the design and development of a therapy for central nervous system disorders.


Patients perception of community pharmacist in bosnia and herzegovina.
Community pharmacists play a significant role in patient/disease management and perception by patients is increasingly important. A self-administered questionnaire was developed consisted of sociodemographic part and 15 questions. Patients have a positive overall perception of community pharmacists that is comparable to most studies in Europe. Community pharmacists' beyond dispensing drugs play a significant role in patient and disease management. This role of the pharmacist is performed through pharmaceutical care. Patient's opinion is increasingly considered to be a useful component in the determination of care outcomes and consumer satisfaction is an integral component of the quality of primary health care. For the purpose of this study we developed self-administered questionnaire consisted of sociodemographic part, and 15 questions. Survey has been conducted in 10 pharmacies. Results are presented in tables and figures and descriptive statistics has been used. We found that patients in Bosnia and Herzegovina have a positive overall perception of community pharmacists and of the services offered from community pharmacies that is comparable to most studies in Europe, but there is still room for improvement of relationships and pharmaceutical services.


Visual analogue scores in assessment of acute mountain sickness.
Acute mountain sickness (AMS) is common on ascent to high altitude, with self assessment being the current method used to assess symptoms. The Lake Louise Self-Report Score (LLSRS) and the Environmental Symptoms Questionnaire (ESQ) are widely used and validated. A Visual Analogue Scale (VAS) may be used as a simpler alternative for AMS assessment. Our aims were to compare a VAS using lines of length 100 mm, for both individual symptoms of AMS and self-assessed overall AMS with both LLSRS and a shortened Environmental Symptoms Questionnaire (ESQc) on ascent to 4392 m. We set out to suggest a specific score as a cut off point for diagnosis of AMS when using the VAS. There were significant positive correlations (p<0.01), between VAS and both LLSRS and ESQc scores for overall AMS and a composite AMS score derived from the individual symptom scores at 4392 m. The sensitivity and specificity of the VAS were calculated as 0.67 and 0.98, respectively, when using the LLSRS as the standard test for comparison, and 0.91 and 0.96, respectively, when using the ESQc for comparison. The cut off point for diagnosis of AMS was calculated to be 22 mm or above when using a VAS for overall AMS or 15 mm or above when using the VAS composite score, when using LLSRS as the comparative test. Our results show significant correlations between the VAS and the LLSRS and ESQc, when assessing AMS at 4392 m. Our study suggests that a VAS could provide a simple alternative method of assessing AMS at high altitude.


Few-cycle laser-driven electron acceleration.
We report on an electron accelerator based on few-cycle (8 fs full width at half maximum) laser pulses, with only 40 mJ energy per pulse, which constitutes a previously unexplored parameter range in laser-driven electron acceleration. The produced electron spectra are monoenergetic in the tens-of-MeV range and virtually free of low-energy electrons with thermal spectrum. The electron beam has a typical divergence of 5-10 mrad. The accelerator is routinely operated at 10 Hz and constitutes a promising source for several applications. Scalability of the few-cycle driver in repetition rate and energy implies that the present work also represents a step towards user friendly laser-based accelerators.


Fungal metabolic model for tyrosinemia type 3: molecular characterization of a gene encoding a 4-hydroxy-phenyl pyruvate dioxygenase from Aspergillus nidulans.
Mutations in the human HPD gene (encoding 4-hydroxyphenylpyruvic acid dioxygenase) cause hereditary tyrosinemia type 3 (HT3). We deleted the Aspergillus nidulans homologue (hpdA). We showed that the mutant strain is not able to grow in the presence of phenylalanine and that it accumulates increased concentrations of tyrosine and 4-hydroxyphenylpyruvic acid, mimicking the human HT3 phenotype.


Enhancing Interfacial Stability and Mechanical Strength of a CoSb3-Based Thermoelectric Junction Using Ti-Based Alloy Barrier Layers.
CoSb3-based filled skutterudites (SKDs) are among the most promising materials for power generation. However, the poor interfacial stability and mechanical strength severely limit their practical application when joined with Cu electrodes. In this study, we propose multiphase Ti-based alloy barrier layers for CoSb3-based thermoelectric junctions to prevent the continuous brittle TiCoSb phase formation. Following the principles of coefficient of thermal expansion matching, we designed three types of Ti80-xNbxCo20 (x = 0, 5, and 10, at.%) barrier layers with the thin intermetallic compound (IMC) layers (<20 μm). Transmission electron microscopy analysis revealed that the interfacial microstructure of the Ti75Nb5Co20/Ce-SKD junction comprises Ti5Sb3, Ti5CoSb3, TiCoSb, and TiSb2 phases, as well as unreacted TiCo, Ti2Co, and Ti(Nb)ss phases, demonstrating a uniform staggered distribution state. After aging tests, the IMC thickness increased gradually from 7 to 12 μm, and the interfacial contact resistivity increased from 7.59 to 15.46 μΩ·cm2. A Cu layer was chosen as a buffer during the brazing process to prevent the formation of cracks and holes. After aging for 360 h at 823 K, the shear strength of the brazed joints remained at ∼21 MPa. Our results demonstrate that the Cu/CuSnP/Cu/Ti75Nb5Co20/Ce-SKD brazed joint exhibits excellent interfacial stability and satisfactory mechanical strength.


A cross-cultural comparison of resilience in adolescents.
The purpose of this study was to continue the process of clarifying the concept of resilience in adolescence. At the completion of the first phase of this clarification process in 1997, it became evident that adolescents believed resilience hurt them more than helped them and encompassed such dimensions as self-protection and survival. To gain the broadest understanding of the adolescent's perception of resilience, this study qualitatively explored those perceptions from adolescents in varied socioeconomic and cultural environments. Using a focus-group format, we queried 40 adolescents from New England and Ghana about their perceptions of adversity, overcoming adversities, and resilience. The results indicated that irrespective of age, gender, culture, and socioeconomic status, all the adolescents believed that they were resilient; however, overcoming adversities and being resilient were different depending on the presence or absence of consistent, loving, caring, mentoring adults who helped the adolescent traverse the adversities of life. Those adolescents who were without such support systems (found predominately in the New England sample) showed survival and self-protective forms of resilience, whereas those with such support systems (found predominately in the Ghanaian sample) showed a connected form of resilience. Further research is needed; however, adolescents have given clear messages in two studies indicating that being resilient can hurt them as much as it may help them. When fostering resilience, consideration should be given to what kind of resilience is being fostered.


A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation.
Neurodegeneration with brain iron accumulation (NBIA) is a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by the abnormal accumulation of brain iron and the progressive degeneration of the nervous system. One of the recently identified subtypes of NBIA is β-propeller protein-associated neurodegeneration (BPAN). BPAN is caused by de novo mutations in the WDR45/WIPI4 (WD repeat domain 45) gene. WDR45 is one of the four mammalian homologs of yeast Atg18, a regulator of autophagy. WDR45 deficiency in BPAN patients and animal models may result in defects in autophagic flux. However, how WDR45 deficiency leads to brain iron overload remains unclear. To elucidate the role of WDR45, we generated a WDR45-knockout (KO) SH-SY5Y neuroblastoma cell line using CRISPR-Cas9-mediated genome editing. Using these cells, we demonstrated that the non-TF (transferrin)-bound iron pathway dominantly mediated the accumulation of iron. Moreover, the loss of WDR45 led to defects in ferritinophagy, a form of autophagy that degrades the iron storage protein ferritin. We showed that impaired ferritinophagy contributes to iron accumulation in WDR45-KO cells. Iron accumulation was also detected in the mitochondria, which was accompanied by impaired mitochondrial respiration, elevated reactive oxygen species, and increased cell death. Thus, our study links WDR45 to specific iron acquisition pathways and ferritinophagy. Cover Image for this issue: https://doi.org/10.1111/jnc.15388.


Portal versus caval venous drainage of small bowel allografts: technical and metabolic consequences.
The potential metabolic and technical consequences of systemic (portacaval anastomosis [PC-A]) as opposed to portal venous drainage (portaportal anastomosis [PP-A]) of orthotopic small bowel isografts was evaluated in a rat model. Rats with portacaval (PC) shunts were studied for comparison. During the study period of 6 months, rats with small bowel grafts (PP-A or PC-A) gained weight at rates equal to that of normal age-matched rats (+40% of the preoperative weight) whereas rats with PC shunts lost 20% of their weight. At autopsy 6 months after operation, rats with PC shunts had significant liver atrophy (2.0% of total body weight) in comparison with rats with orthotopic isografts. Moderate liver atrophy was detected in rats with grafts and PC-A in comparison with those with PP-A (2.6% versus 2.8% of total body weight, statistically not significant). Serum ammonia levels were significantly elevated for PC shunts (560 +/- 148 micrograms/dl) and PC-A (140 +/- 22 micrograms/dl) when compared with PP-A (83 +/- 10 micrograms/dl). In terms of technical difficulties, both PC-A and PP-A could be achieved with the same success rate. Systemic venous drainage for small bowel grafts is followed by metabolic alterations that are similar, although much less pronounced, to those seen after a PC shunt. Thus our findings do not offer compelling reasons to prefer PP-A over PC-A. However, with longer follow-up and the use of hepatotoxic immunosuppressive drugs, these minimal alterations may progress and induce metabolic sequelae of clinical significance. Under these circumstances it would be advisable to use the physiologic portal drainage rather than systemic venous drainage in small bowel transplantation.


Anti-inflammatory effect of maraviroc in an HIV-infected patient with concomitant myositis: a case report.
We report the surprising yet sought impact that an antiretroviral (ARV) regimen containing maraviroc had on an HIV-infected and heavily highly active antiretroviral therapy (HAART)-experienced patient with chronic polymyositis. The patient had elevated creatine kinase (CK) levels in serum for 6 years, reaching peaks over 900 U/L and showing only partial response to high-dose steroids, not responding to HAART withdrawal. The disease started while on second-line HAART and gradually impaired his muscular function, leading to the absolute loss of the ability to stand on his legs. Atherosclerosis and hypertension contributed to the development of myocardial infarction. The association of unboosted atazanavir (ATV) plus maraviroc was designed hoping in a protective role on the cardiovascular system and in an anti-inflammatory effect that some authors have hypothesized. After only 3 months the patient's CK levels had normalized and with the help of rehabilitation he recovered the ability to walk, which he still maintains at the one year of observation.


The Medical Skills Centre at the University of Calgary Medical School.
The aim of the Medical Skills Centre at the University of Calgary is to provide a predictable learning environment and standardized teaching methods in the area of clinical skills teaching. The centre uses volunteer patients and trained actors for all levels of medical education and evaluation. A computer database enables easy access to groups of patients and varying medical issues. This article describes the organization and operation of the Medical Skills Centre and notes a variety of courses which use the unique facilities of the centre.


Aptamer-Based Screens of Human Body Fluids for Biomarkers.
In recent years, aptamers have come to replace antibodies in high throughput multiplexed experiments. The aptamer-based biomarker screening technology, which kicked off in 2010, is capable of interrogating thousands of proteins in a very small sample volume. With this new technology, researchers hope to find clinically appropriate biomarkers for a myriad of illnesses by screening human body fluids. In this work, we have reviewed a total of eight studies utilizing aptamer-based biomarker screens of human body fluids, and have highlighted novel protein biomarkers discovered.


Platelet Toll-Like-Receptor-2 and -4 Mediate Different Immune-Related Responses to Bacterial Ligands.
Background Like immune cells, platelets express toll-like receptors (TLRs) on their surface membrane. TLR2 and TLR4 are able to recognize bacterial antigens and have the potential to influence hemostatic functions and classical intracellular signaling pathways. This study investigated the role of TLR2 and TLR4 for immune-related functions in human platelets. Materials and Methods Washed platelets and neutrophils were prepared from fresh human peripheral blood. Basal-, Pam3CSK4- (as TLR2 agonist) and Lipopolysaccharides (LPS; as TLR4 agonist) -induced CD62P expression, fibrinogen binding and TLR2 or TLR4 expression, intracellular reactive oxygen species (ROS) production in H 2 DCFDA-loaded platelets and uptake of fluorescence-labeled TLR ligands, and fluorophore-conjugated fibrinogen were evaluated by flow cytometry. Analysis of platelet-neutrophil complexes was performed after coincubation of washed platelets and neutrophils in the presence and absence of TLR2 or TLR4 agonists on poly-L-lysine coated surfaces, followed by immunostaining and immunofluorescence imaging. Results Pam3CSK4 rapidly and transiently increased TLR2 and TLR4 expression. Over the course of 30 minutes after activation with Pam3CSK4 and LPS, the expression of both receptors decreased. Pam3CSK4-stimulated intracellular ROS production and the uptake of TLR ligands or fibrinogen much stronger than LPS. Besides, TLR4 activation led to a significant increase of platelet-neutrophil contacts. Conclusion Stimulation leads to rapid mobilization of TLR2 or TLR4 to the platelet surface, presumably followed by receptor internalization along with bound TLR ligands. After activation, platelet TLR2 and TLR4 mediate different immune-related reactions. In particular, TLR2 induces intracellular responses in platelets, whereas TLR4 initiates interactions with other immune cells such as neutrophils.


Setting of the Circadian N(2)-Fixing Rhythm of the Prokaryotic Synechococcus sp. RF-1 while Its nif Gene Is Repressed.
The N(2)-fixing activity of the prokaryotic Synechococcus sp. RF-1 was repressed in the presence of nitrate. When the cultures in nitrate-containing medium were exposed to diurnal light-dark cycles, an endogenous circadian N(2)-fixing rhythm developed after the cells were transferred to nitrate-free medium and incubated in continuous light. The N(2)-fixing phase of the rhythm coincided with the dark phase of the light-dark cycles that were imposed when the cells were in nitrate-containing medium. The results indicate that after the endogenous N(2)-fixing rhythm has been set, it can be kept latent for at least 38 hours before first manifesting itself.


The "ISN'T rule" in healthy participant optic nerve head by confocal scanning laser ophthalmoscopy.
In normal patients the rim had a characteristic configuration with the rim width being broadest in the inferior disc region, followed by the superior, the nasal, and the temporal sector. The aim of this study was to assess whether the rim shape as measured by the Heidelberg Retina Tomograph 3 (HRT3) followed the ISN'T rule or any other specific distribution pattern. This is a prospectively planned cross-sectional study. Two hundred and twenty-six healthy eyes were recruited into this study. All the patients who were included had normal ocular examination, an intraocular pressure less than 21 mm Hg and a normal visual field by the Humphrey Field Analyzer (program 24-2, Swedish Interactive Threshold Analysis standard). For each patient, the optic nerve head was morphometrically evaluated by using the HRT3. All data were analyzed by the analysis of variance test and Tukey's Multiple Comparison Test. When the rim area and rim volume were considered, a statistically significant difference (P<0.001) was found between the temporal rim area and superior, nasal, and inferior rim area. No significant difference was found among the superior, nasal, and inferior rim area. A similar result was found for the cup area. The temporal cup shape measure was significantly (P<0.001) different from the other disc sectors. In healthy participants the rim shape as measured by the HRT did not follow the ISN'T rule, except that the smallest rim part was located in the temporal disc region. The thickness of the rim was similar in the superior and the inferior sectors by HRT.


In-Hospital Management Might Reduce Induction Deaths in Pediatric Patients With Acute Lymphoblastic Leukemia: Results From a Japanese Cohort.
Induction deaths (ID) remain a critical issue in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL). The reported rate of ID in this population is 1% or higher. We speculate that this proportion might be lower in Japan because of mandatory hospitalization during induction therapy to manage complications. We retrospectively analyzed the incidence of ID among children with ALL enrolled in 4 Japanese study groups between 1994 and 2013. Among 5620 children, 41 (0.73%) cases of ID were noted. The median age was 6.5 years; 24 children were female, and 7 had T-cell ALL. Infection was the most common cause of ID (n=22), but the incidence (0.39%) was lower than that reported in western countries. Mortality within 48 hours from the onset of infection was low, comprising 25% of infection-related deaths. The incidence of infections caused by Bacillus species was low. Only 1 patient died because of Aspergillus infection. Fatal infections mostly occurred during the third week of induction therapy. Our findings suggest that close monitoring, stringent infection control, and immediate administration of appropriate antibiotics through hospitalization might be important strategies in reducing the rate of infection-related ID in pediatric patients with ALL.


Charge and Spin Dynamics and Enantioselectivity in Chiral Molecules.
Charge and spin dynamics are addressed in chiral molecules immediately after their instantaneous coupling to an external metallic reservoir. This work describes how a spin polarization is induced in the chiral structure as a response to the charge dynamics. The dynamics indicate that chiral induced spin selectivity is an excited state phenomenon that in the transient regime can be partly captured using a simplistic single-particle description but in the stationary limit definitively shows that electron correlations, e.g., electron-vibration interactions, crucially contribute to sustain an intrinsic spin anisotropy that can lead to a nonvanishing spin selectivity. The dynamics, moreover, provide insight into enantiomer separation, due to different acquired spin polarizations.


Predicting US- and state-level cancer counts for the current calendar year: Part I: evaluation of temporal projection methods for mortality.
A study was undertaken to evaluate the temporal projection methods that are applied by the American Cancer Society to predict 4-year-ahead projections. Cancer mortality data recorded in each year from 1969 through 2007 for the United States overall and for each state from the National Center for Health Statistics was obtained. Based on the mortality data through 2000, 2001, 2002, and 2003, Projections were made 4 years ahead to estimate the expected number of cancer deaths in 2004, 2005, 2006, 2007, respectively, in the United States and in each state, using 5 projection methods. These predictive estimates were compared to the observed number of deaths that occurred for all cancers combined and 47 cancer sites at the national level, and 21 cancer sites at the state level. Among the models that were compared, the joinpoint regression model with modified Bayesian information criterion selection produced estimates that are closest to the actual number of deaths. Overall, results show the 4-year-ahead projection has larger error than 3-year-ahead projection of death counts when the same method is used. However, 4-year-ahead projection from the new method performed better than the 3-year-ahead projection from the current state-space method. The Joinpoint method with modified Bayesian information criterion model has the smallest error of all the models considered for 4-year-ahead projection of cancer deaths to the current year for the United States overall and for each state. This method will be used by the American Cancer Society to project the number of cancer deaths starting in 2012.


Sociocultural predictors of psychological help-seeking attitudes and behavior among Mexican American college students.
Sociocultural variables of acculturation, enculturation, cultural congruity, and perceived social support were used as predictors of psychological help-seeking attitudes and behaviors among 162 Mexican American college students. Multivariate multiple regression analyses indicated that higher cultural congruity, lower perceived social support from family, and higher perceived social support from significant others were significant predictors of positive help-seeking attitudes. In addition, higher acculturation into the dominant society, lower perceived social support from family, and lower perceived social support from friends were significantly predictive of greater help-seeking behavior. Implications for research and practice are discussed.


Effects of contraction mode and stimulation frequency on electrical stimulation-induced skeletal muscle hypertrophy.
We compared the skeletal muscle hypertrophy resulting from isometric (Iso) or eccentric (Ecc) electrical stimulation (ES) training with different stimulation frequencies. Male Wistar rats were assigned to the Iso and Ecc groups. These were divided into three further subgroups that were stimulated at 10 Hz (Iso-10 and Ecc-10), 30 Hz (Iso-30 and Ecc-30), or 100 Hz (Iso-100 and Ecc-100). In experiment 1, the left plantarflexor muscles were stimulated every other day for 3 wk. In experiment 2, mammalian target of rapamycin complex 1 (mTORC1) signaling was investigated 6 h after one bout of ES. The contralateral right muscle served as a control (non-ES). Ecc contractions comprised forced dorsiflexion combined with ES. The peak torque and torque-time integral during ES were higher in the Ecc group than that in the Iso group in all stimulation frequencies examined. The gastrocnemius muscle weight normalized to body weight in ES side was increased compared with the non-ES side by 6, 7, and 17% in the Ecc-30, Iso-100, and Ecc-100 groups, respectively, with a greater gain in Ecc-100 than the Ecc-30 and Iso-100 groups. The p70S6K (Thr389) phosphorylation level was higher in the Ecc-30 and -100 than in the Iso-30 and -100 groups, respectively. The peak torque and torque-time integral were highly correlated with the magnitude of increase in muscle mass and the phosphorylation of p70S6K. These data suggest that ES-induced muscle hypertrophy and mTORC1 activity are determined by loading intensity and volume during muscle contraction independent of the contraction mode. NEW & NOTEWORTHY Eccentric contraction and high-frequency stimulation (HFS) are regarded as an effective way to increase muscle mass by electrical stimulation (ES) training. However, little is known about whether muscle hypertrophy is affected by contraction mode and stimulation frequency in ES training. Here, we provide the evidence that muscle hypertrophy and mammalian target of rapamycin complex 1 activity are determined by mechanical loading during contraction but not on the contraction mode itself, with a greater gain at HFS.


Detection of macrophage activity in atherosclerosis in vivo using multichannel, high-resolution laser scanning fluorescence microscopy.
Molecular and cellular mechanisms of atherogenesis and its treatment are largely being unraveled by in vitro techniques. We describe methodology to directly image macrophage cell activity in vivo in a murine model of atherosclerosis using laser scanning fluorescence microscopy (LSFM) and a macrophage-targeted, near-infrared fluorescent (NIRF) magnetofluorescent nanoparticle (MFNP). Atherosclerotic apolipoprotein E deficient (apoE -/-) mice (n=10) are injected with MFNP or 0.9% saline, and wild-type mice (n=4) are injected with MFNP as additional controls. After 24 h, common carotid arteries are surgically exposed and prepared for LSFM. Multichannel LSFM of MFNP-enhanced carotid atheroma (5x5-microm in-plane resolution) shows a strong focal NIRF signal, with a plaque target-to-background ratio of 3.9+/-1.8. Minimal NIRF signal is observed in control mice. Spectrally resolved indocyanine green (ICG) fluorescence angiograms confirm the intravascular location of atheroma. On ex vivo fluorescence reflectance imaging, greater NIRF plaque signal is seen in apoE -/- MFNP mice compared to controls (p<0.01). The NIRF signal correlates well with immunostained macrophages, both by stained surface area (r=0.77) and macrophage number (r=0.86). The validated experimental methodology thus establishes a platform for investigating macrophage activity in atherosclerosis in vivo, and has implications for the detection of clinical vulnerable plaques.


Architecture-dependent robustness and bistability in a class of genetic circuits.
Understanding the relationship between genotype and phenotype is a challenge in systems biology. An interesting yet related issue is why a particular circuit topology is present in a cell when the same function can supposedly be obtained from an alternative architecture. Here we analyzed two topologically equivalent genetic circuits of coupled positive and negative feedback loops, named NAT and ALT circuits, respectively. The computational search for the oscillation volume of the entire biologically reasonable parameter region through large-scale random samplings shows that the NAT circuit exhibits a distinctly larger fraction of the oscillatory region than the ALT circuit. Such a global robustness difference between two circuits is supplemented by analyzing local robustness, including robustness to parameter perturbations and to molecular noise. In addition, detailed dynamical analysis shows that the molecular noise of both circuits can induce transient switching of the different mechanism between a stable steady state and a stable limit cycle. Our investigation on robustness and dynamics through examples provides insights into the relationship between network architecture and its function.


Cardioprotective effect of dexrazoxane in patients with breast cancer treated with anthracyclines in adjuvant setting: a 10-year single institution experience.
Anthracyclines are highly effective and widely used cytotoxic agents, but their application is often limited by cumulative dose-dependent cardiotoxicity. Dexrazoxane has been shown in several clinical trials to prevent the development of this serious toxicity. The aim of our study was to analyze the incidence of cardiac dysfunction over a 10-year period in patients with breast cancer who were treated with anthracycline-based regimens with addition of dexrazoxane, mainly in an adjuvant setting. We conducted a retrospective analysis on a population of women with breast cancer treated at our institution between January 1993 and October 2003. We reviewed patients' medical records and data on patient characteristics, treatment history, and adverse events that were collected, starting from the time of first visit before starting therapy, with the use of software created and designed for clinical records management in our institution (1999 OK-DH). Patients underwent an ECG assessment prior to starting chemotherapy, and were clinically monitored for cardiac failure. Those who developed signs and symptoms suggestive of cardiac dysfunction underwent further ECG. If clinical findings indicated, echocardiography and further cardiologic investigations were performed. The main outcome measure was the development of signs and symptoms indicative of congestive heart failure (CHF). A total of 318 female patients were treated with an anthracycline (doxorubicin or epirubicin)-based combination chemotherapy regimen during this time, in most cases in the adjuvant setting (n = 285). Most patients (n = 302) had early-stage disease and only 16 women presented with metastatic disease with good life expectancy (at least 1 year). All patients received dexrazoxane 1000 mg/m(2) intravenously prior to anthracycline administration during each chemotherapy cycle. The median follow-up duration was 35 months. During this time, five patients (1.57%) developed signs and symptoms of CHF. No patient at our institution died of heart failure during the period analyzed. Dexrazoxane was well tolerated, with no reports of adverse events associated with this drug. The reported incidence of cardiotoxicity in this study represents a marked reduction compared with historical data for patients receiving anthracycline-based chemotherapy without dexrazoxane. Dexrazoxane appears to have a cardioprotective effect in women with early-stage or advanced breast cancer treated with anthracycline-based combination chemotherapy, mainly as an adjuvant treatment. Prospective, randomized, controlled clinical trials in adjuvant setting should be performed to confirm these results.


Bacillus manliponensis sp. nov., a new member of the Bacillus cereus group isolated from foreshore tidal flat sediment.
A Gram-positive, endospore-forming, new Bacillus species, strain BL4-6(T), was isolated from tidal flat sediment of the Yellow Sea. Strain BL4-6(T) is a straight rod, with motility by peritrichate flagella. The cell wall contains meso-diaminopimelic acid, and the major respiratory quinone is menaquinone-7. The major fatty acids are iso-C(15:0) and summed feature 3 (containing C(16:1) ω7c/iso-C(15:0) 2OH, and/or iso-C(15:0) 2OH/C(16:1) ω7c). Cells are catalase-positive and oxidase-negative. The G+C content of the genomic DNA is 38.0 mol%. Based on a comparative 16S rRNA gene sequence analysis, the isolate belongs to the genus Bacillus, forms a clade with the Bacillus cereus group, and is closely related to Bacillus mycoides (98.5%), Bacillus cereus (98.5%), Bacillus anthracis (98.4%), Bacillus thuringiensis (98.4%), Bacillus weihenstephanensis (98.1%), and Bacillus pseudomycoides (97.5%). The isolate showed less than 85% similarity of the gyrA gene sequence and below 95% similarity of the rpoB gene sequence to the members of this group. DNA-DNA relatedness between strain BL4-6(T) and B. cereus group was found to be in a range of 22.8-42.3%, and thus BL4-6(T) represents a unique species. On the basis of these studies, strain BL4-6(T) (=KCTC 13319(T) =JCM 15802(T)) is proposed to represent the type strain of a novel species, Bacillus manliponensis sp. nov.


Quality Of Educational Environment At Wah Medical College: Assessment By Using Dundee Ready Educational Environment Measure.
Educational environment not only has an impact on the students during the academic years but has its reflections throughout their medical career. The Dundee Ready Educational Environment Measure (DREEM) is an internationally accepted useful tool to analyse undergraduate educational environments in the health professionals. The purpose of this study was to assess how students, across all the five years in a private medical college, perceive their educational environment. It was a cross sectional study, which used the DREEM inventory at Wah Medical College over the course of 6 months (January-June 2015). All 500 students were included in the study. The fifty items DREEM inventory, having the maximum score of two hundred indicating ideal educational environment was used for data collection. The questionnaire was completed by 400 undergraduate medical students (response rate 80%). The overall DREEM score was 122.63/200 (61.3%), indicating that the perception of the learning environment was more positive than negative. Among the highest scoring categories were students' participation in classes, relaxed atmosphere and confidence in passing the annual exams. However, many areas requiring improvement were also brought to attention. Overall, the student's perception of their learning environment at Wah Medical College was found to be positive. This study did bring to light some areas that could be improved upon. This should enable the faculty to adopt changes in their teaching methods to make the learning process more productive and enjoyable for future students.


Regulation of DNA-raised immune responses by cotransfected interferon regulatory factors.
Interferon regulatory factor 1 (IRF-1), IRF-3, and IRF-7 have been tested as genetic adjuvants for influenza virus hemagglutinin (HA) and nucleoprotein vaccine DNAs. Cotransfection of HA with IRF-3 and IRF-7 increased CD4 T-cell responses by 2- to 4-fold and CD8 T-cell responses by more than 10-fold. Following intramuscular deliveries of DNA, both CD4 and CD8 T cells were biased towards type 1 immune responses and the production of gamma interferon. Following gene gun bombardments of DNA, both were biased towards type 2 immune responses and the production of interleukin-4. The biases of the T-cell responses towards type 1 or type 2 were stronger for immunizations with IRF-3 as an adjuvant than for immunizations with IRF-7 as an adjuvant. Moderate adjuvant effects for antibody were observed. The isotypes of the antibody responses reflected the method of DNA delivery; intramuscular deliveries of DNA predominantly raised immunoglobulin G2a (IgG2a), whereas gene gun deliveries of DNA predominantly raised IgG1. These biases were enhanced by the codelivered IRFs. Overall, under the conditions of our experiments, IRF-3 had good activity for T cells, IRF-7 had good activity for both antibody and T cells, and IRF-1 had good activity for antibody.


Objective improvement in adults with cerebellopontine angle arachnoid cysts after surgical treatment.
Intracranial arachnoid cysts are extra-axial benign lesions mainly found in the middle cerebral fossa. Rare case series report various cranial nerve dysfunctions associated with cerebellopontine angle (CPA) cysts and there is no consensus with regard to their surgical management; some reports claiming that subjective improvement in adults with intracranial arachnoid cysts cannot justify surgical treatment. This retrospective study included all 12 consecutive adult patients treated by microsurgical fenestration for symptomatic CPA arachnoid cysts between 2010 and 2019 and using a retrosigmoid approach. Demographic, clinical, surgical, and radiological data were collected from medical files. The main symptoms were audiovestibular in 9 patients (75%) complaining of dizziness and 6 patients (50%) with hearing loss. In addition, 3 patients (25%) reported tinnitus, 3 patients (25%) presented vasovagal syncope, and 1 patient (8.3%) reported facial pain. Surgery improved 5 patients (83%) with pre-operative hearing loss, 7 patients (78%) reporting dizziness, and all patients with vasovagal syncope. All of the patients recovered from at least one symptom. No recurrence was observed with a mean follow-up of 5.5 years. Although most arachnoid cysts are asymptomatic, the CPA location may lead to cranial nerve impairments. Microsurgical fenestration seems to be a simple, safe, and effective technique.


Severe burns in a patient after out-of-hospital CPR.
We present a case of a patient after prolonged cardio-pulmonary resuscitation on hot asphalt, who suffered from first and second degree burns which worsened during hospitalization. The patient was treated with therapeutic hypothermia. Possible effect of therapeutic hypothermia on the course of burns is discussed.


CD44/ERM/F-actin complex mediates targeted nuclear degranulation and excessive neutrophil extracellular trap formation during sepsis.
Neutrophils release neutrophil extracellular traps (NETs) to capture and kill pathogens, but excessive NET release can damage the surrounding tissues. Myeloperoxidase (MPO) and neutrophil elastase (NE) are thought to be important in promoting histone depolymerization and DNA breakage in the nucleus. However, the detailed path by which MPO and NE enter the nucleus is unknown. In the present study, we observed that delayed fusion of azurophilic granules with the nuclear membrane 15-20 min after extracellular degranulation in activated neutrophils. In a subsequent experiment, we further demonstrated that this fusion leads to MPO entry into the nucleus and promotes nuclear histone depolymerization and DNA breakage, a process called 'targeted nuclear degranulation'. This process can be effectively inhibited by dexamethasone and accompanied by the continuous low levels of MPO in the nucleus after PMA stimulation. Meanwhile, we found that 'targeted nuclear degranulation' is dependent on the CD44 translocation and subsequent redistribution of CD44 / ERM (Ezrin/Radixin/Moesin) / F-actin complexes, which guides the movement of azurophilic granules towards the nucleus. Application of ERM phosphorylation inhibitors and importin activity inhibitors significantly reduced the complexes formation and redistribution. Taken together, these findings indicate for the first time that delayed 'targeted nuclear degranulation' after neutrophil activation is a key mechanism of NET formation. CD44/ERM/F-actin complex mediates this process, which providing targets with promising prospects for the precise regulation of NET formation.


Onychogryphosis.
A case of onychogryphosis of the left index nail is presented. This classical toenail dystrophy in our case involves a fingernail and is associated with onychomycosis.


Diminished production of prostaglandin E2 by monocytes of newborns is due to altered fatty acid membrane content and reduced cyclooxygenase activity.
To determine the biochemical basis for reduced PGE2 expression by cord blood monocytes relative to adult peripheral blood monocytes, fatty acid composition of cell membranes together with the amount and activity of enzymes involved in the cyclooxygenase pathway were investigated. Gas chromatographic analysis of mononuclear cell fatty acids showed a significant reduction in long chain fatty acids, including arachidonic acid. Acylase and phospholipase A2 activity, together with lipocortin 1 levels, were similar in cord and adult monocytes. No difference in amounts of the 70-kDa cyclooxygenase type 1 enzyme was observed between the monocyte sources. The 74k-Da cyclooxygenase type 2 enzyme was synthesized de novo upon LPS stimulation in comparable amounts in both cord and adult monocytes, with both monocyte types responding with equal sensitivity to LPS. The ability of microsomes, prepared from cord monocytes, to convert arachidonic acid into eicosanoids of the cyclooxygenase pathway was reduced. In contrast, the ability of acetylated microsomes to convert PGG2 to PGE2 was comparable, suggesting that the deficiency in PGE2 production by cord monocytes is due to reduced activity, specifically at the cyclooxygenase-active site rather than the peroxidase active site. In conclusion, it appears that both reduced fatty acid content and diminished cyclooxygenase activity are responsible for diminished eicosanoid production by cord monocytes.


DRL interresponse-time distributions: quantification by peak deviation analysis.
Peak deviation analysis is a quantitative technique for characterizing interresponse-time distributions that result from training on differential-reinforcement-of-low-rate schedules of reinforcement. It compares each rat's obtained interresponse-time distribution to the corresponding negative exponential distribution that would have occurred if the rat had emitted the same number of responses randomly in time, at the same rate. The comparison of the obtained distributions with corresponding negative exponential distributions provides the basis for computing three standardized metrics (burst ratio, peak location, and peak area) that quantitatively characterize the profile of the obtained interresponse-time distributions. In Experiment 1 peak deviation analysis quantitatively described the difference between the interresponse-time distributions of rats trained on variable-interval 300-s and differential-reinforcement-of-low-rate 72-s schedules of reinforcement. In Experiment 2 peak deviation analysis differentiated between the effects of the psychomotor stimulant d-amphetamine, the anxiolytic compound chlordiazepoxide, and the antidepressant desipramine. The results suggest that peak deviation analysis of interresponse-time distributions may provide a useful behavioral assay system for characterizing the effects of drugs.


The effect of maternal intravenous hydration on amniotic fluid index in oligohydramnios.
Assessing amniotic fluid determines an important dimension of fetal health. Significant relationships of oligohydramnios, which occurs in 1-2% of pregnancies, with abnormal pregnancy outcomes such as intrauterine growth retardation (IUGR), fetal anomalies, umbilical cord compression, fetal distress, preterm childbirth, meconium-stained amniotic fluid, perinatal mortality and cesarean section necessitate the measurement of amniotic fluid volume in many prenatal fetal health assessments. Amniotic fluid volume may significantly fluctuate between different gestational ages. Reduced uteroplacental perfusion can cause oligohydramnios by decreasing fetal renal blood flow and urine output. The appropriate management of isolated term oligohydramnios (ITO) is controversial. This study was performed aimed to assess the effect of maternal intravenous hydration on amniotic fluid index in oligohydramnios. Forty-eight hours after completing fluid therapy, statistically significant differences were observed in the mean AFI in the intervention group (4.06 ± 0.33) and the control group (3.61 ± 0.35) (P < 0.0001) and also between the intervention group (0.532 ± 0.45) and the controls (-0.036 ± 0.18) (P < 0.0001). The results of the present study suggested that maternal intravenous hydration significantly increases AFI in women with oligohydramnios.


Comparing handheld and hands-free cell phone usage behaviors while driving.
The goal of this study was to compare cell phone usage behaviors while driving across 3 types of cell phones: handheld (HH) cell phones, portable hands-free (PHF) cell phones, and integrated hands-free (IHF) cell phones. Naturalistic driving data were used to observe HH, PHF, and IHF usage behaviors in participants' own vehicles without any instructions or manipulations by researchers. In addition to naturalistic driving data, drivers provided their personal cell phone call records. Calls during driving were sampled and observed in naturalistically collected video. Calls were reviewed to identify cell phone type used for, and duration of, cell phone subtasks, non-cell phone secondary tasks, and other use behaviors. Drivers in the study self-identified as HH, PHF, or IHF users if they reported using that cell phone type at least 50% of the time. However, each sampled call was classified as HH, PHF, or IHF if the talking/listening subtask was conducted using that cell phone type, without considering the driver's self-reported group. Drivers with PHF or IHF systems also used HH cell phones (IHF group used HH cell phone in 53.2% of the interactions, PHF group used HH cell phone for 55.5% of interactions). Talking/listening on a PHF phone or an IHF phone was significantly longer than talking/listening on an HH phone (P <.05). HH dialing was significantly longer in duration than PHF or IHF begin/answer tasks. End phone call task for HH phones was significantly longer in duration than the end phone call task for PHF and IHF phones. Of all the non-cell phone-related secondary tasks, eating or drinking was found to occur significantly more often during IHF subtasks (0.58%) than in HH subtasks (0.15%). Drivers observed to reach for their cell phone mostly kept their cell phone in the cup holder (36.3%) or in their seat or lap (29.0% of interactions); however, some observed locations may have required drivers to move out of position. Hands-free cell phone technologies reduce the duration of cell phone visual-manual tasks compared to handheld cell phones. However, drivers with hands-free cell phone technologies available to them still choose to use handheld cell phones to converse or complete cell phone visual-manual tasks for a noteworthy portion of interactions.


Recruitment to a seabird population depends on environmental factors and on population size.
1. A novel capture-mark-recapture (CMR) method was used to build a multistate model of recruitment by young birds to a breeding population of common guillemots Uria aalge on the Isle of May, Scotland. Recruitment of a total of 2757 individually marked guillemots over 17 years was modelled as a process where individuals had to move from an unobservable state at sea, through a nonbreeding state present in the colony, to the breeding state. The probabilities of individuals returning to the colony in a given year, at age 2 and 3-4 years, were positively correlated with an environmental covariate, the winter North Atlantic Oscillation index (WNAO) in the previous years. 2. For 2 year olds, there was a negative relationship with breeding population size, suggesting that density dependence operated in this colony through limitation of food or some other resource. 3. Survival over the first 2 years of life varied with cohort, but was unrelated to the WNAO. Mean survival over this 2-year period was high at 0.576 (95% CI: 0.444; 0.708). 4. This high survival, combined with a low 'local' survival after age 5 years of 0.695 (0-654; 0.733) and observations of Isle of May chicks at other colonies, suggests that most surviving chicks return to the natal colony before deciding whether to recruit there or move elsewhere.


Synthetic Sugar-Only Polymers with Double-Shoulder Task: Bioactivity and Imaging.
The search for novel fluorescent materials has attracted the attention of many researchers. Numerous bioimaging materials based on the aggregation-induced emission (AIE) units have been surging and could be employed in wide areas during the past two decades. In recent few years, the appearance of nonconventional fluorescence emitters without aromatic conjugated structures provides another bioimaging candidate which has the advantage of enhanced biodegradability and relatively low cost, and their luminescent mechanism can be explained by clustering-triggered emission (CTE) like AIE. In our contribution, we utilize nonaromatic sugar as a monomer to prepare a series of glycopolymers with designed components through sunlight-induced reversible addition fragmentation chain transfer polymerization; these glycopolymers can be employed in bioimaging fields due to the bioactivity coming from sugar and CTE capacity.


Mercury-induced conformational changes and identification of conserved surface loops in plasma membrane aquaporins from higher plants. Topology of PMIP31 from Beta vulgaris L.
Aquaporins are integral membrane proteins occurring in mammals, plants, and microorganisms, which serve as channels that permit the bidirectional passage of water through cellular membranes. Higher plants contain abundant levels of aquaporins in both the tonoplast and plasma membrane. Aquaporins contain six transmembrane segments with three surface loops located at the apoplastic face of the membrane and two loops at the cytosolic side. In this study, we probed the topology of plasma membrane aquaporins to determine the effects of divalent cations on aquaporin conformation, and to identify structural features that distinguish plasma membrane intrinsic proteins from tonoplast intrinsic proteins. Plasma membrane vesicles from storage tissue of Beta vulgaris L. were subjected to limited proteolysis, and proteolytic fragmentation patterns were detected using affinity-purified antibodies recognizing aquaporins of 31-kDa. In its native membrane-associated state, the 31-aquaporin band, PMIP31, was refractory to proteolysis by trypsin. However, mercuric compounds specifically induced a conformational change resulting in the exposure of a proteolytic cleavage site and formation of a unique 22-kDa proteolytic fragment (p22). N-terminal sequence analysis of p22 established its identity as an aquaporin-derived fragment. Topological studies using sealed right-side-out plasma membrane vesicles established that the proteolytic cleavage site is located at surface loop C, the second apoplastic loop, immediately preceding the sequence Gly-Gly-Gly-Ala-Asn. The Gly-Gly-Gly-Ala-Asn-X-X-X-X-Gly-Tyr motif of loop C and a 14 amino acid motif in apoplastic loop E, Thr-Gly-Ile/Thr-Asn-Pro-Ala-Arg-Ser-Leu/Phe-Gly-Ala-Ala-Ile/Val-Ile/ Val-Phe/Tyr-Asn are completely conserved in all known higher plant aquaporins of plasma membrane origin and are not present in any of the known tonoplast intrinsic proteins. These results demonstrate that the two highly conserved plasma membrane intrinsic protein surface loops are structural features that clearly distinguish plasma membrane from tonoplast aquaporins.


A scoping review of machine learning in psychotherapy research.
Machine learning (ML) offers robust statistical and probabilistic techniques that can help to make sense of large amounts of data. This scoping review paper aims to broadly explore the nature of research activity using ML in the context of psychological talk therapies, highlighting the scope of current methods and considerations for clinical practice and directions for future research. Using a systematic search methodology, fifty-one studies were identified. A narrative synthesis indicates two types of studies, those who developed and tested an ML model (k=44), and those who reported on the feasibility of a particular treatment tool that uses an ML algorithm (k=7). Most model development studies used supervised learning techniques to classify or predict labeled treatment process or outcome data, whereas others used unsupervised techniques to identify clusters in the unlabeled patient or treatment data. Overall, the current applications of ML in psychotherapy research demonstrated a range of possible benefits for indications of treatment process, adherence, therapist skills and treatment response prediction, as well as ways to accelerate research through automated behavioral or linguistic process coding. Given the novelty and potential of this research field, these proof-of-concept studies are encouraging, however, do not necessarily translate to improved clinical practice (yet).


Exploiting the drug-activating properties of a novel trypanosomal nitroreductase.
Nitroheterocyclic prodrugs have been used to treat trypanosomal diseases for more than 40 years. Recently, the key step involved in the activation of these compounds has been elucidated and shown to be catalyzed by a type I nitroreductase (NTR). This class of enzyme is normally associated with bacteria and is absent from most eukaryotes, with trypanosomes being a major exception. Here we exploit this difference by evaluating the trypanocidal activity of a library of nitrobenzylphosphoramide mustards against bloodstream-form Trypanosoma brucei parasites. Biochemical screening against the purified enzyme revealed that a subset of halogenated nitroaromatic compounds were effective substrates for T. brucei NTR (TbNTR), having apparent K(cat)/K(m) values approximately 100 times greater than nifurtimox. When tested against T. brucei, cytotoxicity mirrored enzyme activity, with 50% inhibitory concentrations of the most potent substrates being less than 10 nM. T. brucei NTR plays a key role in parasite killing: heterozygous lines displayed resistance to the compounds, while parasites overexpressing the enzyme showed hypersensitivity. We also evaluated the cytotoxicities of substrates with the highest trypanocidal activities by using mammalian THP-1 cells. The relative toxicities of these newly identified compounds were much lower than that of nifurtimox. We conclude that halogenated nitrobenzylphosphoramide mustards represent a novel class of antitrypanosomal agents, and their efficacy validates the strategy of specifically targeting NTR activity to develop new therapeutics.


Occurrence of chlorinated and brominated polycyclic aromatic hydrocarbons in surface sediments in Shenzhen, South China and its relationship to urbanization.
One hundred and fourteen surface sediments were collected from the Maozhou River Watershed in Shenzhen, China from December 2009 to January 2010. Three individual chlorinated polycyclic aromatic hydrocarbons (ClPAHs), six individual brominated polycyclic aromatic hydrocarbons (BrPAHs), and five corresponding parent polycyclic aromatic hydrocarbons (PAHs) were determined. The concentration of 9-chlorophenanthrene was the highest ranging from 0.51-289 ng g(-1) (average, 16.5 ng g(-1)). For BrPAHs, the concentration of 2-bromofluorene was the highest ranging from 0.31-266 ng g(-1) (average, 35.3 ng g(-1)). No correlation was observed between the concentrations of ClPAHs and parent PAHs in surface sediments. In addition, there was no correlation between 1-bromopyrene, 7-bromobenz(a)anthracene and 9,10-dibromoanthracene, and corresponding parent PAHs. However, a significant correlation was found between 9-bromophenanthrene and phenanthrene (p < 0.01), between 9-bromoanthracene and anthracene (p < 0.05), and between 2-bromofluorene and fluorene (p < 0.05). Six fly ash samples collected from one of the municipal domestic waste incineration plants in Shenzhen were also analyzed for source identification. The concentration of 7-bromobenz(a)anthracene was the highest, ranging from 3.21-4.08 ng g(-1). In addition, 2-bromofluorene was not detected in all the fly ash samples. No correlation was found between the concentrations of Cl-/BrPAHs and corresponding parent PAHs in fly ashes. We also examined the relationship between the levels of Cl-/BrPAHs in surface sediments and the urbanization process. Our results suggested the levels of individual Cl-/BrPAHs congeners presented a similar increasing trend with the increasing urbanization level.


Wavelet-aided parametric mapping of cerebral dopamine D2 receptors using the high affinity PET radioligand [11C]FLB 457.
The study of human neuroreceptor systems by means of positron emission tomography (PET) and suitable radioligands has proven to be of great importance in research on normal brain functions and the pathophysiology and treatment of neuropsychiatric disorders. A for long identified goal is to produce detailed parametric maps of showing neuroreceptor binding parameters for the entire human brain in vivo. The application of wavelet filters has recently been proposed as a solution to handle the inherently low signal-to-noise ratio of PET images. In the present study we applied the wavelet approach to data obtained from 10 healthy subjects who were examined with [11C]FLB 457. This high affinity dopamine D2-receptor antagonist provides a signal from a range of regions with a hundredfold difference in receptor density and should thus be suitable for evaluation of the wavelet approach. For cross-validation purposes the data were analysed with four methods: a traditional region-of-interest (ROI) based analysis, a pixel-based analysis and two variants of wavelet-aided analyses. In both variants the wavelet filter was spatially applied, but a two-dimensional filter was used in one case and a three-dimensional one in the other. The same linear-graphical binding potential (BP) estimation step was used for all methods and the results of the three parametric mapping techniques were compared to the reference ROI-based method by calculating the average BP of representative ROIs. The pixel-based and the two-dimensional-wavelet-based methods yielded highly correlated but systematically lower values when compared to the reference ROI-based method. The approach utilising three-dimensional wavelet filters yielded BP maps with regional averages closely matching the values of the ROI-based method. The results show that the combination of three-dimensional spatial wavelet filtering with established parameter estimation procedures provides detailed, accurate maps of radioligand binding parameters. Such maps can be used for in inter-individual or multi-condition comparisons of binding parameters at subregional levels.


Abdominal paracentesis and thoracocentesis.
Abdominal paracentesis and thoracocentesis are common bedside procedures with diagnostic, therapeutic and palliative roles. We describe a useful and familiar a useful and familiar technique with the use of a multiple lumen catheter commonly used for central venous line insertion for drainage of ascites or moderate to large pleural effusions. The use of a multiple lumen catheter allows easier and more rapid aspiration of fluid with a smaller probability of the side holes being blocked as compared to the standard needle or single catheter methods. This is particularly useful in situations where the dedicated commercial kits for thoracocentesis and abdominal paracentesis are not readily available.


Hypersusceptibility to azole antifungals in a clinical isolate of Candida glabrata with reduced aerobic growth.
Petite mutations have been described in Saccharomyces cerevisiae and pathogenic yeasts. However, previous studies of the phenotypic traits of these petite mutants reported that they express azole resistance. We describe a clinical isolate of Candida glabrata with a striking association between increased susceptibility to azoles and respiratory deficiency. This isolate was obtained from a urine sample together with a respiration-competent C. glabrata isolate which exhibited azole resistance. The respiratory status of the two isolates was confirmed by cultivation on glycerol-containing agar and oxygraphy. Flow cytometry revealed the normal incorporation of rhodamine 123, and mitochondrial sections with typical cristae were seen by transmission electron microscopy for both isolates. Together, these results suggested a nuclear origin for the reduced respiratory capacity of the hypersusceptible isolate. The sterol contents of these isolates were similar to the sterol content of a reference strain. Sequencing of the ERG11 and PDR1 genes revealed that the sequences were identical in the two isolates, demonstrating their close relatedness. In addition to silent mutations, they carried a nonsense mutation in PDR1 that led to the truncation of transcription factor Pdr1p. They also overexpressed both PDR1 and one of its targets, CDR1, providing a possible explanation for the azole resistance of the respiration-competent isolate. In conclusion, in addition to azole resistance, which is a common feature of C. glabrata mitochondrial petite mutants, the mutation of a nuclear gene affecting aerobic growth may lead to azole hypersusceptibility; however, the mechanisms underlying this phenotype remain to be determined.


Optimisation of atrioventricular delay during exercise improves cardiac output in patients stabilised with cardiac resynchronisation therapy.
Atrioventricular (AV) delay in cardiac resynchronisation therapy (CRT) recipients are typically optimised at rest. However, there are limited data on the impact of exercise-induced changes in heart rate on the optimal AV delay and left ventricular function. The authors serially programmed AV delays in 41 CRT patients with intrinsic sinus rhythm at rest and during two stages of supine bicycle exercise with heart rates at 20 bpm (stage I) and 40 bpm (stage II) above baseline. The optimal AV delay during exercise was determined by the iterative method to maximise cardiac output using Doppler echocardiography. Results were compared to physiological change in PR intervals in 56 normal controls during treadmill exercise. The optimal AV delay was progressively shortened (p<0.05) with escalating exercise level (baseline: 123±26 ms vs. stage I: 102±24 ms vs stage II: 70±22 ms, p<0.05). AV delay optimisation led to a significantly higher cardiac output than without optimisation did during stage I (6.2±1.2 l/min vs. 5.2±1.2 l/min, p<0.001) and stage II (6.8±1.6 l/min vs. 5.9±1.3 l/min, p<0.001) exercise. A linear inverse relationship existed between optimal AV delays and heart rates in CRT patients (AV delay=241-1.61×heart rate, R2=0.639, p<0.001) and healthy controls (R2=0.646, p<0.001), but the slope of regression was significantly steeper in CRT patients (p<0.001). Haemodynamically optimal AV delay shortened progressively with increasing heart rate during exercise, which suggests the need for programming of rate-adaptive AV delay in CRT recipients.


Sudden infant death syndrome: altered aminergic-cholinergic synaptic markers in hypothalamus.
Alterations of sleep are reported to occur in sudden infant death syndrome (SIDS). It is well established that the hypothalamus mediates the onset, maintenance, and timing of sleep, and does so via serotonergic and cholinergic mechanisms. We have investigated serotonergic and cholinergic synaptic markers in the hypothalamus from eight SIDS infants and six age-matched non-SIDS infants between 3 and 7 months of age. By use of established methods, we observed a number of chemical alterations in SIDS hypothalamus: (1) tryptophan content was increased and serotonin content was decreased, (2) serotonin binding was increased and imipramine binding was unchanged, (3) monoamine oxidase-A activity was increased without an effect on monoamine oxidase-B, and (4) choline acetyltransferase activity was decreased and acetylcholinesterase activity was unchanged.


Radiomics methodology for breast cancer diagnosis using multiparametric magnetic resonance imaging.
Purpose: This study aims to develop and compare human-engineered radiomics methodologies that use multiparametric magnetic resonance imaging (mpMRI) to diagnose breast cancer. Approach: The dataset comprises clinical multiparametric MR images of 852 unique lesions from 612 patients. Each MR study included a dynamic contrast-enhanced (DCE)-MRI sequence and a T2-weighted (T2w) MRI sequence, and a subset of 389 lesions were also imaged with a diffusion-weighted imaging (DWI) sequence. Lesions were automatically segmented using the fuzzy C-means algorithm. Radiomic features were extracted from each MRI sequence. Two approaches, feature fusion and classifier fusion, to utilizing multiparametric information were investigated. A support vector machine classifier was trained for each method to differentiate between benign and malignant lesions. Area under the receiver operating characteristic curve (AUC) was used to evaluate and compare diagnostic performance. Analyses were first performed on the entire dataset and then on the subset that was imaged using the three-sequence protocol. Results: When using the full dataset, the single-parametric classifiers yielded the following AUCs and 95% confidence intervals: AUC DCE = 0.84 [0.82, 0.87], AUC T 2 w = 0.83 [0.80, 0.86], and AUC DWI = 0.69 [0.62, 0.75]. The two multiparametric classifiers both yielded AUCs of 0.87 [0.84, 0.89] and significantly outperformed all single-parametric methods classifiers. When using the three-sequence subset, the mpMRI classifiers' performances significantly decreased. Conclusions: The proposed mpMRI radiomics methods can improve the performance of computer-aided diagnostics for breast cancer and handle missing sequences in the imaging protocol.