Reporting of Aboriginal and Torres Strait Islander peoples on the NSW Admitted Patient Data Collection: the 2010 data quality survey.
The reporting of Aboriginal and Torres Strait Islander peoples on the NSW Admitted Patient Data Collection was ascertained using a stratified purposive sample of NSW public hospital patients in 2010. Information was collected by interviewing patients and compared with patient information obtained on admission. The study used the methods used in the national survey by the AIHW in 2007 and the study results were compared to the AIHW survey results. The level of correct reporting was 90.7% (95% CI 84.6-94.2). These results, while indicative, should be interpreted with caution as some people may not have identified themselves as Aboriginal or Torres Strait Islander either on hospital admission or in the survey, and non-random sampling can produce non-representative samples.


Modification of hydraulic conductivity in granular soils using waste materials.
This paper evaluates the use of waste products such as silica fume and fly ash in modification of the granular soils in order to remove some environmental problems and create new useful findings in the field of engineering. It is known that silica fume and fly ash, as well as clay material, are used in geotechnical engineering because of their pozzolanic reactivity and fineness to improve the soil properties needed with respect to engineering purposes. The main objective of this research project was to investigate the use of these materials in geotechnical engineering and to improve the hydraulic properties of soils by means of grouting. For this reason, firstly, suitable grouts in suspension forms were prepared by using silica fume, fly ash, clay and cement in different percentages. The properties of these cement-based grouts were then determined to obtain the desired optimum values for grouting. After that, these grouts were penetrated into the soil samples under pressure. The experimental work indicates that these waste materials and clay improved the physical properties and the fluidity of the cement-based grouts and they also decreased the hydraulic conductivity of the grouted soil samples by sealing the voids of the soil. The results of this study have important findings concerning the use of these materials in soil treatment and the improvement of hydraulic conductivity of the soils.


Predictors of mortality for patients with advanced disease in an HIV palliative care program.
Despite advances in treatment, AIDS and its associated comorbidities remain important causes of death. Traditional HIV prognostic markers may be less useful in predicting death in current late-stage patients than in the era before highly active antiretroviral therapy. We used standardized baseline and follow-up data to describe causes of death and predictors of mortality in a cohort of patients with advanced disease referred to a specialized HIV palliative care program at a large urban medical center. Of 230 patients, 56% were male with a median age of 43 years; 54% were Hispanic and 39% were African American; 41% had a history of injection drug use; 89% had prior AIDS-defining illnesses; and median baseline values included a CD4 count of 39 cells/mm, HIV viral load of 65,202 copies/mL, Karnofsky score of 30, and 5 impaired activities of daily living (ADL). Over a median follow-up of 126 days (range: 1-823 days), 120 patients died; 54% of these died of late-stage HIV disease and/or bacterial pneumonia or sepsis, 19% of non-AIDS-defining cancers, 13% of liver failure and/or cirrhosis, and 12% of other progressive end-organ disease (eg, cardiac, pulmonary, renal). On multivariate analysis, death was predicted only by age (>65 years), baseline number of ADL impairments, and Karnofsky score (P < 0.0001 for all) and not by any AIDS-specific variables. For patients with late-stage disease referred to an HIV palliative care program, age and markers of functional status were more predictive of mortality than traditional HIV prognostic variables. Close to half of all deaths were attributable to non-AIDS-specific causes, including cancer and end-organ failure. These findings suggest the need for renewed study of predictors of mortality and prognostic markers in patients with advanced HIV disease and related comorbidities in the HAART era.


Detailed off-gas measurements for improved modelling of the aeration performance at the WWTP of Eindhoven.
At wastewater treatment plants (WWTPs), the aerobic conversion processes in the bioreactor are driven by the presence of dissolved oxygen (DO). Within these conversion processes, the oxygen transfer is a rate limiting step as well as being the largest energy consumer. Despite this high importance, WWTP models often lack detail on the aeration part. An extensive measurement campaign with off-gas tests was performed at the WWTP of Eindhoven to provide more information on the performance and behaviour of the aeration system. A high spatial and temporal variability in the oxygen transfer efficiency was observed. Applying this gathered system knowledge in the aeration model resulted in an improved prediction of the DO concentrations. Moreover, an important consequence of this was that ammonium predictions could be improved by resetting the ammonium half-saturation index for autotrophs to its default value. This again proves the importance of balancing sub-models with respect to the need for model calibration as well as model predictive power.


Discovery of high-affinity protein binding ligands--backwards.
There is a pressing need for high-affinity protein binding ligands for all proteins in the human and other proteomes. Numerous groups are working to develop protein binding ligands but most approaches develop ligands using the same strategy in which a large library of structured ligands is screened against a protein target to identify a high-affinity ligand for the target. While this methodology generates high-affinity ligands for the target, it is generally an iterative process that can be difficult to adapt for the generation of ligands for large numbers of proteins. We have developed a class of peptide-based protein ligands, called synbodies, which allow this process to be run backwards--i.e. make a synbody and then screen it against a library of proteins to discover the target. By screening a synbody against an array of 8,000 human proteins, we can identify which protein in the library binds the synbody with high affinity. We used this method to develop a high-affinity synbody that specifically binds AKT1 with a K(d)<5 nM. It was found that the peptides that compose the synbody bind AKT1 with low micromolar affinity, implying that the affinity and specificity is a product of the bivalent interaction of the synbody with AKT1. We developed a synbody for another protein, ABL1 using the same method. This method delivered a high-affinity ligand for a target protein in a single discovery step. This is in contrast to other techniques that require subsequent rounds of mutational improvement to yield nanomolar ligands. As this technique is easily scalable, we believe that it could be possible to develop ligands to all the proteins in any proteome using this approach.


Feasibility of simultaneous PET/MR of the carotid artery: first clinical experience and comparison to PET/CT.
The study aimed at comparing PET/MR to PET/CT for imaging the carotid arteries in patients with known increased risk of atherosclerosis. Six HIV-positive men underwent sequential PET/MR and PET/CT of the carotid arteries after injection of 400 MBq of (18)F-FDG. PET/MR was performed a median of 131 min after injection. Subsequently,PET/CT was performed. Regions of interest (ROI) were drawn slice by slice to include the carotid arteries and standardized uptake values (SUV) were calculated from both datasets independently. Quantitative comparison of (18)F-FDG uptake revealed a high congruence between PET data acquired using the PET/MR system compared to the PET/CT system. The mean difference for SUVmean was -0.18 (p < 0.001) and -0.14 for SUVmax (p < 0.001) indicating a small but significant bias towards lower values using the PET/MR system. The 95% limits of agreement were -0.55 to 0.20 for SUVmean and -0.93 to 0.65 for SUVmax. The image quality of the PET/MR allowed for delineation of the carotid vessel wall. The correlations between (18)F-FDG uptake from ROI including both vessel wall and vessel lumen to ROI including only the wall were strong (r = 0.98 for SUVmean and r = 1.00 for SUVmax) indicating that the luminal (18)F-FDG content had minimal influence on the values. The study shows for the first time that simultaneous PET/MR of the carotid arteries is feasible in patients with increased risk of atherosclerosis. Quantification of (18)F-FDG uptake correlated well between PET/MR and PET/CT despite difference in method of PET attenuation correction, reconstruction algorithm, and detector technology.


Corticosteroids for hospitalized patients with mild to critically-ill COVID-19: a multicenter, retrospective, propensity score-matched study.
Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).


Co-benefits of climate mitigation on air quality and human health in Asian countries.
Climate change mitigation involves reducing fossil fuel consumption and greenhouse gas emissions, which is expensive, particularly under stringent mitigation targets. The co-benefits of reducing air pollutants and improving human health are often ignored, but can play significant roles in decision-making. In this study, we quantified the co-benefits of climate change mitigation on ambient air quality and human health in both physical and monetary terms with a particular focus on Asia, where air quality will likely be degraded in the next few decades if mitigation measures are not undertaken. We used an integrated assessment framework that incorporated economic, air chemistry transport, and health assessment models. Air pollution reduction through climate change mitigation under the 2 °C goal could reduce premature deaths in Asia by 0.79 million (95% confidence interval: 0.75-1.8 million) by 2050. This co-benefit is equivalent to a life value savings of approximately 2.8 trillion United States dollars (USD) (6% of the gross domestic product [GDP]), which is decidedly more than the climate mitigation cost (840 billion USD, 2% of GDP). At the national level, India has the highest potential net benefit of 1.4 trillion USD, followed by China (330 billion USD) and Japan (68 billion USD). Furthermore, in most Asian countries, per capita GDP gain and life value savings would increase with per capita GDP increasing. We robustly confirmed this qualitative conclusion under several socioeconomic and exposure-response function assumptions.


Effects of positive mood on attentional breadth for emotional stimuli.
Although earlier studies have related positive emotions to attentional broadening, recent findings point out the complexity of this relation and show that these broadening effects interact with factors such as characteristics of the information that is presented. Besides stimuli characteristics, individual characteristics such as the presence of depressive symptoms could also influence the broadening effects as depressive symptoms have previously been related to a more narrow attentional scope. Therefore, the aim of this study was to further investigate the attentional broadening effects of positive emotions, testing whether this is influenced by the emotional valence of the information presented and secondly, how the presence of depressive symptoms might interact with this relationship. We used a performance-based measure to assess fluctuations in attentional broadening for positive, neutral, and negative stimuli. We assessed the presence and severity of depressive symptoms in an unselected study sample and tested whether these symptoms moderate the relationship between induced positive mood and attentional breadth for emotional information. Results showed no direct relation between positive mood and attentional breadth, regardless of the emotional valence of the stimuli. However, the presence of depressive symptoms moderated this relationship in such a way that among low levels of depressive symptoms, positive mood was related to attentional broadening specifically when positive information was presented, while at high levels of depressive symptoms this relation was reversed. The current findings suggest that both stimuli characteristics, individual characteristics and their interplay should be taken into account when investigating the broadening effects of positive emotions.


Effects of erythropoietin, angiotensin II, and angiotensin-converting enzyme inhibitor on erythroid precursors in patients with posttransplantation erythrocytosis.
Angiotensin-converting enzyme inhibitors (ACEI) have become the treatment of choice for posttransplantation erythrocytosis (PTE). Yet the pathogenesis of PTE and the mechanisms of action of ACEI remain unclear. Therefore, we studied the dose response to erythropoietin (Ep), angiotensin II (AII), and the ACEI enalaprilat on the in vitro proliferation of erythroid progenitors in patients with PTE and in controls. We also evaluated ACE polymorphism in the two groups. Twelve patients with PTE and 12 renal transplant patients without PTE were studied. Erythroid burst-forming units (BFU-E) were isolated from peripheral blood using standard methods. Ep sensitivity was determined for four patients with PTE and three control patients, using 0-3 U/ml Ep. AII dose response was studied in four patients with PTE and five control patients, using AII concentrations of 0-1000 nM. The effect of enalaprilat was studied in eight patients with PTE and eight control patients, using drug concentrations of 0-10 ng/ml. ACE gene insertion/deletion polymorphism was determined by polymerase chain reaction. PTE patients showed a significant shift of the Ep response curve to the left compared with controls, with 50% maximal growth occurring at a lower Ep concentration (0.3 U/ml vs. 0.95 U/ml, P<0.025.) However, there was no difference in the number of BFU-E colonies between PTE patients and controls. AII added to the growth medium produced only minor stimulation in both groups. PTE patients showed significant inhibition of BFU-E growth with 10 ng/ml enalaprilat, but controls showed no inhibition of BFU-E growth with ACEI. There was no difference in ACE polymorphism between PTE and controls. Our data suggest that PTE is associated with increased erythroid progenitor sensitivity to Ep. The effect of ACEI to decrease hematocrit in patients with PTE may be due to inhibition of red cell precursor growth.


Physical fitness of 9 year olds in England: related factors.
To examine the influence of social factors, passive smoking, and other parental health related factors, as well as anthropometric and other measurements on children's cardiorespiratory fitness. This was a cross sectional study. The analysis was based on 22 health areas in England. The subjects were 299 boys and 282 girls aged 8 to 9 years. Parents did not give positive consent for 15% of the eligible sample. A further 25% of the eligible sample did not participate because the cycle-ergometer broke down, study time was insufficient, or they were excluded from the analysis because they were from ethnic minority groups or had missing data on one continuous variable. Cardiorespiratory fitness was determined using the cycle-ergometer test. It was measured in terms of PWC85%-that is, power output per body weight (watt/kg) assessed at 85% of maximum heart rate. The association between children's fitness and biological and social factors was analysed in two stages. Firstly, multiple logistic analysis was used to examine the factors associated with the children's ability to complete the test for at least four minutes. Secondly, multiple linear regression analysis was used to examine the independent association of the factors with PWC85%. In the logistic analysis, shorter children, children with higher blood pressure, and boys with a larger sibship size had poorer fitness. In the multiple regression analysis, only height (p < 0.001) was positively associated, and the sum of skinfold thicknesses at four sites (p = 0.001) was negatively associated with fitness in both sexes. In girls, a positive association was found with pre-exercise peak expiratory flow rate (p < 0.05), and there were negative associations with systolic blood pressure (p < 0.05) and family history of heart attack (p < 0.05). In boys an association was found with skinfold distribution and fitness (p < 0.05), so that children with relatively less body fat were fitter. Social and health behaviour factors such as father's social class, father's employment status, or parents' smoking habits were unrelated to child's fitness. Height and obesity are strongly associated, and systolic blood pressure to a small extent, with children's fitness, but social factors are unrelated.


Correlation of volcanic activity with sulfur oxyanion speciation in a crater lake.
The Yugama crater lake at Kusatsu-Shirane volcano, Japan, contains nearly 2200 tons (2800 parts per million) of polythionate ions (Sn O(6)(2-), where n = 4 to 9). Analytical data on lake water sampled before and during eruptions in 1982 showed that the concentrations of polythionates decreased and sulfate increased in response to the preeruption activities of the subaqueous fumaroles. These changes were observed 2 months before the first phreatic explosion on 26 October 1982. The monitoring of polythionates and sulfate in crater lake water is a promising means of anticipating potential volcanic eruption hazards.


Using Indigenous Standards to Implement the CARE Principles: Setting Expectations through Tribal Research Codes.
Biomedical data are now organized in large-scale databases allowing researchers worldwide to access and utilize the data for new projects. As new technologies generate even larger amounts of data, data governance and data management are becoming pressing challenges. The FAIR principles (Findable, Accessible, Interoperable, and Reusable) were developed to facilitate data sharing. However, the Indigenous Data Sovereignty movement advocates for greater Indigenous control and oversight in order to share data on Indigenous Peoples' terms. This is especially true in the context of genetic research where Indigenous Peoples historically have been unethically exploited in the name of science. This article outlines the relationship between sovereignty and ethics in the context of data to describe the collective rights that Indigenous Peoples assert to increase control over their biomedical data. Then drawing on the CARE Principles for Indigenous Data Governance (Collective benefit, Authority to control, Responsibility, and Ethics), we explore how standards already set by Native nations in the United States, such as tribal research codes, provide direction for implementation of the CARE Principles to complement FAIR. A broader approach to policy and procedure regarding tribal participation in biomedical research is required and we make recommendations for tribes, institutions, and ethical practice.


The association between cingulate cortex glutamate concentration and delay discounting is mediated by resting state functional connectivity.
Humans vary in their ability to delay gratification and impulsive decision making is a common feature in various psychiatric disorders. The level of delay discounting is a relatively stable psychological trait, and therefore neural processes implicated in delay discounting are likely to be based on the overall functional organization of the brain (under task-free conditions) in which state-dependent shifts from baseline levels occur. The current study investigated whether delay discounting can be predicted by intrinsic properties of brain functioning. Fourteen healthy male subjects performed a delay discounting task. In addition, resting state functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (¹H MRS) were used to investigate the relationship between individual differences in delay discounting and molecular and regional measures of resting state (baseline) activity of dorsal anterior cingulate cortex (dACC). Results showed that delay discounting was associated with both dACC glutamate concentrations and resting state functional connectivity of the dACC with a midbrain region including ventral tegmental area and substantia nigra. In addition, a neural pathway was established, showing that the effect of glutamate concentrations in the dACC on delay discounting is mediated by functional connectivity of the dACC with the midbrain. The current findings are important to acknowledge because spontaneous intrinsic brain processes have been proposed to be a potential promising biomarker of disease and impulsive decision making is associated with several psychiatric disorders.


Swept source optical coherence tomography using an all-fiber 1300-nm ring laser source.
The increased sensitivity of spectral domain optical coherence tomography (OCT) has driven the development of a new generation of technologies in OCT, including rapidly tunable, broad bandwidth swept laser sources and spectral domain OCT interferometer topologies. In this work, the operation of a turnkey 1300-nm swept laser source is demonstrated. This source has a fiber ring cavity with a semiconductor optical amplifier gain medium. Intracavity mode selection is achieved with an in-fiber tunable fiber Fabry-Perot filter. A novel optoelectronic technique that allows for even sampling of the swept source OCT signal in k space also is described. A differential swept source OCT system is presented, and images of in vivo human cornea and skin are presented. Lastly, the effects of analog-to-digital converter aliasing on image quality in swept source OCT are discussed.


Assessing the modified receptive field (MRF) theory: Evidence from Sinhalese-English bilinguals.
The current study aimed to test the applicability of the modified receptive field (MRF) theory (Tydgat & Grainger, 2009) with English native speakers (Experiment 1) and Sinhalese native speakers (Experiment 2), who were skilled readers of both Sinhala and Roman scripts. A two-alternative forced choice (2AFC) procedure to measure identification accuracy for all positions in a string of five characters, which consisted of Roman script letters, Sinhala letters or symbols was conducted. For Roman script, the English and Sinhalese speakers displayed analogous results as in previous studies for Roman letters and symbols (i.e., an initial letter advantage and W-shaped function for Roman letters and a Λ-shaped function for symbols). In contrast for Sinhala script, the Sinhalese speakers displayed a strong linear function with accuracy for letter positions 1, 2 and 3 similarly advantaged. We propose that this characteristic pattern for Sinhala script has developed as a specialised adaptive mechanism to optimise the processing of letters when reading in this distinctive script.


Tissue-derived mesenchymal stromal cells used as vehicles for anti-tumor therapy exert different in vivo effects on migration capacity and tumor growth.
Mesenchymal stem cells (MSCs) have been promoted as an attractive option to use as cellular delivery vehicles to carry anti-tumor agents, owing to their ability to home into tumor sites and secrete cytokines. Multiple isolated populations have been described as MSCs, but despite extensive in vitro characterization, little is known about their in vivo behavior.The aim of this study was to investigate the efficacy and efficiency of different MSC lineages derived from five different sources (bone marrow, adipose tissue, epithelial endometrium, stroma endometrium, and amniotic membrane), in order to assess their adequacy for cell-based anti-tumor therapies. Our study shows the crucial importance of understanding the interaction between MSCs and tumor cells, and provides both information and a methodological approach, which could be used to develop safer and more accurate targeted therapeutic applications. We first measured the in vivo migration capacity and effect on tumor growth of the different MSCs using two imaging techniques: (i) single-photon emission computed tomography combined with computed tomography (SPECT-CT), using the human sodium iodine symporter gene (hNIS) and (ii) magnetic resonance imaging using superparamagnetic iron oxide. We then sought correlations between these parameters and expression of pluripotency-related or migration-related genes. Our results show that migration of human bone marrow-derived MSCs was significantly reduced and slower than that obtained with the other MSCs assayed and also with human induced pluripotent stem cells (hiPSCs). The qPCR data clearly show that MSCs and hiPSCs exert a very different pluripotency pattern, which correlates with the differences observed in their engraftment capacity and with their effects on tumor growth. This study reveals differences in MSC recruitment/migration toward the tumor site and the corresponding effects on tumor growth. Three observations stand out: 1) tracking of the stem cell is essential to check the safety and efficacy of cell therapies; 2) the MSC lineage to be used in the cell therapy needs to be carefully chosen to balance efficacy and safety for a particular tumor type; and 3) different pluripotency and mobility patterns can be linked to the engraftment capacity of the MSCs, and should be checked as part of the clinical characterization of the lineage.


NP03, a novel low-dose lithium formulation, is neuroprotective in the YAC128 mouse model of Huntington disease.
Huntington disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene, remains without a treatment to modify the course of the illness. Lithium, a drug widely used for the treatment of bipolar disorder, has been shown to exert neuroprotective effects in a number of models of neurological disease but may have various toxic effects at conventional therapeutic doses. We examined whether NP03, a novel low-dose lithium microemulsion, would improve the disease phenotypes in the YAC128 mouse model of HD. We demonstrate that NP03 improves motor function, ameliorates the neuropathological deficits in striatal volume, neuronal counts, and DARPP-32 expression, and partially rescues testicular atrophy in YAC128 mice. These positive effects were accompanied by improvements in multiple biochemical endpoints associated with the pathogenesis of HD, including normalization of caspase-6 activation and amelioration of deficits in BDNF levels, and with no lithium-related toxicity. Our findings demonstrate that NP03 ameliorates the motor and neuropathological phenotypes in the YAC128 mouse model of HD, and represents a potential therapeutic approach for HD.


A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro.
Extracts of the herb feverfew inhibit human blood platelet aggregation and secretion induced by a number of agents in-vitro and this may relate to the beneficial effects of feverfew in migraine. We previously identified several compounds with antisecretory activity in human blood platelets using adrenaline as the stimulant. In the present study, we have compared the inhibitory activity of one of these compounds, parthenolide, with that of crude feverfew extract. The effects of both on [14C]5-HT secretion from platelets and on platelet aggregation induced by a number of different stimulants were determined. The activating agents studied included the phorbol ester PMA, ADP, arachidonic acid, collagen, the thromboxane mimetic U46619, the calcium ionophore A23187, the diacylglycerol analogue OAG and adrenaline. The results show that there are marked similarities between the effects of feverfew extract and of parthenolide on both [14C]5-HT secretion and platelet aggregation, which is consistent with the effects of feverfew extract on platelets being brought about by parthenolide or similar compounds in the extract. Only in one case, when A23187 was used as the stimulatory agent, was there any discrepancy, which may have been due to materials in the extract other than parthenolide. Both feverfew extract and parthenolide were more effective as inhibitors of the [14C]5-HT secretion and aggregation induced by some agents and not others, and were most effective as inhibitors of the [14C]5-HT secretion (but not the aggregation) induced by PMA. This suggests that the effects of feverfew/parthenolide on the protein kinase C pathway warrants further study.


Preimplantation genetic diagnosis: a systematic review of litigation in the face of new technology.
To study legal cases against IVF facilities pertaining to preimplantation genetic diagnosis (PGD) misdiagnosis. Systematic case law review. University medical center using US legal databases. The IVF recipients using PGD services. Lawsuits pertaining to PGD against IVF facilities. Lawsuits, court rulings, damage awards, and settlements pertaining to PGD after the birth of a child with a genetic defect. Causes of action pertaining to PGD arise from negligence in performing the procedure as well as failure to properly inform patients of key information, such as inherent errors associated with the PGD process, a facility's minimal experience in performing PGD, and the option of obtaining PGD. Courts have sympathized with the financial burden involved in caring for children with disabilities. Monetary damage awards are based on the costs of caring for children with debilitating defects, including lifetime medical and custodial care. Facilities offering PGD services expose themselves to a new realm of liability in which damage awards can easily exceed the limits of a facility's insurance policy. Competent laboratory personnel and proper informed consent--with particular care to inform patients of the inherent inaccuracies of PGD--are crucial in helping deter liability.


RSH enzyme diversity for (p)ppGpp metabolism in Phaeodactylum tricornutum and other diatoms.
The nucleotides guanosine tetraphosphate and pentaphosphate (together known as (p)ppGpp or magic spot) are produced in plant plastids from GDP/GTP and ATP by RelA-SpoT homologue (RSH) enzymes. In the model plant Arabidopsis (p)ppGpp regulates chloroplast transcription and translation to affect growth, and is also implicated in acclimation to stress. However, little is known about (p)ppGpp metabolism or its evolution in other photosynthetic eukaryotes. Here we studied (p)ppGpp metabolism in the marine diatom Phaeodactylum tricornutum. We identified three expressed RSH genes in the P. tricornutum genome, and determined the enzymatic activity of the corresponding enzymes by heterologous expression in bacteria. We showed that two P. tricornutum RSH are (p)ppGpp synthetases, despite substitution of a residue within the active site believed critical for activity, and that the third RSH is a bifunctional (p)ppGpp synthetase and hydrolase, the first of its kind demonstrated in a photosynthetic eukaryote. A broad phylogenetic analysis then showed that diatom RSH belong to novel algal RSH clades. Together our work significantly expands the horizons of (p)ppGpp signalling in the photosynthetic eukaryotes by demonstrating an unexpected functional, structural and evolutionary diversity in RSH enzymes from organisms with plastids derived from red algae.


Bioavailable phytoprostanes and phytofurans from Gracilaria longissima have anti-inflammatory effects in endothelial cells.
An array of bioactive compounds with health-promoting effects has been described in several species of macroalgae. Among them, phytoprostanes (PhytoPs) and phytofurans (PhytoFs), both autoxidation products of α-linolenic acid, have been seen to exert immunomodulatory and antiinflammatory activities in vitro. The purpose of this study was to explore the bioaccesibility, bioavailability, and bioactivity of PhytoPs and PhytoFs obtained from the edible red algae Gracilaria longissima, and to gain insight into the anti-inflammatory activity of their bioavailable fraction in human endothelial cells. The PhytoPs and PhytoFs profile and concentration of G. longissima were determined by UHPLC-QqQ-MS/MS. Algal samples were processed following a standardised digestion method including gastric, intestinal, and gastrointestinal digestion. The bioavailability of the PhytoPs and PhytoFs in the characterized fractions was assessed in a Caco-2 cell monolayer model of the intestinal barrier. The inflammation response of these prostaglandin-like compounds in human endothelial cells, after intestinal absorption, was investigated in vitro. Simulated digestions significantly reduced the concentration of PhytoPs and PhytoFs up to 1.17 and 0.42 μg per 100 g, respectively, on average, although permeability through the Caco-2 cell monolayer was high (up to 88.2 and 97.7%, on average, respectively). PhytoP and PhytoF-enriched extracts of raw algae impaired the expression of ICAM-1 and IL-6 inflammation markers. The inflammation markers progressed in contrast to the relative concentrations of bioactive oxylipins, suggesting pro- or anti-inflammatory activity on their part. In this aspect, the cross-reactivity of these compounds with diverse receptors, and their relative concentration could explain the diversity of the effects found in the current study. The results indicate that PhytoPs and PhytoFs display complex pharmacological profiles probably mediated through their different actions and affinities in the endothelium.


Culture, cross-role consistency, and adjustment: testing trait and cultural psychology perspectives.
Trait and cultural psychology perspectives on cross-role consistency and its relation to adjustment were examined in 2 individualistic cultures, the United States (N=231) and Australia (N=195), and 4 collectivistic cultures, Mexico (N=199), the Philippines (N=195), Malaysia (N=217), and Japan (N=180). Cross-role consistency in trait ratings was evident in all cultures, supporting trait perspectives. Cultural comparisons of mean consistency provided support for cultural psychology perspectives as applied to East Asian cultures (i.e., Japan) but not collectivistic cultures more generally. Some but not all of the hypothesized predictors of consistency were supported across cultures. Cross-role consistency predicted aspects of adjustment in all cultures, but prediction was most reliable in the U.S. sample and weakest in the Japanese sample. Alternative constructs proposed by cultural psychologists--personality coherence, social appraisal, and relationship harmony--predicted adjustment in all cultures but were not, as hypothesized, better predictors of adjustment in collectivistic cultures than in individualistic cultures.


Recurrence of FSGS after Kidney Transplantation in Adults.
FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.


Joint injury causes knee osteoarthritis in young adults.
This review presents recent data on joint injury as the cause of osteoarthritis development in young adults and proposes and discusses a model that highlights how joint injury and other risk factors may contribute to osteoarthritis development through two different pathways: joint-related mechanisms and deconditioning of the musculoskeletal system. Knee osteoarthritis in young adults is common after knee injury. In women who sustained an anterior cruciate ligament injury in soccer, 51% (mean age 31) had radiographic changes after 12 years. Men, 41% (mean age 36) had osteoarthritis after 14 years. An injury to the menisci during middle age resulting in a horizontal tear is more probably the first signal of an already ongoing osteoarthritis process of the knee. Known risk factors seem to contribute to osteoarthritis through pathways related to (1) mechanical aspects of the joint and (2) the musculoskeletal system. Osteoarthritis in young adults is most commonly a result of a previous injury to the knee. Deconditioning of the musculoskeletal system is seen with joint injury, obesity, and aging, all known risk factors for osteoarthritis. Muscular deconditioning contributes to increased joint loads and knee osteoarthritis development and progression. So far, it is unclear whether surgery reduces the development or progression of osteoarthritis. The risk for osteoarthritis development seems to increase as the amount of meniscal tissue removed increases. Knee injury prevention, rehabilitation after knee injuries, regular exercise, maintaining body weight, and a changed locomotion pattern may prevent osteoarthritis initiation and progression in young adults.


Effect of aluminium on iron uptake and transferrin-receptor expression by human erythroleukaemia K562 cells.
Incubation of human erythroleukaemia K562 cells with Al-transferrin inhibited iron uptake from 59Fe-transferrin by about 80%. The inhibition was greater than that produced by a similar quantity of Fe-transferrin. Preincubation of cells for 6 h with either Al-transferrin or Fe-transferrin diminished the number of surface transferrin receptors by about 40% compared with cells preincubated with apo-transferrin. Al-transferrin did not compete significantly with Fe-transferrin for transferrin receptors and, when cells were preincubated for 15 min instead of 6 h, the inhibitory effect of Al-transferrin on receptor expression was lost. Both forms of transferrin also decreased the level of transferrin receptor mRNA by about 50%, suggesting a common regulatory mechanism. Aluminium citrate had no effect on iron uptake or transferrin-receptor expression. AlCl3 also had no effect on transferrin-receptor expression, but at high concentration it caused an increase in iron uptake by an unknown, possibly non-specific, mechanism. Neither Al-transferrin nor AlCl3 caused a significant change in cell proliferation. It is proposed that aluminium, when bound to transferrin, inhibits iron uptake partly by down-regulating transferrin-receptor expression and partly by interfering with intracellular release of iron from transferrin.


The association of season and temperature with adverse pregnancy outcome in two German states, a time-series analysis.
A seasonality of low birth weight (LBW) and preterm birth (PTB) has been described for most regions and there is evidence that this pattern is caused by ambient outdoor temperature. However, the association as such, the direction of effect and the critical time of exposure remain controversial. Logistic, time-series regression was performed on nearly 300,000 births from two German states to study the association between season and daily mean temperature and changes in daily proportions of term LBW (tLBW) or PTB. Analyses were adjusted for time-varying factors. Temperature exposures were examined during different periods of pregnancy. Weak evidence for an association between season of conception, season of birth or ambient outdoor temperature and tLBW or PTB was found. Results of analyses of temperature were not consistent between the two states. Different sources of bias which would have artificially led to stronger findings were detected and are described. No clear evidence for an association between season of conception, season of birth or temperature and tLBW or PTB was found. In the study of pregnancy outcome different sources of bias can be identified which can potentially explain heterogeneous findings of the past.


Implications of ICD-10 for Sarcopenia Clinical Practice and Clinical Trials: Report by the International Conference on Frailty and Sarcopenia Research Task Force.
Establishment of an ICD-10-CM code for sarcopenia in 2016 was an important step towards reaching international consensus on the need for a nosological framework of age-related skeletal muscle decline. The International Conference on Frailty and Sarcopenia Research Task Force met in April 2017 to discuss the meaning, significance, and barriers to the implementation of the new code as well as strategies to accelerate development of new therapies. Analyses by the Sarcopenia Definitions and Outcomes Consortium are underway to develop quantitative definitions of sarcopenia. A consensus conference is planned to evaluate this analysis. The Task Force also discussed lessons learned from sarcopenia trials that could be applied to future trials, as well as lessons from the osteoporosis field, a clinical condition with many constructs similar to sarcopenia and for which ad hoc treatments have been developed and approved by regulatory agencies.


Microsurgical Anatomy of the Hypoglossal and C1 Nerves: Description of a Previously Undescribed Branch to the Atlanto-Occipital Joint.
Distal branches of the C1 nerve that travel with the hypoglossal nerve have been well investigated but relationships of C1 and the hypoglossal nerve near the skull base have not been described in detail. Therefore, the aim of this study was to investigate these small branches of the hypoglossal and first cervical nerves by anatomic dissection. Twelve sides from 6 cadaveric specimens were used in this study. To elucidate the relationship among the hypoglossal, vagus, and first and cervical nerve, the mandible was removed and these nerves were dissected under the surgical microscope. A small branch was found to always arise from the dorsal aspect of the hypoglossal nerve at the level of the transverse process of the atlas and joined small branches from the first and second cervical nerves. The hypoglossal and C1 nerves formed a nerve plexus, which gave rise to branches to the rectus capitis anterior and rectus capitis lateralis muscles and the atlanto-occipital joint. Improved knowledge of such articular branches might aid in the diagnosis and treatment of patients with pain derived from the atlanto-occipital joint. We believe this to be the first description of a branch of the hypoglossal nerve being involved in the innervation of this joint.


Force microscopy with light-atom probes.
The charge distribution in atoms with closed electron shells is spherically symmetric, whereas atoms with partially filled shells can form covalent bonds with pointed lobes of increased charge density. Covalent bonding in the bulk can also affect surface atoms, leading to four tiny humps spaced by less than 100 picometers in the charge density of adatoms on a (001) tungsten surface. We imaged these charge distributions by means of atomic force microscopy with the use of a light-atom probe (a graphite atom), which directly measured high-order force derivatives of its interaction with a tungsten tip. This process revealed features with a lateral distance of only 77 picometers.


Endangered antarctic environments.
The Antarctic continent harbors a range of specialized and sometimes highly localized microbial biotopes. These include biotopes associated with desiccated mineral soils, rich ornithogenic soils, glacial and sea ice, ice-covered lakes, translucent rocks, and geothermally heated soils. All are characterized by the imposition of one or more environmental extremes (including low temperature, wide temperature fluctuations, desiccation, hypersalinity, high periodic radiation fluxes, and low nutrient status). As our understanding of the true microbial diversity in these biotopes expands from the application of molecular phylogenetic methods, we come closer to the point where we can make an accurate assessment of the impacts of environmental change, human intervention, and other natural and unnatural impositions. At present, it is possible to make reasonable predictions about the physical effects of local climate change, but only general predictions on possible changes in microbial community structure. The consequences of some direct human impacts, such as physical disruption of microbial soil communities, are obvious if not yet quantitated. Others, such as the dissemination of nonindigenous microorganisms into indigenous microbial communities, are not yet understood.


New arrangement of interrenal and chromaffin tissues of teleost fishes.
An unusual morphologic arrangement of interrenal and chromaffin tissues has been observed in two families of teleost fishes. In most teleosts in which these cell types occur together in association with the postcardinal veins and their branches, the chromaffin cells are located between the lumen of the vein and the interrenal cells. This typical relationship is reversed in some of the Labridae and Scaridae.


A literature review of the sexual health of women with rheumatoid arthritis.
Sexual health problems are common for women with Rheumatoid Arthritis, RA. Sexual health is covered in the International Classification of Functioning, Disability and Health (ICF) by two different fields: sexual function and intimate relationships, which are included in the ICF core sets for RA. Most patients with RA are female, and there are differences concerning sexual health between women and men with RA.The aim of this study was to explore the literature concerning the effects of RA on the sexual health of female patients, and also recommend solutions to improve the sexual health of women with RA.Sexual health problems can occur before, during and after sexual activities, and can affect women's sexual health in different perspectives. The investigated areas concerning female RA-patients and sexual are general sexual problems, sexual satisfaction, sexual desire, sexual performance, and sexual functioning. RA affects sexual health as a result of pain, reduced joint mobility, fatigue, depression and body image alterations. The investigated material provides few solutions to sexual health problems of female RA-patients. The most commonly mentioned solution is increased information and communication between health professionals and patients. Some of the studies recommend physiotherapy. Further research is needed to understand which types of intervention can help women with RA to improve their sexual health.


Deficient grip force control in schizophrenia: behavioral and modeling evidence for altered motor inhibition and motor noise.
Whether upper limb sensorimotor control is affected in schizophrenia and how underlying pathological mechanisms may potentially intervene in these deficits is still being debated. We tested voluntary force control in schizophrenia patients and used a computational model in order to elucidate potential cerebral mechanisms underlying sensorimotor deficits in schizophrenia. A visuomotor grip force-tracking task was performed by 17 medicated and 6 non-medicated patients with schizophrenia (DSM-IV) and by 15 healthy controls. Target forces in the ramp-hold-and-release paradigm were set to 5 N and to 10% maximal voluntary grip force. Force trajectory was analyzed by performance measures and Principal Component Analysis (PCA). A computational model incorporating neural control signals was used to replicate the empirically observed motor behavior and to explore underlying neural mechanisms. Grip task performance was significantly lower in medicated and non-medicated schizophrenia patients compared to controls. Three behavioral variables were significantly higher in both patient groups: tracking error (by 50%), coefficient of variation of force (by 57%) and duration of force release (up by 37%). Behavioral performance did not differ between patient groups. Computational simulation successfully replicated these findings and predicted that decreased motor inhibition, together with an increased signal-dependent motor noise, are sufficient to explain the observed motor deficits in patients. PCA also suggested altered motor inhibition as a key factor differentiating patients from control subjects: the principal component representing inhibition correlated with clinical severity. These findings show that schizophrenia affects voluntary sensorimotor control of the hand independent of medication, and suggest that reduced motor inhibition and increased signal-dependent motor noise likely reflect key pathological mechanisms of the sensorimotor deficit.


Proximal spherical metatarsal osteotomy for the foot with severe hallux valgus.
A proximal spherical metatarsal osteotomy was devised to correct not only varus deviation of the first metatarsal, but also dorsiflexion. We expected to increase the medial longitudinal arch by adding plantar flexion at the osteotomy site. To investigate the limitations of this procedure for feet with severe hallux valgus, a followup study was performed on patients with preoperative hallux valgus angles greater than or equal to 40 degrees. Forty-eight feet in 37 patients (10 male, 27 female) (60 years; range, 20 to 84 years) were investigated. Mean followup was 4 years and 1 month, ranging from 2 to 8 years. The spherical osteotomy was performed using a curved chisel. A distal soft tissue procedure was done at the same time. Twenty feet received combined operations for their combined deformities. While 81% of patients were satisfied with the results, 50% of those with preoperative hallux valgus angles greater than or equal to 50 degrees had postoperative hallux valgus angle greater than or equal to 20 degrees. In these patients, correction of metatarsus primus varus was good, but correction of valgus deviation of the hallux was fair. Mean correction toward plantar flexion was 1.5 degrees and no increase in arch height was achieved. The proximal spherical osteotomy could consistently achieve satisfactory results for the patients with hallux valgus angles less than 50 degrees. However, the corrections were worse in feet with more severe deformities. Furthermore, plantarflexion at the osteotomy site was offset by displacement at the first tarsometatarsal joint. If plantarflexion is indispensable, arthrodesis of the tarsometatarsal joint is recommended.


Acute Chagas' disease in western Venezuela: a clinical, seroparasitologic, and epidemiologic study.
A clinical, parasitologic, and serologic study carried out between 1988 and 1996 on 59 acute-phase patients in areas of western Venezuela where Chagas' disease is endemic showed 19 symptomatic patterns or groups of symptoms appearing in combination with different frequencies. The symptomatic pattern with the highest frequency was that showing simultaneously fever, myalgia, headache, and Romaña's sign, which was detected in 20% of the acute-phase patients. Asymptomatic individuals and patients with fever as the only sign of the disease made up 15% and 11.9% of the total acute cases, respectively. Statistical correlation analysis revealed that xenodiagnosis and hemoculture were the most reliable and concordant of the five parasitologic methods used; these two methods also showed the highest proportions in detecting any clinical symptomatic pattern in acute-phase patients. A similar high reliability and concordance was obtained with a direct agglutination test, an indirect immunofluorescent antibody test, and an ELISA as serologic tests, which also showed a higher proportion of positive detection of clinical patterns than parasitologic methods (P < 0.001). It is recommended that individuals coming from endemic areas showing mild and/or severe clinical manifestations should be suspected of being in contact or having been in contact with Trypanosoma cruzi, be referred for parasitologic and serologic evaluations to confirm the presumptive clinical diagnosis of acute Chagas' disease, and start specific treatment. The epidemiologic implications of the present findings are discussed and the use of similar methodology to evaluate other areas where Chagas' disease is endemic is suggested.


Skin cancer detection by spectroscopic oblique-incidence reflectometry: classification and physiological origins.
Data obtained from 102 skin lesions in vivo by spectroscopic oblique-incidence reflectometry were analyzed. The participating physicians initially divided the skin lesions into two visually distinguishable groups based on the lesions' melanocytic conditions. Group 1 consisted of the following two cancerous and benign subgroups: (1) basal cell carcinomas and squamous cell carcinomas and (2) benign actinic keratoses, seborrheic keratoses, and warts. Group 2 consisted of (1) dysplastic nevi and (2) benign common nevi. For each group, a bootstrap-based Bayes classifier was designed to separate the benign from the dysplastic or cancerous tissues. A genetic algorithm was then used to obtain the most effective combination of spatiospectral features for each classifier. The classifiers, tested with prospective blind studies, reached statistical accuracies of 100% and 95% for groups 1 and 2, respectively. Properties that related to cell-nuclear size, to the concentration of oxyhemoglobin, and to the concentration of deoxyhemoglobin as well as the derived concentration of total hemoglobin and oxygen saturation were defined to explain the origins of the classification outcomes.


What's in a name? The MMPI-2 PTSD scales.
The MMPI-2 post-traumatic stress disorder scales (PK and PS) were examined with a sample of 96 outpatient anxiety disorder and 97 outpatient traffic accident subjects. PK and PS correlated .96 and showed highly similar correlations with MMPI-2 validity, clinical, content and supplementary scales for both groups, which indicated that these scales are indices of MMPI first-factor variance. This was supported by separate principal components analyses for each group, in which PK and PS contributed the most variance to the first component. Although the groups showed different MMPI-2 mean profiles, neither PK nor PS contributed to discriminant function classification of group members. It is suggested that PK and PS are indices of general emotional distress and maladjustment; implications for their use in diagnosing post-traumatic stress disorder were discussed.


Development of a Bacterial Biosensor for Rapid Screening of Yeast p-Coumaric Acid Production.
Transcription factor-based biosensors are used to identify producer strains, a critical bottleneck in cell factory engineering. Here, we address two challenges with this methodology: transplantation of heterologous transcriptional regulators into new hosts to generate functional biosensors and biosensing of the extracellular product concentration that accurately reflects the effective cell factory production capacity. We describe the effects of different translation initiation rates on the dynamic range of a p-coumaric acid biosensor based on the Bacillus subtilis transcriptional repressor PadR by varying its ribosomal binding site. Furthermore, we demonstrate the functionality of this p-coumaric acid biosensor in Escherichia coli and Corynebacterium glutamicum. Finally, we encapsulate yeast p-coumaric acid-producing cells with E. coli-biosensing cells in picoliter droplets and, in a microfluidic device, rapidly sort droplets containing yeast cells producing high amounts of extracellular p-coumaric acid using the fluorescent E. coli biosensor signal. As additional biosensors become available, such approaches will find broad applications for screening of an extracellular product.


Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-induced nephrotoxicity in rats.
In an attempt to define the role of the pineal secretory melatonin and an analogue, 6-hydroxymelatonin (6-OHM), in limiting oxidative stress, the present study investigated the cisplatin (CP)-induced alteration in the renal antioxidant system and nephroprotection with the two indolamines. Melatonin (5 mg/kg), 6-OHM (5 mg/kg), or an equal volume of saline were administered intraperitoneally (i.p.) to male Sprague Dawley rats 30 min prior to an i.p. injection of CP (7 mg/kg). After CP treatment, the animals each received indolamine or saline every day and were sacrificed 3 or 5 days later and plasma as well as kidney were collected. Both plasma creatinine and blood urea nitrogen increased significantly following CP administration alone; these values decreased significantly with melatonin co-treatment of CP-treated rats. In the kidney, CP decreased the levels of GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio, an index directly related to oxidative stress. When animals were treated with melatonin, the reduction in the GSH/GSSG ratio was prevented. Treatment of CP-enhanced lipid peroxidation in the kidney was again prevented in animals treated with melatonin. The activity of the antioxidant enzyme, glutathione peroxidase (GSH-Px), decreased as a result of CP administration, which was restored to control levels with melatonin co-treatment. Upon histological analysis, damage to the proximal tubular cells was seen in the kidneys of CP-treated rats; these changes were prevented by melatonin treatment. 6-OHM has been shown to have some antioxidative capacity, however, the protective effects of 6-OHM against CP-induced nephrotoxicity were less than those of melatonin. The residual platinum concentration in the kidney of melatonin co-treated rats was significantly lower than that of rats treated with CP alone. It is concluded that administration of CP imposes a severe oxidative stress to renal tissue and melatonin confers protection against the oxidative damage associated with CP. This mechanism may be reasonably attributed to its radical scavenging activity, to its GSH-Px activating property, and/or to its regulatory activity for renal function.


Individualized Asian rhinoplasty: a systematic approach to facial balance.
Asian rhinoplasty, and rhinoplasty performed in other ethnic groups, remains a challenging operation for plastic surgeons. Precise clinical analysis and systematic planning preoperatively are widely accepted as the keys to success. Although a variety of analytical techniques have been published for other ethnic groups, a systematic approach for Asian rhinoplasty remains underrepresented in the current literature. A systematic approach and a stepwise technique were developed concomitantly with concepts in facial balance and proper preoperative evaluation for Asian patients. A retrospective review of 110 cases in 4 years was performed to evaluate the effectiveness of this approach. Follow-up ranged from 6 to 48 months. Satisfactory results were achieved in 86 percent of cases. Typical cases were also reviewed. The systematic approach in Asian rhinoplasty presents a way to link appropriate analysis with specific techniques aimed at the subtleties of Asian rhinoplasty. This leads toward the individual's aesthetic goals. In the authors' experience, this approach allows for predictable and optimized results for this challenging procedure. Therapeutic, IV.


Use of SYTO 13, a fluorescent dye binding nucleic acids, for the detection of microparticles in in vitro systems.
Microparticles (MPs) are small membrane-bound vesicles that are released from activated or dying cells by a blebbing process. These particles contain nuclear and cytoplasmic components and represent unique biomarkers for disease. The small size of particles, however, limits detection using flow cytometry with either light scatter or staining for surface markers. Because MPs contain DNA and RNA, we have explored the use of SYTO 13, a member of the class of SYTO dyes, for particle detection. SYTO 13 is cell permeable and has a high fluorescent yield when bound to DNA or RNA. In this study, we compared detection of MPs using either light scatter or SYTO 13 staining, testing the hypothesis that, with fluorescence detection with SYTO 13, problems of "noise" with light scatter are reduced and the range of MP sizes detected is increased. In these experiments, particles were obtained from lymphoid cell lines treated in vitro to undergo apoptosis. As these results showed, STYO 13 allowed the detection of 1.5-2.9 times as many particles as did light scatter. The increased sensitivity was observed with three different cell lines and was independent of inducing stimulus. Treatment of fixed and permeabilized MPs with DNase and RNase showed that SYTO 13 binding resulted from interaction with both DNA and RNA. Together, these findings indicate that the nucleic acid content of MPs provides the basis for their detection in in vitro systems and suggests the utility of fluorescent dyes like SYTO 13 for more sensitive quantitative assays.


The Metabolic Significance of Intermuscular Adipose Tissue: Is IMAT a Friend or a Foe to Metabolic Health?
Adipose tissues are not homogeneous and show site-specific properties. An elusive and understudied adipose tissue depot, most likely due to its limited accessibility, is the intermuscular adipose tissue (IMAT) depot. Adipose tissue is a pliable organ with the ability to adapt to its physiological context, yet whether that adaptation is harmful or beneficial in the IMAT depot remains to be explored in humans. Potential reasons for IMAT accumulation in humans being deleterious or beneficial include 1) sex and related circulating hormone levels, 2) race and ethnicity, and 3) lifestyle factors (e.g., diet and physical activity level). IMAT quantity per se may not be the driving factor in the etiology of insulin resistance and type 2 diabetes, but rather the quality of the IMAT itself is the true puppeteer. Adipose tissue quality likely influences its secreted factors, which are also likely to influence metabolism of surrounding tissues. The advent of molecular assessments such as transcriptome sequencing (RNAseq), assay for transposase-accessible chromatin using sequencing (ATACseq), and DNA methylation at the single-cell and single-nucleus levels, as well as the potential for ultrasound-guided biopsies specifically for IMAT, will permit more sophisticated investigations of human IMAT and dramatically advance our understanding of this enigmatic adipose tissue.


Aquatic therapy for boys with Duchenne muscular dystrophy (DMD): an external pilot randomised controlled trial.
Standard treatment of Duchenne muscular dystrophy (DMD) includes regular physiotherapy. There are no data to show whether adding aquatic therapy (AT) to land-based exercises helps maintain motor function. We assessed the feasibility of recruiting and collecting data from boys with DMD in a parallel-group pilot randomised trial (primary objective), also assessing how intervention and trial procedures work. Ambulant boys with DMD aged 7-16 years established on steroids, with North Star Ambulatory Assessment (NSAA) score ≥8, who were able to complete a 10-m walk test without aids or assistance, were randomly allocated (1:1) to 6 months of either optimised land-based exercises 4 to 6 days/week, defined by local community physiotherapists, or the same 4 days/week plus AT 2 days/week. Those unable to commit to a programme, with >20% variation between NSAA scores 4 weeks apart, or contraindications to AT were excluded. The main outcome measures included feasibility of recruiting 40 participants in 6 months from six UK centres, clinical outcomes including NSAA, independent assessment of treatment optimisation, participant/therapist views on acceptability of intervention and research protocols, value of information (VoI) analysis and cost-impact analysis. Over 6 months, 348 boys were screened: most lived too far from centres or were enrolled in other trials; 12 (30% of the targets) were randomised to AT (n = 8) or control (n = 4). The mean change in NSAA at 6 months was -5.5 (SD 7.8) in the control arm and -2.8 (SD 4.1) in the AT arm. Harms included fatigue in two boys, pain in one. Physiotherapists and parents valued AT but believed it should be delivered in community settings. Randomisation was unattractive to families, who had already decided that AT was useful and who often preferred to enrol in drug studies. The AT prescription was considered to be optimised for three boys, with other boys given programmes that were too extensive and insufficiently focused. Recruitment was insufficient for VoI analysis. Neither a UK-based RCT of AT nor a twice weekly AT therapy delivered at tertiary centres is feasible. Our study will help in the optimisation of AT service provision and the design of future research. ISRCTN41002956.


Strategies for the prevention of autoimmune type 1 diabetes.
European experts on autoimmune Type 1 diabetes met for 2 days in October 2010 in Cambridge, to review the state-of-the-art and to discuss strategies for prevention of Type 1 diabetes (http://www-gene.cimr.cam.ac.uk/todd/sub_pages/T1D_prevention_Cambridge_workshop_20_21Oct2010.pdf). Meeting sessions examined the epidemiology of Type 1 diabetes; possible underlying causes of the continuing and rapid increase in Type 1 diabetes incidence at younger ages; and lessons learned from previous prevention trials. Consensus recommendations from the meeting were: 1. Resources such as national diabetes registries and natural history studies play an essential role in developing and refining assays to be used in screening for risk factors for Type 1 diabetes. 2. It is crucial to dissect out the earliest physiological events after birth, which are controlled by the susceptibility genes now identified in Type 1 diabetes, and the environmental factors that might affect these phenotypes, in order to bring forward a mechanistic approach to designing future prevention trials. 3. Current interventions at later stages of disease, such as in newly diagnosed Type 1 diabetes, have relied mainly on non-antigen-specific mechanisms. For primary prevention-preventing the onset of autoimmunity-interventions must be based on knowledge of the actual disease process such that: participants in a trial would be stratified according the disease-associated molecular phenotypes; the autoantigen(s) and immune responses to them; and the manipulation of the environment, as early as possible in life. Combinations of interventions should be considered as they may allow targeting different components of disease, thus lowering side effects while increasing efficacy.


Molecular aggregation state and photovoltaic properties of chlorophyll-doped conducting poly(3-hexylthiophene)/MCM-41 nanocomposites.
Chlorophyll (Chl) was immobilized into a 1,4-butanediol-modified MCM-41 (BMCM-41) intercalated by poly(3-hexylthiophene) (P3HT) to form BMCM-41/P3HT/Chl nanocomposites having P3HT contents of 10, 30, 60, and 90 wt % from a solution-casting method. Wide-angle X-ray diffraction and transmission electron microscopy studies indicate that the pore structure of MCM-41 was retained after surface modification and a subsequent P3HT intercalation process. Scanning electron microscopy images showed that the BMCM-41 nanoparticles dispersed into the polymer matrix of BMCM-41/P3HT/Chl, and the sample with 10 wt % P3HT content gives the most homogeneous nanoparticle dispersion. Nitrogen adsorption-desorption results confirmed that the P3HT intercalation and Chl immobilization inside the BMCM-41 mesopore were successfully carried out. The pore volume and surface area of BMCM-41 decreased significantly when the amount of P3HT was increased from 10 to 90 wt %. The UV-vis study showed a blue shift of the pi-pi* transition band of P3HT in the spectra of BMCM-41/P3HT/Chl nanocomposites. The FT-IR study indicates an increase of the thiophene ring stretching and a decrease of the C horizontal lineO stretching when P3HT and Chl were inside the mesopore. The photovoltaic property of Chl-doped P3HT was improved significantly upon the addition of BMCM-41 nanoparticles, and BMCM-41/P3HT-10/Chl exhibits the highest incident photon-to-current conversion efficiency of 7.16%.


Real-time tracking of the autophagy process in living cells using plasmonically enhanced Raman spectroscopy of fucoidan-coated gold nanoparticles.
To date, a variety of biological assays such as immunostaining, western blotting, enzyme-linked immunosorbent assay (ELISA), and flow cytometry have been used to analyze and trace important biological events and therapies. In addition to these techniques, the application of microscopic analytical techniques such as matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry and Raman spectroscopy is increasing, allowing information to be obtained at the molecular level. In this study, we have conducted real-time tracking of autophagy, a cellular process that has recently been attracting significant attention. To achieve this purpose, we performed Raman spectroscopy on human oral squamous carcinoma cells (HSC3) incubated with bioactive molecule-modified plasmonic gold nanoparticles. The bioactive molecule-nanoparticle complexes were synthesized using fucoidan, a biopolymer that induces autophagy. By using this platform, it was possible to trace the entire autophagic process successively from cell introduction to autophagic apoptosis. This fusion of nanocomposites and spectroscopic techniques is expected to enable more complex biological processes to be pursued at the molecular level in the future.


Evolution of oculomotor nerve paresis after endovascular coiling of posterior communicating artery aneurysms: a neuro-ophthalmological perspective.
Guglielmi detachable coil treatment is becoming an accepted alternative to microsurgical clipping for select intracerebral aneurysms. Resolution of oculomotor nerve paresis (ONP) after endovascular packing was claimed to be complete in two prior series, with three and six cases. We describe the evolution of ONP after Guglielmi detachable coil treatment of posterior communicating artery aneurysms, and we search for endovascular and patient factors correlated with the degree of functional nerve recovery. Twelve cases of ONP attributable to posterior communicating artery aneurysms were treated with Guglielmi detachable coils between 1999 and 2002. Eleven patients were available for follow-up monitoring. The degree of ONP was recorded at admission, at discharge, after 3 months, and at yearly intervals thereafter. The size of the aneurysm, the duration of ONP before coiling, the degree of coiling, age, and the presence of other microvascular risk factors were correlated with the degree of nerve recovery. Complete resolution of ONP did not occur in any of the 11 cases in this series. However, residual oculomotor nerve deficits did not cause diplopia with primary gaze for 10 of 11 patients. Clinically significant ptosis did not persist for any of the patients. The pupil remained minimally affected in all cases. Although mass effect remains after endovascular packing, oculomotor nerve dysfunction improves comparably to the recovery observed after surgical clipping. Contrary to previous reports, typical residual oculomotor nerve deficits persist. Older age and the presence of microvascular risk factors seem to be detrimental to ONP recovery.


The treatment of stable paediatric forearm fractures using a cast that may be removed at home: comparison with traditional management in a randomised controlled trial.
We investigated whether, in the management of stable paediatric fractures of the forearm, flexible casts that can be removed at home are as clinically effective, cost-effective and acceptable to both patient and parent as management using a cast conventionally removed in hospital. A single-centre randomised controlled trial was performed on 317 children with a mean age of 9.3 years (2 to 16). No significant differences were seen in the change in Childhood Health Assessment Questionnaire index score (p = 0.10) or EuroQol 5-Dimensions domain scores between the two groups one week after removal of the cast or the absolute scores at six months. There was a significantly lower overall median treatment cost in the group whose casts were removed at home (£150.88 (sem 1.90) vs £251.62 (sem 2.68); p < 0.001). No difference was seen in satisfaction between the two groups (p = 0.48).


Implementing emergency department-based HIV testing in a low-resource setting: The value of a structured feasibility assessment tool.
HIV is a worldwide health problem with continuing high rates of new infections in many parts of the world. This lack of progress in decreasing overall incidence rates has sparked innovative HIV testing strategies, including expansion of testing into the emergency department (ED) setting. Emergency departments have been shown to be high-yield testing venues in the United States and other developed world settings. The feasibility of expanding public health HIV services in the ED in limited-resource countries is unclear. We performed a cross-sectional feasibility assessment of a convenience sample of four hospitals in the Eastern Cape, South Africa. We administered three adapted interview tools from a previously field-tested survey instrument at each facility (total of 10 interviews) to gather an overview of the health facility, their HIV counselling and testing services, and their laboratory services. All of the health facilities had access to basic commodities such as water and electricity. Many had severe human resource limitations and provided care to wide population catchment areas. In addition, there was little integration of HIV testing into current daily ED operations. Hospital staff identified numerous barriers to future ED testing efforts. Although control of the HIV epidemic requires innovative testing strategies and treatment, specific assessments are warranted on how to incorporate routine HIV testing into an acute care facility like the ED, which typically has many competing priorities. The use of a prospective structured tool incorporating both barriers and benefits can provide valuable field-tested guidance for increased programme planning for HIV testing.


Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems.
Understanding and apprehension of the characteristics and circumstances in which mesenchymal stem cells (MSCs) affect and make alterations (enhance or reduce) to the growth of tumors and metastasis spread is pivotal, not only for reaching the possibility to employ MSCs as drug delivery systems, but also for making forward movement in the existing knowledge of involvement of major factors (tumor microenvironment, soluble signaling molecules, etc.) in the process of carcinogenesis. This capability is reliable because MSCs present a great basis for engineering and constructions of new systems to target cancers, intended to secrete therapeutic proteins in the tumor region, or for delivering of oncolytic viruses' directly at the tumor site (targeted chemotherapy with enzyme prodrug conversion or induction of tumor cell apoptosis). MSCs as a crucial segment of the tumor surroundings and their confirmed tumor tropism, are assumed to be an open gateway for the design of promising drug delivery systems. The presented paper reviews current publications in this fieldwork, searches out the most recent patents that were published after 2012 (WO2014066122, US20140017787, WO2015100268, US20150086515), and tries to present the current progress and future prospective on the design and development in anti-cancer drug delivery systems based on MSCs.


Frequency and pathological characteristics of drug-induced liver injury in a tertiary medical center.
Drug-induced liver injury (DILI) accounts for approximately 10% of acute hepatitis cases. DILI can arise as idiosyncratic or intrinsic injury from hundreds of drugs, herbals, and nutritional supplements and is essential to recognize as one of the differential diagnoses of hepatitis in a liver biopsy. The purpose of this study is to investigate the frequency and pathological characteristics of DILI related to the variety of hepatotoxic agents. We searched our pathology database for all patients with hepatitis diagnosed on liver biopsy from January 2012 to May 2016, and selected patients with a diagnosis of DILI. Electronic medical records were reviewed for patient medication list, history of herbal medicine or supplement use, and pre-biopsy liver function test (LFT) results. Clinical and pathologic correlation was used to determine the causative or related agents for DILI. We then assessed histopathologic features of liver injury and categorized biopsy findings as primarily bile duct injury, lobular/portal hepatitis, or mixed changes. Six hundred four total liver biopsies for hepatitis or liver injury were identified, of which 70 cases (11.6%) carried the diagnosis of DILI confirmed by clinical correlation. The most common etiologies associated with DILI were supplements and herbal products (31.4%), antimicrobials (14.3%), chemotherapeutics (11.4%), antilipidemics (7.1%) and immunomodulatory agents (7.1%). LFT results positively correlated with histological findings. Nutritional/herbal supplements have emerged as one of the major hepatotoxicity agents. DILI can manifest as predominantly hepatitis, bile duct injury or combination. Histological pattern recognition in the liver biopsy may help identify specific hepatotoxic agents causing DILI.


Regulation of Reduced Folate Carrier (RFC) by Vitamin D Receptor at the Blood-Brain Barrier.
Folates are essential for brain development and function. Folate transport in mammalian tissues is mediated by three major folate transport systems, i.e., reduced folate carrier (RFC), proton-coupled folate transporter (PCFT), and folate receptor alpha (FRα), known to be regulated by ligand-activated nuclear receptors, such as vitamin D receptor (VDR). Folate uptake at the choroid plexus, which requires the actions of both FRα and PCFT, is critical to cerebral folate delivery. Inactivating FRα or PCFT mutations cause severe cerebral folate deficiency resulting in early childhood neurodegeneration. The objective of this study was to investigate the role of RFC in folate uptake at the level of the blood-brain barrier (BBB) and its potential regulation by VDR. We detected robust expression of RFC in different in vitro BBB model systems, particularly in immortalized cultures of human cerebral microvascular endothelial cells (hCMEC/D3) and isolated mouse brain capillaries. [3H]-methotrexate uptake by hCMEC/D3 cells at pH 7.4 was inhibited by PT523 and pemetrexed, antifolates with high affinity for RFC. We also showed that activation of VDR through calcitriol (1,25-dihydroxyvitamin D3) exposure up-regulates RFC mRNA and protein expression as well as function in hCMEC/D3 cells and isolated mouse brain capillaries. We further demonstrated that RFC expression could be down-regulated by VDR-targeting siRNA, further confirming the role of VDR in the direct regulation of this folate transporter. Together, these data suggest that augmenting RFC functional expression could constitute a novel strategy for enhancing brain folate delivery for the treatment of neurometabolic disorders caused by loss of FRα or PCFT function.


Modular peptide-functionalized gold nanorods for effective glioblastoma multicellular tumor spheroid targeting.
Glioblastoma multiforme (GBM) contains a population of tumor initiating stem-like cells, termed cancer stem cells (CSCs). These CSCs, which are resistant to chemo- and radiotherapy, are thought to persist after treatment and drive tumor recurrence. Thus, it is believed that the elimination of CSCs can lead to GBM remission. GBM CSCs express Nestin on their surface, and can be therefore targeted via this protein. Gold nanorods (AuNRs) functionalized with an engineered, modular peptide that recognizes Nestin (NesPEG-AuNRs) were used to target the models of solid tumors originated from human GBM CSC multicellular tumor spheroids (MCTS). In our study, we show that NesPEG-AuNRs have low cytotoxicity, are efficiently taken up by MCTS, and distribute uniformly throughout our tumor models, not only at the periphery as often seen in other nanoparticle systems. NesPEG-AuNR uptake by MCTS appears to be mediated by an energy/caveolae endocytic mechanism. Moreover, plasmon excitation of AuNRs in the near-infrared (NIR) region results in the production of localized heat. Consequently, NesPEG-AuNR cytotoxicity is only observed during NIR-irradiation in MCTS with a high intracellular AuNR content. The intracellular accumulation/diffusion of NesPEG-AuNRs and NIR-irradiation result in photothermally induced GBM CSC apoptosis and MCTS growth inhibition. In summary, these data suggest that the combination of the Nestin recognizing peptide with AuNRs contributes to better tumor accumulation/penetration, and thus in GBM CSC elimination. Moreover, due to the modularity of our peptide design, the Nestin-binding peptide sequence can be exchanged for peptides targeting other surface markers for the treatment of various types of tumors.


Modulation of fibroblast growth factor-2 receptor binding, signaling, and mitogenic activity by heparin-mimicking polysulfonated compounds.
Basic fibroblast growth factor (FGF-2) interacts with high-affinity tyrosine-kinase fibroblast growth factor receptors (FGFRs) and low-affinity heparan sulfate proteoglycans (HSPGs) in target cells. Both interactions are required for FGF-2-mediated biological responses. Here we report the FGF-2 antagonist activity of novel synthetic sulfonic acid polymers with distinct chemical structures and molecular masses (MMs). PAMPS [poly(2-acrylamido-2-methyl-1-propanesulfonic acid)], (MM approximately 7,000-10,000), PAS [poly(anetholesulfonic acid)], (MM approximately 9,000-11,000), PSS [poly(4-styrenesulfonic acid)], (MM = 70,000), and poly(vinylsulfonic acid) (MM = 2,000), inhibited FGF-2 binding to HSPGs and FGFRs in fetal bovine aortic endothelial GM 7373 cells. They also abrogated the formation of the HSPG/FGF-2/FGFR ternary complex, as evidenced by their capacity to prevent FGF-2-mediated cell-cell attachment of FGFR-1-overexpressing, HSPG-deficient Chinese hamster ovary cells to wild-type HSPG-bearing cells. Direct interaction of the polysulfonates with FGF-2 was demonstrated by their ability to protect the growth factor from proteolytic cleavage. Accordingly, molecular modeling, based on the crystal structure of the interaction of FGF-2 with a heparin hexamer, showed the feasibility of docking PAMPS into the heparin-binding domain of FGF-2. In agreement with their FGF-2-binding capacity, PSS, PAS, and PAMPS inhibited FGF-2-induced cell proliferation in GM 7373 cells and murine brain microvascular endothelial cells. The antiproliferative activity of these compounds was associated with the abrogation of FGF-2-induced tyrosine phosphorylation of FGFR-1. Moreover, the polysulfonates PSS and PAS inhibited FGF-2-induced activation of mitogen-activated protein kinase-1/2, involved in FGF-2 signal transduction. In conclusion, sulfonic acid polymers bind FGF-2 by mimicking heparin interaction. These compounds may provide a tool to inhibit FGF-2-induced endothelial cell proliferation in angiogenesis and tumor growth.


Traits of riparian woody plants responding to hydrological and hydraulic conditions: a northern Swedish database.
The main goal of this study was to create a database that ultimately serves further studies on riparian vegetation and flow response guilds in the boreal region and on transferability of results across different regions. To achieve this aim, we compiled traits for all woody riparian species in northern Sweden which, directly or indirectly, underlie their responses to hydrological and hydraulic conditions, between October 2012 and April 2015. Consulted sources of information were diverse, ranging from scientific to informative and whose accuracy might or might not be verified. They were focused on particular or several traits and species from concrete areas to a worldwide perspective. Sources were characterized by different degrees of accessibility and showed a wide variety of descriptions, categorical and ordinal classifications, and numerical information for each trait. Our effort was to synthesize information for each trait from all sources into the common frame of our own database, following own defined criteria so that comparisons between species are congruent. Therefore, this data set is unique in that it comprehensively combines and homogenizes morphological, phenological, reproductive, and ecological data for 59 woody, riparian, boreal species and from 118 sources of information, that would otherwise be scattered and hardly available.


Caulerpenyne binding to tubulin: structural modifications by a non conventional pharmacological agent.
The most widely used molecules in cancer chemotherapy are Vinca-alkaloids and Taxoids, numerous chemists attempted the synthesis of analogs which bind to their well-known tubulin pharmacological site. Unfortunately, tumors develop resistance to these compounds; therefore the definition of anchoring points and potential binding sites for new drugs on tubulin is of major interest. Caulerpenyne (Cyn), the major secondary metabolite synthesized by the green marine alga Caulerpa taxifolia could be one of these drugs, since it inhibits the assembly of tubulin and MTP (Barbier et al., 2001). We observed that the tubulin-Cyn complex is poorly reversed. Cyn did not bind to sulfhydryl groups and the measure of the extent of binding is 1.6 +/- 0.2 suggesting two potential binding sites. Then, we demonstrated by competition measurements that Cyn did not interact to colchicine, Taxol and Vinca-alkaloid binding domain. Finally, mass spectrometric analysis of proteolytic cleavage of tubulin-Cyn complex demonstrated that Cyn did not bind covalently to tubulin and evidenced two good candidate regions for Cyn binding, one on alpha-tubulin and the other on beta-tubulin.


Solubility of cellulose in supercritical water studied by molecular dynamics simulations.
The insolubility of cellulose in ambient water and most aqueous systems presents a major scientific and practical challenge. Intriguingly though, the dissolution of cellulose has been reported to occur in supercritical water. In this study, cellulose solubility in ambient and supercritical water of varying density (0.2, 0.7, and 1.0 g cm(-3)) was studied by atomistic molecular dynamics simulations using the CHARMM36 force field and TIP3P water. The Gibbs energy of dissolution was determined between a nanocrystal (4 × 4 × 20 anhydroglucose residues) and a fully dissociated state using the two-phase thermodynamics model. The analysis of Gibbs energy suggested that cellulose is soluble in supercritical water at each of the studied densities and that cellulose dissolution is typically driven by the entropy gain upon the chain dissociation while simultaneously hindered by the loss of solvent entropy. Chain dissociation caused density augmentation around the cellulose chains, which improved water-water bonding in low density supercritical water whereas the opposite occurred in ambient and high density supercritical water.


Sensing Gram-negative bacteria: a phylogenetic perspective.
Gram-negative bacteria represent a major group of pathogens that infect all eukaryotes from plants to mammals. Gram-negative microbe-associated molecular patterns include lipopolysaccharides and peptidoglycans, major immunostimulatory determinants across phyla. Recent advances have furthered our understanding of Gram-negative detection beyond the well-defined pattern recognition receptors such as TLR4. A B-type lectin receptor for LPS and Lysine-motif containing receptors for peptidoglycans were recently added to the plant arsenal. Caspases join the ranks of mammalian cytosolic immune detectors by binding LPS, and make TLR4 redundant for septic shock. Fascinating bacterial evasion mechanisms lure the host into tolerance or promote inter-bacterial competition. Our review aims to cover recent advances on bacterial messages and host decoding systems across phyla, and highlight evolutionarily recurrent strategies.


Effect of fruit and vegetable concentrates on endothelial function in metabolic syndrome: a randomized controlled trial.
Dehydrated fruit and vegetable concentrates provide an accessible form of phytonutrient supplementation that may offer cardioprotective effects. This study assessed the effects of two blends of encapsulated juice powder concentrates (with and without added berry powders) on endothelial function in persons with metabolic syndrome, a risk factor for type 2 diabetes and cardiovascular disease. Randomized, double blind, placebo controlled crossover clinical trial with three treatment arms. 64 adults with metabolic syndrome were enrolled and received 8-week sequences of each blend of the concentrates and placebo. The primary outcome measure was change in endothelial function (assessed as flow-mediated dilatation of the brachial artery) 2 hr after consuming a 75 g glucose load, after 8-weeks of daily consumption (sustained) or 2 hr after consumption of a single dose (acute). Secondary outcome measures included plasma glucose, serum insulin, serum lipids, and body weight. No significant between-group differences in endothelial function with daily treatment for 8 weeks were seen. No other significant treatment effects were discerned in glucose, insulin, lipids, and weight. Encapsulated fruit and vegetable juice powder concentrates did not alter insulin or glucose measures in this sample of adults with metabolic syndrome. clinicaltrials.gov NCT01224743.


Analgesia nociception index and systemic haemodynamics during anaesthetic induction and tracheal intubation: A secondary analysis of a randomised controlled trial.
Direct laryngoscopy and tracheal intubation is a noxious stimulation that induces significant stress response. Currently, this nociceptive response is assessed mainly by haemodynamic changes. Recently, analgesia nociception index (ANI) is introduced into anaesthesia practice and provides objective information about parasympathetic (low nociceptive stress) and sympathetic (high nociceptive stress) balance, which reflects the degree of intraoperative nociception/analgesia. This study evaluated the changes in ANI and haemodynamics during anaesthetic induction and intubation, and their correlation during tracheal intubation. Sixty adult patients scheduled for elective brain tumour surgery under general anaesthesia were studied for changes in ANI, heart rate (HR) and mean blood pressure (MBP) during anaesthetic induction and intubation. This was a secondary analysis of a previously published trial. Linear mixed effects model was used to evaluate changes in ANI, HR and MBP and to test correlation between ANI and haemodynamics. Anaesthetic induction reduced ANI (but not below the critical threshold of nociception of 50) and MBP, and increased the HR (P < 0.001). Direct laryngoscopy and tracheal intubation resulted in increase in HR and MBP with decrease in ANI below the threshold of 50 (P < 0.001). A linear negative correlation was observed between ANI and HR; r = -0.405, P < 0.001, and ANI and MBP; r = -0.415, P = 0.001. Significant changes are observed in ANI during anaesthetic induction and intubation. There is a negative linear correlation between ANI and systemic haemodynamics during intubation.


Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.
Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.


Cost-effectiveness of pneumococcal vaccination strategies for the elderly in Korea.
Although the 13-valent pneumococcal conjugate vaccine (PCV13) showed good efficacy against pneumococcal disease in the the CAPiTA trial, the 23-valent pneumococcal polysaccharide vaccination (PPSV23) program has been ongoing for older adults aged ≥ 65 years in Korea since May of 2013. This study aimed to evaluate the cost-effectiveness of the current vaccination strategy (a single-dose PPSV23 vaccination) compared to a single-dose PCV13 vaccination and sequential PCV13-PPSV23 vaccinations in the elderly population aged ≥ 65 years. Using a Markov model, the incremental cost-effectiveness ratios (ICERs) of three vaccination strategies were assessed in a societal context. The transition probabilities, utility weights to estimate quality adjusted life year (QALY), and disease treatment costs were either calculated or cited from published data and the Health Insurance Review and Assessment Service. Simulations were performed in hypothetical cohorts of Korean adults aged ≥ 19 years. The vaccine effectiveness of PPSV23 was cited from a Cochrane Review report, while PCV13 effectiveness data were gathered from the CAPiTA trial. Current PPSV23 vaccination strategies were cost-effective (ICER, $25,786 per QALY). However, the administration of PCV13 as a substitute for PPSV23 was shown to be more cost-effective than PPSV23 vaccination (ICER, $797 per QALY). Sequential PCV13-PPSV23 vaccination was also more cost-effective than PPSV23 for elderly people aged ≥ 65 years. In sensitivity analysis assuming significant PPSV23 effectiveness (50%) against non-bacteremic pneumococcal pneumonia, the PCV13 vaccination strategy was superior to the PPSV23 vaccination strategy in terms of cost-effectiveness. The results suggest that PCV13 vaccination is more cost-effective in elderly subjects aged ≥ 65 years compared to the current PPSV23 vaccination strategy. When complete data is obtained in 2018 on the maximal herd effects of childhood PCV13 immunization, the incidence of pneumococcal pneumonia and the cost-effectiveness of vaccination strategies need to be reassessed.