Pharmacological mechanisms for left ventricular unloading in clinical congestive heart failure. Differential effects of nitroprusside, phentolamine, and nitroglycerin on cardiac function and peripheral circulation.
We compared cardiocirculatory actions of the commonly employed systemic vasodilators, intravenous (iv) nitroprusside (NP), iv phentolamine (PH), and sublingual nitroglycerin (NTG), causing left ventricular (LV) unloading in 29 chronic coronary subjects with congestive failure to determine whether they produce disparate responses in LV function by different relaxing actions on systemic resistance and capacitance beds. Each drug equally lowered systemic arterial pressures to a small extent, whereas heart rate rose slightly with NTG. Cardiac catheterization showed a decline in end-diastolic pressure with NTG (19 to 8 mm Hg) which was greater (P less than 0.05) than with NP and PH (21 to 11). Cardiac index increased (P less than 0.05) during NP (2.68 to 2.93 liters/min per m2) and PH (2.60 to 3.02) but was unchanged (2.83) by NTG. Stroke work increased with PH, ejection fraction rose with NP and PH, and mean ejection rate increased with each, whereas pressure-time per minute fell and end-diastolic volume decreased with each agent. Total systemic vascular resistance declined (P less than 0.001) during NP and PH (1,475 to 1,200 dynes sec cm-5) but was unchanged (1,487) by NTG. Plethysmographically, forearm vascular resistance (FVR) decreased (P less than 0.01) with NP and PH (61.6 to 39.1 mm Hg/ml per 100 g/min) but not (52.4) by NTG. The decreases in venous tone (VT) with NTG (18.2 to 9.3 mm Hg/ml) and NP (18.5 to 9.8) were greater (P less than 0.05) than with PH (18.8 to 13.1) FVR/VT percent changes of 0.96, 1.62, and 0.53 with NP, PH, and NTG indicated balanced systemic arteriolovenous relaxation by iv NP, greater arteriolar dilation with iv PH, and predominant venous dilation by sublingual NTG. Thus, vasodilators produce disparate modifications of LV function by their differing alterations of preload and impedance, which are dependent upon relative extents of relaxation of systemic resistance and capacitance vessels characteristic of each agent as used clinically.


Development of a potential reference material for evaluating antioxidant activity.
Phenolic phytochemical are known to perform several functions ranging from phytoprotectants, to protecting lipids in food products, to antioxidant activity in animals and humans. The need for a common standard mixture containing multiple phenolic phytochemicals is critical for the development of a robust validation assay for accurately quantifying antioxidant activity in various matrixes. Different research groups have used A wide array of single purified reference phenolic compounds in this regard. A 5 compound mixture (caffeic acid, morin hydrate, hesperetin, catechin hydrate, and epigallocatechin gallate) containing phenolic compounds from 4 subgroups (phenolic acid, flavone, flavanone, and flavan-3-ol) was prepared. The mixture was assayed for stability evaluation by high-performance liquid chromatography (HPLC) using a diode array detection procedure for a 3 month time interval. HPLC analysis confirmed that there was no significant interaction between different components of the mixture. The among-sample relative standard deviation (RSD) of all 5 phenolic compounds, as well as the total HPLC area, was < 1%. The RSD due to instrument variation was < 2% and the total RSD among-days was < 5%. These results unambiguously suggest that the sample was stable for a 3 month time interval in an amber vial stored in a refrigerator below 5 degrees C. This mixture is currently being used for the single-laboratory validation study for the assay of total phenolic content by the Folin-Ciocalteu method and the antioxidant capacity by oxygen radical absorbing capacity procedure.


Impact of socioeconomic status on adverse cardiac events after coronary angioplasty: a cohort study.
Socioeconomic status (SES) has been associated with adverse cardiovascular events in coronary atherosclerotic disease. However, it is unclear how SES impacts adverse cardiac events in patients treated with percutaneous coronary intervention (PCI). We determined SES based on educational, economic and occupational parameters for 630 consecutive patients who underwent PCI at our centre between 01 June 2015 and 01 June 2016. The patients were divided into low and high SES groups, and they were followed up for 12 months. Patients were matched at baseline for demographic and procedural characteristics; multivariate analysis was used to adjust for baseline and procedural variables. Postprocedure compliance to medications was analysed. At 12 months, the primary composite end point of major adverse cardiac events (MACE) - consisting of death, non-fatal myocardial infarction, target lesion revascularisation, target vessel revascularisation - was compared between the groups. The high SES group had a higher prevalence of diabetes mellitus (p=0.03; OR 0.74%, 95% CI 0.53% to 1.03%) and a stronger family history of ischaemic heart disease (p=0.003; OR 0.53%, 95% CI 0.33% to 0.84%). Low SES was associated with lower compliance with medication (p=0.01; OR 2.22%, 95% CI 1.19% to 4.15%). At 12 months, the primary composite end point of MACE was found to be higher in the low SES group (p=0.01); higher MACE was primarily driven by cardiac mortality (p<0.001). Low SES was found to be an independent predictor of MACE (HR 1.84%, 95% CI 1.16% to 2.96%). Low SES was associated with a higher incidence of major adverse cardiac events in patients undergoing PCI and was an independent predictor of MACE at 12 months.


Building the foundations for sustainable development: a case for global investment in the capabilities of adolescents.
Investment in the capabilities of the world's 1·2 billion adolescents is vital to the UN's Sustainable Development Agenda. We examined investments in countries of low income, lower-middle income, and upper-middle income covering the majority of these adolescents globally to derive estimates of investment returns given existing knowledge. The costs and effects of the interventions were estimated by adapting existing models and by extending methods to create new modelling tools. Benefits were valued in terms of increased gross domestic product and averted social costs. The initial analysis showed high returns for the modelled interventions, with substantial variation between countries and with returns generally higher in low-income countries than in countries of lower-middle and upper-middle income. For interventions targeting physical, mental, and sexual health (including a human papilloma virus programme), an investment of US$4·6 per capita each year from 2015 to 2030 had an unweighted mean benefit to cost ratio (BCR) of more than 10·0, whereas, for interventions targeting road traffic injuries, a BCR of 5·9 (95% CI 5·8-6·0) was achieved on investment of $0·6 per capita each year. Interventions to reduce child marriage ($3·8 per capita each year) had a mean BCR of 5·7 (95% CI 5·3-6·1), with the effect high in low-income countries. Investment to increase the extent and quality of secondary schooling is vital but will be more expensive than other interventions-investment of $22·6 per capita each year from 2015 to 2030 generated a mean BCR of 11·8 (95% CI 11·6-12·0). Investments in health and education will not only transform the lives of adolescents in resource-poor settings, but will also generate high economic and social returns. These returns were robust to substantial variation in assumptions. Although the knowledge base on the impacts of interventions is limited in many areas, and a major research effort is needed to build a more complete investment framework, these analyses suggest that comprehensive investments in adolescent health and wellbeing should be given high priority in national and international policy.


Overview on biological activities and molecular characteristics of sulfated polysaccharides from marine green algae in recent years.
Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits.


Oxygen in the treatment of spinal cord decompression sickness.
Twenty-five anesthetized dogs were used to find the optimum Po2 for the delayed treatment of spinal cord decompression sickness (DCS). They were instrumented for the measurement of physiological variables and somatosensory spinal evoked potentials (SEP) given an air dive of 15 min at 10 bar (300 ft) and decompressed in under 6 min. At the surface SEP were observed for signs of DCS. Fifteen minutes after cord DCS was observed in the SEP, the dogs were compressed to 5.0 bar breathing one of 5 gas mixtures giving a Po2 of 1.0, 1.5, 2.0, 2.5, or 3.0 bar. At the start of therapy all groups were in a similar physiological state with a similar loss of SEP. Between 40 and 120 min, recovery was significantly different (P less than 0.05) between the groups, most SEP recovery having occurred within 15 min. The treatments ended with 22, 32, 70, 66, and 42% recovery, respectively. It would appear that the optimum Po2 is around 2.0 bar.


Prospective and episodic memory in relation to hippocampal volume in adults with spina bifida myelomeningocele.
The present study examined prospective and episodic memory in relation to age, functional independence, and hippocampal volume in younger to middle-aged adults with spina bifida myelomeningocele (SBM) and typically developing (TD) adults. Prospective and episodic memory, as well as hippocampal volume, was reduced in adults with SBM relative to TD adults. Neither memory performance nor hippocampal volume showed greater decrements in older adults. Lower hippocampal volume was associated with reduced prospective memory in adults with SBM, and this relation was specific to the hippocampus and not to a contrast structure, the amygdala. Prospective memory mediated the relation between hippocampal volume and functional independence in adults with SBM. The results add to emerging evidence for reduced memory function in adults with SBM and provide quantitative evidence for compromised hippocampal macrostructure as a neural correlate of reduced memory in this population.


CO2 in indoor environments: From environmental and health risk to potential renewable carbon source.
In the developed world, individuals spend most of their time indoors. Poor Indoor Air Quality (IAQ) has a wide range of effects on human health. The burden of disease associated with indoor air accounts for millions of premature deaths related to exposure to Indoor Air Pollutants (IAPs). Among them, CO2 is the most common one, and is commonly used as a metric of IAQ. Indoor CO2 concentrations can be significantly higher than outdoors due to human metabolism and activities. Even in presence of ventilation, controlling the CO2 concentration below the Indoor Air Guideline Values (IAGVs) is a challenge, and many indoor environments including schools, offices and transportation exceed the recommended value of 1000 ppmv. This is often accompanied by high concentration of other pollutants, including bio-effluents such as viruses, and the importance of mitigating the transmission of airborne diseases has been highlighted by the COVID-19 pandemic. On the other hand, the relatively high CO2 concentration of indoor environments presents a thermodynamic advantage for direct air capture (DAC) in comparison to atmospheric CO2 concentration. This review aims to describe the issues associated with poor IAQ, and to demonstrate the potential of indoor CO2 DAC to purify indoor air while generating a renewable carbon stream that can replace conventional carbon sources as a building block for chemical production, contributing to the circular economy.


Viscoelastic properties of a mixed culture biofilm from rheometer creep analysis.
The mechanical properties of mixed culture biofilms were determined by creep analysis using an AR1000 rotating disk rheometer. The biofilms were grown directly on the rheometer disks which were rotated in a chemostat for 12 d. The resulting biofilms were heterogeneous and ranged from 35 microns to 50 microns in thickness. The creep curves were all viscoelastic in nature. The close agreement between stress and strain ratio of a sample tested at 0.1 and 0.5 Pa suggested that the biofilms were tested in the linear viscoelastic range and supported the use of linear viscoelastic theory in the development of a constitutive law. The experimental data was fit to a 4-element Burger spring and dashpot model. The shear modulus (G) ranged from 0.2 to 24 Pa and the viscous coefficient (eta) from 10 to 3000 Pa. These values were in the same range as those previously estimated from fluid shear deformation of biofilms in flow cells. A viscoelastic biofilm model will help to predict shear related biofilm phenomena such as elevated pressure drop, detachment, and the flow of biofilms over solid surfaces.


The use of mineral trioxide aggregate in endodontics.
Mineral trioxide aggregate (MTA), composed mainly of tricalcic silicate, tricalcic alluminate, bismuth oxide, is a particular endodontic cement. It is made of hydrophilic fine particles that harden in the presence of dampness or blood. It is biocompatible, radiopaque and it is harder to infiltrate, compared to classic materials for root filling such as amalgam, cements, Super-EBA, and IRM. and SEM studies of sections and copies in resin of root neoapices filled with amalgam, IRM, Super-EBA and MTA, as well as tests of microinfiltration have shown that MTA has excellent sealing capacities. It requires a working time of about 5 min and a hardening time that varies from 2 h and 45 min to 4 h according to the density of the air entrapped during mixing and the dampness of the receiving site. The long hardening time reduces internal tensions and the incidence of marginal infiltration, but it forces to definitively fill the tooth in the following sitting, with an interval of at least 3 days from the MTA application. Clinical experience shows how MTA is a material of choice in cases not only of endodontic surgery, apicectomy and retrograde filling but also in the sealing filling of perforations of the pulp chamber and of the root, stripping, internal reabsorptions, readaptations, lacerations, and apical transports. It has been used with success also in direct cappings and in apexifications instead of calcium hydroxide, leading to quicker therapies and more predictable The authors outline the operative phases of the different treatments proposed, make a survey of the most important studies published so far and hope that a new sealing cement with more reduced hardening times will soon be available.


Selective interaction of complexin with the neuronal SNARE complex. Determination of the binding regions.
Complexins are evolutionarily conserved proteins that specifically bind to soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes and thus may regulate SNARE function. Using purified proteins, we have performed a detailed analysis of the structure of complexin and of its interaction with SNARE proteins. NMR spectroscopy revealed that isolated complexins have no tertiary structure but contain an unusual alpha-helical middle domain of approximately 58 amino acids that overlaps with the most highly conserved region of the molecules. Complexins form a stable stoichiometric complex with the central domain of the ternary SNARE complex, whereas no binding was observed to monomeric SNAREs. Using a combination of limited proteolysis, deletion mutagenesis, and NMR spectroscopy, we found that the helical middle region of complexin is responsible for binding to the SNARE complex. Binding was highly sensitive to substitution of syntaxin 1 or synaptobrevin 2 with other SNARE homologs but less sensitive to substitution of SNAP-25. In addition, a stretch of 12 amino acids in the middle of the SNARE motif of syntaxin 1A was able to confer binding activity to the non-binding relative syntaxin 4. Furthermore, disassembly of ternary complexes is not affected by complexins. We conclude that complexins are specific ligands of the neuronal core complex that bind with a central alpha-helical domain, probably to the middle of the surface groove formed by synaptobrevin and syntaxin. Complexins may regulate the function of ternary complexes and control membrane fusion through this interaction.


Physiology of the circadian timing system: predictive versus reactive homeostasis.
Since Cannon first formulated the concept of homeostasis 60 years ago, attention has been focused on the corrective responses initiated after the steady state of the organism is perturbed. In this lecture it is argued that the concept of homeostasis should be extended to include the precisely timed mechanisms of the circadian (and circannual) timing system which enables organisms to predict when environmental challenges are most likely to occur. A mature understanding of homeostasis should encompass both "reactive" responses to changes in physiological variables which have already occurred and the "predictive" responses initiated in anticipation of predictably timed challenges. Such predictive responses have particular value because they enable physiological mechanisms to be utilized immediately, even if they involve a delay of several hours, by activating them at a suitable time in advance of a probable challenge. However, conflicts may often occur between predictions and reality. Examples from sleep-wake behavior, thermoregulation, blood volume homeostasis, and the regulation of potassium balance show that predictive responses often compromise the effectiveness of reactive homeostatic mechanisms even to the point of risking the survival of the organism. It must be concluded that the day-night cycle of the natural environment has played a fundamental role in shaping the evolutionary development of homeostatic mechanisms because of the dominating predictability of diurnal changes in illumination, temperature, food availability, and predator activity.


An accurate full-dimensional permutationally invariant potential energy surface for the interaction between H2O and CO.
The interaction between H2O and CO has been the subject of numerous experimental and theoretical investigations for a long time due to their important roles in various environments, such as the atmosphere, combustion of hydrocarbons, and the interstellar medium. In this work, the first full-dimensional accurate potential energy surface (PES) was developed for the CO + H2O system based on ca. 102 000 points calculated at the level of an explicitly correlated coupled-cluster method with single, double, and perturbative triple excitations with the augmented correlation-consistent polarized triple zeta basis set (CCSD(T)-F12a/AVTZ) using the permutation invariant polynomial-neural network (PIP-NN) method. The geometries, energies, and frequencies of the two complex wells, CO-H2O and OC-H2O, and one transition state connecting them, as well as some interconversions between different conformers, are accurately reproduced by the PES, thanks to the small fitting error of only 1.08 meV. With full-dimensional degrees of freedom considered in the PES, we found that there exist strong dependences of the CO and OH bond lengths on the OC-H2O and CO-H2O interaction energies, which is not possible in reduced dimensional PESs. Finally, classical dynamics was carried out to study the energy transfer between H2O and CO with different initial vibrational energies in H2O and different vibrational states in CO.


Psychological interventions for post-traumatic stress disorder in refugees and asylum seekers: A systematic review and meta-analysis.
There is a high prevalence of post-traumatic stress disorder (PTSD) in refugee and asylum seeker populations which can pose distinct challenges for mental health professionals. This review included 16 randomised controlled trials (RCTs) with 1111 participants investigating the effect of psychological interventions on PTSD in these populations. We searched PsychInfo, ProQuest (including selected databases ASSIA, IBSS, PILOTS), Web of Science, the Cochrane Central Database of Controlled Studies (CENTRAL) and Cochrane Database for Systematic Reviews (CDSR) to identify peer-reviewed, primary research articles up to May 2018. We used rigorous methods to assess the quality of included trials and evidence using Cochrane, SURE and GRADE systems. 525 trials were reviewed, 16 were included with 15 contributed to meta-analyses. Despite the challenges of conducting research in this field we found evidence for trauma-focused psychological interventions for PTSD in this population. Following sub-group analyses, we found evidence to support the use of EMDR and Narrative Exposure Therapy for PTSD symptoms. We considered these findings in relation to the broader PTSD treatment literature and related literature from survivors of large scale conflict. These findings suggest that trauma focused psychological therapies can be effective in improving symptoms for refugees and asylum seekers with PTSD.


Near-infrared spectroscopy and indocyanine green derived blood flow index for noninvasive measurement of muscle perfusion during exercise.
Near-infrared spectroscopy (NIRS) with the tracer indocyanine green (ICG) may be used for measuring muscle blood flow (MBF) during exercise, if arterial ICG concentration is measured simultaneously. Although pulse dye densitometry allows for noninvasive measurement of arterial dye concentration, this technique is sensitive to motion and may not be applicable during exercise. The aim of this study was to evaluate a noninvasive blood flow index (BFI), which is derived solely from the muscle ICG concentration curve. In 10 male cyclists 5 mg ICG were injected into an antecubital vein at rest and during cycling at 30, 60, 70, 80, 90, and 100% of previously determined maximal work load. Simultaneously blood was withdrawn through a photodensitometer at 20 ml/min from the radial artery to measure arterial ICG concentration. To measure muscle tissue ICG concentrations, two sets of NIRS optodes were positioned on the skin, one over the left seventh intercostal space and the other over the left vastus lateralis muscle. MBF was calculated from the arterial and muscle concentration data according to Fick's principle. BFI was calculated solely from the muscle concentration curve as ICG concentration difference divided by rise time between 10 and 90% of peak. During exercise mean BFI values changed similarly to MBF in both intercostal and quadriceps muscles and showed excellent correlations with MBF: r = 0.98 and 0.96, respectively. Individual data showed some scattering among BFI and MBF values but still reasonable correlations of BFI with MBF: r = 0.73 and 0.72 for intercostal and quadriceps muscles, respectively. Interobserver variability, as analyzed by Bland-Altman plots, was considerably less for BFI than MBF. These data suggest that BFI can be used for measuring changes in muscle perfusion from rest to maximal exercise. Although absolute blood flow cannot be determined, BFI has the advantages of being essentially noninvasive and having low interobserver variability.


Pavlovian-to-instrumental transfer in Anorexia Nervosa: A pilot study on conditioned learning and instrumental responding to low- and high-calorie food stimuli.
Anorexia Nervosa is characterized by persistent restraint eating despite severe negative consequences and often a chronic course of the disease. Recent theoretical models suggest that abnormalities in reward processing and incentive salience of disorder-compatible stimuli as observed in addictive behaviours contribute to the development and maintenance of Anorexia Nervosa. The aim of the present study was to investigate the process of the acquisition of food-related conditioned responses and the influence of conditioned low-calorie and high-calorie food stimuli on instrumental responding for different foods. A Pavlovian-to-instrumental transfer paradigm and questionnaires on eating disorder psychopathology (EDE-Q, EDI-2) were administered to patients with Anorexia Nervosa (n = 39) and healthy controls (n = 41). Results indicated that patients with Anorexia Nervosa showed deficits of the acquisition of knowledge of the experimental contingencies. Nevertheless, in patients with Anorexia Nervosa and healthy controls instrumental responding for low- and high-calorie food rewards was affected by stimuli conditioned to these rewards; no group differences were observed. Importantly, in Anorexia Nervosa, instrumental responding for low-calorie food increased with increasing severity of eating disorder psychopathology suggesting weight-loss directed behaviour. Future studies are warranted to enhance our understanding of deficits of reward-associated learning and to replicate and extend findings with regard to the impact of conditioned stimuli on instrumental responding. At present, our findings suggest that cognitive treatment interventions might be warranted that challenge dysfunctional beliefs about weight loss.


Antivenomic approach of different Crotalus durissus collilineatus venoms.
Our group has previously performed a proteomic study verifying that individual variations can occur among Crotalus durissus collilineatus venoms. These variations may lead to differences in venom toxicity and may result in lack of neutralization of some components by antivenom. In this way, this study aimed to evaluate the Brazilian anticrotalic serum capacity in recognizing twenty-two Crotalus durissus collilineatus venoms, as well as their fractions. The indirect enzyme-linked immunosorbent assay (ELISA) was chosen to evaluate the efficacy of heterologous anticrotalic serum produced by Instituto Butantan (Brazil) in recognizing the twenty-two Crotalus durissus collilineatus venoms and the pool of them. Moreover, the venom pool was fractionated using reversed-phase fast protein liquid chromatography (RP-FPLC) and the obtained fractions were analyzed concerning antivenom recognition. Evaluation of venom variability by ELISA showed that all venom samples were recognized by the Brazilian anticrotalic antivenom. However, some particular venom fractions were poorly recognized. This study demonstrated that the Brazilian anticrotalic serum recognizes all the different twenty-two venoms of C. d. collilineatus and their fractions, although in a quantitatively different way, which may impact the effectiveness of the antivenom therapy. These results confirm the need to use a pool of venoms with the greatest possible variability in the preparation of antivenoms, in order to improve their effectiveness.


Unusual ophthalmic artery origin: Implications for intraarterial chemotherapy of retinoblastoma.
We report two pediatric retinoblastoma patients with unusual ophthalmic artery (OA) origins who were referred to our interventional neuroradiology department for intraarterial chemotherapy. The first patient had double OAs arising from the ipsilateral internal carotid artery and a central retinal artery (CRA) arising from the more cranially located artery, whereas the second patient had an OA originating from the A1 segment of the ipsilateral anterior cerebral artery. In both cases the CRA arose from the artery entering the orbit through the optic foramen. Both patients tolerated the procedures well. To the best of our knowledge, our retinoblastoma patients with unusual OA origins are the first in the literature in which detailed knowledge of the orbital vasculature and especially CRA origin carried immediate clinical implications, altering access strategies. These variations were proved both by flat-panel detector computed tomography findings and superselective injections of OAs with unusual origins. Our results show that in patients with retinoblastoma, a detailed angiographic work-up may be necessary to evaluate the orbital vasculature and possible abnormal origin of the OA. Recognition of possible variations of OA origin and its branching patterns is of the utmost importance for successful treatment and avoidance of adverse events among retinoblastoma patients.


Dependence of forced vital capacity manoeuvre on time course of preceding inspiration in patients with restrictive lung disease.
In normal subjects and patients with airway obstruction, flows during a forced vital capacity (FVC) manoeuvre are higher after a fast inspiration without an end-inspiratory pause (manoeuvre 1) as compared to a slow inspiration with an end-expiratory pause of approximately 5 s (manoeuvre 2). In this study, we investigated the influence of these manoeuvres on maximal expiratory volume-time and flow-volume curves in patients with restrictive lung disease. Eleven patients with restrictive lung disease were studied. Their average (+/-SD) lung function test results were: FVC=55+/-12% predicted value, forced expiratory volume in one second (FEV1) 52+/-20% pred, FEV1/FVC 85+/-6%, total lung capacity 55+/-8% pred, and carbon monoxide transfer factor 47+/-18% pred. The patients performed the two FVC manoeuvres in random order. We compared the ensuing spirograms and maximal expiratory flow-volume curves from which peak expiratory flow, FEV1, FEV1/FVC, maximal mid-expiratory flow, and maximal flows were computed. All spirometric indices were significantly higher with manoeuvre 1 than 2. Maximal expiratory flows at the same lung volume were also significantly higher with manoeuvre 1 than 2, in all patients. Routine spirometric indices, obtained during a forced vital capacity manoeuvre depend on the time course of the preceding inspiration in patients with restrictive lung disease. Therefore, the forced vital capacity manoeuvre should be standardized if used in clinical, epidemiological and research studies.


The fabrication, characterisation and electrochemical investigation of screen-printed graphene electrodes.
We report the fabrication, characterisation (SEM, Raman spectroscopy, XPS and ATR) and electrochemical implementation of novel screen-printed graphene electrodes. Electrochemical characterisation of the fabricated graphene electrodes is undertaken using an array of electroactive redox probes and biologically relevant analytes, namely: potassium ferrocyanide(II), hexaammine-ruthenium(III) chloride, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), β-nicotinamide adenine dinucleotide (NADH), L-ascorbic acid (AA), uric acid (UA) and dopamine hydrochloride (DA). The electroanalytical capabilities of the fabricated electrodes are also considered towards the sensing of AA and DA. The electrochemical and (electro)analytical performances of the fabricated screen-printed graphene electrodes are considered with respect to the relative surface morphologies and material compositions (elucidated via SEM, Raman, XPS and ATR spectroscopy), the density of electronic states (% global coverage of edge-plane like sites/defects) and the specific fabrication conditions utilised. Comparisons are made between two screen-printed graphene electrodes and alternative graphite based screen-printed electrodes. The graphene electrodes are fabricated utilising two different commercially prepared 'graphene' inks, which have long screen ink lifetimes (>3 hours), thus this is the first report of a true mass-reproducible screen-printable graphene ink. Through employment of appropriate controls/comparisons we are able to report a critical assessment of these screen-printed graphene electrodes. This work is of high importance and demonstrates a proof-of-concept approach to screen-printed graphene electrodes that are highly reproducible, paving the way for mass-producible graphene sensing platforms in the future.


Insight into the defects of cage-type silica mesoporous crystals with Fd3m symmetry: TEM observations and a new proposal of "polyhedron packing" for the crystals.
Silica mesoporous crystals were synthesized by using a gemini cationic surfactant (C(18-3-1)) as the directing agent, carboxyethylsilanetriol sodium salt as the co-structure directing agent (CSDA), and varying amounts of HCl. By using transmission electron microscopy (TEM) we observed 1) a structural change from the close-packed structures of spherical micelles--face-centered cubic (Fm3m) and hexagonal close-packed (P6(3)/mmc)--to Fd3m structures with an increase of HCl and 2) a few structural defects in the crystals with Fd3m symmetry. The structure of a crystal with Fd3m symmetry is described as one of the tetrahedrally close-packed (tcp) structures consisting of 5(12) and 5(12)6(4) polyhedra. The observed TEM images of the structural defects were explained well through use of simulated TEM images by introducing new 13-15 polyhedra comprising 5(12)6(2), 5(12)6(3), 4(1)5(10)6(2), 4(2)5(8)6(5), and 4(1)5(10)6(4), which have been observed in bubbles by Matzke. The mesostructural changes and defect formation are discussed in terms of the hardness of micelles composed of surfactant/CSDA/silica species that have formed through a change of the interaction between the surfactant and CSDA, which causes the micelles to change from a regime of close-packing to one of minimum-area packing.


Long-term Patient-Reported Outcomes in Postmastectomy Breast Reconstruction.
Previous outcome studies comparing implant and autologous breast reconstruction techniques have been limited by short-term follow-up, single-center design, and a lack of rigorous patient-reported outcome data. An understanding of the expected satisfaction and breast-related quality of life associated with each type of procedure is central to the decision-making process. To determine outcomes reported by patients undergoing postmastectomy breast reconstruction using implant or autologous techniques 2 years after surgery. Patients were recruited from 11 centers (57 plastic surgeons) across North America for the Mastectomy Reconstruction Outcomes Consortium study, a prospective, multicenter trial, from February 1, 2012, to July 31, 2015. Women undergoing immediate breast reconstruction using implant or autologous tissue reconstruction after mastectomy for cancer treatment or prophylaxis were eligible. Overall, 2013 women (1490 implant and 523 autologous tissue reconstruction) met the inclusion criteria. All patients included in this analysis had 2 years of follow-up. Procedure type (ie, implant vs autologous tissue reconstruction). The primary outcomes of interest were scores on the BREAST-Q, a validated, condition-specific, patient-reported outcome instrument, which were collected prior to and at 2 years after surgery. The following 4 domains of the BREAST-Q reconstruction module were evaluated: satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being. Responses from each scale were summed and transformed on a 0 to 100 scale, with higher numbers representing greater satisfaction or quality of life. Of the 2013 women in the study (mean [SD] age, 48.1 [10.5] years for the group that underwent implant-based reconstruction and 51.6 [8.7] years for the group that underwent autologous reconstruction), 1217 (60.5%) completed questionnaires at 2 years after reconstruction. After controlling for baseline patient characteristics, patients who underwent autologous reconstruction had greater satisfaction with their breasts (difference, 7.94; 95% CI, 5.68-10.20; P < .001), psychosocial well-being (difference, 3.27; 95% CI, 1.25-5.29; P = .002), and sexual well-being (difference, 5.53; 95% CI, 2.95-8.11; P < .001) at 2 years compared with patients who underwent implant reconstruction. At 2 years, patients who underwent autologous reconstruction were more satisfied with their breasts and had greater psychosocial well-being and sexual well-being than did those who underwent implant reconstruction. These findings can inform patients and their clinicians about expected satisfaction and quality of life outcomes of autologous vs implant-based procedures and further support the adoption of shared decision making in clinical practice.


[Jervell and Lange-Nielsen syndrome].
A rare case of the congenital cardiological syndrome of Jervell and Lange-Nielsen in a 6-year old boy is analyzed. A literature survey of the clinical picture, treatment of and prognosis in this and related to it the Romano-Ward syndrome is given.


Cigarette smoking during pregnancy.
Maternal smoking during pregnancy is associated with several adverse developmental outcomes in the offspring. These include preterm delivery, spontaneous abortion, growth restriction, increased risk of sudden infant death syndrome (SIDS), as well as long-term behavioral and psychiatric disorders. However, the underlying physiological mechanisms for these ill-effects are not fully understood. The aim of this paper is to review the animal and human data to date, linking in utero smoke exposure to negative neurodevelopmental outcomes. It is known that nicotine from cigarette smoke exerts its effects by affecting placental vasculature, and also by nicotinic acetylcholine receptor binding in fetal membranes. Thus, subsequent consequences involve a cascade of events causing not only dysregulation of the nicotinic and muscarinic, but also catecholaminergic and serotonergic neurotransmitter systems. These observations provide some insight into how smoking can impair neurodevelopment, but the long-term neurotransmitter involvement in dysregulation of emotion and attention awaits further elucidation. It is important that pregnant women are warned of the detrimental effects of smoking, and encouraged to abstain for healthy fetal development.


Does occupational exposure to formaldehyde cause hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells?
Several cross-sectional studies of a single population of workers exposed to formaldehyde at one of two factories using or producing formaldehyde-melamine resins in China have concluded that formaldehyde exposure induces damage to hematopoietic cells that originate in the bone marrow. Moreover, the investigators interpret observed differences between groups as evidence that formaldehyde induces myeloid leukemias, although the mechanisms for inducing these diseases are not obvious and recently published scientific findings do not support causation. Our objective was to evaluate hematological parameters and aneuploidy in relation to quantitative exposure measures of formaldehyde. We obtained the study data for the original study (Zhang et al. 2010 ) and performed linear regression analyses. Results showed that differences in white blood cell, granulocyte, platelet, and red blood cell counts are not exposure dependent. Among formaldehyde-exposed workers, no association was observed between individual average formaldehyde exposure estimates and frequency of aneuploidy, suggested by the original study authors to be indicators of myeloid leukemia risk.


Regulation of adrenocortical cardiotonic steroid production by dopamine and PKA signaling.
There is growing evidence that the adrenal cortex is the source of cardiotonic steroid (CS) regulators of sodium, potassium-ATPase (NKA). The control of adrenocortical production CS may play a critical role in mediating renal and vascular responses involved in arterial hypertension. Dopamine (DA) controls renal NKA by direct regulatory phosphorylation and indirectly by modification of aldosterone release. In the present studies, Y-1 adrenocortical cell cultures which have been shown to produce a cardiotonic steroid indistinguishable from the known vertebrate steroid, marinobufagenin (MBG), were treated with various agents to stimulate or antagonize dopamine signaling pathways. We demonstrate that Y-1 cells express both pharmacological types of dopamine receptor (DA1 and DA2). Treatment of Y-1 cells with DA stimulated MBG production in a dose range similar to that shown to inhibit aldosterone production by the adrenal cortex. Experiments with specific DA1 and DA2 receptor agonists and antagonists were performed and allowed us to attribute the DA stimulatory effect to a DA1 type receptor. The DA stimulatory effect on MBG depended on protein kinase A (PKA) and could be blocked by Rp-cAMPS. Although both basal and forskolin-stimulated progesterone production by Y-1 cells were profoundly inhibited in Y-1 cell lines expressing the dominant negative type I regulatory subunit of PKA, both basal and forskolin-stimulated MBG production were demonstrated in these lines. This evidence suggests a possible role of DA1 signaling through camp-mediated activation of the type II PKA holoenzyme in the adrenal cortex.


Comparison of New Single-Use Digital Flexible Ureteroscope Versus Nondisposable Fiber Optic and Digital Ureteroscope in a Cadaveric Model.
To evaluate LithoVue, the new single-use digital flexible ureteroscope, in a human cadaveric model and compare it with a nondisposable fiber optic and digital flexible ureteroscopes. LithoVue, a conventional fiber optic, and digital flexible ureteroscopes were each tested in four renal units of recently deceased female cadavers by three surgeons. The following parameters were analyzed: accessibility to the kidney and navigation of the entire collecting system with and without ureteral access sheath (UAS), lower pole access measuring the deflection of the ureteroscope with the working channel empty, and with inside two different baskets and laser fibers. A subjective evaluation of maneuverability and visibility was assessed by each surgeon at the end of every procedure. Kidney access into the Renal unit 1 was not possible without UAS for all ureteroscopes because of noncompliant ureter at the level of sacroiliac joint. The reusable digital ureteroscope was unable to reach one calix of the lower pole and one calix of the upper pole (Renal units 2 and 3) without UAS placement. Lower pole access with baskets and laser fibers was possible for each ureteroscope after UAS placement. No statistically significant differences were detected in angle deflection between ureteroscopes. The digital ureteroscope was preferred for visibility in all procedures: LithoVue for maneuverability in six procedures, fiber optic in five procedures, and the digital ureteroscope in one procedure. LithoVue seems to be comparable with conventional ureteroscopes in terms of visibility and manipulation into the collecting system in fresh human cadavers. Further studies in humans are needed to determine the clinical value of this new instrument.


Regulation of the Rad53 protein kinase in signal amplification by oligomer assembly and disassembly.
Rad53, the ortholog of mammalian Chk2, is a major DNA damage checkpoint effector kinase in Saccharomyces cerevisiae. Despite extensive studies on the genetic requirements for Rad53 activation and its linkage downstream to checkpoint responses, the mechanism of Rad53 activation is not completely understood. Rad53-dependent signal amplification is thought to be a primary force that accelerates checkpoint signal transduction processes in response to DNA damage. Rad53 forms oligomers upon DNA damage in vivo. It is not clear how oligomer formation affects Rad53 activation and what is the mechanism of Rad53 oligomerization. Here, we monitor Rad53 oligomer assembly and disassembly in vitro. These processes are ATP-dependent and are regulated through phosphorylation. Mutations in FHA or SCD domains of RAD53 compromise intermolecular autophosphorylation activity and these domains are indispensable for Rad53 oligomerization. The mediator Rad9 is not necessary for Rad53 oligomerization. Rad53 kinase activity is required for disassembly of Rad53 oligomers in vivo after DNA damage. Moreover, induced oligomerization of Rad53 efficiently activates Rad53 in the absence of Mec1 in vivo. The results support the conclusions that Rad53/Chk2 homo-oligomerization is an evolutionarily conserved mechanism that drives Rad53/Chk2 activation and promotes signal amplification in DNA damage responses.


Neuroprotective effect of resveratrol against late cerebral ischemia reperfusion induced oxidative stress damage involves upregulation of osteopontin and inhibition of interleukin-1beta.
This study was carried out to investigate the expression pattern and role of osteopontin (OPN) in late global ischemia-reperfusion (I/R) injury with or without resveratrol (RES) pre-treatment. Young male rats were divided into 3 groups (n = 12) of I) sham, II) I/R model group and III) I/R + RES. Vehicle and RES (20 mg/kg) were administered to designed groups intraperitoneally 30 days prior global I/R injury (2-VO) induction and continued for 7 days, later. Then, percentages of infarct areas, mRNA levels of OPN, inducible nitric oxide synthase (iNOS) and other biochemical parameter related to endogenous antioxidants activities and inflammation were measured in the cerebral cortices of all groups. Significant elevations in the levels of malondialdehyde (MDA), the inflammatory mediator interleukin 1β (IL-1β), chemokines (KC and MIP-2) and adhesive molecules (ICAM-1) as well as parallel reductions in enzymes activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and chloramphenicol acetyltransferase (CAT) were observed in the cerebral homogenates of rats with late I/R injury. Associated with these changes, mRNA levels of OPN were significantly downregulated and those of iNOS and Bax were upregulated. All these changes were reversed by in 2-VO I/R induced rats pre-administered RES. These findings suggest that inhibition of sustained inflammatory response driven by IL-1β, decreased activities of endogenous antioxidants and downregulation of OPN induced upregulation of iNOS play important roles in the pathogenesis of neurodegeneration during late cerebral I/R injury, effects that can be modulated by RES which might explain its neuroprotection effect during late global ischemia.


Staphylococcus aureus bacteremia in patients receiving pegylated interferon-alpha and ribavirin for chronic hepatitis C virus infection.
Bacteremia has rarely been reported in patients receiving treatment for hepatitis C virus (HCV) infection. We describe the features and investigation of four cases of Staphylococcus aureus bacteremia occurring between 3 November 2004 and 10 January 2005 in patients on therapy for chronic HCV infection. The unusual occurrence of S. aureus bacteremia in a series of patients led to an epidemiologic investigation and molecular typing methods were employed to assess the relatedness of cases. The mean time of bacteremia onset was week 10 of HCV treatment. No patient had neutropenia previously. The average duration of bacteremia was 2.6 days and complications included acute renal failure (2/4), disseminated intravascular coagulopathy (DIC) with sepsis syndrome (1/4), septic arthritis (1/4), spinal epidural abscess (1/4) and endocarditis (1/4). Two patients were in the same weight class for dosing, but no other epidemiologic links were found. One patient admitted to intravenous drug use (IVDU) and a second was suspected of IVDU. The two other patients were cirrhotic, but had no further identifiable risk factors. All bacterial isolates were methicillin-susceptible. By pulsed-field gel electrophoresis, two cases were found to have identical bacterial strains. However, fluorescent-based amplified fragment-length polymorphism analysis demonstrated distinct band patterns in all four cases. The epidemiologic data and molecular analysis of this cluster of S. aureus bacteremia cases among patients receiving combination therapy for treatment of chronic HCV infection suggest that these cases were not related. Additionally, IVDU and cirrhosis, but not neutropenia, are identified as potential risk factors for this uncommon complication of HCV therapy.


Living donor kidney transplantation using laparoscopically procured multiple renal artery kidneys and right kidneys.
The use of kidneys with multiple renal arteries (MRA) and right kidneys procured laparoscopically for living donor kidney transplantation (LDKT) remains controversial. We aimed to evaluate the short- and long-term outcomes of recipients of LDKT using laparoscopically procured MRA and right kidneys. We reviewed the medical records of all LDKT recipients with laparoscopically procured kidneys from 2000 to 2009. Pediatric recipients and recipients of positive crossmatch and/or ABO-incompatible transplants were excluded. We compared the outcomes of recipients of MRA kidneys with those receiving single renal artery (SRA) kidneys and the outcomes of recipients of right kidneys with those of left kidneys. Renal function was measured by iothalamate clearance and estimated by the abbreviated Modification of Diet in Renal Disease equation. Multiple renal artery kidneys (192 2-artery and 18 3-artery kidneys) were used in 210 (18.5%) of 1,134 transplantations. The most common reconstructive technique used for MRA kidneys was a side-to-side anastomosis (64.3%). There were no significant differences in vascular complications (1.1% vs 2.4%, p = 0.17), urologic complications (3.1% vs 2.9%, p = 0.47), graft survival at 1 year (94.6% vs 96.1%, p = 0.37), and 1-year iothalamate clearance (64 mL/min/1.73 m(2) vs 66 mL/min/1.73 m(2), p = 0.52) between recipients of SRA and MRA kidneys. Five-year graft survival was similar for recipients of SRA and MRA kidneys (83.6% vs 82.6%, p = 0.82) and for recipients of left vs right kidneys (83.7% vs 82.6%, p = 0.70). Excellent long-term outcomes can be obtained after LDKT using laparoscopically procured MRA and right-sided donor kidneys. Unavailability of an SRA left kidney should not preclude LDKT.


Retinal nitric oxide and malonyldialdehyde levels following photodynamic therapy.
To determine the retinal nitric oxide (NO) and malonyldialdehyde (MDA) levels following photodynamic therapy (PDT). Seven Dutch-belted rabbits received dextrose, while seven others received 2 mg/kg verteporfin infusion over a period of 15 minutes in a dim-lit room. Irradiation to a 1.5 mm diameter intact chorioretinal area in the right eye of verteporfin-infused rabbits, was started 5 minutes after the end of infusion. Three groups were control (dextrose infusion), infusion with verteporfin (left eyes were not irradiated), and irradiation after verteporfin injection (right eyes were irradiated). On the fifth day of the experiment, the eyes were enucleated. The retinas were subsequently frozen and homogenized. Nitrite, a stable end-product of NO and MDA, was measured using the spectrophotometer. Protein concentrations were measured by the Lowry method. Tissue NO and MDA levels were expressed as μmol/gprt and nmol/mgprt, respectively. The mean retinal NO and MDA levels of the control, infusion, and irradiation groups were 24.67 ± 6.66, 0.11 ± 0.02; 45.90 ± 15.52, 0.21 ± 0.09; and 84.43 ± 14.96 μmol/gprt, 0.58 ± 0.14 nmol/mgprt, respectively. The mean retinal NO levels were significantly elevated in the infusion and irradiation groups compared with the control group ( p :0.004; p :0.001). The mean retinal MDA levels were significantly elevated in the infusion and irradiation groups compared to the control one ( p :0.026; p :0.001). Also the mean retinal NO and MDA levels in the irradiation group were found to be significantly higher than the infusion group ( p :0.018; p :0.018). Not only PDT, but also verteporfin infusion alone resulted in NO and MDA level increments in the retina, which might be toxic.


Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori to human gastric cells.
We studied the inhibitory effect of Cladosiphon fucoidan on the attachment of Helicobacter pylori (H. pylori), a gastroduodenal pathogen, to human gastric cell lines. The bacterial binding in these cell lines was inhibited more by Cladosiphon fucoidan (IC50 = 16-30 mg/mL), than by the fucoidan from Fucus (IC50 > 30 mg/mL). Dextran sulfate, another sulfated polysaccharide, did not inhibit the binding at all. Pre-incubating the bacterial suspension with fucoidans reinforced the inhibitory ability of these components, and reduced the IC50 value of Cladosiphon fucoidan to approximately 1 mg/mL. However, the binding was not inhibited by pre-treatment of gastric cells with these components. It was also shown that this fucoidan blocks both Leb- and sulfatide-mediated attachment of H. pylori to gastric cells. Furthermore, fucoidan-binding proteins were found on the H. pylori cell surface by Western blot analysis. Thus, the inhibitory effect exerted by Cladosiphon fucoidan on binding between H. pylori and gastric cells might result from the coating with this component of the bacterial surface.


Association of age at menarche with increasing number of fibroids in a cohort of women who underwent standardized ultrasound assessment.
Age at menarche has been associated with several reproductive conditions, and frequencies differ by race. Racial disparities also impact fibroid risk. We comprehensively examined the relationship between age at menarche, fibroid characteristics, and race. Women were enrolled in Right From the Start (2001-2010), a multistate study that systematically screened for fibroids during very early pregnancy. Endovaginal ultrasounds were conducted, and fibroid presence, number, type, volume, and diameter were recorded according to standardized definitions. Generalized estimating equations adjusted for correlations within study site were used to estimate associations between age at menarche and fibroid status and to test for interactions with race. Of 5,023 participants, 11% had a fibroid. Seven percent underwent menarche before 11 years of age and 11% at 15 years or later. We did not observe interactions between age at menarche and race. A 1-year increase in age at menarche was inversely associated with fibroids (adjusted risk ratio = 0.87, 95% confidence interval: 0.82, 0.91). Early age at menarche had a similar positive association in individual analyses with fibroid size, type, and location but was stronger for multiple fibroids (adjusted risk ratio = 0.75, 95% confidence interval: 0.68, 0.83). Our findings confirm other reports of an association between age at menarche and fibroid development (regardless of characteristics), demonstrate no effect modification by race, and suggest a stronger association for women with multiple fibroids, possibly reflecting a stronger association for early-onset disease.


Corticosteroids: way upstream.
Studies into the mechanisms of corticosteroid action continue to be a rich bed of research, spanning the fields of neuroscience and endocrinology through to immunology and metabolism. However, the vast literature generated, in particular with respect to corticosteroid actions in the brain, tends to be contentious, with some aspects suffering from loose definitions, poorly-defined models, and appropriate dissection kits. Here, rather than presenting a comprehensive review of the subject, we aim to present a critique of key concepts that have emerged over the years so as to stimulate new thoughts in the field by identifying apparent shortcomings. This article will draw on experience and knowledge derived from studies of the neural actions of other steroid hormones, in particular estrogens, not only because there are many parallels but also because 'learning from differences' can be a fruitful approach. The core purpose of this review is to consider the mechanisms through which corticosteroids might act rapidly to alter neural signaling.


Influence of Subcutaneous Adipose Tissue and Skeletal Muscle Thickness on Rectus Femoris Echo Intensity in Younger and Older Males and Females.
Ultrasound measurements of muscle echo intensity are commonly used surrogates of muscle composition (eg, intramuscular adipose tissue). However, given that soundwaves are increasingly attenuated with tissue depth, the interpretation of echo intensity may be confounded by adipose and skeletal muscle thickness. Our objectives are to compare the associations between adipose or muscle tissue thickness and rectus femoris echo intensity in younger and older males and females. Participants included in this analysis were derived from 3 previously published cohorts of younger (<45 years) and older (≥60 years) males and females. Ultrasound images of the rectus femoris were evaluated for muscle thickness, echo intensity, and subcutaneous adipose tissue thickness. Older adults (n: 49 males, 19 females) had a higher body mass index (P = .001) compared with younger adults (n: 37 males, 49 females). Muscle thickness was negatively associated with echo intensity in older males (r = -0.59) and females (r = -0.53), whereas no associations were observed in younger males (r = 0.00) or females (r = -0.11). Subcutaneous adipose tissue thickness displayed no associations with echo intensity in any group. Despite the known influence of subcutaneous adipose tissue thickness on beam attenuation, we observed no association with muscle echo intensity, indicating that adipose tissue correction may be required to better understand muscle echo intensity across differences in adiposity. The negative associations between muscle thickness and echo intensity in older, but not younger adults, suggests these associations may be related to the co-occurrence of skeletal muscle atrophy and intramuscular adipose tissue infiltration with advancing age.


Dietary fiber intake and total mortality: a meta-analysis of prospective cohort studies.
Greater intake of dietary fiber has been associated with lower risk of several chronic diseases. Some observational studies have examined the association between dietary fiber intake and total mortality, but the results were inconclusive. We conducted a meta-analysis of data from prospective cohort studies to quantitatively assess the association. Eligible studies were identified by searching the PubMed and Embase databases for all articles published through November 30, 2013, and by reviewing the reference lists of retrieved articles. Study-specific estimates adjusting for potential confounders were combined to calculate a pooled relative risk and 95% confidence interval using a random-effects model. Seven prospective cohort studies of dietary fiber intake and total mortality, including 62,314 deaths among 908,135 participants, were identified. The pooled adjusted relative risk of total mortality for the highest category of dietary fiber intake versus the lowest was 0.77 (95% confidence interval: 0.74, 0.80). In a dose-response meta-analysis, the pooled adjusted relative risk for a 10-g/day increment of dietary fiber intake was 0.89 (95% confidence interval: 0.85, 0 92). By source of fiber, cereal and, to a lesser extent, vegetable fiber were significantly associated with lower total mortality, while fruit fiber showed no association. In conclusion, high dietary fiber intake may reduce the risk of total mortality.


Adaptation, dissemination, and evaluation of a cancer palliative care curriculum for the Indian health system.
In 2006, the Indian Health Service (IHS) and the National Cancer Institute (NCI) collaborated to develop an interdisciplinary palliative training program for health professionals in the Indian health system. Their goal was to improve clinician knowledge and skills in palliative care, to train future trainers, and to increase access to palliative care for American Indians and Alaska Natives. The combined program of participant self-study utilizing a multimedia CD-ROM and train-the-trainer seminars followed the curriculum entitled Education in Palliative and End-of-Life Care for Oncology (EPEC-O) with American Indian and Alaska Native Cultural Considerations. Three seminars trained 89 interdisciplinary health providers from throughout the Indian health system. Evaluations demonstrated increased clinician self-reported knowledge and confidence to train and high satisfaction with training. Forty-two of 67 participants completed an anonymous post-conference Web questionnaire. Nearly half had conducted or definitively planned palliative education sessions, and 57 percent started new palliative services at their practice sites.


Lysosomal enzyme binding receptor protein from monkey brain and its phosphorylation.
The lysosomal enzyme binding receptor protein isolated from monkey brain by phosphomannan-Sepharose affinity chromatography was phosphorylated by [gamma-32P] ATP by protein kinases tightly associated with the receptor protein. A greater than 200 kDa protein was phosphorylated on both serine and tyrosine residues and a approximately 45 kDa protein was phosphorylated on only serine residues as evidenced by SDS-gel electrophoresis, autoradiography and phosphoamino acid analysis [(Panneerselvam, Ramamoorthy & Balasubramanian (1987) Biochem Biophys Res Commun, 147, 927-935)]. 125I-labelled lysosomal enzymes could be cross-linked to the receptor protein in the presence of disuccinimidyl suberate. Phosphorylation of the receptor on both serine and tyrosine residues was inhibited by quercetin, polylysine and polymyxin B. Catalytic subunit of cyclic AMP-dependent protein kinase preferentially phosphorylated the approximately 45 kDa protein. In the presence of Triton X-100, phosphorylation of a few additional protein bands on non-tyrosine residues was observed. There was a marked reduction in the efficiency of binding lysosomal enzymes by the phosphorylated receptor protein in comparison to the unphosphorylated receptor protein.


Clusterin enhances AKT2-mediated motility of normal and cancer prostate cells through a PTEN and PHLPP1 circuit.
Clusterin (CLU) is a chaperone-like protein with multiple functions. sCLU is frequently upregulated in prostate tumor cells after chemo- or radiotherapy and after surgical or pharmacological castration. Moreover, CLU has been documented to modulate the cellular homolog of murine thymoma virus akt8 oncogene (AKT) activity. Here, we investigated how CLU overexpression influences phosphatidylinositol 3'-kinase (PI3K)/AKT signaling in human normal and cancer epithelial prostate cells. Human prostate cells stably transfected with CLU were broadly profiled by reverse phase protein array (RPPA), with particular emphasis on the PI3K/AKT pathway. The effect of CLU overexpression on normal and cancer cell motility was also tested. Our results clearly indicate that CLU overexpression enhances phosphorylation of AKT restricted to isoform 2. Mechanistically, this can be explained by the finding that the phosphatase PH domain leucine-rich repeat-containing protein phosphatase 1 (PHLPP1), known to dephosphorylate AKT2 at S474, is markedly downregulated by CLU, whereas miR-190, a negative regulator of PHLPP1, is upregulated. Moreover, we found that phosphatase and tensin homolog (PTEN) was heavily phosphorylated at the inhibitory site S380, contributing to the hyperactivation of AKT signaling. By keeping AKT2 phosphorylation high, CLU dramatically enhances the migratory behavior of prostate epithelial cell lines with different migratory and invasive phenotypes, namely prostate normal epithelial 1A (PNT1A) and prostatic carcinoma 3 (PC3) cells. Altogether, our results unravel for the first time a circuit by which CLU can switch a low migration phenotype toward a high migration phenotype, through miR-190-dependent downmodulation of PHLPP1 expression and, in turn, stabilization of AKT2 phosphorylation.


Results and limitations of outpatient and overnight stay laminectomies for lumbar spinal stenosis.
At our centre, laminectomies have been traditionally performed as inpatient surgery. A gradual change in practice occurred between 2010 and 2013 to try to do these procedures as outpatient or overnight stay surgery. We conducted a retrospective cohort study of consecutive patients having laminectomies over 2 18-month periods: before the change in practice and after full implementation of the outpatient/overnight stay protocol. We collected information on patient characteristics (age, sex, American Society of Anesthesiologists [ASA] classification, home address, number of laminectomy levels, estimated blood loss) and patient outcome (complications, hospital length of stay, 30-day readmissions). We found no significant difference in age, sex, ASA classification, number of laminectomy levels, or estimated blood loss between the 2 cohorts. There was a change in the number of outpatient (from 0 to 25) and overnight stay laminectomies (from 0 to 13). There was an increase in total (inpatient, overnight stay and outpatient) laminectomies from 41 to 82, and an increase in patients from out of our region from 15% to 32%. There was 1 readmission within 30 days that occurred in the first cohort. We found that outpatient and overnight stay laminectomies can be done safely, with no patients requiring postoperative admission to hospital or readmissions within 30 days. They can be done in patients from out of town who need to travel home postoperatively. It is possible to safely reduce the level of resources used for spine surgery by carrying out laminectomies as outpatient or overnight stay surgery in select patients.


The effects of lyophilization on flexural stiffness of extrasynovial and intrasynovial tendon.
Tendon or ligament reconstructions often use autologous or allogenic tendons from either extrasynovial or intrasynovial sources. Allograft tendons must be lyophilized for preservation before transplantation, a process which can impact mechanical properties of the graft. Reconstituted graft properties that are similar to native tendon are desirable. Although tensile and compressive properties of tendons have been investigated, there is a paucity of information describing flexural properties of tendon, which can impact the gliding resistance. This study aims to design a testing method to quantify tendon flexural modulus, and investigate the effects of lyophilization/rehydration procedures on tendon flexibility. A total of 20 peroneus longus tendons (extrasynovial) and 20 flexor digitorum profundus tendons (intrasynovial) were collected. Ten of each tendon were processed with 5 freeze-thaw cycles followed by lyophilization and rehydration with saline solution (0.9%). Bend testing was conducted on tendons to quantify the flexural modulus with and without processing. As canine FDP tendons contain fibrous and fibrocartilaginous tissue regions, the flexural moduli were measured in both regions. Flexural modulus of rehydrated, lyophilized extrasynovial PL tendon was significantly lower than that of similarly processed intrasynovial FDP tendon (p < 0.001). Flexural moduli of both the fibrocartilaginous and non-fibrocartilaginous regions of intrasynovial tendon significantly increased after lyophilization (p < 0.001). The flexural modulus of the fibrocartilaginous region was significantly higher than that of the non-fibrocartilaginous region in intrasynovial tendon (p < 0.001). Lyophilization significantly increases the flexural modulus of extrasynovial and intrasynovial tendons, and flexural modulus differs significantly between these two tendon types. Increases in stiffness caused by lyophilization may impact the mechanical performance of the allograft in vivo.


Movement of fluorescein monoglucuronide in the rabbit cornea. Diffusion in the stroma and endothelial permeability.
The movement of fluorescein monoglucuronide, a fluorescent metabolite of fluorescein, was studied in the rabbit cornea in vitro and in vivo. A stromal strip was exposed to fluorescein monoglucuronide, and the diffusion rate and the distribution in the stroma were measured every hr for 24 hr. The diffusion coefficient was 0.94 +/- 0.11 (+/- S.D.) X 10(-6) cm2/sec, and the saline/stroma distribution ratio was in a range of 0.67 to 0.69. The concentration of fluorescein monoglucuronide in the anterior chamber and the cornea was measured every hr for 8 hr following intravenous administration. The endothelial permeability was 4.7 +/- 1.0 X 10(-4) cm/min, and the aqueous/cornea distribution ratio was 0.56 +/- 0.05. It appears that the corneal endothelial permeability in the living eye determined hitherto from systemic administration of fluorescein is most likely the permeability to fluorescein monoglucuronide.


A shovel with a perforated blade reduces energy expenditure required for digging wet clay.
A shovel with a blade perforated with small holes was tested to see whether a worker would use less whole-body energy to dig wet clay than with a shovel with an opaque blade. A perforated shovel is hypothesized to require less whole-body energy on the basis of adhesion theory; a smaller surface area would require less physical effort to dig and release soil from the blade. The study involved 13 workers from an electric utility who dug wet clay with two 1.5-m long-handled point shovels, which differed only in blade design (perforated and opaque). Oxygen consumption was measured with a portable system while each worker dug wet clay at a self-regulated pace for 10 min. There was no significant difference in number of scoops dug during the 10-min sessions, but workers dug 9.5% more weight of clay with the perforated shovel than with the conventional shovel (404 kg vs. 369 kg, respectively). Furthermore, stable oxygen uptake normalized to weight of participant and to the weight of clay dug revealed that participants expended 11.7% less relative energy per kilogram of clay dug with the perforated shovel. A point shovel with a perforated blade is recommended for digging and shoveling wet clay. However, the extra weight that workers chose to dig with the perforated shovel may increase the loading on the spine and may offset the metabolic advantages. Manual shoveling is a common task, and workers may experience less whole-body and muscle fatigue when using a perforated shovel.


AttentionDDI: Siamese attention-based deep learning method for drug-drug interaction predictions.
Drug-drug interactions (DDIs) refer to processes triggered by the administration of two or more drugs leading to side effects beyond those observed when drugs are administered by themselves. Due to the massive number of possible drug pairs, it is nearly impossible to experimentally test all combinations and discover previously unobserved side effects. Therefore, machine learning based methods are being used to address this issue. We propose a Siamese self-attention multi-modal neural network for DDI prediction that integrates multiple drug similarity measures that have been derived from a comparison of drug characteristics including drug targets, pathways and gene expression profiles. Our proposed DDI prediction model provides multiple advantages: (1) It is trained end-to-end, overcoming limitations of models composed of multiple separate steps, (2) it offers model explainability via an Attention mechanism for identifying salient input features and (3) it achieves similar or better prediction performance (AUPR scores ranging from 0.77 to 0.92) compared to state-of-the-art DDI models when tested on various benchmark datasets. Novel DDI predictions are further validated using independent data resources. We find that a Siamese multi-modal neural network is able to accurately predict DDIs and that an Attention mechanism, typically used in the Natural Language Processing domain, can be beneficially applied to aid in DDI model explainability.


Cell cycle-dependent changes in microtubule dynamics in living cells expressing green fluorescent protein-alpha tubulin.
LLCPK-1 cells were transfected with a green fluorescent protein (GFP)-alpha tubulin construct and a cell line permanently expressing GFP-alpha tubulin was established (LLCPK-1alpha). The mitotic index and doubling time for LLCPK-1alpha were not significantly different from parental cells. Quantitative immunoblotting showed that 17% of the tubulin in LLCPK-1alpha cells was GFP-tubulin; the level of unlabeled tubulin was reduced to 82% of that in parental cells. The parameters of microtubule dynamic instability were compared for interphase LLCPK-1alpha and parental cells injected with rhodamine-labeled tubulin. Dynamic instability was very similar in the two cases, demonstrating that LLCPK-1alpha cells are a useful tool for analysis of microtubule dynamics throughout the cell cycle. Comparison of astral microtubule behavior in mitosis with microtubule behavior in interphase demonstrated that the frequency of catastrophe increased twofold and that the frequency of rescue decreased nearly fourfold in mitotic compared with interphase cells. The percentage of time that microtubules spent in an attenuated state, or pause, was also dramatically reduced, from 73.5% in interphase to 11.4% in mitosis. The rates of microtubule elongation and rapid shortening were not changed; overall dynamicity increased 3.6-fold in mitosis. Microtubule release from the centrosome and a subset of differentially stable astral microtubules were also observed. The results provide the first quantitative measurements of mitotic microtubule dynamics in mammalian cells.


Batrachochytrium dendrobatidis in Germany: distribution, prevalences, and prediction of high risk areas.
In Germany, the pathogenic fungus Batrachochytrium dendrobatidis (Bd) was detected in 11 indigenous frog species, 4 newt species, and 1 salamander species in 64 out of the 181 locations (35%) investigated. Among the 3450 samples collected between 2003 and 2011, 284 (8.2%) were positive for Bd infections. The highest prevalences were observed in Alytes obstetricans (17.8% of individuals, 20% of populations), followed by Ichthyosaura alpestris (14.7%, 22.2%), Bombina variegata (13.9%, 38.5%), and water frogs comprising 2 species, Pelophylax lessonae and P. ridibundus, and their hybrid form P. esculentus (13.5%, 29.0%). Bd is widespread; areas of higher prevalence were detected in eastern, southeastern, western, and southwestern Germany. Our data indicate that drift fencing of amphibians is not a risk factor for the anthropogenic spread of Bd. Although chytridiomycosis outbreaks have never been observed in Germany, it cannot be excluded that Bd infections affect the dynamics of local amphibian populations. Among the questions still to be answered is whether juveniles are more susceptible to Bd infections than adults. Further work, especially long-term observations including capture-mark-recapture studies, is required to clarify the impact Bd has on amphibians in Germany and Central Europe.


5-Fluorouracil augmentation of dihydrofolate reductase gene transcripts containing intervening sequences in methotrexate-resistant KB cells.
Several fragments of the human dihydrofolate reductase gene (tetrahydrofolate dehydrogenase, 5,6,7,8-tetrahydrofolate NADP+ oxidoreductase, EC 126.96.36.199) were isolated from gene-amplified KB7B cells and characterized. Recombinant plasmids containing intron sequences were constructed. Probes prepared from these plasmids were tested for dihydrofolate reductase precursor mRNA specificity via solution hybridization studies and Northern blot analysis. One probe, p0.69EH, was shown to be specific for dihydrofolate reductase RNA by its greatly enhanced level of hybridization with total RNA from dihydrofolate reductase gene-amplified versus non-amplified cells. In addition, solution hybridization studies with various classes of RNA and Northern blot analysis revealed that p0.69EH hybridizes predominantly with polyadenylated, high molecular weight, nuclear RNA species. Subsequent solution hybridization studies revealed a disproportionate 5-fluorouracil-induced increase in dihydrofolate reductase intron-containing RNA over dihydrofolate reductase mRNA. These results suggest that 5-fluorouracil incorporation into RNA may inhibit the conversion of precursor mRNA to mature mRNA.


Increased susceptibility of dyslipidemic LSR+/- mice to amyloid stress is associated with changes in cortical cholesterol levels.
Alzheimer's disease (AD) is a neurodegenerative disease that has been linked to changes in cholesterol metabolism. Neuronal cholesterol content significantly influences the pro-apoptotic effect of amyloid-β peptide42 (Aβ42), which plays a key role in AD development. We previously reported that aged mice with reduced expression of the lipolysis stimulated lipoprotein receptor (LSR+/-), demonstrate membrane cholesterol accumulation and decreased intracellular lipid droplets in several brain regions, suggesting a potential role of LSR in brain cholesterol distribution. We questioned if these changes rendered the LSR+/- mouse more susceptible to Aβ42-induced cognitive and biochemical changes. Results revealed that intracerebroventricular injection of oligomeric Aβ42 in male 15-month old LSR+/+ and LSR+/- mice led to impairment in learning and long-term memory and decreased cortical cholesterol content of both groups; these effects were significantly amplified in the Aβ42-injected LSR+/- group. Total latency of the Morris test was significantly and negatively correlated with cortical cholesterol content of the LSR+/- mice, but not of controls. Significantly lower cortical PSD95 and SNAP-25 levels were detected in Aβ42-injected LSR+/- mice as compared to Aβ42-injected LSR+/+ mice. In addition, 24S-hydroxy cholesterol metabolite levels were significantly higher in the cortex of LSR+/- mice. Taken together, these results suggest that changes in cortex cholesterol regulation as a result of the LSR+/- genotype were linked to increased susceptibility to amyloid stress, and we would therefore propose the aged LSR+/- mouse as a new model for understanding the link between modified cholesterol regulation as a risk factor for AD.


Development of an In Vitro Ocular Platform to Test Contact Lenses.
Currently, in vitro evaluations of contact lenses (CLs) for drug delivery are typically performed in large volume vials, which fail to mimic physiological tear volumes. The traditional model also lacks the natural tear flow component and the blinking reflex, both of which are defining factors of the ocular environment. The development of a novel model is described in this study, which consists of a unique 2-piece design, eyeball and eyelid piece, capable of mimicking physiological tear volume. The models are created from 3-D printed molds (Polytetrafluoroethylene or Teflon molds), which can be used to generate eye models from various polymers, such as polydimethylsiloxane (PDMS) and agar. Further modifications to the eye pieces, such as the integration of an explanted human or animal cornea or human corneal construct, will permit for more complex in vitro ocular studies. A commercial microfluidic syringe pump is integrated with the platform to emulate physiological tear secretion. Air exposure and mechanical wear are achieved using two mechanical actuators, of which one moves the eyelid piece laterally, and the other moves the eyeballeyepiece circularly. The model has been used to evaluate CLs for drug delivery and deposition of tear components on CLs.


Reconstruction of the Abdominal Wall in Anatomical Plans. Pre- and Postoperative Keys in Repairing "Cold" Incisional Hernias.
The clinical results of the vertical "vest-over-pants" Mayo repair were evaluated, and the risk factors for incisional hernia recurrence were studied. The purpose of this study is to point out the importance of reducing pre and post operative risk factors in the incisional hernia repair process in order to achieve a physiologically normal abdominal wall. Twenty patients diagnosed with incisional hernia underwent an abdominal reconstruction procedure using the Mayo (Paletot) technique at Bichat Claude Bernard Hospital between 2005 and 2015. All procedures were performed by a single surgeon and all patients were pre-operatively prepared, identifying all coexisting conditions and treating them accordingly before undergoing surgery. All patients underwent at least one surgical operation before the hernia repair procedure and a quarter had experienced at least three, prior to this one. Nine patients had a body mass index of >30 kg/m2. Additional risk factors and comorbidities included obesity in 45%, diabetes mellitus in 10%, smoking in 55%, and high blood pressure in 40%. Hernia defect width was from 3 cm (25% F) to 15 cm (5% M) of which nine patients (45%) had a 10 cm defect. Most of the patients had an average hospitalization of 7 days. The patients were carefully monitored and were called on periodic consultations after 3, 6, and 12 months from the moment of the procedure. Patient feedback regarding hernia recurrence and complaints about the scar were noted. Physical examination is essential in determining the hernia recurrence therefore the scar was examined for any abnormalities that may have occurred, which was defined as any palpable or detected fascial defect located within seven centimeters of the hernia repair. Post-operative complications: seroma formation, wound hematoma, superficial and deep wound infection, recurrences and chronic pain were followed and no complications were registered during the follow-up period. Reducing the risk factors to a minimum prior to surgery will increase the success of the incisional hernia repair and generate a positive impact on the patient's quality of life. The lofty goal of significant weight loss prior to elective hernia has shown to be the key factor in using the Mayo technique for incisional hernia repair. This study demonstrates that the Mayo repair technique is a suitable and trustworthy alternative for repairing incisional hernias with very good results. It's costs are minimal and it can be easily reproduced, even by less experienced surgeons.


Sonographic diagnostic criteria for screening Sjögren's syndrome.
The objective of this study is to establish readily applied sonographic diagnostic criteria for Sjögren's syndrome. Sonographic images of 79 cases of previously suspected Sjögren's syndrome (including 43 actual cases) were analyzed retrospectively for the following characteristic features: (1) multiple hypoechoic areas, (2) multiple hyperechoic lines or spots, (3) multiple hypoechoic areas surrounded with hyperechoic lines or spots, and (4) obscuration of the gland configuration. Logistic regression analysis was used to extract valuable sonographic findings. Sonographic images of 80 prospective patients (of whom 48 proved to have Sjögren's syndrome) were scored prospectively using selected features to verify the usefulness of the established criteria. Three sonographic findings in parotid and submandibular glands were selected by logistic regression analysis and retrospective and prospective patients compared. Experienced observers could differentiate positive cases of Sjögren's syndrome from negative controls to a highly significant degree. Findings correlated very well with sialographic grading. Sonography can be substituted for sialography when applying the selected criteria in screening for Sjögren's syndrome.


Combining a breathing model and tumor-specific rigidity constraints for registration of CT-PET thoracic data.
Diagnosis and therapy planning in oncology applications often rely on the joint exploitation of two complementary imaging modalities, namely Computerized Tomography (CT) and Positron Emission Tomography (PET). While recent technical advances in combined CT/PET scanners enable 3D CT and PET data of the thoracic region to be obtained with the patient in the same global position, current image data registration methods do not account for breathing-induced anatomical changes in the thoracic region, and this remains an important limitation. This paper deals with the 3D registration of CT thoracic image volumes acquired at two different instances in the breathing cycle and PET volumes of thoracic regions. To guarantee physiologically plausible deformations, we present a novel method for incorporating a breathing model in a non-linear registration procedure. The approach is based on simulating intermediate lung shapes between the two 3D lung surfaces segmented on the CT volumes and finding the one most resembling the lung surface segmented on the PET data. To compare lung surfaces, a shape registration method is used, aligning anatomical landmark points that are automatically selected on the basis of local surface curvature. PET image data are then deformed to match one of the CT data sets based on the deformation field provided by surface matching and surface deformation across the breathing cycle. For pathological cases with lung tumors, specific rigidity constraints in the deformation process are included to preserve the shape of the tumor while guaranteeing a continuous deformation.


Feasibility of Micro-Computed Tomography Imaging for Direct Assessment of Surgical Resection Margins During Breast-Conserving Surgery.
To analyze the feasibility and accuracy of micro-computed tomography (micro-CT) for surgical margin assessment in breast excision specimen. Two data sets of 30 micro-CT scans were retrospectively evaluated for positive resection margins by four observers in two phases, using pathology as a gold standard. Results of phase 1 were evaluated to define micro-CT evaluation guidelines for phase 2. Interobserver agreement was also assessed (kappa). In addition, a prospective study was conducted in which 40 micro-CT scans were directly acquired, reconstructed, and evaluated for positive resection margins by one observer. A suspect positive resection margin on micro-CT was annotated onto the specimen with ink, enabling local validation by pathology. Main outcome measures were accuracy, sensitivity, specificity, and positive predictive value (PPV). Average accuracy, sensitivity, specificity, and PPV for the four observers were 63%, 38%, 70%, and 22%, respectively, in phase 1 and 72%, 40%, 78%, and 26%, respectively, in phase 2. The interobserver agreement was fair [kappa (range), 0.31 (0.12-0.80) in phase 1 and 0.23 (0-0.43) in phase 2]. In the prospective study 70% of the surgical resection margins were correctly evaluated. Ten specimens were annotated for positive resection margins, which correlated with three positive and three close (<1 mm) margins on pathology. Sensitivity, specificity, and PPV were 38%, 78%, and 30%, respectively. Micro-CT imaging of breast excision specimen has moderate accuracy and considerable interobserver variation for analysis of surgical resection margins. Especially sensitivity and PPV need to be improved before micro-CT-based margin assessment can be introduced in clinical practice.


Transplacental effects of maternal feeding with high fat diets on lipid exchange and response of the splenic lymphoid system in mice offspring exposed to low doses of carcinogen.
We studied whether feeding pregnant female mice with different fats affects lipid exchange and activity of the splenic lymphoid system in offspring exposed to low doses of carcinogen. Female mice were fed diets with either 7% or 15% corn oil or olive oil. The 4-week-old offspring of these mice were transferred to a chow diet, and exposed to a low dose of the carcinogen, dimethylbenz(a)antracene (2 mg/kg). Results of experiments were studied 5 months later. Concentrations of polyunsaturated linoleic and oleic acids were determined in the blood and liver of mothers and offspring. The activity of the splenic immune system in offspring was studied using immunohistochemical methods for evaluating the number of different types of lymphocytes (B and T cells), mitotic and apoptotic indexes and the number of Fas-positive lymphocytes. Serum concentrations of the fatty acids examined were unchanged in the blood of the mothers and their offspring. Concentration of both linoleic and oleic acids was significantly higher in the liver of mothers fed the 15% olive-oil or corn-oil diets. This high level was maintained in linoleic acid in offspring of mothers fed the 15% olive-oil diet. Spleen weight was higher in offspring of mothers fed a 15% corn-oil diet compared to those fed the 7% corn-oil diet. The 15% olive-oil diet slightly decreased the weight of the spleen compared to counterparts fed the 15% corn-oil diet. Immunohistochemical studies showed that the olive diet, partially of 15%, significantly stimulated B-cell blast transformation. The finding reflects the reaction of B lymphocyte-producing splenic zones to the carcinogenic effect, though to a weak extent. T lymphocyte-producing zones did not respond to the diets studied, probably due to the weak carcinogenic effect and lack of tumor appearance. The Fas activity of both B and T cells in the spleen was stimulated by the carcinogen and enhanced by feeding the mothers on the olive-oil diet. Maternal feeding with a diet rich in olive oil before pregnancy results in stimulation of morphological and functional attributes of the splenic immune system of the offspring, particularly related to producing of B lymphocytes.


Isoreticular two-dimensional covalent organic frameworks synthesized by on-surface condensation of diboronic acids.
On-surface self-condensation of 1,4-benzenediboronic acid was previously shown to yield extended surface-supported, long-range-ordered two-dimensional covalent organic frameworks (2D COFs). The most important prerequisite for obtaining high structural quality is that the polycondensation (dehydration) reaction is carried out under slightly reversible reaction conditions, i.e., in the presence of water. Only then can the subtle balance between kinetic and thermodynamic control of the polycondensation be favorably influenced, and defects that are unavoidable during growth can be corrected. In the present study we extend the previously developed straightforward preparation protocol to a variety of para-diboronic acid building blocks with the aim to tune lattice parameters and pore sizes of 2D COFs. Scanning tunneling microscopy is employed for structural characterization of the covalent networks and of noncovalently self-assembled structures that form on the surface prior to the thermally activated polycondensation reaction.


Serum selenium and subsequent risk of prostate cancer.
It is suspected that selenium is protective against prostate cancer. To test this hypothesis, we conducted a nested case-control study in a cohort of 9345 Japanese-American men examined between 1971 and 1977. At the time of examination, a blood specimen was obtained, and the serum was frozen. After a surveillance period of more than 20 years, 249 tissue-confirmed incident cases of prostate cancer were identified. Their stored sera and those of 249 matched controls were measured for selenium levels. Odds ratios for prostate cancer, based on quartiles of serum selenium levels, were determined using the General Estimating Equations approach. The multivariate odds ratio for the highest quartile was 0.5 (95% confidence interval, 0.3-0.9) with a two-sided P for trend of 0.02. The inverse association was more notable for cases with advanced disease and for cases diagnosed 5-15 years after phlebotomy. However, the association was mainly present in current or past cigarette smokers rather than nonsmokers, which leads to caution in the interpretation of the results.


Local fit evaluation of structural equation models using graphical criteria.
Evaluation of model fit is critically important for every structural equation model (SEM), and sophisticated methods have been developed for this task. Among them are the χ² goodness-of-fit test, decomposition of the χ², derived measures like the popular root mean square error of approximation (RMSEA) or comparative fit index (CFI), or inspection of residuals or modification indices. Many of these methods provide a global approach to model fit evaluation: A single index is computed that quantifies the fit of the entire SEM to the data. In contrast, graphical criteria like d-separation or trek-separation allow derivation of implications that can be used for local fit evaluation, an approach that is hardly ever applied. We provide an overview of local fit evaluation from the viewpoint of SEM practitioners. In the presence of model misfit, local fit evaluation can potentially help in pinpointing where the problem with the model lies. For models that do fit the data, local tests can identify the parts of the model that are corroborated by the data. Local tests can also be conducted before a model is fitted at all, and they can be used even for models that are globally underidentified. We discuss appropriate statistical local tests, and provide applied examples. We also present novel software in R that automates this type of local fit evaluation. (PsycINFO Database Record


Towards Precision Medicine in Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) is a remarkable condition characterised by diversity amongst its clinical features and immunological abnormalities. In this review, we attempt to capture the major immunological changes linked to the pathophysiology of lupus and discuss the challenge it presents in moving towards the concept of precision medicine. Currently broadly similar types of drugs, e.g., steroids, immunosuppressives, hydroxychloroquine are used to treat many of the diverse clinical features of SLE. We suspect that, as the precise immunopathological abnormalities differ between the various organs/systems in lupus patients, it will be some time before precision medicine can be fully applied to SLE.


Some effects of chlorimipramine and imipramine on the schedule-controlled behavior of the pigeon.
The effects of imipramine and chlorimipramine on schedule-controlled behavior were compared by examining the effects of both drugs on the performance of pigeons under a multiple fixed-interval 600-s fixed-ratio 30-response (mult FI 600 FR 30) schedule of grain presentation and under a mult FI 200 FI 200 schedule in which responding in one component was punished. Imipramine decreased the rate of FR 30 responding at slightly lower doses than or the same doses as those needed to decrease the rate of FI 600 responding. In contrast, chlorimipramine decreased the rate of FI 600 responding at lower doses than those needed to decrease the rate of FR responding. These effects of chlorimipramine were similar to those of chlorpromazine subsequently determined in the same pigeons. Imipramine and chlorimipramine increased proportionally more or decreased proportionally less the lower rates of responding during the first half of the FI 600 than the higher rates of responding during the second half. When the effects of imipramine or chlorimipramine on performance under the mult FI 200 FI 200 schedule were determined, both imipramine and chlorimipramine affected the rates of punished responding and unpunished responding similarly. Thus, while some effects of chlorimipramine on the schedule-controlled behavior of the pigeon are similar to the effects of imipramine, other effects of chlorimipramine more strongly resemble those of chlorpromazine in the pigeon.


[The support of adequate maternal and fetal gas exchange during abdominal delivery under endotracheal anesthesia].
Fetal gas exchange and a neonate's status were found to be closely related to the capacity of controlled maternal pulmonary ventilation during abdominal delivery. To calculate the minute volume of ventilation, correction factors were proposed. The optimization of gas exchange during an operation was provided by sombrevin. The proposed procedure decreased the incidence of fetal hypoxia and neonatal asphyxia.


Levels of antibiotic resistance genes in manure, biosolids, and fertilized soil.
Increasing antibiotic resistance genes in the environment may pose a threat to public health. In this study, tetracycline and sulfonamide resistance genes (Tet-W, Tet-O, and Sul-I) were quantified in 24 manure samples from three farms and 18 biosolids samples from seven different wastewater treatment plants using quantitative polymerase chain reaction methods. Concentrations of Tet-W and Tet-O genes were observed to be significantly higher (p < 0.05) in manure than in biosolids samples. The background soil samples showed significantly lower concentration of the above genes compared with manure and biosolids. Lime-stabilized biosolids showed significantly (p < 0.05) lower concentration of antibiotic resistance genes compared with other biosolids treatment methods. Elevated levels of antibiotic resistance genes (Tet-W, Tet-O, and Sul-I) were observed in the amended soil samples after the land application of manure or biosolids (Site A) monitored for a period of about 4 mo. However, at another site (Site B), no significant increase (p > 0.05) in concentration of antibiotic resistance genes was observed after biosolids application on soil. Even though the concentration of antibiotic resistance genes in manure was statistically higher than that in biosolids, when they were applied on land, the contribution to the soil depended on the background soil concentration and the soil characteristics. Further study of multiple soil samples in various locations is needed.