The effects of advanced age on the incidence of supraventricular arrhythmias after pneumonectomy in dogs.
Because advanced age is the strongest independent risk factor for the development of supraventricular arrhythmias after lung resection, we compared the incidence and premorbid events of supraventricular arrhythmias after pneumonectomy in young and elderly dogs with the aim of better understanding potential age-related arrhythmogenic mechanisms. Right pneumonectomy was performed in 15 male mongrel dogs ("old" > or =8 yr [n = 8], "young" <4 yr [n = 7]) and the electrocardiogram continuously recorded by an implantable telemetry system for 1 wk before euthanizing. After surgery, 7 of 8 older animals (88%) developed a total of 23 episodes of sustained (>30 s) paroxysmal supraventricular tachycardia (SVT), compared with 0 of 7 (0%) young dogs, P = 0.0014. Analysis of heart rate over the 60 min preceding the onset of SVT revealed a progressive increase in sinus rhythm beginning 15 min before the arrhythmia. Comparison of the heart rate and rhythm obtained in younger animals from the corresponding postoperative hour demonstrated that although older animals developed more atrial (P = 0.03) and ventricular premature contractions (P = 0.056) and episodes of nonsustained ventricular tachycardia (P = 0.01), heart rate was similar for both groups until the increase in elderly dogs preceding the onset of SVT. Histologic examination of the atria showed interstitial fibrosis in old but not young animals. In addition, 4 of 8 (50%) elderly animals exhibited an inflammatory response within the atria consistent with acute myo- and epicarditis. We conclude that elderly dogs have an increased supraventricular arrhythmogenic potential within the first week after pneumonectomy than younger animals, perhaps because of increased atrial fibrosis and inflammation. Heart rate analysis before SVT onset suggests that adrenergic predominance was a probable responsible trigger. In this canine pneumonectomy model, advanced age was associated with an increased incidence of supraventricular arrhythmias, perhaps because of increased atrial fibrosis and inflammation.


Pentavalent ions dependency of mammalian adenosine kinase.
The enzyme adenosine kinase (AK) has been purified to homogeneity from Syrian hamster and bovine livers. The purified enzymes from both these sources have a Mr of approximately 38 kDa, as determined by gel-filtration and SDS-polyacrylamide gel electrophoresis. A novel characteristic of AK observed here is that its catalytic activity shows a nearly complete dependence upon the presence of pentavalent ions such as phosphate (P(i)), arsenate or vanadate. Maximal AK activity was observed in the presence of either 2-3 mM P(i), or 5-10 mM arsenate, or 10-20 mM vanadate. A low basal level of AK activity (1-5% of maximal) observed in the absence of these ions is attributed to P(i) contamination in the adenine nucleotides preparations. The presence of P(i) had no effect on the K m for ATP (0.4 mM), but it markedly increased the affinity of the enzyme for adenosine. The K(m) of AK for adenosine in presence of 0, 0.1 mM and 2 mM P(i) was estimated to be 1.4 mu M, 0.77 mu M and 0.095 mu M, respectively. Free P(i) showed no exchange with any of the reactants during the assay conditions, and its presence had no effect on the thermostability of the enzyme. These observations suggest that the pentavalent ions such as phosphate may be playing an important role in the enzyme's catalytic mechanism by facilitating either binding of adenosine to the enzyme or in the formation of an enzyme-ATP-adenosine complex.


Delayed Echo Enhancement Imaging to Quantify Myocardial Infarct Size.
Perfluoropropane droplets formulated from commercial microbubbles exhibit different acoustic characteristics than their parent microbubbles, most likely from enhanced endothelial permeability. This enhanced permeability may permit delayed echo-enhancement imaging (DEEI) similar to delayed enhancement magnetic resonance imaging (DE-MRI). We hypothesized this would allow detection and quantification of myocardial scar. In 15 pigs undergoing 90 minutes of left anterior descending ischemia by either balloon (n = 13) or thrombotic occlusion (n = 2), DE-MRI was performed at 2-24 days postocclusion. Delayed echo-enhancement imaging was performed at 2-4 minutes following an intravenous injection of 1 mL of 50% Definity (Lantheus Medical) compressed into 180 nm droplets; DEEI was attempted in all pigs with single-pulse harmonic imaging at 1.7 transmit/3.4 MHz receive. Myocardial defects observed with DEEI were quantified (percentage of infarct area) and compared with DE-MRI as well as postmortem staining. In six pigs, multipulse low-mechanical index (MI) fundamental nonlinear imaging (FNLI) with intermittent high-MI impulses was performed to determine whether droplet activation within the infarct zone was achievable with a longer pulse duration. The range of infarct size area by DE-MRI ranged from 0% to 46% of total left ventricular area. Single-pulse harmonic imaging detected a contrast defect that correlated closely with infarct area by DE-MRI (r = 0.81, P = .0001). The FNLI high-MI impulses resulted in droplet activation in both the infarct and normal zones. Harmonic subtraction of the FNLI images resulted in infarct zone enhancement that also correlated closely with infarct size (r = 0.83; P = .04). Droplets were observed on postmortem transmission electron microscopy within myocytes of the infarct and remote normal zone. Intravenously Definity nanodroplets can be utilized to detect and quantify infarct zone at the bedside using DEEI techniques.


Discovery of Selective Inhibitors Targeting Acetylcholinesterase 1 from Disease-Transmitting Mosquitoes.
Vector control of disease-transmitting mosquitoes is increasingly important due to the re-emergence and spread of infections such as malaria and dengue. We have conducted a high throughput screen (HTS) of 17,500 compounds for inhibition of the essential AChE1 enzymes from the mosquitoes Anopheles gambiae and Aedes aegypti. In a differential HTS analysis including the human AChE, several structurally diverse, potent, and selective noncovalent AChE1 inhibitors were discovered. For example, a phenoxyacetamide-based inhibitor was identified with a 100-fold selectivity for the mosquito over the human enzyme. The compound also inhibited a resistance conferring mutant of AChE1. Structure-selectivity relationships could be proposed based on the enzymes' 3D structures; the hits' selectivity profiles appear to be linked to differences in two loops that affect the structure of the entire active site. Noncovalent inhibitors of AChE1, such as the ones presented here, provide valuable starting points toward insecticides and are complementary to existing and new covalent inhibitors.


Nuciferine Protects against Obesity-Induced Nephrotoxicity through Its Hypolipidemic, Anti-Inflammatory, and Antioxidant Effects.
High-fat diets (HFD) could cause obesity, trigger lipid accumulation, and induce oxidative stress and inflammation, leading to kidney damage. This study aimed to elucidate the protective effects of nuciferine on HFD-caused nephrotoxicity and explore the underlying mechanisms in Kunming mice and palmitic acid-exposed HK-2 cells. In obese mice, nuciferine notably alleviated HFD-induced chronic renal dysfunction and delayed renal fibrosis progression and podocyte apoptosis, as evidenced by the increased expressions of renal function factors BUN, CRE, and UA and the decreased expressions of key protein factors TGF-β1, p-Samd3, Wnt-1, and β-catenin. Nuciferine also effectively attenuated HFD-induced renal lipid accumulation via the AMPK-mediated regulation of FAS and HSL expressions and suppressed inflammation and oxidative stress via the AMPK-mediated Nrf-2/HO-1 and TLR4/MyD88/NF-κB pathways. In addition, consistent with the results of animal experiments, nuciferine remarkably reversed cell damage and attenuated lipid accumulation, inflammation, and oxidative stress in palmitic acid-exposed HK-2 cells through the AMPK-mediated signaling pathway. Therefore, nuciferine could be a new food-derived protective agent to offset obesity and correlative kidney damage.


Cerebellar nodulectomy impairs spatial memory of vestibular and optokinetic stimulation in rabbits.
Natural vestibular and optokinetic stimulation were used to investigate the possible role of the cerebellar nodulus in the regulation and modification of reflexive eye movements in rabbits. The nodulus and folium 9d of the uvula were destroyed by surgical aspiration. Before and after nodulectomy the vertical and horizontal vestibuloocular reflexes (VVOR, HVOR) were measured during sinusoidal vestibular stimulation about the longitudinal (roll) and vertical (yaw) axes. Although the gain of the HVOR (G(HVOR) = peak eye movement velocity/peak head velocity) was not affected by the nodulectomy, the gain of the VVOR (G(VVOR)) was reduced. The gains of the vertical and horizontal optokinetic reflexes (G(VOKR), G(HOKR)) were measured during monocular, sinusoidal optokinetic stimulation (OKS) about the longitudinal and vertical axes. Following nodulectomy, there was no reduction in G(VOKR) or G(HOKR). Long-term binocular OKS was used to generate optokinetic afternystagmus, OKAN II, that lasts for hours. After OKAN II was induced, rabbits were subjected to static pitch and roll, to determine how the plane and velocity of OKAN II is influenced by a changing vestibular environment. During static pitch, OKAN II slow phase remained aligned with earth-horizontal. This was true for normal and nodulectomized rabbits. During static roll, OKAN II remained aligned with earth-horizontal in normal rabbits. During static roll in nodulectomized rabbits, OKAN II slow phase developed a centripetal vertical drift. We examined the suppression and recovery of G(VVOR) following exposure to conflicting vertical OKS for 10-30 min. This vestibular-optokinetic conflict reduced G(VVOR) in both normal and nodulectomized rabbits. The time course of recovery of G(VVOR) after conflicting OKS was the same before and after nodulectomy. In normal rabbits, the head pitch angle, at which peak OKAN II velocity occurred, corresponded to the head pitch angle maintained during long-term OKS. If the head was maintained in a "pitched-up" or "pitched-down" orientation during long-term OKS, the subsequently measured OKAN II peak velocity occurred at the same orientation. This was not true for nodulectomized rabbits, who had OKAN II peak velocities at head pitch angles independent of those maintained during long-term OKS. We conclude that the nodulus participates in the regulation of compensatory reflexive movements. The nodulus also influences "remembered" head position in space derived from previous optokinetic and vestibular stimulation.


How profitable is methamphetamine dealing in Australia?
The illicit drug trade is the largest in value among global illicit commodities, at some $320 billion US dollars, according to the UN World Drug Report. Endeavours to control such a large illicit market would be enhanced by improved understanding of the economics of the trade. However, due to its illicit nature many aspects of the illicit drug market are largely unknown. This study explored one economic aspect of illicit drug dealing, profitability, with the aim of developing a better picture of the financial gains from illicit drug dealing. Data were obtained from judges sentencing remarks, key informants from law enforcement, and other published reports which detail the prices paid for methamphetamine in Australia. The financial margins attained from non-crystal methamphetamine dealing in Australia were calculated by examining the best fit for the relationship between prices and quantities: in this case a power law. If it is assumed that a single deal is divided ("cut") between 4 times and 20 times before selling to the next customer, the mark-ups can range from 24% to 59%. The mark-ups appear low compared with those found in US research, but similar to those found in UK research. To our knowledge, this is the first attempt to analyse profitability of methamphetamine dealing in Australia. The findings of this study will help in understanding the motivations and decisions of drug dealers, and potentially assist drug law enforcement agencies to design better strategies to dismantle supply chain linkages which generate excessive profits.


Elastic anomalies in Fe-Cr alloys.
Using ab initio alloy theory, we determine the elastic parameters of ferromagnetic and paramagnetic Fe(1-c)Cr(c) (0 ≤ c ≤ 1) alloys in the body centered cubic crystallographic phase. Comparison with the experimental data demonstrates that the employed theoretical approach accurately describes the observed composition dependence of the polycrystalline elastic moduli. The predicted single-crystal elastic constants follow complex anomalous trends, which are shown to originate from the interplay between magnetic and chemical effects. The nonmonotonic composition dependence of the elastic parameters has marked implications on the micro-mechanical properties of ferrite stainless steels.


Rainfall affects leaching of pre-emergent herbicide from wheat residue into the soil.
No-tillage with stubble retention is a widely used cropping system for its conservation and yield benefits. The no-tillage farming system in southern Australia relies heavily on herbicides for weed management, but heavy crop residues may have a negative impact on the activity of pre-emergent herbicides applied. Any herbicide intercepted by the crop residue may not reach the soil surface without timely rainfall and may dissipate due to volatilisation, photo-degradation and/or microbial activity. Two experiments were carried out to investigate the interception of prosulfocarb, pyroxasulfone, and trifluralin herbicides by wheat residue and retention following simulated rainfall. For the first experiment, there were four simulated rainfall amounts (0, 5, 10, and 20 mm), three intensities (5, 10, and 20 mm h-1) and five application times (immediately after spraying herbicide, 6 h, 1, 7, and 14 days after spraying). In the second experiment, 20 mm of rainfall was applied at 10 mm h-1 in either 4 × 5 mm rainfall events over two days, 2 × 10 mm rainfall events over one day, or a single 20 mm rainfall event, with a no-rainfall control treatment. Bioassays were used to assess the herbicide activity/availability in the soil and remaining on the residue, using cucumber (Cucumis sativus L.) and Italian ryegrass (Lolium multiflorum Lam.) as indicator plants. At higher rainfall amounts, most of the herbicide leached from the stubble into the soil soon after application; more so with rain in one event rather than multiple events. However, the intensity of rainfall had no effect. Pyroxasulfone leached easily from the residue to the soil to potentially offer good weed control, prosulfocarb had an intermediary leaching effect, while only a small amount of trifluralin leached from stubble after rain. Therefore, in no-tillage situations with large amounts of crop residue present on the soil surface, herbicides that leach easily from the residue should be considered, like pyroxasulfone.


Differential dynamic microscopy: a high-throughput method for characterizing the motility of microorganisms.
We present a fast, high-throughput method for characterizing the motility of microorganisms in three dimensions based on standard imaging microscopy. Instead of tracking individual cells, we analyze the spatiotemporal fluctuations of the intensity in the sample from time-lapse images and obtain the intermediate scattering function of the system. We demonstrate our method on two different types of microorganisms: the bacterium Escherichia coli (both smooth swimming and wild type) and the biflagellate alga Chlamydomonas reinhardtii. We validate the methodology using computer simulations and particle tracking. From the intermediate scattering function, we are able to extract the swimming speed distribution, fraction of motile cells, and diffusivity for E. coli, and the swimming speed distribution, and amplitude and frequency of the oscillatory dynamics for C. reinhardtii. In both cases, the motility parameters were averaged over ∼10(4) cells and obtained in a few minutes.


Activity motifs reveal principles of timing in transcriptional control of the yeast metabolic network.
Significant insight about biological networks arises from the study of network motifs--overly abundant network subgraphs--but such wiring patterns do not specify when and how potential routes within a cellular network are used. To address this limitation, we introduce activity motifs, which capture patterns in the dynamic use of a network. Using this framework to analyze transcription in Saccharomyces cerevisiae metabolism, we find that cells use different timing activity motifs to optimize transcription timing in response to changing conditions: forward activation to produce metabolic compounds efficiently, backward shutoff to rapidly stop production of a detrimental product and synchronized activation for co-production of metabolites required for the same reaction. Measuring protein abundance over a time course reveals that mRNA timing motifs also occur at the protein level. Timing motifs significantly overlap with binding activity motifs, where genes in a linear chain have ordered binding affinity to a transcription factor, suggesting a mechanism for ordered transcription. Finely timed transcriptional regulation is therefore abundant in yeast metabolism, optimizing the organism's adaptation to new environmental conditions.


Perceptions and uptake of health insurance for maternal care in rural Kenya: a cross sectional study.
In Kenya, maternal and child health accounts for a large proportion of the expenditures made towards healthcare. It is estimated that one in every five Kenyans has some form of health insurance. Availability of health insurance may protect families from catastrophic spending on health. The study intended to determine the factors affecting the uptake of health insurance among pregnant women in a rural Kenyan district. This was cross-sectional study that sampled 139 pregnant women attending the antenatal clinic at a level 5 hospital in a Kenyan district. The information was collected through a pretested interview schedule. The median age of the study participants was 28 years. Out of the 139 respondents, 86(62%) planned to pay for their deliveries through insurance. There was a significant relationship between insurance uptake and marital status Adjusted odds ratio (AOR) 6.4(1.4-28.8). Those with tertiary education were more likely to take up insurance AOR 5.1 (1.3-19.2). Knowing the benefits of insurance and the limits the insurance would settle in claims was associated with an increase in the uptake of insurance AOR 7.6(2.3-25.1), AOR 6.4(1.5-28.3) respectively. Monthly income and number of children did not affect insurance uptake. Being married, tertiary education and having some knowledge on how insurance premiums are paid are associated with uptake of medical insurance. Information generated from this study if utilized will bring a better understanding as to why insurance coverage may be low and may provide a basis for policy changes among the insurance companies to increase the uptake.


Improving public health control of schistosomiasis with a modified WHO strategy: a model-based comparison study.
Schistosomiasis is endemic in many low-income and middle-income countries. To reduce infection-associated morbidity, WHO has published guidelines for control of schistosomiasis based on targeted mass drug administration (MDA) and, in 2017, on supplemental snail control. We compared the current WHO guideline-based strategies from 2012 to an alternative, adaptive decision making framework for control in heterogeneous environments, to estimate their predicted relative effectiveness and time to achievement of defined public health goals. In this model-based comparison study, we adapted an established transmission model for Schistosoma infection that couples local human and snail populations and includes aspects of snail ecology and parasite biology. We calibrated the model using data from high-risk, moderate-risk, and lower-risk rural villages in Kenya, and then simulated control via MDA. We compared 2012 WHO guidelines with a modified adaptive strategy that tested a lower-prevalence threshold for MDA and shorter intervals between implementation, evaluation, and modification. We also explored the addition of snail control to this modified strategy. The primary outcomes were the proportion of simulations that achieved the WHO targets in children aged 5-14 years of less than 5% (2020 morbidity control goal) and less than 1% (2025 elimination as a public health problem goal) heavy infection and the mean duration of treatment required to achieve these goals. In high-risk communities (80% baseline prevalence), current WHO strategies for MDA were not predicted to achieve morbidity control (<5% prevalence of heavy infections) in 80% of simulations over a 10-year period, whereas the modified adaptive strategy was predicted to achieve this goal in over 50% of simulations within 5 years. In low-risk and moderate-risk communities, current WHO guidelines from 2012 were predicted to achieve morbidity control in most simulations (96% in low-risk and 41% for moderate-risk), although the proposed adaptive strategy reached this goal in a shorter period (mean reduction of 5 years). The model predicted that the addition of snail control to the proposed adaptive strategy would achieve morbidity control in all high-risk communities, and 54% of communities could reach the goal for elimination as a public health problem (<1% heavy infection) within 7 years. The modified adaptive decision making framework is predicted to be more effective than the current WHO guidelines in reaching 2025 public health goals, especially for high-prevalence regions. Modifications in current guidelines could reduce the time and resources needed for countries who are currently working on achieving public health goals against schistosomiasis. University of Georgia Research Foundation, The Bill & Melinda Gates Foundation, and the Medical Scientist Training Program at Stanford University School of Medicine.


Characterizing trajectories of anxiety, depression, and criminal offending in male adolescents over the 5 years following their first arrest.
Youth in the juvenile justice system evince high rates of mental health symptoms, including anxiety and depression. How these symptom profiles change after first contact with the justice system and - importantly - how they are related to re-offending remains unclear. Here, we use latent growth curve modeling to characterize univariate and multivariate growth of anxiety, depression, and re-offending in 1216 male adolescents over 5 years following their first arrest. Overall, the group showed significant linear and quadratic growth in internalizing symptoms and offending behaviors over time such that levels decreased initially after first arrest followed by a small but significant upturn occurring a few years later. Crucially, multivariate growth models revealed strong positive relationships between the rates of growth in internalizing symptoms and offending behaviors such that improvements in mental health related to greater decreases in offending, and vice versa. These results highlight the reciprocal nature of internalizing and externalizing problems in adolescence, underscoring the importance of considering mental health alongside offending in the juvenile justice system.


A new general biomarker-based incidence estimator.
Estimating disease incidence from cross-sectional surveys, using biomarkers for "recent" infection, has attracted much interest. Despite widespread applications to HIV, there is currently no consensus on the correct handling of biomarker results classifying persons as "recently" infected long after the infections occurred. We derive a general expression for a weighted average of recent incidence that-unlike previous estimators-requires no particular assumption about recent infection biomarker dynamics or about the demographic and epidemiologic context. This is possible through the introduction of an explicit timescale T that truncates the period of averaging implied by the estimator. The recent infection test dynamics can be summarized into 2 parameters, similar to those appearing in previous estimators: a mean duration of recent infection and a false-recent rate. We identify a number of dimensionless parameters that capture the bias that arises from working with tractable forms of the resulting estimator and elucidate the utility of the incidence estimator in terms of the performance of the recency test and the population state. Estimation of test characteristics and incidence is demonstrated using simulated data. The observed confidence interval coverage of the test characteristics and incidence is within 1% of intended coverage. Biomarker-based incidence estimation can be consistently adapted to a general context without the strong assumptions of previous work about biomarker dynamics and epidemiologic and demographic history.


Contemporary management of voice and swallowing disorders in patients with advanced lung cancer.
Advanced lung cancer can cause changes to swallowing and communication function. Direct tumour invasion, dyspnoea and deconditioning can all impact on swallowing function and communication. Cancer treatment, if administered, may cause or compound symptoms. In this study, the nature of swallowing and communication difficulties in patients with advanced lung cancer will be discussed, and management options including medical management, speech and language therapy (SLT) intervention, and surgical interventions will be considered. Advanced lung cancer can result in voice and swallowing difficulties, which can increase symptom burden and significantly impact on quality of life (QOL). There is a growing evidence base to support the use of injection laryngoplasty under local anaesthetic to offer immediate improvement in voice, swallowing and overall QOL. There is limited literature on the nature and extent of voice and swallowing impairment in patients with lung cancer. Well designed studies with robust and sensitive multidimensional dysphagia and dysphonia assessments are required. Outcome studies examining interventions with clearly defined treatment goals are required. These studies should include both functional and patient-reported outcome measures to develop the evidence base and to ensure that interventions are both timely and appropriate.


Comparison of structural covariance with functional connectivity approaches exemplified by an investigation of the left anterior insula.
The anterior insula is a multifunctional region involved in various cognitive, perceptual and socio-emotional processes. In particular, a portion of the left anterior insula is closely associated with working memory processes in healthy participants and shows gray matter reduction in schizophrenia. To unravel the functional networks related to this left anterior insula region, we here combined resting state connectivity, meta-analytic-connectivity modeling (MACM) and structural covariance (SC) in addition to functional characterization based on BrainMap meta-data. Apart from allowing new insight into the seed region, this approach moreover provided an opportunity to systematically compare these different connectivity approaches. The results showed that the left anterior insula has a broad response profile and is part of multiple functional networks including language, memory and socio-emotional networks. As all these domains are linked with several symptoms of schizophrenia, dysfunction of the left anterior insula might be a crucial component contributing to this disorder. Moreover, although converging connectivity across all three connectivity approaches for the left anterior insula were found, also striking differences were observed. RS and MACM as functional connectivity approaches specifically revealed functional networks linked with internal cognition and active perceptual/language processes, respectively. SC, in turn, showed a clear preference for highlighting regions involved in social cognition. These differential connectivity results thus indicate that the use of multiple forms of connectivity is advantageous when investigating functional networks as conceptual differences between these approaches might lead to systematic variation in the revealed functional networks.


Reconfigurable 3D plasmonic metamolecules.
A reconfigurable plasmonic nanosystem combines an active plasmonic structure with a regulated physical or chemical control input. There have been considerable efforts on integration of plasmonic nanostructures with active platforms using top-down techniques. The active media include phase-transition materials, graphene, liquid crystals and carrier-modulated semiconductors, which can respond to thermal, electrical and optical stimuli. However, these plasmonic nanostructures are often restricted to two-dimensional substrates, showing desired optical response only along specific excitation directions. Alternatively, bottom-up techniques offer a new pathway to impart reconfigurability and functionality to passive systems. In particular, DNA has proven to be one of the most versatile and robust building blocks for construction of complex three-dimensional architectures with high fidelity. Here we show the creation of reconfigurable three-dimensional plasmonic metamolecules, which execute DNA-regulated conformational changes at the nanoscale. DNA serves as both a construction material to organize plasmonic nanoparticles in three dimensions, as well as fuel for driving the metamolecules to distinct conformational states. Simultaneously, the three-dimensional plasmonic metamolecules can work as optical reporters, which transduce their conformational changes in situ into circular dichroism changes in the visible wavelength range.


Influence of mercury from fly ash on cattle reared nearby thermal power plant.
Cattle grazing nearby coal-fired power stations are exposed to fly ash. The present investigation aims to assess the environmental and health impacts of fly ash containing mercury emitted from thermal power plant. The health effect of fly ash were studied using 20 lactating cattle reared within a 5-km radius of s thermal power plant for the possible effect of fly ash such as the alterations in hematological and biochemical parameters of blood, milk, and urine. Results indicated that the hemoglobin levels (6.65 ± 0.40 g/dl) were significantly reduced in all the exposed animals. Biochemical parameters viz., blood urea nitrogen (27.35 ± 1.19 mg/dl), serum glutamate oxaloacetate transaminase (43.39 ± 3.08 IU/l), albumin, and creatinine were found to be increased, whereas serum glutamate pyruvic transaminase (29.26 ± 2.02) and Ca(2+) were observed to be statistically insignificant in exposed animals. Mercury concentrations estimated in the blood, milk, and urine of exposed (n = 20) and control (n = 20) animals were 7.41 ± 0.86, 4.75 ± 0.57, 2.08 ± 0.18, and 1.05 ± 0.07, 0.54 ± 0.03, 0.20 ± 0.02 μg/kg, respectively. The significant increase (P < 0.01) in the levels of mercury in blood, milk, and urine of exposed animals in comparison to control indicated that the alterations of biochemical parameters in exposed cattle could be due to their long term exposure to fly ash mercury which may have direct or indirect impact on human populations via food chain.


Consumption of vegetables and fruits and urothelial cancer incidence: a prospective study.
Although most epidemiological studies concerning urothelial cancer support a possible protective effect of vegetable and fruit consumption, previous studies have been inconsistent with regard to which vegetables and fruits may be responsible for an inverse association. The association between the consumption of 21 vegetables and nine fruits and urothelial cancer risk was assessed in the Netherlands Cohort Study among 120,852 men and women aged 55-69 years at baseline in 1986. After 6.3 years of follow-up, 538 incident cases and 2,953 subcohort members with complete vegetable data and 569 cases and 3,123 subcohort members with complete fruit data were available for case-cohort analyses. In multivariable case-cohort analyses, the following age-, sex-, and smoking-adjusted incidence rate ratios for groups of vegetable and fruit consumption were observed (comparing highest versus lowest quintile of consumption): total vegetables, 0.91 [95% confidence interval (CI): 0.65-1.27]; cooked vegetables, 0.98 (CI: 0.71-1.35); raw vegetables, 1.10 (CI: 0.78-1.53); cooked leafy vegetables, 0.89 (CI: 0.65-1.23); raw leafy vegetables, 0.94 (CI: 0.73-1.22); pulses, 1.03 (CI: 0.74-1.44); brassicas, 0.75 (CI: 0.54-1.04); allium vegetables, 0.89 (CI: 0.67-1.19); total fruit, 0.74 (CI: 0.53-1.04); and citrus fruit, 0.85 (CI: 0.62-1.17). For three separate items (cauliflower, cooked carrots, and mandarins), a statistically significant inverse association was seen, whereas for other specific vegetables or fruit, no statistically significant association was observed. The data are suggestive of an inverse association between the consumption of brassicas, total fruit, and urothelial cancer risk, whereas total vegetable consumption did not appear to be associated with urothelial cancer risk.


AAV gene therapy for Tay-Sachs disease.
Tay-Sachs disease (TSD) is an inherited neurological disorder caused by deficiency of hexosaminidase A (HexA). Here, we describe an adeno-associated virus (AAV) gene therapy expanded-access trial in two patients with infantile TSD (IND 18225) with safety as the primary endpoint and no secondary endpoints. Patient TSD-001 was treated at 30 months with an equimolar mix of AAVrh8-HEXA and AAVrh8-HEXB administered intrathecally (i.t.), with 75% of the total dose (1 × 1014 vector genomes (vg)) in the cisterna magna and 25% at the thoracolumbar junction. Patient TSD-002 was treated at 7 months by combined bilateral thalamic (1.5 × 1012 vg per thalamus) and i.t. infusion (3.9 × 1013 vg). Both patients were immunosuppressed. Injection procedures were well tolerated, with no vector-related adverse events (AEs) to date. Cerebrospinal fluid (CSF) HexA activity increased from baseline and remained stable in both patients. TSD-002 showed disease stabilization by 3 months after injection with ongoing myelination, a temporary deviation from the natural history of infantile TSD, but disease progression was evident at 6 months after treatment. TSD-001 remains seizure-free at 5 years of age on the same anticonvulsant therapy as before therapy. TSD-002 developed anticonvulsant-responsive seizures at 2 years of age. This study provides early safety and proof-of-concept data in humans for treatment of patients with TSD by AAV gene therapy.


A Whole-Genome Scan for Association with Invasion Success in the Fruit Fly Drosophila suzukii Using Contrasts of Allele Frequencies Corrected for Population Structure.
Evidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here, we characterized the genome response of the spotted wing drosophila Drosophila suzukii during the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic variants associated with the status (invasive versus native) of the sampled populations based on a newly developed statistic, we called C2, that contrasts allele frequencies corrected for population structure. We evaluated this new statistical framework using simulated data sets and implemented it in an upgraded version of the program BayPass. We identified a relatively small set of single-nucleotide polymorphisms that show a highly significant association with the invasive status of D. suzukii populations. In particular, two genes, RhoGEF64C and cpo, contained single-nucleotide polymorphisms significantly associated with the invasive status in the two separate main invasion routes of D. suzukii. Our methodological approaches can be applied to any other invasive species, and more generally to any evolutionary model for species characterized by nonequilibrium demographic conditions for which binary covariables of interest can be defined at the population level.


Invasive group G streptococcal infections: a review of 37 cases.
Beta-hemolytic streptococci group A, B, and D which cause many diseases have been well studied. Infection caused by group G Streptococcus has increased in clinical significance, and thus is attracting more physicians attention. This retrospective analysis reports clinical experience with such infections at the Veterans General Hospital-Taipei. Medical records of invasive group G streptococcal isolates from March 1991 to April 1994 were reviewed. Thirty-seven cases were included. There were 33 males and 4 females with a mean age of 67.4. Major underlying diseases included diabetes (24.3%), cardiovascular diseases (21.6%), malignancy (21.6%), bone or joint diseases (18.9%) and cirrhosis of the liver (13.5%). Only 8.1% cases had no underlying disease. The most common portal of entry was the skin (64.9%). There was a wide spectrum of clinical manifestations, including cellulitis (32.4%), arthritis or osteomyelitis (16.2%), endocarditis (8.1%), meningitis (8.1%), peritonitis (8.1%), empyema (5.4%) and primary bacteremia (27%). All of these isolates were susceptible to penicillin, oxacillin, cefazolin, clindamycin and vancomycin. Ten patients died, and five of these expired from group G streptococcal infections. Group G Streptococcus is a low virulent microorganism. Clinical improvement after therapy is fast. Poor response to antibiotics should prompt investigation of the underlying diseases or undrained foci of infection.


Teratocarcinomas induced by embryonic stem (ES) cells lacking vimentin: an approach to study the role of vimentin in tumorigenesis.
Vimentin is a class III intermediate filament protein widely expressed in the developing embryo and in cells of mesenchymal origin in the adult. Vimentin knock-out mice develop and reproduce without any obvious defect. This is an unexpected finding in view of the high degree of conservation of the vimentin gene among vertebrates. However, it does not exclude the possibility of a role for vimentin in pathological conditions, like tumorigenesis. To address this question directly, we have used a teratocarcinoma model involving the injection of ES cells into syngeneic mice. ES cells lacking vimentin were generated from 129/Sv Vim-/- mice with high efficiency. The absence of vimentin did not affect ES cell morphology, viability or growth rate in vitro. Tumours were induced by subcutaneous injection of either Vim-/- or Vim+/+ ES cells into Vim+/+ and Vim-/- mice, in order to analyse the effect of the absence of vimentin in either the tumorigenic cells or the host mice. No significant differences were found in either tumour incidence, size or vascularization of teratocarcinomas obtained with all possible combinations. Vim-/- ES-derived tumours showed the same cellular composition typical of teratocarcinomas induced by wild-type ES cells together with a very similar apoptotic pattern. Taken together, these results demonstrate that in this model vimentin is not essential for efficient tumour growth and differentiation in vivo.


Spectrum and range of oxidative stress responses of human lens epithelial cells to H2O2 insult.
Oxidative stress (OS) is believed to be a major contributor to age-related cataract and other age-related diseases. cDNA microarrays were used to identify the spectrum and range of genes with transcript levels that are altered in response to acute H(2)O(2)-induced OS in human lens epithelial (HLE) cells. HLE cells were treated with 50 microM H(2)O(2) for 1 hour in the absence of serum, followed by a return to complete medium. RNAs were prepared from treated and untreated cells at 0, 1, 2, and 8 hours after H(2)O(2) treatment. The data showed 1171 genes that were significantly up- and downregulated in response to H(2)O(2) treatment. Several functional subcategories of genes were identified, including those encoding DNA repair proteins, antioxidant defense enzymes, molecular chaperones, protein biosynthesis enzymes, and trafficking and degradation proteins. Differential expression of selected genes was confirmed at the level of RNA and/or protein. Many of the identified genes (e.g., glutathione S-transferase [MGST2], thioredoxin reductase beta, and peroxiredoxin 2) have been identified as participants in OS responses in the lens and other systems. Some genes induced by OS in the current study (e.g., oxygen regulated protein [ORP150] and heat shock protein [HSP40]) are better known to respond to other forms of stress. Two genes (receptor tyrosine kinase [AXL/ARK] and protein phosphatase 2A) are known to be differentially expressed in cataract. Most of the genes point to a novel pathways associated with OS. The present data provide a global perspective on those genes that respond to acute OS, point to novel genes and pathways associated with OS, and set the groundwork for understanding the functions of OS-related genes in lens protection and disease.


Skin-fold thickness and training volume in ultra-triathletes.
We investigated the relationship between variables of anthropometry and training volume on race performance in 29 male non-professional ultra-triathletes. Anthropometric variables were determined in order to calculate body mass index, sum of skin-folds and percent body fat. Participants kept a comprehensive training diary recording their training volume in hours and kilometres in the 3 months before the race. The relationship of anthropometry and average weekly training volume with race performance was investigated with linear regression analysis. The sum of 8 skin-fold thicknesses was associated with total race time (r (2)=0.33, p<0.001), whereas the average weekly training volume was not (r (2)=0.00, p>0.05). The training volume showed no association with the sum of 8 skin-folds (r (2)=0.00, p>0.05). The sum of 8 skin-folds was neither associated with speed in the swim (r (2)=0.10, p>0.05) nor in the bike split (r (2)=0.10, p>0.05) but showed a significant association with speed in the run split (r (2)=0.38, p<0.0001). We concluded that anthropometry was of more importance than training volume in male Triple Iron triathletes and that these athletes were close to runners regarding the relationship of anthropometry with race performance.


International workshop on insecticide resistance in vectors of arboviruses, December 2016, Rio de Janeiro, Brazil.
Vector-borne diseases transmitted by insect vectors such as mosquitoes occur in over 100 countries and affect almost half of the world's population. Dengue is currently the most prevalent arboviral disease but chikungunya, Zika and yellow fever show increasing prevalence and severity. Vector control, mainly by the use of insecticides, play a key role in disease prevention but the use of the same chemicals for more than 40 years, together with the dissemination of mosquitoes by trade and environmental changes, resulted in the global spread of insecticide resistance. In this context, innovative tools and strategies for vector control, including the management of resistance, are urgently needed. This report summarizes the main outputs of the first international workshop on Insecticide resistance in vectors of arboviruses held in Rio de Janeiro, Brazil, 5-8 December 2016. The primary aims of this workshop were to identify strategies for the development and implementation of standardized insecticide resistance management, also to allow comparisons across nations and across time, and to define research priorities for control of vectors of arboviruses. The workshop brought together 163 participants from 28 nationalities and was accessible, live, through the web (> 70,000 web-accesses over 3 days).


Pathogenic determinants and mechanisms of ALS/FTD linked to hexanucleotide repeat expansions in the C9orf72 gene.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two apparently distinct neurodegenerative diseases, the former characterized by selective loss of motor neurons in the brain and spinal cord and the latter characterized by selective atrophy of frontal and temporal lobes. Over the years, however, growing evidence from clinical, pathological and genetic findings has suggested that ALS and FTD belong to the same clinic-pathological spectrum disorder. This concept has been further supported by the identification of the most common genetic cause for both diseases, an aberrantly expanded hexanucleotide repeat GGGGCC/ CCCCGG sequence located in a non-coding region of the gene C9orf72. Three hypotheses have been proposed to explain how this repeats expansion causes diseases: 1) C9orf72 haploinsufficiency-expanded repeats interfere with transcription or translation of the gene, leading to decreased expression of the C9orf72 protein; 2) RNA gain of function-RNA foci formed by sense and antisense transcripts of expanded repeats interact and sequester essential RNA binding proteins, causing neurotoxicity; 3) Repeat associated non-ATG initiated (RAN) translation of expanded sense GGGGCC and antisense CCCCGG repeats produces potential toxic dipeptide repeat protein (DPR). In this review, we assess current evidence supporting or arguing against each proposed mechanism in C9 ALS/FTD disease pathogenesis. Additionally, controversial findings are also discussed. Lastly, we discuss the possibility that the three pathogenic mechanisms are not mutually exclusive and all three might be involved in disease.


Long-Lived Triplet Excited States of Bent-Shaped Pentacene Dimers by Intramolecular Singlet Fission.
Intramolecular singlet fission (ISF) is a promising photophysical process to construct more efficient light energy conversion systems as one excited singlet state converts into two excited triplet states. Herein we synthesized and evaluated bent-shaped pentacene dimers as a prototype of ISF to reveal intrinsic characters of triplet states (e.g., lifetimes of triplet excited states). In this study, meta-phenylene-bridged TIPS-pentacene dimer (PcD-3Ph) and 2,2'-bipheynyl bridged TIPS-pentacene dimer (PcD-Biph) were newly synthesized as bent-shaped dimers. In the steady-state spectroscopy, absorption and emission bands of these dimers were fully characterized, suggesting the appropriate degree of electronic coupling between pentacene moieties in these dimers. In addition, the electrochemical measurements were also performed to check the electronic interaction between two pentacene moieties. Whereas the successive two oxidation peaks owing to the delocalization were observed in a directly linked-pentacene dimer (PcD) by a single bond, the cyclic voltammograms in PcD-Biph and PcD-3Ph implied the weaker interaction compared to that of p-phenylene-bridged TIPS-pentacene dimer (PcD-4Ph) and PcD. The femtosecond and nanosecond transient absorption spectra clearly revealed the slower ISF process in bent-shaped pentacene dimers (PcD-Biph and PcD-3Ph), more notably, the slower relaxation of the excited triplet states in PcD-Biph and PcD-3Ph. Namely, the quantum yields of triplet states (ΦT) by ISF approximately remain constant (ca. 180-200%) in all dimer systems, whereas the lifetimes of the triplet excited states became much longer (up to 360 ns) in PcD-Biph as compared to PcD-4Ph (15 ns). Additionally, the lifetimes of the corresponding triplet states in PcD-Biph and PcD-3Ph were sufficiently affected by solvent viscosity. In particular, the lifetimes of PcD-Biph triplet state in THF/paraffin (1.0 μs) increased up to approximately three times as compared to that in THF (360 ns), whereas those of PcD-4Ph were quite similar in both solvent.


Unsafe sexual behavior and correlates of risk in a probability sample of men who have sex with men in the era of highly active antiretroviral therapy.
To assess the levels and correlates of potential exposure to and transmission of HIV in a contemporary, community-based probability sample of men who have sex with men (MSM). In 2003, 311 sexually active MSM participated in a random-digit dial telephone survey in Seattle neighborhoods with a high prevalence of MSM. The primary outcomes were potential exposure to and transmission of HIV, defined as unprotected anal intercourse with a man of opposite or unknown HIV status in the preceding 12 months. Fourteen percent of respondents reported being HIV-positive, 77% reported being HIV-negative, and 8% had not been tested. Of 241 HIV-negative MSM, 25 (10%; 95% confidence interval [CI], 7-15%) were potentially exposed to HIV; among 45 HIV-positive MSM, 14 (31%; 95% CI, 20-46%) were potential HIV-transmitters. Among HIV-negative men, the strongest bivariate correlates of potential exposure to HIV were recent bacterial sexually transmitted disease (odds ratio [OR], 5.8), number of recent male sexual partners (OR, 1.01 per partner), recent sex at a bathhouse (OR, 9.1), and recent use of sildenafil (OR, 4.4), amyl nitrite (OR, 6.2), and methamphetamine (OR, 8.0). Among HIV-infected men, the strongest correlates of potential HIV transmission were recent use of amyl nitrite (OR, 3.1), number of recent male sex partners (OR, 1.07 per partner), and having a male spouse or domestic partner (OR, 0.3). Most MSM knew their HIV status and adopted safer sexual behaviors to reduce their risk of HIV acquisition or transmission. However, 10% of HIV-negative MSM and 31% of HIV-positive MSM recently engaged in behaviors that placed them at high risk for acquiring or transmitting HIV.


Swift nanopattern formation of PS-b-PMMA and PS-b-PDMS block copolymer films using a microwave assisted technique.
Microphase separation of block copolymer (BCPs) thin films has high potential as a surface patterning technique. However, the process times (during thermal or solvent anneal) can be inordinately long, and for it to be introduced into manufacturing, there is a need to reduce these times from hours to minutes. We report here BCP self-assembly on two different systems, polystyrene-b-polymethylmethacrylate (PS-b-PMMA) (lamellar- and cylinder-forming) and polystyrene-b-polydimethylsiloxane (PS-b-PDMS) (cylinder-forming) by microwave irradiation to achieve ordering in short times. Unlike previous reports of microwave assisted microphase segregation, the microwave annealing method reported here was undertaken without addition of solvents. Factors such as the anneal time and temperature, BCP film thickness, substrate surface type, etc. were investigated for their effect of the ordering behavior. The microwave technique was found to be compatible with graphoepitaxy, and in the case of the PS-b-PDMS system, long-range translational alignment of the BCP domains was observed within the topographic patterns. To demonstrate the usefulness of the method, the BCP nanopatterns were turned into an 'on-chip' resist by an initial plasma etch and these were used to transfer the pattern into the substrate.


Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides.
Lipids in fresh human milk do not inactivate viruses but become antiviral after storage of the milk for a few days at 4 or 23 degrees C. The appearance of antiviral activity depends on active milk lipases and correlates with the release of free fatty acids in the milk. A number of fatty acids which are normal components of milk lipids were tested against enveloped viruses, i.e., vesicular stomatitis virus, herpes simplex virus, and visna virus, and against a nonenveloped virus, poliovirus. Short-chain and long-chain saturated fatty acids had no or a very small antiviral effect at the highest concentrations tested. Medium-chain saturated and long-chain unsaturated fatty acids, on the other hand, were all highly active against the enveloped viruses, although the fatty acid concentration required for maximum viral inactivation varied by as much as 20-fold. Monoglycerides of these fatty acids were also highly antiviral, in some instances at a concentration 10 times lower than that of the free fatty acids. None of the fatty acids inactivated poliovirus. Antiviral fatty acids were found to affect the viral envelope, causing leakage and at higher concentrations, a complete disintegration of the envelope and the viral particles. They also caused disintegration of the plasma membranes of tissue culture cells resulting in cell lysis and death. The same phenomenon occurred in cell cultures incubated with stored antiviral human milk. The antimicrobial effect of human milk lipids in vitro is therefore most likely caused by disintegration of cellular and viral membranes by fatty acids. Studies are needed to establish whether human milk lipids have an antimicrobial effect in the stomach and intestines of infants and to determine what role, if any, they play in protecting infants against gastrointestinal infections.


Relationships among severity and duration of clinical mastitis and sire transmitting abilities for somatic cell score, udder type traits, productive life, and protein yield.
The objective of this study was to determine the relationships among severity and duration of clinical mastitis during first and second lactation and sire transmitting abilities for somatic cell score, udder type traits, productive life, and protein yield. Recording of clinical episodes began at first parturition for 1704 Holstein cows (in six Pennsylvania herds and one Nebraska herd) and continued into second lactation for 1055 of these cows. A total of 456 cows (sired by 168 bulls) had at least one clinical episode during first lactation, and 230 cows (sired by 100 bulls) had at least one clinical episode during second lactation. A severity code from 1 (normal milk) to 5 (acute systemic mastitis) was assigned daily (for up to 30 d after detection) to all quarters that had clinical mastitis. Only the severity codes for the first clinical episode to occur during first and second lactation are considered here. The initial and maximum severity codes, as well as the natural logarithms of both the sum of severity codes that were above normal (> 1) and the total days severity codes were above normal were regressed on herd (a classification variable), age at first calving, days in milk at clinical detection, and sire transmitting abilities taken one at a time. Linear and nonlinear effects were estimated for sire transmitting abilities. Separate analyses were conducted on dependent variables that considered severity and duration of clinical mastitis from: all organisms, coagulase-negative staphylococci, coliform species, streptococci other than Streptococcus agalactiae, and the most common environmental organisms (coliform species and streptococci other than Streptococcus agalactiae). Daughters of sires that transmit the lowest somatic cell score had the least severe and shortest clinical episodes from environmental organisms during first lactation. Selection for lower somatic cell score may reduce the severity and duration of clinical episodes from environmental organisms during first lactation.


Induction of kappa transcription by interferon-gamma without activation of NF-kappa B.
The induction of immunoglobulin kappa light chain expression in 70Z/3 pre-B cells treated with bacterial lipopolysaccharide (LPS) requires the activation of the B cell-specific factor NF-kappa B, which binds to the kappa enhancer motif, GGGACTTTCC. This sequence alone can function as a tissue-specific enhancer for LPS-induced gene expression. A potent inhibitor of B lymphopoiesis [transforming growth factor-beta (TGF-beta)] was used to explore the mechanisms in the activation of kappa transcription by LPS and by interferon-gamma (IFN-gamma). TGF-beta inhibited LPS-induced kappa transcription but not the activation and in vitro binding of NF-kappa B. This indicates that NF-kappa B activation, while necessary, is not sufficient for LPS-induced kappa transcription. TGF-beta had no effect on IFN-gamma-induced kappa transcription, and NF-kappa B was not activated by IFN-gamma. These results reveal that LPS and IFN-gamma activate transcription through different mechanisms.


Host recombination is dependent on the degree of parasitism.
Parasites and hosts are involved in a continuous coevolutionary process leading to genetic changes in both counterparts. To understand this process, it is necessary to track host responses, one of which could be an increase in sex and recombination, such as is proposed by the Red Queen hypothesis. In this theoretical framework, the inducible recombination hypothesis states that B-chromosomes (genome parasites that prosper in natural populations of many living beings) elicit an increase in host chiasma frequency that is favoured by natural selection because it increases the proportion of recombinant progeny, some of which could be resistant to both B-chromosome effects and B-accumulation in the germline. We have found a clear parallelism between host recombination and the evolutionary status of the B-chromosome polymorphism, which provides explicit evidence for inducible recombination and strong support for the Red Queen hypothesis.


The incidence of fatal pulmonary embolism after knee replacement with no prophylactic anticoagulation.
We made a prospective study of the incidence of fatal pulmonary embolism in patients after total knee replacement with no prophylactic anticoagulation. There were 499 consecutive patients having 527 knee replacements. They all wore anti-thromboembolic stockings and were mobilised 48 hours after surgery. No patient was lost to follow-up. One patient died of pulmonary embolism 22 days after operation. There were no other deaths within three months of operation. The incidence of fatal pulmonary embolism was 0.19% (95% confidence interval: 0 to 0.6%). Fatal pulmonary embolism is rare after total knee replacement without prophylactic anticoagulation and the routine anticoagulation of these patients is of doubtful value.


Evaluating the effects of maternal positions in childbirth: An overview of Cochrane Systematic Reviews.
The purpose of this study is to conduct an overview of Cochrane systematic reviews (SRs) evaluating the effects of maternal positions in childbirth in order to compile existing evidence for relevant research questions that have been addressed by more than one review, to provide a succinct summary of the up-to-date evidence and to identify areas for future research. An electronic search was conducted in the Cochrane database. Two primary outcomes were the duration of labor and birth, and operative birth. The quality of included reviews was assessed using the AMSTAR criteria, and the quality of the evidence was rated using the GRADE criteria. We included 3 Cochrane SRs. There was a significant mean difference (MD) found in the duration of the first stage by 1 hour and 22 minutes (MD= -1.21; 95% CI: -2.35 - -0.07, I2=94%) and reduction in caesarean section rates (RR=0.71; 95% CI: 0.54-0.94, I2=0%) in the upright birth position group compared with the horizontal. Also, there was a statistically significant difference in the duration (minutes) of the second stage of labor (MD= -6.16; 95% CI: -9.74 - -2.59, I2=91%) and a reduction in assisted vaginal birth rates (RR=0.75, 95% CI: 0.66-0.86, I2=29%) in the upright group compared with the horizontal without epidural analgesia. The quality of evidence within the reviews was very low to moderate. There is currently a limited body of evidence to clearly assess the benefits and risks of assuming upright positions during childbirth. The overview highlights the need for high-quality research studies, involving better definition and comprehensive assessment of the effects of squatting during childbirth.


Unusual intramolecular CHO hydrogen bonding interaction between a sterically bulky amide and uranyl oxygen.
The selective separation of toxic heavy metals such as uranyl can be accomplished using ligands with stereognostic hydrogen bonding interactions to the uranyl oxo group, as proposed by Raymond and co-workers (T. S. Franczyk, K. R. Czerwinski and K. N. Raymond, J. Am. Chem. Soc., 1992, 114, 8138-8146). Recently, several ligands possessing this weak interaction have been proposed involving the hydrogen bonding of NH and OH based moieties with uranyl oxygen. We herein report the structurally and spectroscopically characterized CHO hydrogen bonding using a sterically bulky amide based ligand. In conjunction with experiments, electronic structure calculations are carried out to understand the structure, binding and the strength of the CHO hydrogen bonding interactions. This weak interaction is mainly due to the steric effect caused by a bulky substituent around the donor group which has direct relevance in designing novel ligands in nuclear waste management processes. Although the kinetics are very slow, the ligand is also highly selective to uranyl in the presence of other interfering ions such as lanthanides.


Huntington's disease: genetic heterogeneity in black African patients.
Huntington's disease (HD) has been reported to occur rarely in black patients. A new genetic variant- Huntington's disease-like 2 (HDL2)--occurring more frequently in blacks, has recently been described. The absence of an expanded trinucleotide repeat at the chromosome 4 HD locus was previously regarded as a way of excluding classic HD. The objective of this paper is to describe a number of black patients with genetically proven HD and to review its occurrence in Africa. Eleven black families (12 subjects), with genetically proven HD, are described: 9 from the Dr George Mukhari Hospital, and 2 from private practice in Tshwane. Chorea was present in all 12 patients and cognitive decline in 9. Nine had an age of onset between 30 and 50 years. Six families exhibited expansion of the trinucleotide repeat at the chromosome 4, IT 15 gene (HD), and 5 a junctophilin (JPH3) trinucleotide expansion at chromosome 16 (HDL2). The HDL2 subtype showed a tendency towards a later age of onset. The clinical presentation of the two genotypes (i.e. HD and HDL2) appears to be similar. The actual rate of occurrence of HD in blacks may require re-assessment. Considering the number of Huntington's chorea patients occurring in our area (Garankuwa), the possibility of clustering of the condition arises.


High-dose therapy with 90Yttrium-labeled monoclonal antibody CC49: a phase I trial.
A Phase I trial of increasing administered activities of 90yttrium (90Y)-labeled monoclonal antibody (MAb) CC49 was conducted to determine whether extrahematopoietic toxicity occurred with this radioimmunoconjugate. Twelve patients with various gastrointestinal tract cancers were administered a tracer dose of 111In-labeled MAb CC49 for biodistribution and pharmacokinetic studies. Patients then underwent a single treatment with increasing administered activities of 90Y-labeled MAb CC49 (0.3, 0.4, and 0.5 mCi/kg). Biodistribution studies, using 111In-labeled MAb CC49 as a surrogate, were determined using planar and single photon emission computed tomography imaging. Pharmacokinetic studies were performed by measuring radioactivity in blood samples taken at intervals after radioimmunoconjugate infusions. Tissue biopsies of tumor metastases and related normal tissues (liver and bone marrow) were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using these data. Toxicity was evaluated using the National Cancer Institute Common Toxicity Criteria. No dose limiting extrahematopoietic toxicity was identified in the range of administered activities used in this study. Radioimmunolocalization based on planar and single photon emission computed tomography images 111In-labeled MAb CC49 showed heterogeneous (nonspecific) liver and splenic uptake. Liver metastases were usually photopenic, and extrahepatic metastases showed faint to moderate uptake. The alpha and beta half-lives of 111In-labeled MAb CC49 and 90Y-labeled MAb CC49 in the blood were similar. Absorbed radiation dose estimates in metastatic tumor sites ranged from 180 to 3000 cGy. The percentage of injected dose/kg of tumor ranged from 1.12 to 18.14; however, tumor:normal liver ratios were consistently <1. No objective responses were observed. Doses of up to 0.5 mCi/kg could be administered with reversible grade IV myelotoxicity. Absorbed radiation dose in tumor was suboptimal, even at the highest administered activity level. Deposition of 90Y in liver was high, and estimates of absorbed dose in liver equaled or exceeded that which could be achieved in metastatic tumor sites. Strategies to enhance access of radioimmunoconjugates in tumor and diminish deposition in the liver need to be developed for effective treatment using MAb CC49 with chelated radiometals.


Structured Professional Judgment to Assist the Evaluation and Safety Planning of Suicide Risk: The Risk of Suicide Protocol (RoSP).
Background: The Risk of Suicide Protocol (RoSP) is a structured professional judgment (SPJ) scheme designed in line with NICE guidelines to improve clinicians' ability to evaluate and manage suicide risk. Aims: This study aimed to evaluate the efficacy of RoSP in two settings: (1) unexpected deaths of people in the community who were known to mental health services; and (2) an inpatient hospital specializing in the assessment and treatment of patients with personality disorder. Method: In Study 1, information from a database of unexpected deaths (N = 68) within an NHS health board was used to complete a RoSP assessment (blind to cause of death) and information from the Coroner's Court was used to assign people to suicide vs. natural causes/accidental death. In Study 2, patients (N = 62) were assessed on the RoSP upon admission to hospital and their self-injurious behaviors were recorded over the first 3 months of admission. Results: (1) Evaluations using RoSP were highly reliable in both samples (ICCs 0.93-0.98); (2) professional judgment based on the RoSP was predictive of completed suicide in the community sample (AUC = 0.83) and; (3) was predictive of both suicide attempts (AUC = 0.81) and all self-injurious behaviors (AUC = 0.80) for the inpatient sample. Conclusion: RoSP is a reliable and valid instrument for the structured clinical evaluation of suicide risk for use in inpatient psychiatric services and in community mental health services. RoSP's efficacy is comparable to well-established structured professional judgment instruments designed to predict other risk behavior (e.g., HCR-20 and the prediction of violence). The use of RoSP for the clinical evaluation of suicide risk and safety-planning provides a structure for meeting NICE guidelines for suicide prevention and is now evidence-based.


STEM Through Authentic Research and Training Program (START) for Underrepresented Communities: Adapting to the COVID-19 Pandemic.
The STEM Through Authentic Research and Training (START) Program is a new program integrating academic, social, and professional experiences, in the theme of exomedicine, to build a pipeline into college for first generation and traditionally underrepresented students by providing year-round authentic opportunities and professional development for high school students and teachers. In response to the COVID-19 pandemic, the START Program has worked with the local Fayette County public school and community partners to provide content to over 300 students through: virtual laboratory tours with community partner Space Tango, "meet a scientist" discussions, and online near-peer student demonstrations aimed at making the practice of STEM disciplines approachable. Furthermore, the START Program has partnered with Higher Orbits to provide at-home, space-themed learning kits for students to develop teamwork, communication, and STEM principles while engaging in online content with teachers, professionals, and astronauts. Finally, the START Program has moved its training platforms online, including receiving College Reading and Learning Association (CRLA) Peer Educator accreditation for our near-peer mentoring and coaching training. As a result, the START Program is better positioned to address this critical need in STEM education, while reaching more students in the community than possible with face-to-face interactions alone.


Inspiratory muscle training in heart disease and heart failure: a review of the literature with a focus on method of training and outcomes.
Evidence to date strongly suggests that poor inspiratory muscle performance is associated with dyspnea, poor exercise tolerance and poor functional status in patients with heart failure (HF). A growing body of literature has examined the effects of inspiratory muscle training (IMT) in HF patients with the majority of studies reporting favorable effects on several of the above limitations and a substantial number of related deficiencies due to inadequate inspiration and inspiratory muscle strength and endurance. The domains and manifestations of HF, which were significantly improved by IMT in one or more of the 18 out of 19 studies of IMT, included dyspnea, quality of life, balance, peripheral muscle strength and blood flow, peripheral muscle sympathetic nervous activity, heart rate, respiratory rate, peak VO₂, 6-min walk test distance, ventilation, VE/VCO₂ slope, oxygen uptake efficiency, circulatory power, recovery oxygen kinetics and several indices of cardiac performance. This paper will also review the available IMT literature with a focus on methods of IMT and clinical outcomes. Key differences between available IMT methods will be highlighted with a goal to improve IMT efforts and decrease the pathophysiological manifestations of heart disease and HF.


Impairment in the cognitive functioning of men with fragile X-associated tremor/ataxia syndrome (FXTAS).
Disorders associated with fragile X syndrome involve a trinucleotide (CGG) repeat expansion in the FMR1 gene. Recently, a progressive movement disorder (fragile X-associated tremor/ataxia syndrome [FXTAS]) has been identified in premutation carriers, persons with 55 to 200 CGG repeats. In addition to ataxia, action tremor, and Parkinsonism, early case reports suggested that FXTAS involves impaired cognition, but the precise nature of the impairment has not been elucidated. In this first, preliminary study of the subject, circumscribed aspects of cognitive functioning were examined in 25 men with FXTAS. Subjects' performance on the cognitive tests was compared with normative data. Scores on two measures of executive cognitive functioning showed a high prevalence of substantial impairment. Capacity for inhibition was severely affected in one-quarter of this highly educated sample; information processing speed was profoundly impaired in most subjects. Although mean verbal and performance IQ scores were not significantly different from the general population, they were quite low given the sample's educational level. Cognitive and functional impairment was greater for men with more CGG repeats, although number of repeats was not associated with age of onset of either tremor or ataxia. The results provide evidence that FXTAS involves marked impairment of executive cognitive abilities.


Modeling soft, permeable matter with the proper generalized decomposition (PGD) approach, and verification by means of nanoindentation.
Understanding sliding and load-bearing mechanisms of biphasic soft matter is crucial for designing synthetic replacements of cartilage, contact-lens materials or coatings for medical instruments. Interstitial fluid pressurization is believed to be the intrinsic load-carrying phenomenon governing the frictional properties. In this study, we have characterized permeability and identified the fluid contribution to the support of load during Atomic Force Microscopy (AFM) nanoindentation of soft polymer brushes in aqueous environments, by means of the Proper Generalized Decomposition (PGD) approach. First, rate-dependent AFM nanoindentation was performed on a poly(acrylamide) (PAAm) brush in an aqueous environment, to probe the purely elastic as well as poro-viscoelastic properties. Second, a biphasic model decoupling the fluid and solid load contributions was proposed, using Darcy's equation for liquid flow in porous media. Using realistic time-dependent simulations requires many direct solutions of the 3D partial differential equation, making modeling very time-consuming. To efficiently alleviate the time-consumption of multi-dimensional modeling, we used PGD to solve a Darcy model defined in a 7D domain, considering all the unknowns and material properties as extra coordinates of the problem. The obtained 7D simulation results were compared to the experimental results by using a direct Newton algorithm, since all sensitivities with respect to the model parameters are readily available. Thus, a simulation-based solution for depth- and rate-dependent permeability can be obtained. From the PGD-based model permeability is calculated, and the velocity- and pressure-fields in the material can be obtained in real-time in 3D by adjusting the parameters to the experimental values. The result is a step forward in understanding the fluid flow, permeability and fluid contributions to the load support of biphasic soft matter.


Cognitive and behavioral functioning in 82 patients with trigonocephaly.
The main objective of the present study was to assess the prevalence rates of attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, and features of autism spectrum disorders in trigonocephalic patients, using validated instruments and by ruling out the confounding influence of IQ. The second aim was to assess the association between extracranial anomalies and cognitive and/or behavioral problems in patients with trigonocephaly. Objectives were studied in 82 trigonocephalic patients aged 4 to 18 years at the Erasmus Medical Center in Rotterdam, The Netherlands. Features of autism spectrum disorders were assessed using the Social Communication Questionnaire. Attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder were assessed with the Diagnostic Interview Schedule for Children-Parent Version. The presence and nature of extracranial anomalies were ascertained by a clinician. Mental retardation (IQ <70) was present in 9 percent of patients with trigonocephaly. Findings indicated a 70 percent versus 24 percent prevalence of psychopathology (attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, or features of autism spectrum disorder) in patients with IQ levels of, respectively, <85 and ≥85. In the latter group, psychopathology was not significantly more common than expected based on prevalence rates reported in community samples. Extracranial anomalies were significantly correlated with lower IQ levels. However, when adjusted for IQ, the presence of extracranial malformations was not associated with an increased risk of behavioral problems. The relatively high prevalence of behavioral problems in patients with trigonocephaly seems to be mainly attributable to the co-occurrence of trigonocephaly and low intelligence.


Tobacco smoke and nicotine suppress expression of activating signaling molecules in human dendritic cells.
Cigarette smoke has significant toxic effects on the immune system, and increases the risk of developing autoimmune diseases; one immunosuppressive effect of cigarette smoke is that it inhibits the T cell-stimulating, immunogenic properties of myeloid dendritic cells (DCs). As the functions of DCs are regulated by intra-cellular signaling pathways, we investigated the effects of cigarette smoke extract (CSE) and nicotine on multiple signaling molecules and other regulatory proteins in human DCs to elucidate the molecular basis of the inhibition of DC maturation and function by CSE and nicotine. Maturation of monocyte-derived DCs was induced with the TLR3-agonist poly I:C or with the TLR4-agonist lipopolysaccharide, in the absence or presence of CSE or nicotine. Reverse-phase protein microarray was used to quantify multiple signaling molecules and other proteins in cell lysates. Particularly in poly I:C-matured DCs, cigarette smoke constituents and nicotine suppressed the expression of signaling molecules associated with DC maturation and T cell stimulation, cell survival and cell migration. In conclusion, constituents of tobacco smoke suppress the immunogenic potential of DCs at the signaling pathway level.


Contact Allergy to (Ingredients of) Toothpastes.
The literature on contact allergy to (ingredients of) toothpastes is critically reviewed. We have found 47 case reports, small case series (n = 2-5) and citations published between 1900 and 2016 describing more than 60 patients allergic to toothpastes, and in addition 3 larger case series and many descriptions of toothpaste allergy among selected groups of patients. Allergic reactions usually manifest as cheilitis with or without dermatitis around the mouth, less frequently by oral symptoms. Formerly, many reactions were caused by cinnamon derivatives; more recently, reported allergens are diverse. A semiopen test or closed patch test with the toothpaste "as is" may be performed as an initial test, but a positive reaction should always be followed by confirmatory tests. The role of contact allergy to toothpastes in patients with oral symptoms (stomatitis, glossitis, gingivitis, buccal mucositis, burning, soreness, and possibly burning mouth syndrome and recurrent aphthous ulcers) is unclear and should be further investigated.


Changes in the sleep-wake rhythm, sleep quality, mood, and quality of life of patients receiving treatment for lung cancer: A longitudinal study.
Studies on the diurnal sleep-wake rhythm of patients with lung cancer have mostly examined patients cross-sectionally, whereas the effects of lung cancer treatment over time have rarely been considered. Through long-term longitudinal tracking of patients with lung cancer, this study examined changes in their sleep-wake rhythm, sleep quality, anxiety, depressive symptoms, fatigue and quality of life (QoL) at various treatment stages. In addition, factors affecting their QoL were explored. Hierarchical linear modeling was adopted to analyze a convenience sample of 82 patients with lung cancer. The changes in their sleep-wake rhythm, sleep, mood (anxiety, depressive symptoms and fatigue) and QoL were observed at five time points: prior to treatment and at weeks 6, 12, 24 and 48 after the start of the treatment. The effects of sex, age, cancer stage, treatment type, comorbidities and time were controlled to determine the predictors of patients' QoL. The results showed that patients' sleep-wake rhythms were poor before treatments. Compared with baseline, the sleep-wake rhythms of the patients significantly improved at week 48, and anxiety significantly improved at weeks 6, 12, 24 and 48. By contrast, their fatigue became exacerbated at weeks 8 and 48. Moreover, QoL improved significantly from week 6 until the end of the treatment period. QoL was negatively affected by poor sleep quality (β = -0.69, p = 0.00) and depressive symptoms (β = -2.59, p < 0.001) and positively affected by regular sleep-wake rhythms (β = 0.23, p = 0.001). Therefore, clinical health-care professionals should focus more attention to the fatigue levels of patients with lung cancer before, during and after treatment. Health-care professionals may also need to provide such patients with health education regarding sleep hygiene and with emotional support to assist them in maintaining regular sleep-wake rhythms in order to improve their QoL.


Muscle systems and motility of early animals highlighted by cnidarians from the basal Cambrian.
Although fossil evidence suggests that various animal groups were able to move actively through their environment in the early stages of their evolution, virtually no direct information is available on the nature of their muscle systems. The origin of jellyfish swimming, for example, is of great interest to biologists. Exceptionally preserved muscles are described here in benthic peridermal olivooid medusozoans from the basal Cambrian of China (Kuanchuanpu Formation, ca. 535 Ma) that have direct equivalent in modern medusozoans. They consist of circular fibers distributed over the bell surface (subumbrella) and most probably have a myoepithelial origin. This is the oldest record of a muscle system in cnidarians and more generally in animals. This basic system was probably co-opted by early Cambrian jellyfish to develop capacities for jet-propelled swimming within the water column. Additional lines of fossil evidence obtained from ecdysozoans (worms and panarthropods) show that the muscle systems of early animals underwent a rapid diversification through the early Cambrian and increased their capacity to colonize a wide range of habitats both within the water column and sediment at a critical time of their evolutionary radiation.


Cloning and expression of the essential gene for poly(A) polymerase from S. cerevisiae.
Poly(A) polymerase is essential for the maturation of messenger RNA, adding tracts of adenosine residues to the 3' end of precursor RNA generated by endonucleolytic cleavage. This mechanism of mRNA 3' processing seems to be similar in yeast and in higher eucaryotes, although there are differences in the recognition signals in the pre-mRNA. Here we describe the cloning of the gene for yeast poly(A) polymerase. The enzyme is encoded by a single and essential gene located near the centromere on the left arm of chromosome 11. Poly(A) polymerase purified from recombinant Escherichia coli has the same physical and biochemical properties as the yeast enzyme. The yeast poly(A) polymerase shares features of sequence with its mammalian homologue.


Electromagnetic hypersensitivity (EHS, microwave syndrome) - Review of mechanisms.
Electromagnetic hypersensitivity (EHS), known in the past as "Microwave syndrome", is a clinical syndrome characterized by the presence of a wide spectrum of non-specific multiple organ symptoms, typically including central nervous system symptoms, that occur following the patient's acute or chronic exposure to electromagnetic fields in the environment or in occupational settings. Numerous studies have shown biological effects at the cellular level of electromagnetic fields (EMF) at magnetic (ELF) and radio-frequency (RF) frequencies in extremely low intensities. Many of the mechanisms described for Multiple Chemical Sensitivity (MCS) apply with modification to EHS. Repeated exposures result in sensitization and consequent enhancement of response. Many hypersensitive patients appear to have impaired detoxification systems that become overloaded by excessive oxidative stress. EMF can induce changes in calcium signaling cascades, significant activation of free radical processes and overproduction of reactive oxygen species (ROS) in living cells as well as altered neurological and cognitive functions and disruption of the blood-brain barrier. Magnetite crystals absorbed from combustion air pollution could have an important role in brain effects of EMF. Autonomic nervous system effects of EMF could also be expressed as symptoms in the cardiovascular system. Other common effects of EMF include effects on skin, microvasculature, immune and hematologic systems. It is concluded that the mechanisms underlying the symptoms of EHS are biologically plausible and that many organic physiologic responses occur following EMF exposure. Patients can have neurologic, neuro-hormonal and neuro-psychiatric symptoms following exposure to EMF as a consequence of neural damage and over-sensitized neural responses. More relevant diagnostic tests for EHS should be developed. Exposure limits should be lowered to safeguard against biologic effects of EMF. Spread of local and global wireless networks should be decreased, and safer wired networks should be used instead of wireless, to protect susceptible members of the public. Public places should be made accessible for electrohypersensitive individuals.


Engaging urban residents in assessing neighborhood environments and their implications for health.
Researchers have worked to delineate the manner in which urban environments reflect broader social processes, such as those creating racially, ethnically and economically segregated communities with vast differences in aspects of the built environment, opportunity structures, social environments, and environmental exposures. Interdisciplinary research is essential to gain an enhanced understanding of the complex relationships between these stressors and protective factors in urban environments and health. The purpose of this study was to examine the ways that multiple factors may intersect to influence the social and physical context and health within three areas of Detroit, Michigan. We describe the study design and results from seven focus groups conducted by the Healthy Environments Partnership (HEP) and how the results informed the development of a survey questionnaire and environmental audit tool. The findings from the stress process exercise used in the focus groups described here validated the relevance of a number of existing concepts and measures, suggested modifications of others, and evoked several new concepts and measures that may not have been captured without this process, all of which were subsequently included in the survey and environmental audit conducted by HEP. Including both qualitative and quantitative methods can enrich research and maximize the extent to which research questions being asked and hypotheses being tested are driven by the experiences of residents themselves, which can enhance our efforts to identify strategies to improve the physical and social environments of urban areas and, in so doing, reduce inequities in health.


Activation of brain glucose metabolism ameliorating cognitive impairment in APP/PS1 transgenic mice by electroacupuncture.
An essential feature of Alzheimer's disease (AD) is implicated in brain energy metabolic impairment that is considered underlying pathogenesis of cognitive impairment. Therefore, therapeutic interventions to allay cognitive deficits that target energy metabolism may be an efficacy strategy in AD. In this study, we found that electroacupuncture (EA) at the DU20 acupoint obviously increased glucose metabolism in specific brain regions such as cortex, hippocampus, cingulate gyrus, basal forebrain septum, brain stem, and cerebellum in APP/PS1 transgenic mice by animal 18F-Fluoro-2-deoxy-D-Glucose (18F-FDG)/positron emission tomography (PET) imaging, accompanied by cognitive improvements in the spatial reference learning and memory and memory flexibility and novel object recognition performances. Further evidence shown energy metabolism occurred in neurons or non-neuronal cells of the cortex and hippocampus in terms of the co-location of GLUT3/NeuN and GLUT1/GFAP. Simultaneously, metabolic homeostatic factors were critical for glucose metabolism, including phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and AKT serine/threonine kinase. Furthermore, EA-induced phosphorylated AMPK and AKT inhibited the phosphorylation level of the mammalian target of rapamycin (mTOR) to decrease the accumulation of amyloid-beta (Aβ) in the cortex and hippocampus. These findings are concluded that EA is a potential therapeutic target for delaying memory decline and Aβ deposition of AD. The AMPK and AKT are implicated in the EA-induced cortical and hippocampal energy metabolism, which served as a contributor to improving cognitive function and Aβ deposition in a transgenic mouse model of AD.


Differentiating between genuine damage and falsified damage to a garment following an alleged sexual assault.
An allegation of sexual assault was made in which a bra was torn off by the assailant causing extensive damage; however, it was observed that the hook and eye fastening was still intact. It was felt that it was not possible for a garment to receive such damage without damage to the hook and eye fastening, thus indicating that the complainant caused the damage to the bra herself to support a false allegation. Reconstruction experiments were conducted in which the conditions of the allegation were simulated utilizing a range of similar bras. Following the infliction of damage, the hook and eye fastenings were examined. In eight of nine experiments, the hook and eye fastening were intact, despite the application of enough force to cause separation of the bra cups in five of the experiments. This shows that bras may suffer extensive damage without damage to the hook and eye fastening.


Implant-Abutment Connections: A Review of Biologic Consequences and Peri-implantitis Implications.
Clinicians very often have seen marginal bone loss around dental implants at the crest level early on after implant placement and uncovering. Early clinical publications had suggested that this bone loss occurred during the first year of loading. Thus, numerous attempts have been made to minimize or eliminate such bone loss. However, the timing and reason for this bone loss are not always apparent. The objective of this study was to review the evidence regarding marginal bone loss around dental implants from the standpoint of biologic consequences to help understand marginal bone changes around dental implants. One hypothesis for the bone loss around these implants was related to the presence of bacteria in the interfaces between the implant and abutment connections. The literature was reviewed regarding the three major types of implant-abutment crestal connections, including butt-joint, platform-switched, and no interface (tissue-level or one-body). This review article revealed that 1.5 to 2.0 mm of bone loss occurred around bone-level, butt-joint connections when the interface was created because the microgap was wide enough for penetration and colonization of bacteria, and that this bone loss was not observed around implants with no interface because they did not have a contaminated interface at the bone crest. Many studies have shown an advantage in the amount of marginal bone resorption for implants with a platform-switched connection, and there appears to be a significantly different biologic reaction. Recent publications indicate that such contaminated implant-abutment connections might have an effect on peri-implantitis and failure over time.


Continuous wavelet transform for non-stationary vibration detection with phase-OTDR.
We propose the continuous wavelet transform for non-stationary vibration measurement by distributed vibration sensor based on phase optical time-domain reflectometry (OTDR). The continuous wavelet transform approach can give simultaneously the frequency and time information of the vibration event. Frequency evolution is obtained by the wavelet ridge detection method from the scalogram of the continuous wavelet transform. In addition, a novel signal processing algorithm based on the global wavelet spectrum is used to determine the location of vibration. Distributed vibration measurements of 500 Hz and 500 Hz to 1 kHz sweep events over 20 cm fiber length are demonstrated using a single mode fiber.


Na+/H+ exchanger regulatory factor 1 overexpression-dependent increase of cytoskeleton organization is fundamental in the rescue of F508del cystic fibrosis transmembrane conductance regulator in human airway CFBE41o- cells.
We have demonstrated that Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) overexpression in CFBE41o- cells induces a significant redistribution of F508del cystic fibrosis transmembrane conductance regulator (CFTR) from the cytoplasm to the apical membrane and rescues CFTR-dependent chloride secretion. Here, we observe that CFBE41o- monolayers displayed substantial disassembly of actin filaments and that overexpression of wild-type (wt) NHERF1 but not NHERF1-Delta Ezrin-Radixin-Moesin (ERM) increased F-actin assembly and organization. Furthermore, the dominant-negative band Four-point one, Ezrin, Radixin, Moesin homology (FERM) domain of ezrin reversed the wt NHERF1 overexpression-induced increase in both F-actin and CFTR-dependent chloride secretion. wt NHERF1 overexpression enhanced the interaction between NHERF1 and both CFTR and ezrin and between ezrin and actin and the overexpression of wt NHERF1, but not NHERF1-DeltaERM, also increased the phosphorylation of ezrin in the apical region of the cell monolayers. Furthermore, wt NHERF1 increased RhoA activity and transfection of constitutively active RhoA in CFBE41o- cells was sufficient to redistribute phospho-ezrin to the membrane fraction and rescue both the F-actin content and the CFTR-dependent chloride efflux. Rho kinase (ROCK) inhibition, in contrast, reversed the wt NHERF1 overexpression-induced increase of membrane phospho-ezrin, F-actin content, and CFTR-dependent secretion. We conclude that NHERF1 overexpression in CFBE41o- rescues CFTR-dependent chloride secretion by forming the multiprotein complex RhoA-ROCK-ezrin-actin that, via actin cytoskeleton reorganization, tethers F508del CFTR to the cytoskeleton stabilizing it on the apical membrane.


Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States.
Hepatitis C virus (HCV) infection may contribute to the development of diabetes mellitus. This relationship has not been investigated at the population level, and its biological mechanism remains unknown. To examine the prevalence of type 2 diabetes among persons with HCV infection in a representative sample of the general adult population of the United States. Cross-sectional national survey. The Third National Health and Nutrition Examination Survey, 1988-1994. 9841 persons older than 20 years of age for whom data on HCV infection and diabetes were complete. The presence of diabetes was ascertained by using American Diabetes Association guidelines based on fasting plasma glucose measurement and medication history. Presence of HCV infection was assessed by testing for serum HCV-specific antibodies (anti-HCV). Of the 9841 persons evaluated, 8.4% had type 2 diabetes and 2.1% were anti-HCV positive. Type 2 diabetes occurred more often in persons who were older, were nonwhite, had a high body mass index, and had low socioeconomic status. Type 2 diabetes was less common in persons who acknowledged previous illicit drug use. After adjustment for these factors, persons 40 years of age or older with HCV infection were more than three times more likely than those without HCV infection to have type 2 diabetes (adjusted odds ratio, 3.77 [95% CI, 1.80 to 7.87]). None of the 19 persons with type 1 diabetes were anti-HCV positive. In the United States, type 2 diabetes occurs more often in persons with HCV infection who are older than 40 years of age.


UV photolysis for relieved inhibition of sulfadiazine (SD) to biomass growth.
UV photolysis was used to relieve inhibition of biomass growth by sulfadiazine (SD), a broad-spectrum anti-microbial. To investigate the effects of SD on biomass growth, three substrates-glucose alone (G), glucose plus sulfadiazine (G+SD), and glucose plus photolyzed SD (G+PSD)-were used to culture the bacteria acclimated to glucose. The biomass was strongly inhibited when SD was added into the glucose solution, but inhibition was relieved to a significant degree when the SD was treated with UV irradiation as a pretreatment. The biomass growth kinetics were described well by the Monod model when glucose was used as a substrate alone, but the kinetics followed a hybrid Aiba model for non-competitive inhibition when SD was added to the solution. When photolyzed SD was added to glucose solution to replace original SD, the growth still followed Aiba inhibition, but inhibition was significantly relieved: the maximum specific growth rate (μ max) increased by 17 %, and the Aiba inhibition concentration increased by 60 %. Aniline, a major product of UV photolysis, supported the growth of the glucose-biodegrading bacteria. Thus, UV photolysis of SD significantly relieved inhibition by lowering the SD concentration and by generating a biodegradable product.