Engineered extracellular matrices with controlled mechanics modulate renal proximal tubular cell epithelialization.
Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI. PEG diacrylate based hydrogels were generated with orthogonal control of mechanics and cell-substrate interactions. Using this platform, we found that increased substrate stiffness promotes RPTEC spreading and proliferation. RPTECs showed similar degrees of apoptosis and Yes-associated protein (YAP) nuclear localization regardless of stiffness, suggesting these were not key mediators of the effect. However, focal adhesion formation, cytoskeletal organization, focal adhesion kinase (FAK) activation, and extracellular signal-regulated kinase (ERK) activation were all enhanced with increasing substrate stiffness. Inhibition of ERK activation substantially attenuated the effect of stiffness on proliferation. In long-term culture, hydrogel stiffness promoted the formation of more complete epithelial monolayers with tight junctions, cell polarity, and an organized basement membrane. These data suggest that increased stiffness potentially may have beneficial consequences for the renal tubular epithelium during recovery from AKI.


Mitral Annular Calcification In Stage 5 Chronic Kidney Disease On Dialysis Therapy.
Mitral Annular Calcification (MAC) is a degenerative process involving the mitral valve and is a marker of advanced cardiovascular disease. Prevalence in the general population is upto 10% and increases in advanced age, diabetes mellitus, chronic kidney disease (CKD), end stage renal disease (upto 40%) and mitral valve prolapse.The aims of this study were to assess the prevalence of MAC in CKD5D patients and correlate with patients' characteristics. Echocardiograms were obtained in 84 hemodialysis patients. Association of MAC with various patient characteristics was studied. Data was analysed using SPSS-22. The mean age of the patients was 63.38±12.3 years and 48 (57%) were males. Sixty-eight patients (81%) had DM and 79 (94%) had hypertension. MAC was present in 37 out of 84 (44%) patients. Sixty-four (72%) had IHD. The presence of MAC correlated significantly with IHD (Odds Ratio 6.42, p=0.006). Mean follow up of the patients was 30.30±29.22 months and 37 (44%) suffered mortality during this period. Patients on dialysis for longer than 36 months had an elevated risk of developing MAC (OR=3.32, p=0.019). Patients with the following risk factors: serum PO4 greater than 5.5 (OR=2.03), DM (OR=1.95), HTN (OR=3.35), Age >60 (OR=1.83), AFIB (OR=1.28); had an observable increase in incidence of MAC with time but they weren't statistically significant. Mitral Annular Calcification is common in hemodialysis patients and correlates significantly with IHD. Our findings support the recommendation by KDIGO 2017 guidelines on Mineral and Bone Disease on the use of echocardiography for the detection of valvular calcification.


Who seeks residential treatment? A report of patient characteristics, pathology, and functioning in females at a residential treatment facility.
There has been a growth in the availability and use of residential treatment for eating disorders. Yet there is a paucity of information on the individuals who seek this treatment. This study provides data on 259 consecutive patients (116 adults and 143 adolescents) entering residential treatment for their eating disorders. Upon admission all patients provided individual characteristics data and the following measures: the Eating Disorder Inventory-3 (EDI-3), the Beck Depression Inventory-II, the Beck Anxiety Inventory, the Eating Disorder Quality of Life (EDQOL), and the SF-36 Health Survey-Version 2. Findings are presented by diagnosis (anorexia nervosa, bulimia nervosa, eating disorder not otherwise specified) and age (adult and adolescent). Results show that 61% of adolescents and 80% of adults were above the clinical cutoff for depression, and 59% of adolescents and 78% of adults were above the clinical cutoff for anxiety. Scores on the EDI-3 are presented by subscale and diagnosis. Very low quality of life is reported for both adults and adolescents on the EDQOL. For both adolescents and adults the SF-36 showed average population scores for the physical scale but very low mental scores. Implications for these findings and future directions for this work are discussed.


Toward an acoustic typology of motor speech disorders.
Acoustic methods have progressed to the point that an acoustic typology of the motor speech disorders can be constructed from a parameteric assessment of the speech subsystems (e.g., phonation, nasal resonance, vowel articulation, consonant articulation, intonation, and rhythm). The results of this analysis can be interpreted in respect to global functions in speech (e.g., voice quality, intelligibility, and prosody). This paper reviews studies showing that specific acoustic analyses have demonstrated or potential value toward the overall goal of constructing acoustic profiles of dysarthria and apraxia of speech. Several different acoustic measures are relevant to the study of the motor speech disorders, and these are increasingly supported by normative data and by guidelines for clinical application. Examples of these applications are discussed for a variety of specific neurologic diseases or perceptual types of disorder. Acoustic studies are useful in the study of motor speech disorders and recent progress points to a parametric analysis.


Signal transduction networks in rheumatoid arthritis.
Signal transduction pathways regulate cellular responses to stress and play a critical role in inflammation. The complexity and specificity of signalling mechanisms represent major hurdles for developing effective, safe therapeutic interventions that target specific molecules. One approach is to dissect the pathways methodically to determine their hierarchy in various cell types and diseases. This approach contributed to the identification and prioritisation of specific kinases that regulate NF-kappa B and the mitogen activated protein (MAP) kinase cascade as especially attractive targets. Although significant issues remain with regard to the discovery of truly selective kinase inhibitors, the risks that accompany inhibition of fundamental signal transduction mechanisms can potentially be decreased by careful dissection of the pathways and rational target selection.


The most common diet results in low reproduction in a generalist seabird.
Dietary specialization has been described across a wide range of taxa in the animal kingdom. Fitness consequences are, however, not well documented. We examined the reproductive consequences of different dietary specializations in the herring gull Larus argentatus, an omnivorous seabird, using an extensive dataset which includes breeding and dietary data of 10 successive years. We hypothesized that pairs that focused on prey of higher energetic value would yield higher fledging rates. An alternative hypothesis is that pairs that relied on more resources simultaneously would reproduce better. The novelty of this study is that we used continuous measurements representing dietary composition and degree of specialization rather than restricting our analysis to predefined categories. By relating these two continuous measurements for diet to several proxies for reproductive success, we show clear consequences of dietary choice. Most pairs concentrated on bivalves, a prey type not particularly rich in energy. Pairs feeding on energy-rich prey (e.g., "domestic refuse and fishery discards") during chick rearing were found to have a higher reproductive success, supporting the first hypothesis. Pairs that used more resources did not clearly have a higher reproductive success. The majority of the pairs did not switch to energy-rich prey during chick rearing, despite low breeding outcome. We discuss how trade-offs between factors such as resource availability, predictability, and the time and energy needed to obtain certain prey species may influence resource selection.


Apparatus to measure the vapor pressure of slowly decomposing compounds from 1 Pa to 105 Pa.
This article describes an apparatus and method for measuring vapor pressures in the range from 1 Pa to 105 Pa. Its three distinctive elements are : (1) the static pressure measurements were made with only a small temperature difference between the vapor and the condensed phase, (2) the sample was degassed in situ, and (3) the temperature range extended up to 200 °C. The apparatus was designed to measure metal-organic precursors, which often are toxic, pyrophoric, or unstable. Vapor pressures are presented for naphthalene, ferrocene, diethyl phthalate, and TEMAH (tetrakisethylmethylaminohafnium). Also presented are data for the temperature-dependent decomposition rate of TEMAH.


Directed polymers and interfaces in random media: free-energy optimization via confinement in a wandering tube.
We analyze, via Imry-Ma scaling arguments, the strong disorder phases that exist in low dimensions at all temperatures for directed polymers and interfaces in random media. For the uncorrelated Gaussian disorder, we obtain that the optimal strategy for the polymer in dimension 1+d with 0<d<2 involves at the same time (i) a confinement in a favorable tube of radius R(S) approximately L (nu(S) ) with nu(S) =1/(4-d)<1/2 (ii) a superdiffusive behavior R approximately Lnu with nu=(3-d)/(4-d)>1/2 for the wandering of the best favorable tube available. The corresponding free energy then scales as F approximately Lomega with omega=2nu-1 and the left tail of the probability distribution involves a stretched exponential of exponent eta=(4-d)/2. These results generalize the well known exact exponents nu=2/3, omega=1/3, and eta=3/2 in d=1, where the subleading transverse length R(S) approximately L(1/3) is known as the typical distance between two replicas in the Bethe ansatz wave function. We then extend our approach to correlated disorder in transverse directions with exponent alpha and/or to manifolds in dimension D+d= d(t) with 0<D<2. The strategy of being both confined and superdiffusive is still optimal for decaying correlations ( alpha<0 ), whereas it is not for growing correlations ( alpha>0 ). In particular, for an interface of dimension ( d(t) -1) in a space of total dimension 5/3< d(t) <3 with random-bond disorder, our approach yields the confinement exponent nu(S) =( d(t) -1)(3- d(t) )/(5 d(t) -7). Finally, we study the exponents in the presence of an algebraic tail 1/ V1+micro in the disorder distribution, and obtain various regimes in the (micro,d) plane.


[Ultrasonic diagnosis in aneurysm of the abdominal aorta].
The sonographic diagnostics of an aneurysm of the abdominal aorta has obtained a high value on account of the high reliability and the rapid availability of the investigation in connection with the absolute safety of the method. Form, extension, calcification, haemodynamics, thrombosis and dissection of an aneurysm of the aorta can sonographically be demonstrated and measured by longitudinal and transversal sections. As non-invasive approach the ultrasound tomography in the order of the graduated diagnostic method stands before the computed tomography which is not always at once available and before the angiography which have their qualification in the case of a planned operative approach above all for the purpose of the exact topographic differentiation between suprarenal and infrarenal extension.


Moisture-driven xylogenesis in Pinus ponderosa from a Mojave Desert mountain reveals high phenological plasticity.
Future seasonal dynamics of wood formation in hyperarid environments are still unclear. Although temperature-driven extension of the growing season and increased forest productivity are expected for boreal and temperate biomes under global warming, a similar trend remains questionable in water-limited regions. We monitored cambial activity in a montane stand of ponderosa pine (Pinus ponderosa) from the Mojave Desert for 2 consecutive years (2015-2016) showing opposite-sign anomalies between warm- and cold-season precipitation. After the wet winter/spring of 2016, xylogenesis started 2 months earlier compared to 2015, characterized by abundant monsoonal (July-August) rainfall and hyperarid spring. Tree size did not influence the onset and ending of wood formation, highlighting a predominant climatic control over xylem phenological processes. Moisture conditions in the previous month, in particular soil water content and dew point, were the main drivers of cambial phenology. Latewood formation started roughly at the same time in both years; however, monsoonal precipitation triggered the formation of more false rings and density fluctuations in 2015. Because of uncertainties in future precipitation patterns simulated by global change models for the Southwestern United States, the dependency of P. ponderosa on seasonal moisture implies a greater conservation challenge than for species that respond mostly to temperature conditions.


Continuing conversation about continuing bonds.
The article is a response to the contributions the special issue of Death Studies on continuing bonds. The contributions indicate that the conversation among scholars has clarified our thinking on how bonds function in individual grief. The author discussed two issues to help keep the conversation moving: (a) the relationship of continuing bonds to the complex we call adjustment to or resolution of grief, and (b) the social and communal nature of continuing bonds. In the first, the author concluded that the hypothesis that continuing bonds either help or hinder grief adjustment too simple to account for the evidence. In the second, he argued that cultural/political narratives are woven into individual grief narratives and if we do not include community, cultural, and political narratives in our understanding of continuing bonds we are in danger building bereavement theory that applies to only a small portion of one population in one historical time.


synbreed: a framework for the analysis of genomic prediction data using R.
We present a novel R package named synbreed to derive genome-based predictions from high-throughput genotyping and large-scale phenotyping data. The package contains a comprehensive collection of functions required to fit and cross-validate genomic prediction models. All functions are embedded within the framework of a single, unified data object. Thereby a versatile genomic prediction analysis pipeline covering data processing, visualization and analysis is established within one software package. The implementation is flexible with respect to a wide range of data formats and models. The package fills an existing gap in the availability of user-friendly software for next-generation genetics research and education. synbreed is open-source and available through CRAN http://cran.r-project.org/web/packages/synbreed. The latest development version is available from R-Forge. The package synbreed is released with a vignette, a manual and three large-scale example datasets (from package synbreedData). email@example.com Supplementary data are available at Bioinformatics online.


Development of the Gastrointestinal Mucosal Barrier.
In young rabbits, advancing age and natural feeding promote the development of an efficient mucosal barrier capable of protecting the host's circulation from penetration by potentially antigenic macromolecules.


The effect of catecholamine depletion by alpha-methyl-para-tyrosine on measures of cognitive performance and sleep in abstinent MDMA users.
(+/-) 3, 4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug of abuse and a brain serotonin (5-HT) neurotoxin in animals. Growing evidence suggests that humans who use MDMA recreationally can also develop 5-HT neurotoxic injury, although functional consequences have been difficult to identify. Twenty-five abstinent MDMA users and 23 non-MDMA using controls were studied to determine whether pharmacologic depletion of brain catecholamines by alpha-methyl-para-tyrosine (AMPT) would differentially effect MDMA users on measures of cognition and sleep, two processes dually modulated by brain serotonergic and catecholaminergic neurons. During a 5-day in-patient study, all subjects underwent formal neuropsychiatric testing, repeated computerized cognitive testing, and all-night sleep studies. At baseline, MDMA users had performance deficits on tasks of verbal and visuospatial working memory and displayed increased behavioral impulsivity on several computerized tasks, reflecting a tendency to perform quickly at the expense of accuracy. Baseline sleep architecture was also altered in abstinent MDMA users compared to controls. AMPT produced differential effects in MDMA users compared to controls on several cognitive and sleep measures. Differences in cognitive performance, impulsivity, and sleep were significantly correlated with MDMA use. These data extend findings from earlier studies demonstrating cognitive deficits, behavioral impulsivity, and sleep alterations in abstinent MDMA users, and suggest that lasting effects of MDMA lead to alterations in the ability to modulate behaviors reciprocally influenced by 5-HT and catecholamines. More research is needed to determine potential relationships between sleep abnormalities, cognitive deficits and impulsive behavior in abstinent MDMA users.


Effect of concentrates restriction on feed consumption, diet digestibility, and nitrogen utilization in captive Asian elephants (Elephas maximus).
In order to study the effect of concentrates restriction on feed consumption, diet digestibility, and utilization of nitrogen in captive Asian elephants (Elephas maximus), two feeding trials were conducted on three juveniles, four sub-adults, and three adults. During trial I, the conventional zoo diets of juveniles, sub-adults, and adult contained 22, 17, and 16% of concentrates on dry matter (DM) basis, respectively. During trial II, the amount of concentrate was reduced by 50%. A digestion trial of five days collection period was conducted during each period. The animals ate more roughages when concentrates were restricted. Intake of DM (g/kg BW(0.75) /day) was highest in sub-adults, followed by juveniles and adults. Apparent digestibility of crude protein (CP), neutral detergent soluble (NDS), and supply of digestible energy (DE) was highest in juveniles, followed by sub-adults and adults. Based upon the estimated metabolic fecal nitrogen (MFN) and calculated endogenous urinary nitrogen (EUN) and dermal losses, minimum dietary CP required to meet maintenance requirement was estimated to be 6.12, 6.05, and 5.97% in juveniles, sub-adults, and adults, respectively. Restriction of concentrates resulted in decreased (P < 0.05) digestibility of DM and GE, but the diet still supplied adequate amounts of DE and CP to fulfill estimated requirements of energy and protein during the period of experimentation. Thus, the concentrates portion of the diets of captive Asian elephants should be fed in a restricted way so as to reduce the intake of excessive calories and the potential risk of obesity.


Crystal structures, thermal stabilities, and dissolution behaviours of tinidazole and the tinidazole-vanillic acid cocrystal: insights from energy frameworks.
The crystal structures of the antimicrobial drug tinidazole [TNZ; systematic name: 1-(2-ethylsulfonylethyl)-2-methyl-5-nitroimidazole, C8H13N3O4S] and the 1:1 cocrystal of TNZ with the naturally occurring compound vanillic acid (VA; systematic name: 4-hydroxy-3-methoxybenzoic acid, C8H8O4), namely, the TNZ-VA cocrystal, were determined by single-crystal X-ray analysis at 100 K. The supramolecular structure of the TNZ-VA cocrystal is composed of a carboxylic acid dimer and an O-H...N(heterocycle) synthon in the form of layers made up of O-H...N and O-H...O hydrogen bonds. The layers are joined via C-H...O hydrogen bonds, π-π stacking and C-H...π interactions. The energy framework analysis, together with interaction energy calculations using the DLPNO-CCSD(T) method, indicates that the TNZ-VA cocrystal inherits strong interactions from the TNZ and VA crystals, which accounts for the enhanced thermal stability and reduced dissolution rate. To the best of our knowledge, this is the first example of a cocrystal containing TNZ.


Antibiotic resistance in bacteria isolated from freshwater aquacultures and prediction of the persistence and toxicity of antimicrobials in the aquatic environment.
The occurrence of antibiotic-resistant bacteria isolated from freshwater aquaculture effluents was investigated. The bacterial strains were collected from four different freshwater aquaculture effluents (catfish, trout, eel, and loach). Based on sequence of 16S rRNA, a total of 20 bacterial strains was isolated and one half of the isolated bacteria were Aeromonas sp. The antimicrobial sensitivity test was performed using the disc diffusion method. Individual antibiotic-resistant bacteria to antimicrobials were 41.7% and multiple antibiotic resistant bacteria were 58.3%. The disinfection of antibiotic-resistant bacteria by electron beam (E-beam) irradiation was carried out using an electron accelerator. Antibiotic-resistant bacteria were effectively disinfected by E-beam irradiation. The isolated bacteria were completely disinfected at a dose of less than 2 kGy. The persistence and toxicity of each antimicrobial in the aquatic environment was estimated due to the human health and ecosystems. In order to estimate the persistence and toxicity of antimicrobials in the aquatic environment, two quantitative structure activity relationship (QSAR) models were used. The persistence and toxicity of each antimicrobial were influenced on its hydrophobicity. In addition, QSAR models showed that isoelectric point and hydrogen bonding acceptor are key parameters to estimate the persistence and toxicity of antimicrobials in the aquatic environment.


Neuroradiologic and clinicopathologic features of oculoleptomeningeal type amyloidosis.
To clarify the pathogenesis of leptomeningeal amyloidosis in familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C (FAP ATTR Y114C). The authors analyzed eight FAP ATTR Y114C patients. Six patients showed CNS symptoms associated with leptomeningeal amyloidosis. To examine the function of the blood-CSF barrier and blood-brain barrier (BBB), the authors performed CSF and MRI studies. The authors also performed a histopathologic study of autopsy specimens to examine the distribution of amyloid deposition in the CNS. CSF study showed high total protein concentrations and increased albumin CSF/serum concentration quotients (Qalb; an indication of blood-CSF barrier function). MRI with gadolinium (Gd) revealed enhancement from brainstem to spinal cord. Serial brain MRI studies with FLAIR images after Gd administration showed Gd leakage into the subarachnoid space (two patients). These findings suggested the blood-CSF barrier and BBB dysfunctions. Constructive interference in steady state (CISS) three-dimensional Fourier transformation (CISS-3DFT) sequence analysis demonstrated amyloid-induced funiculus structures joining the spinal cord and dura mater (one patient). Histopathologic study revealed intense amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. These distributions of amyloid deposition are unique compared to other TTR related leptomeningeal amyloidosis. Patients with familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C had CNS disorders related to amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. The pathogenesis of CNS disorders may reflect disruption of the blood-CSF barrier and blood-brain barrier by amyloid deposition.


Advanced oxidation protein products activate intrarenal renin-angiotensin system via a CD36-mediated, redox-dependent pathway.
Activation of intrarenal renin-angiotensin system (RAS) has a detrimental effect on the progression of chronic kidney diseases (CKDs), although the regulation of intrarenal RAS remains unclear. The aim of the present study was to evaluate the role of advanced oxidation protein products (AOPPs) in intrarenal RAS activation. AOPPs upregulated the expression of almost all components of RAS and increased activity of angiotensin-converting enzyme in cultured proximal tubular epithelial cells. The triggering effect of AOPP-albumin was 100-times stronger than that of unmodified albumin. The effect of AOPP-albumin was mainly mediated by a CD36-dependent, redox-sensitive signaling involving activation of protein kinase Cα, NADPH oxidase, and nuclear factor-κB/activation protein-1. Chronic AOPP-albumin loading in unilateral nephrectomy rats resulted in deposition of AOPPs in renal tubular cells accompanied with local RAS activation and functional perturbations such as increase in urinary albumin excretion. Accumulation of AOPPs was also detected in human renal tubular cells and correlated with expression of angiotensin II in renal biopsies from 19 patients with IgA nephropathy. This study demonstrated for the first time that AOPPs modified albumin functions as a strong trigger of intrarenal RAS via a CD36-mediated, redox-dependent pathway. Given the fact that accumulation of AOPPs is prevalent in diabetes and CKD, targeting AOPPs could be a strategy for the therapeutic intervention of CKD. Antioxid. Redox Signal. 18, 19-35.


Synthesis, antiulcer and antidepressive activity of 4-(4-halophenyl)-2-phenyl-1,2,3,4-tetrahydroisoquinolines.
4-(4-halophenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolines 2a-c have been synthesized by two methods and their biochemical and pharmacological properties have been studied. Biochemical investigations showed that all the compounds are strong inhibitors of DA, NE and 5-HT reuptake, the strongest effect being observed with compound 2b (R = Br). 2a-c exhibited a strong antiulcer activity on an experimental model of stress-induced ulcers with minimal doses (0.1 to 3.0 mg/kg), the effect of 2b being 30 times higher as compared to the H2-antagonist Ranitidin. At higher doses (10 to 30 mg/kg) 2b and 2c inhibited the Reserpinptosis. The most active compound in the reuptake inhibition 2b, expressed a high antidepressive activity in some other tests, comparable to that of the antidepressant Nomifensin. 2b has been selected for further pharmacological testing under the code name AN12.


Coevolution of vaccination behavior and perceived vaccination risk can lead to a stag-hunt-like game.
Voluntary vaccination is effective to prevent infectious diseases from spreading. Both vaccination behavior and cognition of the vaccination risk play important roles in individual vaccination decision making. However, it is not clear how the coevolution of the two shapes population-wide vaccination behavior. We establish a coupled dynamics of epidemic, vaccination behavior, and perceived vaccination risk with three different time scales. We assume that the increase of vaccination level inhibits the rise of perceived vaccination risk, and the increase of perceived vaccination risk inhibits the rise of vaccination level. It is shown that the resulting vaccination behavior is similar to the stag-hunt game, provided that the basic reproductive ratio is moderate and that the epidemic dynamics evolves sufficiently fast. This is in contrast with the previous view that vaccination is a snowdriftlike game. And we find that epidemic breaks out repeatedly and eventually leads to vaccine scares if these three dynamics evolve on a similar time scale. Furthermore, we propose some ways to promote vaccination behavior, such as controlling side-effect bias and perceived vaccination costs. Our work sheds light on epidemic control via vaccination by taking into account the coevolutionary dynamics of cognition and behavior.


Bleeding After Endoscopic Resection of Colonic Adenomatous Polyps Sized 4-10 mm.
Introduction: Colonoscopy with polypectomy is an efficacious procedure in reducing the risk of colorectal cancer development, the precursor are adenomatous polyps. The most common method for resection of polyps measuring 4-10 mm are cold (CSP) and hot snare polypectomy (HSP). CSP has a lower incidence of adverse events, especially delayed post-polypectomy bleeding. Aim: To evaluate the presence of immediate and delayed bleeding in the cold snare polypectomy of sub-centimeter polyps of the colon compared with hot snare polypectomy. Materials and Methods: This prospective clinical study is comprised all patients who were incidentally detected to have adenomatous colonic polyps measuring 4-10 mm during a colonoscopy screening. Polypectomy was done with (hot snare) or without electrocautery (cold snare). After removal of polyps, immediate bleeding, delayed bleeding, and methods for were analyzed. Results: The CSP and HSP groups included 116 patients, 113 (54.4%) polyps in 61 (52.6%) patients with CSP while 95 (45.6%) polyps in 55 (47.4%) patients with HSP. 25 (22.1%) polyps after CSP had immediate bleeding. In 5 patients (20.0%), five hemostatic clips were inserted after CSP for bleeding longer than 150 sek. The average percentage difference between immediate bleeding versus total number of resected polyps using the cold snare method is not statistically significant (p<0.05) (Difference test, p=0.0000). Delayed bleeding was not registered using this method. In the second investigated group (HSP), one patient had delayed bleeding. This was stopped with 2 clips. Immediate bleeding was not registered. Conclusion: CSP is safer than HSP in resecting colon polyps sized 4-10 mm, without risk of delayed bleeding.


Su Yang Decoction induces human colon carcinoma cell apoptosis by activating caspases.
Su Yang Decoction (SYD) is a popular healthcare product comprised of various brassicaceous vegetables known to exhibit anticancer activity. However, the effects of SYD on tumor growth, following its combination with brassicaceous vegetables into a compound formula, require further investigation. In the present study, a quality control of SYD was subjected to high-performance liquid chromatography for the quantitative and qualitative determination of sulforaphane, the main anticancer component of SYD. SYD inhibited colon cancer cell proliferation in a dose- and time-dependent manner and induced G1 phase arrest in colon cancer HT-29 cell lines. In addition, SYD triggered caspase-mediated apoptosis in a dose-dependent manner and induced the cleavage of poly (ADP-ribose) polymerase, tumor necrosis factor superfamily member 10, X-linked inhibitor of apoptosis, and truncated BH3 interacting domain death agonist. Furthermore, the expression of FADD-like interleukin-1β-converting enzyme (FLICE)-like inhibitory proteins (FLIPs) and long isoform of FLICE-inhibitory protein was reduced by SYD and the direct targeting of cellular-FLIP with small interfering RNA inhibited colon cancer cell proliferation and decreased the SYD concentration required for proliferation inhibition. SYD treatment was also associated with the translocation of proapoptotic BCL2 associated X, apoptosis regulator to the mitochondria and the release of cytochrome c from the mitochondria to the cytosol. The aforementioned results indicate that SYD exerts anti-colorectal cancer effects through an underlying mechanism that may involve caspase activation.


Barriers to and Facilitators of Implementing Peer Support Services for Criminal Justice-Involved Individuals.
This study sought to examine perceived barriers to and facilitators of the adoption, implementation, and sustainability of community-based mental health peer support services for criminal justice-involved individuals, also known as "forensic peer support" (FPS). Qualitative interviews were conducted with stakeholders (N=14) and peer specialists (N=37) to better understand delivery of peer support services for justice-involved individuals in Pennsylvania. Thematic analysis followed by directed content analysis was used to identify factors in three a priori implementation categories based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) model: initial facilitators (adoption), barriers (implementation), and facilitators (maintenance) to long-term sustainability. Initial service adoption was facilitated by buy-in from recovery-oriented gatekeepers in the criminal justice system. Unique implementation barriers included the chasm between the orientations of the two systems (recovery vs. punitive) and formal and informal limitations on the employment of individuals with criminal justice system exposure. For services to be sustainable and have an impact over the long term, FPS advocates and workers must develop rapport with on-the-ground employees of the criminal justice system. Funding barriers specific to the criminal justice system limited the adoption, implementation, and maintenance of FPS services. Although many of the factors that affect FPS service implementation were similar to those identified in the broader peer support literature, important differences must be addressed for successful FPS service delivery. Within the criminal justice system, both policies and norms presented barriers to the expansion of peer support services for justice-involved individuals.


Direct data capture using hand-held computers in rural Burkina Faso: experiences, benefits and lessons learnt.
To assess our experiences of using hand-held computers (personal digital assistants, PDAs) for direct data capture in a large community-based geo-referenced survey in rural Burkina Faso, highlighting benefits and lessons learnt from their use. A population-based geo-referenced survey of over 500 000 people was undertaken using PDAs with in-built GPS receivers and the resulting database analysed in terms of successful completion, error rates and interview durations. Surveys were successfully completed for 84 861 households (98.3%) by 127 interviewers. The data input error rate was assessed at 0.24%, with more than half of the errors being made by less than 10% of the interviewers. Faster interviewers were not less accurate. Time-stamped and geo-referenced data allowed reconstruction of particular interviewer-day activities. Although the survey setting was challenging, the feasibility of using direct data capture on a large scale was well established. We learnt that, with more experience, we could have made better use of real-time entry and quality control checking procedures. The work involved in designing and setting up a complex survey on PDAs prior to data collection should not be underestimated.


Lantibiotics produced by Actinobacteria and their potential applications (a review).
The phylum Actinobacteria, which comprises a great variety of Gram-positive bacteria with a high G+C content in their genomes, is known for its large production of bioactive compounds, including those with antimicrobial activity. Among the antimicrobials, bacteriocins, ribosomally synthesized peptides, represent an important arsenal of potential new drugs to face the increasing prevalence of resistance to antibiotics among microbial pathogens. The actinobacterial bacteriocins form a heterogeneous group of substances that is difficult to adapt to most proposed classification schemes. However, recent updates have accommodated efficiently the diversity of bacteriocins produced by this phylum. Among the bacteriocins, the lantibiotics represent a source of new antimicrobials to control infections caused mainly by Gram-positive bacteria and with a low propensity for resistance development. Moreover, some of these compounds have additional biological properties, exhibiting activity against viruses and tumour cells and having also potential to be used in blood pressure or inflammation control and in pain relief. Thus, lantibiotics already described in Actinobacteria exhibit potential practical applications in medical settings, food industry and agriculture, with examples at different stages of pre-clinical and clinical trials.


Phytoremediation of petroleum-contaminated soil by Salicornia: from PSY activity to physiological and morphological communications.
Petroleum is one of the critical environmental pollutants. Salicornia can grow in petroleum-contaminated soil. Therefore, the potential of two Iranian Salicornia species, S. persica Akhani and S. iranica Akhani, for phytoremediation of soils contaminated with 0.2% or 2% petroleum was evaluated over short (1 and 10 h) and long (100 days) periods of time. In addition, some key factors including the expression analysis of phytoene synthase, physiological and morphological factors were studied. Both species reduced the petroleum in 0.2% and 2% petroleum-contaminated soils to 40% and 60% of the initial amount, respectively. The expression of PSY increased twice more than the control 10 h after 0.2% petroleum stress and the carotenoid content increased twice more than the control. Chlorophyll a and total chlorophyll decreased three times less than the control in both contamination levels, while chlorophyll b decreased three times less than the control only in 2% contamination. The proline content peaked 10 h after 2% stress as it was 10 times more than the control. Promoter analysis of PSY showed the existence of responsive cis-acting elements to abscisic acid suggesting the key role of this gene in abiotic stresses.


Dissipative quantum systems and the heat capacity.
We present a detailed study of the quantum dissipative dynamics of a charged particle in a magnetic field. Our focus of attention is the effect of dissipation on the low- and high-temperature behaviors of the specific heat at constant volume. After providing a brief overview of two distinct approaches to the statistical mechanics of dissipative quantum systems, viz., the ensemble approach of Gibbs and the quantum Brownian motion approach due to Einstein, we present exact analyses of the specific heat. While the low-temperature expressions for the specific heat, based on the two approaches, are in conformity with power-law temperature dependence, predicted by the third law of thermodynamics, and the high-temperature expressions are in agreement with the classical equipartition theorem, there are surprising differences between the dependencies of the specific heat on different parameters in the theory, when calculations are done from these two distinct methods. In particular, we find puzzling influences of boundary confinement and the bath-induced spectral cutoff frequency. Further, when it comes to the issue of approach to equilibrium, based on the Einstein method, the way the asymptotic limit (t-->infinity) is taken seems to assume significance.


Regulating the Efficacy of Inhibition Through Trafficking of γ-Aminobutyric Acid Type A Receptors.
Trafficking of anesthetic-sensitive receptors within the plasma membrane, or from one cellular component to another, occurs continuously. Changes in receptor trafficking have implications in altering anesthetic sensitivity. γ-Aminobutyric acid type A receptors (GABAARs) are anion-permeable ion channels and are the major class of receptor in the adult mammalian central nervous system that mediates inhibition. GABAergic signaling allows for precise synchronized firing of action potentials within brain circuits that is critical for cognition, behavior, and consciousness. This precision depends upon tightly controlled trafficking of GABAARs into the membrane. General anesthetics bind to and allosterically enhance GABAARs by prolonging the open state of the receptor and thereby altering neuronal and brain circuit activity. Subunit composition and GABAAR localization strongly influence anesthetic end points; therefore, changes in GABAAR trafficking could have significant consequences to anesthetic sensitivity. GABAARs are not static membrane structures but are in a constant state of flux between extrasynaptic and synaptic locations and are continually endocytosed and recycled from and to the membrane. Neuronal activity, posttranslational modifications, and some naturally occurring and synthetic compounds can influence the expression and trafficking of GABAARs. In this article, we review GABAARs, their trafficking, and how phosphorylation of GABAAR subunits can influence the surface expression and function of the receptor. Ultimately, alterations of GABAAR trafficking could modify anesthetic end points, both unintentionally through pathologic processes but potentially as a therapeutic target to adjust anesthetic-sensitive GABAARs.


Effects of leg dominance on performance of ballet turns (pirouettes) by experienced and novice dancers.
Turns (pirouettes) are an important movement in ballet and may be affected by "lateral bias". This study investigated physiological differences exhibited by experienced and novice dancers, respectively, when performing pirouette with dominant and non-dominant leg supports, respectively. Thirteen novice and 13 experienced dancers performed turns on dominant or non-dominant legs. The maximum ankle plantarflexion, knee extension and hip extension were measured during the single-leg support phase. The inclination angle of rotation axis is the angle between instantaneous rotation axis and global vertical axis in the early single-leg support phase. Both groups exhibited a greater hip extension, knee extension, and ankle plantarflexion when performing a turn on the non-dominant leg. For experienced dancers, the inclination angle of rotation axis during the pre-swing phase was generally smaller for dominant leg support than non-dominant leg. However, no significant difference was found in inclination angle of rotation axis of novice dancers. For experienced dancers, an improved performance is obtained when using the dominant leg for support. By contrast, for novice dancers, the performance is independent of choice of support leg. The significant lateral bias in experienced dancers indicates the possible influence of training. That is, repetitive rehearsal on the preferred leg strengthens the impact of side dominance in experienced dancers.


Yellow-light sensitization of a ligand photosubstitution reaction in a ruthenium polypyridyl complex covalently bound to a rhodamine dye.
The ruthenium complex [Ru(terpy)(bpy)(Hmte)](2+) ([1](2+)), where terpy is 2,2';6',2''-terpyridine, bpy is 2,2'-bipyridine, and Hmte is 2-methylthioethan-1-ol, poorly absorbs yellow light, and although its quantum yield for the photosubstitution of Hmte by water is comparable at 570 nm and at 452 nm (0.011(4) vs. 0.016(4) at 298 K at neutral pH), the photoreaction using yellow photons is very slow. Complex [1](2+) was thus functionalized with rhodamine B, an organic dye known for its high extinction coefficient for yellow light. Complex [Ru(Rterpy)(bpy)(Hmte)](3+) ([2](3+)) was synthesized, where Rterpy is a terpyridine ligand covalently bound to rhodamine B via a short saturated linker. [2]Cl3 shows a very high extinction coefficient at 570 nm (44,000 M(-1) cm(-1)), but its luminescence upon irradiation at 570 nm is completely quenched in aqueous solution. The quantum yield for the photosubstitution of Hmte by water in [2](3+) was comparable to that in [1](2+) at 570 nm (0.0085(6) vs. 0.011(4), respectively), which, in combination with the much better photon collection, resulted in a higher photosubstitution rate constant for [2](3+) than for [1](2+). The energy of yellow photons is thus transferred efficiently from the rhodamine antenna to the ruthenium center, leading to efficient photosubstitution of Hmte. These results bring new opportunities for extending the photoactivation of polypyridyl ruthenium complexes towards longer wavelengths.


Induced antioxidant activity in hospital staff occupationally exposed to ionizing radiation.
Occupational exposure to low levels of ionizing radiation (IR) in radiology department staff may affect their antioxidant status. The aim of this study was to evaluate the oxidative stress parameters in radiology staff that are occupationally exposed to IR in a hospital setting. The study population included 40 exposed radiology staff and 30 control subjects. The radiation doses of exposed staff ranged between 0.10 and 3.8 milligray (mGy) per month. The subjects' antioxidant status was determined by measuring the activities of copper zinc-superoxide dismutase (CuZn-SOD), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) enzymes, and the levels of malondialdehyde (MDA) in erythrocytes. Our results showed that the activities of erythrocyte CuZn-SOD and Se-GPx enzymes observed for the radiation exposed group were significantly higher than in the controls. The activity of CAT enzyme and MDA levels were significantly lower in the exposed group than in the controls. Moreover, we investigated the influence of confounding factors on antioxidant enzymes or lipid peroxidation (LP), but we could not find any associations between them. Our study indicates the presence of stimulant effect of chronic low-dose radiation in exposed individuals, resulting in enhanced resistance to oxidative stress.


Comparative ultrastructure of fibrin networks of a dog after thrombotic ischaemic stroke.
A cerebrovascular accident or stroke is a rare condition in dogs, but previous studies suggest that it is now increasingly being recognised. Platelets and fibrin networks are involved in haemostasis,which is disrupted during a thrombotic event. In this study we investigate the ultrastructure of the fibrin networks of a dog that had suffered ischaemic stroke, following suspected thromboembolism from clots that became dislodged during catheter maintenance (flushing with heparinised saline) 2 days after carotid artery catheter insertion. Fibrin networks of blood samples that were collected immediately after the stroke, 15 min after treatment with streptokinase and 24 h after treatment, were studied. The results were compared to those of two control dogs. During a stroke, fibrin morphology changes to form a thick, matted layer.Post-treatment ultrastructure shows that the fibrin morphology returns to that comparable to controls. Our results show that during thrombotic risk, fibrin network morphology changes visibly and reduces the fibrinolytic activity of the coagulation system.


Troubleshooting a Rare Anatomic Variation with Intraoperative Navigation in a Patient with Bilateral C2 Pars Fractures.
C2 pars fractures occur most commonly after traumatic hyperextension injuries. Although a significant number of cases may heal with conservative measures, some require surgical intervention. Anatomical variations of the V3 segment of the vertebral artery are not uncommon and may present an obstacle to safe instrumentation. Intraoperative CT-guided navigation is a useful tool in these cases, but the limitations of accuracy in the upper cervical spine especially in the context of unstable injuries must be understood to avoid complication. In this case we present a rare anatomic variation of the vertebral artery size and position in conjunction with bilateral C2 pars fractures treated successfully by surgical fixation. This article highlights the important technical details of the posterior instrumentation of unstable atlas pars fractures with the aid of intraoperative navigation.


Inadequacies in antiretroviral therapy use among Aboriginal and other Canadian populations.
We undertook this study to provide a profile of Aboriginal people initiating antiretroviral therapy and their response to treatment. Aboriginal peoples were identified through self-report. Baseline socio-demographics and risk factors were compared between Aboriginal and non-Aboriginal participants as were baseline factors associated with two consecutive plasma viral load measures below 500 copies/ml using contingency table analysis. Multivariate survival analysis of the prognostic factors associated with time to two consecutive plasma viral load measures below 500 copies/ml among eligible participants was undertaken to characterize response to antiretroviral therapy. There were 892 participants with available data for this analysis, of those 146 (16%) self-identified as Aboriginal. Aboriginal participants were more likely to be female (p < or = 0.001), have lower baseline plasma viral loads (p = 0.010), be co-infected with HCV (p < 0.001), live in unstable housing (p < or = 0.001), and report an income of >10K CDN (p < or = 0.001) per annum. Aboriginal people were less likely to report men who have sex with men (p < or = 0.001) and more likely to report injection drug use (p < or = 0.001) as a risk factor for HIV infection. Aboriginal participants were more likely to receive double versus triple combination antiretroviral therapy (p = 0.002), be less adherent in the first year on therapy (p = 0.001) and to have a physician less experienced with treating HIV (p < or = 0.001). When these factors were controlled for, Aboriginal people treated with triple combination therapy were as likely to respond and suppress their viral load below 500 copies. In the era of HAART, our results indicate that Aboriginal people living with HIV/AIDS were less likely to receive optimal therapy. However, when Aboriginals did receive triple drug therapy they suppressed just as well as non-Aboriginals.


Neuregulin 1-induced AKT phosphorylation in monozygotic twins discordant for schizophrenia.
Patients with schizophrenia exhibit decreased neuregulin 1 (NRG1)-stimulated AKT phosphorylation in peripheral lymphoblasts. Here, we examined this peripheral marker in monozygotic twins discordant for schizophrenia and in healthy monozygotic twins without psychiatric disorders. B lymphoblasts were stimulated with NRG1a (65 amino-acid residue recombinant protein from the epidermal growth factor [EGF] domain) for 30min. The protein isolated from the cells was analysed by Western blotting. The dependent measure was the ratio of phosphorylated AKT (pAKT) and total AKT at baseline (without NRG1 stimulation) and after NRG1 stimulation (pAKT/AKT). The results revealed that in the case of the unaffected co-twins of patients with schizophrenia, NRG1-stimulated pAKT/AKT ratio was in between the values of their co-twins with schizophrenia and that of the healthy control twin pairs. When the affected twins with schizophrenia were compared with their unaffected co-twins using a Mann-Whitney U-test, we found significantly lower NRG1-induced pAKT/AKT ratios in the patients relative to their unaffected co-twins (p=0.004). However, using a more conservative analysis (Kruskal-Wallis ANOVA followed tests for multiple comparisons), this difference was not significant. The unaffected co-twins of patients with schizophrenia did not differ significantly from the healthy control twins. In the baseline condition, the pAKT/AKT ratios were similar in all groups. These results indicate that impaired AKT-related intracellular signaling is partly related to the developed illness and cannot fully be explained by the genetic background of schizophrenia.


Estimation of total daily energy expenditure and its components by monitoring the heart rate of Japanese endurance athletes.
The estimation of total daily energy expenditure (TEE) or the energy needs of athletes is important for maintaining a proper energy balance during training. This study was conducted to measure the TEE of Japanese middle- and long-distance runners using a heart-rate monitoring method (the HR method), and to ascertain the impact of three key energy expenditure (EE) components occurring within the day: sleep, exercise (training) and inactivity (other daily habitual activities). Additionally, energy balance was evaluated by comparing TEE with energy intake (EI). The mean TEE of six male athletes aged 19-21 y was 4,514+/-739 kcal/d and their mean EI was 3,784+/-91 kcal/d during the training period of 11 d. This negative energy balance led to a significant decline in body weight (p<0.01), indicating that proper care should be taken to balance energy during training. The mean daily EEs during sleep, inactivity, and exercise were 536+/-46 (12.0% of TEE), 1,722+/-145 (38.7%), and 2,255+/-658 (49.3%) kcal/d, respectively. There was a significant correlation between TEE and exercise EE (p<0.01) in the athletes. The TEE of the endurance athletes was higher than expected and significantly affected by exercise EE, indicating that the TEE of athletes, in general, must be carefully evaluated before incorporating nutritional support for them.


Guidelines for the management and treatment of periodic fever syndromes: Cryopyrin-associated periodic syndromes (cryopyrinopathies - CAPS).
To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions.


Common host-derived chemicals increase catches of disease-transmitting mosquitoes and can improve early warning systems for Rift Valley fever virus.
Rift Valley fever (RVF), a mosquito-borne zoonosis, is a major public health and veterinary problem in sub-Saharan Africa. Surveillance to monitor mosquito populations during the inter-epidemic period (IEP) and viral activity in these vectors is critical to informing public health decisions for early warning and control of the disease. Using a combination of field bioassays, electrophysiological and chemical analyses we demonstrated that skin-derived aldehydes (heptanal, octanal, nonanal, decanal) common to RVF virus (RVFV) hosts including sheep, cow, donkey, goat and human serve as potent attractants for RVFV mosquito vectors. Furthermore, a blend formulated from the four aldehydes and combined with CO(2)-baited CDC trap without a light bulb doubled to tripled trap captures compared to control traps baited with CO(2) alone. Our results reveal that (a) because of the commonality of the host chemical signature required for attraction, the host-vector interaction appears to favor the mosquito vector allowing it to find and opportunistically feed on a wide range of mammalian hosts of the disease, and (b) the sensitivity, specificity and superiority of this trapping system offers the potential for its wider use in surveillance programs for RVFV mosquito vectors especially during the IEP.


mtDNA mutations variously impact mtDNA maintenance throughout the human embryofetal development.
Mitochondria are the largest generator of ATP in the cell. It is therefore expected that energy-requiring processes such as oocyte maturation, early embryonic or fetal development, would be adversely impacted in case of mitochondrial deficiency. Human mitochondrial DNA (mtDNA) mutations constitute a spontaneous model of mitochondrial failure and offer the opportunity to study the consequences of energetic defects over fertility and embryofetal development. This review provides an update on the mtDNA metabolism in the early preimplantation embryo, and compiles data showing the impact of mtDNA mutations over mtDNA segregation. Despite convincing evidences about the essential role of mitochondria in oogenesis and preimplantation development, no correlation between the presence of a mtDNA mutation and fertilization failure, impaired oocyte quality, or embryofetal development arrest was found. In some cases, mutant cells might upregulate their mitochondrial content to overcome the bioenergetic defects induced by mtDNA mutations, and might escape negative selection. Finally we discuss some of the clinical consequences of these observations.


Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in Angiogenesis: Isoform-Specific Effects.
Angiogenesis is the formation of new blood vessels from preexisting ones and is implicated in physiologic vascular development, pathologic blood vessel growth, and vascular restoration. This is in contrast to vasculogenesis, which is de novo growth of vessels from vascular precursors, or from vascular repair that occurs when circulating endothelial progenitor cells home into an area and develop into blood vessels. The objective of this review is to discuss the isoform-specific role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in physiologic and pathologic angiogenesis and vascular repair, but will not specifically address vasculogenesis. As the major source of reactive oxygen species (ROS) in vascular endothelial cells (ECs), NOX has gained increasing attention in angiogenesis. Activation of NOX leads to events necessary for physiologic and pathologic angiogenesis, including EC migration, proliferation and tube formation. However, activation of different NOX isoforms has different effects in angiogenesis. Activation of NOX2 promotes pathologic angiogenesis and vascular inflammation, but may be beneficial in revascularization in the hindlimb ischemic model. In contrast, activation of NOX4 appears to promote physiologic angiogenesis mainly by protecting the vasculature during ischemia, hypoxia and inflammation and by restoring vascularization, except in models of oxygen-induced retinopathy and diabetes where NOX4 activation leads to pathologic angiogenesis.


alpha-Synuclein-synaptosomal membrane interactions: implications for fibrillogenesis.
alpha-Synuclein exists in two different compartments in vivo-- correspondingly existing as two different forms: a membrane-bound form that is predominantly alpha-helical and a cytosolic form that is randomly structured. It has been suggested that these environmental and structural differences may play a role in aggregation propensity and development of pathological lesions observed in Parkinson's disease (PD). Such effects may be accentuated by mutations observed in familial PD kindreds. In order to test this hypothesis, wild-type and A53T mutant alpha-synuclein interactions with rat brain synaptosomal membranes were examined. Previous data has demonstrated that the A30P mutant has defective lipid binding and therefore was not examined in this study. Electron microscopy demonstrated that wild-type alpha-synuclein fibrillogenesis is accelerated in the presence of synaptosomal membranes whereas the A53T alpha-synuclein fibrillogenesis is inhibited under the same conditions. These results suggested that subtle sequence changes in alpha-synuclein could significantly alter interaction with membrane bilayers. Fluorescence and absorption spectroscopy using environment sensitive probes demonstrated variations in the inherent lipid properties in the presence and absence of alpha-synuclein. Addition of wild-type alpha-synuclein to synaptosomes did not significantly alter the membrane fluidity at either the fatty acyl chains or headgroup space, suggesting that synaptosomes have a high capacity for alpha-synuclein binding. In contrast, synaptosomal membrane fluidity was decreased by A53T alpha-synuclein binding with concomitant packing of the lipid headgroups. These results suggest that alterations in alpha-synuclein-lipid interactions may contribute to physiological changes detected in early onset PD.


Estradiol-sensitive afferents modulate long-term episodic firing patterns of GnRH neurons.
GnRH neurons comprise the final common pathway of an estrogen-sensitive pattern generator controlling fertility. To determine estradiol effects on GnRH neuron firing patterns, adult transgenic mice were ovariectomized (OVX), and half were treated with estradiol (OVX+E). One week later targeted single-unit extracellular recordings were made from GnRH neurons identified by green fluorescent protein expression. Estradiol markedly affected GnRH neuron firing patterns, increasing the percentage and duration of time these cells were quiescent (< or = 1 action current/min). Estradiol increased the interval between episodes of increased firing rate determined by Cluster analysis of recordings more than 45 min (OVX+E 38.8 +/- 7.2 min, OVX 16.7 +/- 2.1 min, n = 6 each). Possible mechanisms of estradiol modulation were examined by simultaneously blocking ionotropic secretion of gamma-aminobutyric acid and glutamatergic receptors. This treatment had no effect on cells from OVX mice (n = 10), indicating episodic firing of GnRH neurons is not driven by activation of these receptors. Receptor blockade eliminated estradiol effects on GnRH neurons in the midventral preoptic area (n = 7) but not elsewhere (n = 7). Individual GnRH neurons thus display episodic firing patterns at intervals previously reported for secretory pulses. Estradiol modulates episode frequency to exert feedback control; in a substantial subset of GnRH neurons, estradiol feedback is enforced via GABAergic and/or glutamatergic afferents.


Shape control of single crystalline bismuth nanostructures.
A synthesis approach for shape control of single crystalline Bi nanostructures has been developed. By controlling the molar ratio of PVP and Bi in a polyol process, Bi nanocubes with an edge length of approximately 60-80 nm, triangular nanoplates with an edge length of 200-500 nm, and nanospheres with an average diameter of 75 nm have been successfully synthesized. In the same synthetic process, Bi nanobelts with lengths of up to 80 microm and widths of up to 0.6 microm were synthesized in large quantities by introducing a trace amount of Fe3+ species into the reaction system. These single crystalline nanostructure Bi materials are expected to find potential applications in a variety of areas including high efficiency thermoelectric devices.


Ca(2+)-activated K+ channels in rat otic ganglion cells: role of Ca2+ entry via Ca2+ channels and nicotinic receptors.
1. Intracellular recordings were made from neurones in the rat otic ganglion in vitro in order to investigate their morphological, physiological and synaptic properties. We took advantage of the simple structure of these cells to test for a possible role of calcium influx via nicotinic acetylcholine receptors during synaptic transmission. 2. Cells filled with biocytin comprised a homogeneous population with ovoid somata and sparse dendritic trees. Neurones had resting membrane potentials of -53 +/- 0.7 mV (n = 69), input resistances of 112 +/- 7 M omega, and membrane time constants of 14 +/- 0.9 ms (n = 60). Upon depolarization, all cells fired overshooting action potentials which were followed by an apamin-sensitive after-hyperpolarization (AHP). In response to a prolonged current injection, all neurones fired tonically. 3. The repolarization phase of action potentials had a calcium component which was mediated by N-type calcium channels. Application of omega-conotoxin abolished both the repolarizing hump and the after-hyperpolarization suggesting that calcium influx via N-type channels activates SK-type calcium-activated potassium channels which underlie the AHP. 4. The majority (70%) of neurones received innervation from a single preganglionic fibre which generated a suprathreshold excitatory postsynaptic potential mediated by nicotinic acetylcholine receptors. The other 30% of neurones also had one or more subthreshold nicotinic inputs. 5. Calcium influx via synaptic nicotinic receptors contributed to the AHP current, indicating that this calcium has access to the calcium-activated potassium channels and therefore plays a role in regulating cell excitability.


Evaluating the Serum Levels of Beclin-1 and Mammalian/Mechanistic Target of Rapamycin (mTOR) in Three Different Professional Categories.
The possible associations between occupational factors and autophagy - a catabolic process that is evolutionarily conserved and serves as a vital cornerstone in maintaining cellular balance - remain largely unexplored. We assessed serum levels of beclin-1, a principal effector of autophagy, and the mammalian/mechanistic target of rapamycin (mTOR), a protein recognized for its part in suppressing autophagy, within a group of healthy individuals hailing from three different professional fields, each characterized by its unique working conditions. A total of 60 men were recruited from three distinct occupational categories: airline pilots, construction laborers, and fitness trainers. Each group consisted of 20 subjects who were selected during routine occupational health appointments. Serum levels of beclin-1 and mTOR were measured using commercially available immunoassays and compared among the three categories. Fitness instructors had the highest concentration of beclin-1 (3.1 ± 0.9 ng/mL). Construction workers followed with a mean of 2.4 ± 0.4 ng/mL, while airline pilots had the lowest levels at 1.9 ± 0.5 ng/mL (one-way analysis of variance, P < 0.001). In terms of mTOR levels, construction workers had the highest concentration (5.9 ± 1.9 ng/mL), followed by airline pilots (4.4 ± 1.7 ng/mL). Fitness instructors, on the other hand, had the lowest mTOR levels (3.5 ± 1.2 ng/mL; one-way analysis of variance, P < 0.001). Serum levels of autophagy biomarkers can vary among healthy individuals based on their professional roles. Considering the crucial function autophagy serves in both health and disease, further investigations are crucial to deepen our comprehension of the potential implications of autophagy in the field of occupational medicine.


[Effect of serotonin and noradrenaline on the magnitude of the response of the command neurons for defensive behavior in Helix lucorum L].
Changes in synaptic responses of identified command neurones of avoidance behaviour to the electric nerve stimulation were investigated in the isolated nervous system of the snail during bath application of serotonin or noradrenaline. Serotonin (10(-5) M) elicited an increase of summary EPSP amplitude in the cells without changes of input resistance and resting potential. Noradrenaline (10(-5) M) application evoked an increase of EPSP amplitude, accompanied by an increase of the input resistance. Mechanisms of serotonin and noradrenaline influence on synaptic responses are discussed.


Electron microscope study of the kinetics of the fiber-to-crystal transition of sickle cell hemoglobin.
The intermediates and the rate-limiting step in the crystallization of deoxygenated sickle hemoglobin have been determined by a kinetic study with the use of electron microscopy. In slowly stirred solutions of deoxygenated hemoglobin S [Pumphrey, J. & Steinhardt, J. (1977) J. Mol. Biol. 112, 359--375], the sequential appearance of fibers have a diameter of approximately equal to 210 A, bundles of aligned fibers in well-ordered arrays, "thick" fibers of approximately equal to 470 A diameter, and microcrystals is observed. Only the fibers having a diameter of approximately equal to 210 A and bundles of aligned fibers are assigned as kinetically important intermediates of the fiber-to-crystal transition. Addition of microscopic seed crystals obtained from slowly stirred solutions of deoxyhemoglobin S to a solution composed of only fibers and hemoglobin monomers results in more rapid crystallization than in control solutions. Addition of seed crystals after the formation of bindles of aligned fibers does not alter the overall kinetics of crystallization. The results demonstrate that alignment of fibers is the rate-limiting step in the crystallization process and results in formation of nucleation sites for crystal growth.


Reactions of Group 8, 9, and 10 monocations (Fe+, Co+, Ni+, Ru+, Rh+, Pd+, Os+, Ir+, Pt+) with phosphane in the gas phase.
The reactions of Group 8, 9 and 10 monocations with phosphane were studied under single-collision conditions in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Fe(+) is completely unreactive, Co(+) reacts slowly and shows both adduct formation and P-H bond activation, and Ni(+) reacts slowly as well but shows adduct formation only. In contrast to their first-row congeners, the investigated second- and third-row transition metal monocations show facile P-H bond activations. Remarkably, extensive dehydrogenations of the collision complexes yield cations MPH(+), MP(2) (+), MP(3)H(+), MP(4) (+) and so on. Exceptional behaviour is shown by the two d(9) cations palladium (whose "dehydrogenation power" is rather limited) and platinum (which gives rise to a great manifold of only partially dehydrogenated species as well). Collision-induced dissociation experiments suggest that P(2) and PH units are formed as ligands.


Insights into the Rearrangement of the Molecular Assembly Structure of 6-Aminonicotinic Acid in Its Hydrated Environment.
Water, as a ubiquitous and essential component of life, is known to have a significant impact on the structure and function of organic molecules. In this study, we investigate the role of water in the phase transition of organic molecular assembly structures by scanning tunneling microscopy at room temperature. The results show that the -O-H···O hydrogen induced by water molecules can lead to a significant structural transition in the molecular assembly, specifically through selective weakening of -C-H···O between 6-aminonicotinic acid and the formation of new -O-H···O bonds between 6-aminonicotinic acid and water molecules. Subsequent thermal treatment of these molecular assembly structures reveals that the formation of -N-H···O hydrogen bonds induced by water molecules has created a different pathway for the phase transition of the molecular assembly structure. This knowledge has important implications for the design of organic molecules with specific nanostructures that can be controlled through hydration.


Pharmacokinetics and hemodynamic effects of tiapamil: exercise performance, thallium stress scintigraphy, and radionuclide ventriculography.
The pharmacokinetic behavior and hemodynamic effects of tiapamil, a calcium antagonist, were studied in 16 cardiac patients during an eight-day treatment course, giving oral doses of 600 mg daily. The hemodynamic effects were investigated using exercise performance tests, thallium stress scintigraphy, and radionuclide ventriculography. The areas under the plasma concentration-time curve after the final dose were greater than after the first dose for both tiapamil (+53 per cent) and its metabolite (+24 per cent). One possible explanation is that tiapamil undergoes saturable intestinal wall metabolism. Alternatively, like verapamil, it may undergo a saturable hepatic elimination process. The hemodynamic test series showed that, despite increasing the exercise tolerance, tiapamil significantly reduced the rate-pressure product, an index of myocardial oxygen requirement. Regional myocardial perfusion clearly improved. Ventriculography showed a significant increase in ejection fraction (+18 per cent), cardiac index (+12 per cent), and stroke volume index (+19 per cent). At the same time, the measured mean arterial pressure decreased significantly by about 10 per cent and the calculated peripheral vascular resistance, by about 19 per cent.


Bone mineralization changes in saw operators.
In vibration disease the impact on bone and joint systems is considered to be the least frequent one. It includes a degenerative component, rare necrotic alteration and osteoporosis, together with cystic alterations, in the carpal bones. The authors concentrated only on osteoporosis in the proximal parts of upper extremities. They evaluated by X-rays of the thorax the extent of mineralization and, consequently, the osteoporosis of the clavicles. For that purpose they used the corticodiaphyseal Barnett-Nordin index (BNI). In a group of 107 chain saw operators whose both upper extremities had been exposed to the impact of vibration exceeding the threshold limit while operating a chain saw, a statistically significant difference was established in the mineralization of clavicles. These findings contrasted with a control group of 107 healthy males who had never worked with vibrating equipment. The authors did not establish a statistically significant dependence of these changes on simultaneously diagnosed traumatic vasoneurosis and neuropathy. After the risk elimination of vibration the value of the BNI indicates the dynamics and the reversibility of the parameter under observation. These findings suggest that osteoporosis due to the impact of vibrations is by no means a rare phenomenon. It does not affect only the distal parts of the upper extremities. Similarly as angiological and neurological changes, osteoporosis tends towards spontaneous adjustment, once the risk of vibrations has been eliminated.


Reproductive factors and risk of breast carcinoma in a study of white and African-American women.
Few studies have investigated the association between reproductive factors and the risk of breast carcinoma among African-American women. The authors assessed whether the number of full-term pregnancies, age at first full-term pregnancy, and total duration of breastfeeding were associated with similar relative risk estimates in white and African-American women in a large multicenter, population-based case-control study of breast carcinoma. Case patients were 4567 women (2950 white women and 1617 African-American women) ages 35-64 years with newly diagnosed invasive breast carcinoma between 1994 and 1998. Control patients were 4668 women (3012 white women and 1656 African-American women) who were identified by random-digit dialing and were frequency matched to case patients according to study center, race, and age. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. For white women, the reduction in risk of breast carcinoma per full-term pregnancy was 13% among younger women (ages 35-49 years) and 10% among older women (ages 50-64 years). The corresponding risk reductions for African-American women were 10% and 6%, respectively. Risk decreased significantly with increasing number of full-term pregnancies for both races and both age categories. Duration of lactation was inversely associated with breast carcinoma risk among younger parous white (trend P = 0.0001) and African-American (trend P = 0.01) women. African-American women tended to have more children compared with white women, but parity rates were lower in younger women than in older women in both racial groups. However, breastfeeding was substantially more common in young white women than in young African-American women. Overall, parity and lactation had similar effects on breast carcinoma risk in white and African-American women. If younger African-American women now are giving birth to fewer children than in the past, without a substantial increase in breastfeeding, breast carcinoma rates may continue to increase at a more rapid rate among these women compared with white women.


Reconstructing phylogeny by quadratically approximated maximum likelihood.
Maximum likelihood (ML) for phylogenetic inference from sequence data remains a method of choice, but has computational limitations. In particular, it cannot be applied for a global search through all potential trees when the number of taxa is large, and hence a heuristic restriction in the search space is required. In this paper, we derive a quadratic approximation, QAML, to the likelihood function whose maximum is easily determined for a given tree. The derivation depends on Hadamard conjugation, and hence is limited to the simple symmetric models of Kimura and of Jukes and Cantor. Preliminary testing has demonstrated the accuracy of QAML is close to that of ML.


[Hydroxyethyl starch in the treatment of Bell's facial paralysis. A clinical study].
Nowadays an infusion therapy composed of cortisone, low-molecular dextran, and pentoxifylline is the most common treatment of Bell's palsy. During recent years it has become well known that low-molecular dextran has several severe side effects (e.g. acute renal failure). - At the ENT Department of the University of Göttingen 33 patients with Bell's palsy were treated with an infusion therapy which replaced low-molecular dextran by hydroxyethyl starch. Before and after therapy patients underwent a special diagnostic procedure for the facial nerve function consisting of --determination of the degree of paralysis and secondary defects (14) --a complete electrophysiological examination. The patients were followed up for at least 6 months. It was found that 97% of the patients had a complete functional recovery.


The in situ staining of muscles during development with the cholinesterase technique.
Developing muscles from forelegs of 11- to 18-day-old mouse embryos were stained in situ for cholinesterase with the copper-ferrocyanide technique. The skin of the legs represents a diffusion barrier for the incubation medium. Therefore, in older embryos the skin was mechanically removed after trypsin digestion. In younger embryos the skin remained on the forelegs after trypsin treatment. With this technique it is possible to follow the establishment of the muscular pattern in the legs.


[Checkup of the 40 years old man].
According to a study published by the European Commission in 2011 and including 290 millions men from 34 different countries, among which Switzerland, the male population has a much higher mortality and morbidity rate than its female counterpart. When a man reaches his fortierth year, he is at the top of his abilities in many areas : he benefits from a strong life experience and the deficits related to aging do not impact his wellbeing yet. What about his health ? Most of the recommendations in terms of screening begin at age 50. So forties can appear as a grey area. This article reviews the screening indicated for a patient around forty years old. It intends to offer a complement to publications regarding screening and prevention that are regularly published in this journal.


Polymers in crowded environment under stretching force: Globule-coil transitions.
We study flexible polymer macromolecules in a crowded (porous) environment, modeling them as self-attracting self-avoiding walks on site-diluted percolative lattices in space dimensions d=2,3 . The influence of stretching force on the polymer folding and the properties of globule-coil transitions are analyzed. Applying the pruned-enriched Rosenbluth chain-growth method, we estimate the transition temperature TTheta between collapsed and extended polymer configurations and construct the phase diagrams of the globule-coil coexistence when varying temperature and stretching force. The transition to a completely stretched state, caused by applying force, is discussed as well.


Gaze Restriction and Reactivation of Place-bound Content Drive Eye Movements During Mental Imagery.
When we imagine a picture, we move our eyes even though the picture is physically not present. These eye movements provide information about the ongoing process of mental imagery. Eye movements unfold over time, and previous research has shown that the temporal gaze dynamics of eye movements in mental imagery have unique properties, which are unrelated to those in perception. In mental imagery, refixations of previously fixated locations happen more often and in a more systematic manner than in perception. The origin of these unique properties remains unclear. We tested how the temporal structure of eye movements is influenced by the complexity of the mental image. Participants briefly saw and then maintained a pattern stimulus, consisting of one (easy condition) to four black segments (most difficult condition). When maintaining a simple pattern in imagery, participants restricted their gaze to a narrow area, and for more complex stimuli, eye movements were more spread out to distant areas. At the same time, fewer refixations were made in imagery when the stimuli were complex. The results show that refixations depend on the imagined content. While fixations of stimulus-related areas reflect the so-called 'looking at nothing' effect, gaze restriction emphasizes differences between mental imagery and perception.


Bis(4'-hy-droxy-biphenyl-4-carboxyl-ato-κO)(1,10-phenanthroline-κN,N')zinc.
In the title compound, [Zn(C(13)H(9)O(3))(2)(C(12)H(8)N(2))], the Zn(II) atom is located on a twofold rotation axis and has a distorted tetra-hedral coordination with two N atoms from the phenanthroline ligand arranged around the twofold axis and two O atoms from two symmetry-related 4'-hy-droxy-biphenyl-4-carboxyl-ate ligands. The mol-ecules are linked by O-H⋯O hydrogen bonds, forming a chain developing parallel to [101].


Photoionization and ionic dissociation of the C3 H3 NS molecule induced by soft X-ray near the C1s edge.
Time of flight mass spectrometry, electron-ion coincidence, and ion yield spectroscopy were employed to investigate for the first time the thiazole (C3 H3 NS) molecule in the gas phase excited by synchrotron radiation in the soft X-ray domain. Total ion yield (TIY) and photoelectron-photoion coincidence (PEPICO) spectra were recorded as a function of the photon energy in the vicinity of the carbon K edge (C1s). The C1s resonant transitions as well as the core ionization thresholds have been determined from the profile of TIY spectrum, and the features were discussed. The corresponding partial ion yields were determined from the PEPICO spectra for the cation species produced upon the molecular photodissociation. Additional ab initio calculations have also been performed from where relevant structural and electronic configuration parameters were obtained for this molecule.


Efferocytosis of Apoptotic Neutrophils Enhances Control of Mycobacterium tuberculosis in HIV-Coinfected Macrophages in a Myeloperoxidase-Dependent Manner.
Tuberculosis remains a big threat, with 1.6 million deaths in 2017, including 0.3 million deaths among patients with HIV. The risk of developing active disease increases considerably during an HIV coinfection. Alveolar macrophages are the first immune cells to encounter the causative agent Mycobacterium tuberculosis, but during the granuloma formation other cells are recruited in order to combat the bacteria. Here, we have investigated the effect of efferocytosis of apoptotic neutrophils by M. tuberculosis and HIV-coinfected macrophages in a human in vitro system. We found that the apo-ptotic neutrophils enhanced the control of M. tuberculosis in single and HIV-coinfected macrophages, and that this was dependent on myeloperoxidase (MPO) and reactive oxygen species in an autophagy-independent manner. We show that MPO remains active in the apoptotic neutrophils and can be harnessed by infected macrophages. In addition, MPO inhibition removed the suppression in M. tuberculosis growth caused by the apoptotic neutrophils. Antimycobacterial components from apoptotic neutrophils could thus increase the microbicidal activity of macrophages during an M. tuberculosis/HIV coinfection. This cooperation between innate immune cells could thereby be a way to compensate for the impaired adaptive immunity against M. tuberculosis seen during a concurrent HIV infection.


Hemostasis and global fibrinolytic capacity in chronic liver disease.
Accelerated fibrinolysis associated with liver disease can be demonstrated by various tests that are either nonspecific in liver disease or that demonstrate only an extrinsic pathway. In the present study we used a new method to assess the global fibrinolytic capacity (GFC) of both the intrinsic and extrinsic pathways in patients with chronic liver disease. Forty patients with the diagnosis of chronic liver disease were included in the study. Seventeen age-matched and gender-matched healthy control individuals were enrolled as a control group. The GFC was studied with semiquantitative macrolatex agglutination. The study population consisted of 40 patients with chronic liver disease (group 1, patients with chronic hepatitis; group 2, patients with cirrhosis; group 3, patients with hepatocellular carcinoma), mean age 53.3 +/- 13 years, and a control group (group 4) consisting of 17 healthy individuals (mean age 55 +/- 12.2 years). The GFC was significantly higher in patients than in control individuals (13.8 +/- 9 microg/ml, 13.6 +/- 11 microg/ml, 14.1 +/- 14 microg/ml, 1.9 +/- 2.2 microg/ml, respectively; P < 0.05). There was no difference between the patient groups (P > 0.05). There was a significant positive relationship between the GFC and the prothrombin time and activated partial thromboplastin time values (P < 0.05). A negative correlation was also observed between the GFC and thrombocyte counts (P < 0.05). In conclusion, our results suggest that patients with chronic liver disease have hyperfibrinolysis, as reflected by the increased GFC. Elucidation of the GFC in chronic liver disease can reflect the net fibrinolytic capacity of those patients who are prone to hyperfibrinolysis resulting in bleeding tendencies and hemorrhages.


How Can People Be so Good at Intercepting Accelerating Objects if They Are so Poor at Visually Judging Acceleration?
People are known to be very poor at visually judging acceleration. Yet, they are extremely proficient at intercepting balls that fall under gravitational acceleration. How is this possible? We previously found that people make systematic errors when trying to tap on targets that move with different constant accelerations or decelerations on interleaved trials. Here, we show that providing contextual information that indicates how the target will decelerate on the next trial does not reduce such errors. Such errors do rapidly diminish if the same deceleration is present on successive trials. After observing several targets move with a particular acceleration or deceleration without attempting to tap on them, participants tapped as if they had never experienced the acceleration or deceleration. Thus, people presumably deal with acceleration when catching or hitting a ball by compensating for the errors that they made on preceding attempts.


Host-adapted Cryptosporidium spp. in Canada geese (Branta canadensis).
The prevalence and distribution of Cryptosporidium spp. in the fecal droppings of the free-living waterfowl Canada geese were examined at 13 sites in Ohio and Illinois. On the basis of the analysis of the small-subunit rRNA gene by PCR, followed by restriction fragment length polymorphism analysis and DNA sequencing, 49 (23.4%) of 209 fecal specimens collected from 10 sites (76.9%) were positive for Cryptosporidium spp. The following five Cryptosporidium species and genotypes were identified: Cryptosporidium goose genotype I (in 36 specimens), Cryptosporidium goose genotype II (in 9 specimens), Cryptosporidium duck genotype (in 1 specimen), Cryptosporidium parvum (in 4 specimens), and C. hominis (in 2 specimens). Cryptosporidium goose genotype I was the most prevalent parasite and was found at all five Cryptosporidium-positive sites in Ohio and at four of five positive sites in Illinois, followed by Cryptosporidium goose genotype II, which was found at two of five positive sites in Ohio and at four of five positive sites in Illinois. Cryptosporidium goose genotype II was detected for the first time, and it is phylogenetically related to goose genotype I and the duck genotype. All three genotypes have not so far been reported in humans, and their pathogenicity in geese has not been determined. Only 10.2% of the Cryptosporidium-positive specimens had C. parvum and C. hominis. The results of this study indicate that Canada geese might only serve as accidental carriers of cryptosporidia infectious to humans and probably play a minor role in the animal-to-human transmission cycle of the pathogen.


Lung functions and chest radiographs in shipyard workers exposed to asbestos.
Lung functions and diffusing capacity for carbon monoxide were examined in 299 shipyard workers occupationally exposed to asbestos, among whom there was an equal number of smokers and non-smokers. The workers were classified into groups according to the lung fibrosis profusion and the length and width of the pleural plaques in accordance with the 1980 ILO International Classifications of Pneumoconioses. With regard to the profusion of the parenchyma, workers classified in category 2 (subcategories 2/1 and 2/2) had significantly lower FVC and FEV1 values than the workers in categories 0 (P < 0.01) and 1 (P < 0.05). With an increase in the category of profusion there was a trend towards a fall in mean MEF25, MEF50 and MEF75 values, but it was not significant. Diffusing capacity for carbon monoxide was identical for all categories. There were no significant differences between the workers without pleural plaques and those with visible plaques in respect to lung function values. With an increase in the length and width of the plaques FVC, FEV1, MEF25 and MEF75 values tended to become lower. The results demonstrate that the changes detected on the radiographs of the lungs and pleura are the early indicators of possible asbestos disease in shipyard workers.


Association between phosphodiesterase-5 inhibitors and nonarteritic anterior ischemic optic neuropathy.
Use of phosphodiesterase-5 (PDE-5) inhibitors has been reported to be a risk factor for development of nonarteritic anterior ischemic optic neuropathy (NAION) in males, based largely on a number of case reports. The objective of our study was to determine whether men who use this class of medications are more likely than a matched control group to develop NAION. A pharmacoepidemiological nested case-control study was used to examine the above association in a health claims database of physician diagnoses and prescription medication dispensing. Cases of NAION were matched with corresponding controls and correlated with the use of PDE-5 inhibitors. A conditional logistic regression model was used to estimate rate ratios for development of NAION with use of PDE-5 inhibitors. A total of 1,109 cases of NAION were found and matched to 1,237,290 controls identified within the database. Cases were more likely to have hyperlipidemia, diabetes, hypertension, myocardial infarction, and cerebrovascular accident in the year preceding their NAION. The adjusted rate ratio for any use of PDE-5 inhibitor in the year before the NAION was 1.01 (95% confidence interval [CI], 0.79-1.28); recent use of a PDE-5 inhibitor in the 30 days before the NAION also had no significant association, with an adjusted rate ratio of 0.96 (95% CI, 0.75-1.23). Results for individual PDE-5 inhibitors did not achieve statistical significance. Our results do not suggest any association between having a prescription filled for PDE-5 inhibitor medication and receiving a diagnosis code for NAION. This is consistent with other studies in the literature that have failed to elucidate a plausible mechanism by which these drugs might compromise circulation at the optic nerve head.


Erdheim-Chester disease with prominent pulmonary involvement associated with eosinophilic granuloma of mandibular bone.
We report a patient with eosinophilic granuloma localized to the left mandible who was subsequently shown to have Erdheim-Chester disease involving the lower extremities, omentum and lung. The diagnosis of eosinophilic granuloma was based on the presence of typical CD1a+ Langerhans' cell granulomas in a biopsy of mandible. The diagnosis of Erdheim-Chester disease was established on the basis of the pattern of radioisotopic uptake by long bones, seen on a technetium bone scan, and the presence of characteristic histopathological features in biopsies of lung and peritoneum. The pathological findings in lung were compatible with the abnormalities observed by tomodensitometry, but strikingly different from those seen in Langerhans' cell granulomatosis. The differences in the histological features of pulmonary involvement seen in the two diseases, and the possible relationship between Langerhans' cell granulomatosis and Erdheim-Chester disease, are discussed.


Regulation of hypoxia-inducible gene expression after HIF activation.
Hypoxia causes dramatic changes in the expression profiles of genes that encode glycolytic enzymes, vascular endothelial growth factors, erythropoietin, and other factors in a tissue-specific manner through activating hypoxia-inducible transcription factors (HIFs) such as HIF1α and HIF2α. It has been elucidated that the activity of HIFs is fundamentally regulated by their protein stability in an oxygen-dependent manner. However, little is known about how stabilized HIFs regulate transcription of their target genes in hypoxic cells. Additionally, the roles of HIF3α, the third member of the HIFs, are still enigma due to its various splicing variants and the complicated phenotypes of Hif3a-gene modified mouse lines. Here, we summarize how molecular systems fine-tune hypoxia-inducible transcription with the cooperation of HIFs and their negative regulators, including IPAS, one of the HIF3α splicing variants. Since epigenetic mechanisms contribute to stress-inducible and cell-type specific gene regulation, the HIF-dependent reorganization of nucleosome structures in hypoxia-inducible gene promoters is also discussed.


Predictive factors for changes in remnant stump length during and after the treatment of incompetent truncal saphenous veins using cyanoacrylate.
The VenaSeal™ Closure System is a non-thermal, non-tumescent venous closure device that employs a cyanoacrylate adhesive to occlude incompetent veins for superficial truncal reflux. The aim was to examine patient, Duplex-defined venous characteristics and treatment-related factors that may predict variances in remnant stump length at the sapheno-femoral and sapheno-popliteal junctions in the peri-procedural period. A total of 73 patients (87 legs; 85 great saphenous veins; 11 small saphenous veins) of median age 63 years (range 26-86 years) underwent VenaSeal™ Closure System ablation. 44/85 (52%) great saphenous veins were treated with a modified instructions-for-use technique of using double-dose injection of glue (0.3 cc) at initial deposition for great saphenous veins diameters >6 mm. Median great saphenous veins and small saphenous veins lengths ablated were 48.0 cm (range 13-69 cm) and 32.0 cm (range 19-40 cm), respectively. A total of 62/87 (71.3%) legs had CEAP classification 4-6. A completion Duplex scan was performed immediately and 1 week post-procedure to measure remnant stump lengths at the sapheno-femoral and sapheno-popliteal junctions. Multivariate regression modelling was used to look for predictors of remnant stump length. Mean sapheno-femoral and sapheno-popliteal junctions stump lengths immediately post procedure were 33.0 mm (range 0-58 mm) and 27 mm (range 5-33 mm), -17.0 mm and -23.0 mm less than the expected 50-mm baseline length, respectively. At 1 week post-procedure, mean sapheno-femoral and sapheno-popliteal junctions stump lengths were 25.0 mm and 25.0 mm, respectively, the former found to be shorter compared to immediately post-procedure (25 mm vs 33 mm; p < 0.05). Multivariate analysis found larger upper thigh great saphenous veins diameter at sapheno-femoral junction to be predictive of shorter remnant stump lengths immediately post-procedure (<30 mm stump distance). Larger sapheno-femoral junction diameters and pre-existing ischemic heart disease for the sapheno-femoral junction and larger small saphenous veins diameters and age for the sapheno-popliteal junction were predictive of interval shortening of the measured remnant lengths found at the completion of the procedure and 1 week later. Initial double-dosing application of glue was not found to be predictive of shorter stump lengths. In patients undergoing VenaSeal™ Closure System ablation for superficial truncal reflux, larger upper thigh great saphenous veins diameters predicted shorter remnant sapheno-femoral junction stump lengths immediately post-procedure. Comparing stump lengths at one week to immediately after procedure, larger sapheno-femoral junctions and ischemic heart disease predicted shorter stump lengths at the sapheno-femoral junction, while larger small saphenous vein diameters predicted shorter stump lengths at the sapheno-popliteal junction.