Specific treatment of problems of the spine (STOPS): design of a randomised controlled trial comparing specific physiotherapy versus advice for people with subacute low back disorders.
Low back disorders are a common and costly cause of pain and activity limitation in adults. Few treatment options have demonstrated clinically meaningful benefits apart from advice which is recommended in all international guidelines. Clinical heterogeneity of participants in clinical trials is hypothesised as reducing the likelihood of demonstrating treatment effects, and sampling of more homogenous subgroups is recommended. We propose five subgroups that allow the delivery of specific physiotherapy treatment targeting the pathoanatomical, neurophysiological and psychosocial components of low back disorders. The aim of this article is to describe the methodology of a randomised controlled trial comparing specific physiotherapy treatment to advice for people classified into five subacute low back disorder subgroups. A multi-centre parallel group randomised controlled trial is proposed. A minimum of 250 participants with subacute (6 weeks to 6 months) low back pain and/or referred leg pain will be classified into one of five subgroups and then randomly allocated to receive either physiotherapy advice (2 sessions over 10 weeks) or specific physiotherapy treatment (10 sessions over 10 weeks) tailored according to the subgroup of the participant. Outcomes will be assessed at 5 weeks, 10 weeks, 6 months and 12 months following randomisation. Primary outcomes will be activity limitation measured with a modified Oswestry Disability Index as well as leg and back pain intensity measured on separate 0-10 Numerical Rating Scales. Secondary outcomes will include a 7-point global rating of change scale, satisfaction with physiotherapy treatment, satisfaction with treatment results, the Sciatica Frequency and Bothersomeness Scale, quality of life (EuroQol-5D), interference with work, and psychosocial risk factors (Orebro Musculoskeletal Pain Questionnaire). Adverse events and co-interventions will also be measured. Data will be analysed according to intention to treat principles, using linear mixed models for continuous outcomes, Mann Whitney U tests for ordinal outcomes, and Chi-square, risk ratios and risk differences for dichotomous outcomes. This trial will determine the difference in outcomes between specific physiotherapy treatment tailored to each of the five subgroups versus advice which is recommended in guidelines as a suitable treatment for most people with a low back disorder. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000834257.


Two-dimensional intraventricular flow mapping by digital processing conventional color-Doppler echocardiography images.
Doppler echocardiography remains the most extended clinical modality for the evaluation of left ventricular (LV) function. Current Doppler ultrasound methods, however, are limited to the representation of a single flow velocity component. We thus developed a novel technique to construct 2D time-resolved (2D+t) LV velocity fields from conventional transthoracic clinical acquisitions. Combining color-Doppler velocities with LV wall positions, the cross-beam blood velocities were calculated using the continuity equation under a planar flow assumption. To validate the algorithm, 2D Doppler flow mapping and laser particle image velocimetry (PIV) measurements were carried out in an atrio-ventricular duplicator. Phase-contrast magnetic resonance (MR) acquisitions were used to measure in vivo the error due to the 2D flow assumption and to potential scan-plane misalignment. Finally, the applicability of the Doppler technique was tested in the clinical setting. In vitro experiments demonstrated that the new method yields an accurate quantitative description of the main vortex that forms during the cardiac cycle (mean error for vortex radius, position and circulation). MR image analysis evidenced that the error due to the planar flow assumption is close to 15% and does not preclude the characterization of major vortex properties neither in the normal nor in the dilated LV. These results are yet to be confirmed by a head-to-head clinical validation study. Clinical Doppler studies showed that the method is readily applicable and that a single large anterograde vortex develops in the healthy ventricle while supplementary retrograde swirling structures may appear in the diseased heart. The proposed echocardiographic method based on the continuity equation is fast, clinically-compliant and does not require complex training. This technique will potentially enable investigators to study of additional quantitative aspects of intraventricular flow dynamics in the clinical setting by high-throughput processing conventional color-Doppler images.


A single exposure to severe stressors causes long-term desensitisation of the physiological response to the homotypic stressor.
Although some laboratories have reported that a single session of stress is able to induce a long-lasting sensitisation of the hypothalamic-pituitary-adrenal (HPA) response to further exposures to stress, we have found that a single exposure to severe emotional (immobilisation, restraint or shock) or systemic (endotoxin) stressors reduces the responsiveness of the HPA to the same, but not to a novel (heterotypic), stressor, in which case a slight sensitisation was observed. Long-term desensitisation has been found to reduce not only secretion of peripheral HPA hormones (ACTH and corticosterone), but also to reduce responses of central components of the HPA axis (c-fos and CRF gene expression at the level of the paraventricular nucleus of the hypothalamus, PVN). In addition, desensitisation also applies to the impact of the stressor on food intake and, probably, to stress-induced hyperglycaemia. The development of long-term desensitisation of the HPA axis does not appear to be a universal consequence of exposure to severe stressors as it was not observed in response to insulin-induced hypoglycaemia. Whether or not the development of long-term effects of stress depend on the specific pathways activated by particular stressors remains to be tested. The observed desensitisation of the HPA axis in response to the homotypic stressor shows two special features which makes it difficult to be interpreted in terms of an habituation-like process: (a) the effect increased with time (days to weeks) elapsed between the first and second exposure to the stressor, suggesting a progressive maturational process; and (b) the stronger the stressor the greater the long-term desensitisation. Therefore, it is possible that desensitisation of the HPA axis is the sum of two different phenomena: long-term effects and habituation-like processes. The contribution of the former may be more relevant with severe stressors and longer inter-stress intervals, and that of the latter with mild stressors and repeated exposures. Long-term stress-induced changes may not take place at the level of the PVN itself, but in brain nuclei showing synaptic plasticity and putatively involved in the control of the HPA axis and other physiological responses. As for the precise areas involved, these remain to be characterized.


A model for assessing occupational exposure to extremely low-frequency magnetic fields in fabrication rooms in the Semiconductor Health Study.
A model was created to assess occupational exposure to extremely low-frequency magnetic fields (ELF-MF) among semiconductor fabrication-room (fab) workers. This model was based on the assumption that each subject's exposure arose from being near identifiable ELF-MF sources or being in areas with high ELF-MF levels. To assess ELF-MF exposures, the model superimposed subjects' time-activity patterns (patterns of how and where they spent their time) with measurements of magnetic-field levels from devices and work areas. This model, which was validated by personal dosimetry on 192 persons in three fabs, predicted actual time-weighted average exposures with a correlation coefficient of 0.62. The inability of the model to predict individual exposures more accurately was attributed to unforseen sources of elevated ELF-MF (transformers, distribution panels, sources in adjacent rooms) or to errors in subjects' judgments of time spent near devices. These unpredictable errors are intrinsic to the method used to estimate exposure.


Spatiotemporal Quantification of Lithium both in Electrode and in Electrolyte with Atomic Precision via Operando Neutron Absorption.
The commercial uptake of lithium-sulfur (Li-S) batteries is undermined by their rapid performance decay and short cycle life. These problems originate from the dissolution of lithium polysulfide in liquid electrolytes, causing charge and active material to shuttle between electrodes. The dynamics of intractable polysulfide migration at different length scales often tend to escape the probing ability of many analytical techniques. Spatial and temporal visualization of Li in Li-S electrodes and direct mechanistic understanding of how polysulfides are regulated across Li-S batteries starting from current collector and active layer coating to electrode-electrolyte interface are still lacking. To address this we employ neutron depth profiling across Li-S electrodes using the naturally occurring isotope, 6Li, which yields direct spatial information on Li-S electrochemistry. Using three types of Li-S electrodes, namely, carbon-sulfur, carbon-sulfur with 10% lithium titanium oxide (LTO), and carbon-sulfur with LTO membrane, we provide direct evidence for the migration, adsorption, and confinement of polysulfides in Li-S cells at work. Our findings further provide insights into the dynamics of polysulfide dissolution and re-utilization in relation to Li-S battery capacity and longevity to aid rational electrode designs toward high-energy, safe, and low-cost batteries.


Drugs in the brain.
In our studies on the entry of drugs into the central nervous system we have found the technique of autoradiography combined with radioassay to be a valuable research tool. It has disclosed such unsuspected phenomena as the dual routes of entry into the brain of acetazolamide. Although many factors controlling drug entry remain to be studied, we propose certain general conclusions. 1) The anatomical boundaries of brain are clearly reflected by the penetration and accumulation of all compounds we have studied-a finding that confirms the original proposition that whole-brain homogenates are inadequate for the study of drug and brain relationships. 2) Circulation, expressed as egional blood flow or volume of capillary blood, was seldom decisive in nfluencing entry or accumulation of exogenous substances in the brain. To date, the only compounds demonstrated to be circulation-dependent are trifluoroiodomethane and thiopental. Both are extremely fat-soluble. Tissue binding appears to be an additional factor in the case of thiopental. 3) Penetration is retarded by myelin. All substances we have studied have shown a relatively slower rate of entry into this tissue. In immature brain, before myelinization has taken lace, the primordial white matter is readily penetrated. We have suggested that entry into mature white matter is retarded by the lamellated membranes of the myelin sheath, which should be regarded, therefore, as a component of the blood-brain barrier. The small interstitial space indicated by the limited entry of sulfate ion is an additional hindrance to dispersal of exogenous substances into brain parenchyma. The blood-brain barrier is a complex anatomical, physiological, and biochemical phenomenon, and no unitary hypothesis is adequate to embrace all the observed events. 4) Accumulation of a drug in the brain implies some form of binding or interaction between drug and tissue. Findings on injection of phenobarbital, thiopental, or diphenylhydantoin illustrate such an accumulation. These binding interactions may be nonspecific, as is probable in the case of drugs bound to plasma protein. However, a more fundamental significance is suggested when a drug is found to bind, react with, or accumulate in, a specific anatomical structure of the brain. We have made reference to this possibility in connection with the localization of isonicotinic acid hydrazide or its metabolites in the hippocampus (46), and we have also reported the striking accumulation of acetazolamide in hippocampus, caudate nucleus, and hypothalamus. Although the binding process is poorly understood, further investigation of these phenomena should lead to a clearer understanding of regional variations in brain chemistry. While one should not assume that the demonstration of a focal concentration of a drug implies site of action, correlation between pharmacological action, electrophysiological events, biochemical changes, and temporal and regional drug concentrations may indeed exist (47).


Profiles of COVID-19 Impact on Informal Caregivers of Older Mexican Americans.
Objectives: This manuscript is a descriptive exploratory study of the impact of the COVID-19 pandemic for caregivers of very old Mexican Americans. Methods: Using data from Wave 10 of the Hispanic Established Population for the Epidemiological Study of Elderly (2021), we examined the characteristics of caregivers of very old Mexican Americans by their perceived level of impact from the pandemic. We examined sociodemographic characteristics, COVID-19 testing and vaccination, stress and depression, and health of caregivers and care recipients. Results: Caregivers who reported the most impact were more likely to report financial and emotional stress. They reported more depressive symptoms and high levels of distress related to neuropsychological behavior symptoms of their care recipient. Discussion: High levels of depressive symptoms, financial stress, and neuropsychological behavior symptoms illustrate that the concerns of caregivers before the pandemic were heightened during the pandemic.


Single-molecule spectroscopy of LHCSR1 protein dynamics identifies two distinct states responsible for multi-timescale photosynthetic photoprotection.
In oxygenic photosynthesis, light harvesting is regulated to safely dissipate excess energy and prevent the formation of harmful photoproducts. Regulation is known to be necessary for fitness, but the molecular mechanisms are not understood. One challenge has been that ensemble experiments average over active and dissipative behaviours, preventing identification of distinct states. Here, we use single-molecule spectroscopy to uncover the photoprotective states and dynamics of the light-harvesting complex stress-related 1 (LHCSR1) protein, which is responsible for dissipation in green algae and moss. We discover the existence of two dissipative states. We find that one of these states is activated by pH and the other by carotenoid composition, and that distinct protein dynamics regulate these states. Together, these two states enable the organism to respond to two types of intermittency in solar intensity-step changes (clouds and shadows) and ramp changes (sunrise), respectively. Our findings reveal key control mechanisms underlying photoprotective dissipation, with implications for increasing biomass yields and developing robust solar energy devices.


Modelling the effectiveness of techniques for reducing heat strain in Royal Navy nuclear, biological and chemical cleansing stations' teams.
High temperatures, combined with wearing nuclear biological chemical (NBC) individual protective equipment (IPE), produce significant heat strain in personnel working in ships' NBC cleansing stations (CS) and limit the ability of ships to operate in a contaminated environment. This report reviews the potential solutions to this problem and concludes that only a method of actively cooling personnel will reduce heat strain and increase the number of people that can be processed through ships' NBC CS. Amongst the wide range of cooling equipment that might offer a benefit, only hand immersion in cold water and ice-vests are practically useful for use in NBC CS. To assess how effective these techniques are likely to be INM has modelled the thermal effects under environmental conditions expected in the CS when operating in a hot climate. The model predicted that hand immersion in cold water (10 degrees C) would be the most effective cooling method, providing that personnel were able to take regular rest periods to immerse the hands. If it is preferred that personnel in the CS be able to work continuously, then ice-vests would be effective. The safe total work time that can be achieved in a three hour period without a cooling intervention is approximately 72 minutes, regular rest periods must be taken throughout the three hour work period, to total of 108 minutes. Safe work times can be increased to 99 minutes by using an ice-vest and 117 minutes by using hand immersion in 10 degrees C water, with required rest times reduced accordingly, thereby increasing capacity of CS teams to decontaminate personnel.


[Immunodiagnostic findings in patients with kala-azar].
Using three immunoreactions (complement-fixation reaction; enzyme immune test; indirect immunofluorescence), antibody formation was tested in 66 patients with kala-azar and 74 controls (blood donors; accident patients). Moderately elevated and high antibody levels for each of three reactions were defined to provide diagnostic criteria. Moderately high or high antibody concentrations against Leishmania antigen were found in one of the three immunoreactions in 9 patients, in two of the three in 21, and in all three in 36 (55%). No Leishmania antigen was found in the serum of the controls. Similar results were obtained for 80% of those serum samples which had been sent in over a period of seven months to check for Leishmania antibodies (455 of 566 samples). In 25 of the remaining 111 serum samples moderate or high antigen concentrations were demonstrated, but in 21 of them in only one test. Leishmania antibodies were found to persist for several months after the clinical symptoms had disappeared. In 22 kala-azar patients the IgG concentrations were clearly elevated (greater than 3000 mg/dl), in five the IgM concentrations were elevated (greater than 400 mg/dl), while the IgA concentrations were normal or slightly decreased. The data indicate that kala-azar cases can be diagnosed with three appropriate immunoreactions which measure antibody concentrations.


The chaperonin CCT interacts with and mediates the correct folding and activity of three subunits of translation initiation factor eIF3: b, i and h.
eIF3 (eukaryotic initiation factor 3) is the largest and most complex eukaryotic mRNA translation factor in terms of the number of protein components or subunits. In mammals, eIF3 is composed of 13 different polypeptide subunits, of which five, i.e. a, b, c, g and i, are conserved and essential in vivo from yeasts to mammals. In the present study, we show that the eukaryotic cytosolic chaperonin CCT [chaperonin containing TCP-1 (tailless complex polypeptide 1)] binds to newly synthesized eIF3b and promotes the correct folding of eIF3h and eIF3i. Interestingly, overexpression of these last two subunits is associated with enhanced translation of specific mRNAs over and above the general enhancement of global translation. In agreement with this, our data show that, as CCT is required for the correct folding of eIF3h and eIF3i subunits, it indirectly influences gene expression with eIF3i overexpression enhancing both cap- and IRES (internal ribosome entry segment)-dependent translation initiation, whereas eIF3h overexpression selectively increases IRES-dependent translation initiation. Importantly, these studies demonstrate the requirement of the chaperonin machinery for the correct folding of essential components of the translational machinery and provide further evidence of the close interplay between the cell environment, cell signalling, cell proliferation, the chaperone machinery and translational apparatus.


Binding of NF-κB to nucleosomes: effect of translational positioning, nucleosome remodeling and linker histone H1.
NF-κB is a key transcription factor regulating the expression of inflammatory responsive genes. How NF-κB binds to naked DNA templates is well documented, but how it interacts with chromatin is far from being clear. Here we used a combination of UV laser footprinting, hydroxyl footprinting and electrophoretic mobility shift assay to investigate the binding of NF-κB to nucleosomal templates. We show that NF-κB p50 homodimer is able to bind to its recognition sequence, when it is localized at the edge of the core particle, but not when the recognition sequence is at the interior of the nucleosome. Remodeling of the nucleosome by the chromatin remodeling machine RSC was not sufficient to allow binding of NF-κB to its recognition sequence located in the vicinity of the nucleosome dyad, but RSC-induced histone octamer sliding allowed clearly detectable binding of NF-κB with the slid particle. Importantly, nucleosome dilution-driven removal of H2A-H2B dimer led to complete accessibility of the site located close to the dyad to NF-κB. Finally, we found that NF-κB was able to displace histone H1 and prevent its binding to nucleosome. These data provide important insight on the role of chromatin structure in the regulation of transcription of NF-κB dependent genes.


A controlled comparison of simulated and real ECT.
Two groups of 16 patients with depressive psychosis took part in a controlled evaluation of electro-convulsive therapy (ECT). One group received six brief pulse unilateral shocks under conventional anaesthesia and muscle relaxation; the second group underwent the same procedure without receiving shocks. Outcome was assessed by a separate investigator using the Hamilton Rating Scale for Depression under double-blind conditions. The results showed that this form of ECT was only superior to the control treatment for one item in the scale, a finding which could have occurred by chance. The results suggest that the ECT pre-treatment procedure has an important therapeutic effect. This casts some doubt on current views of the effectiveness of electro-convulsive therapy in general, and of brief pulse unilateral ECT in particular.


The impact of sampling, PCR, and sequencing replication on discerning changes in drinking water bacterial community over diurnal time-scales.
High-throughput and deep DNA sequencing, particularly amplicon sequencing, is being increasingly utilized to reveal spatial and temporal dynamics of bacterial communities in drinking water systems. Whilst the sampling and methodological biases associated with PCR and sequencing have been studied in other environments, they have not been quantified for drinking water. These biases are likely to have the greatest effect on the ability to characterize subtle spatio-temporal patterns influenced by process/environmental conditions. In such cases, intra-sample variability may swamp any underlying small, systematic variation. To evaluate this, we undertook a study with replication at multiple levels including sampling sites, sample collection, PCR amplification, and high throughput sequencing of 16S rRNA amplicons. The variability inherent to the PCR amplification and sequencing steps is significant enough to mask differences between bacterial communities from replicate samples. This was largely driven by greater variability in detection of rare bacteria (relative abundance <0.01%) across PCR/sequencing replicates as compared to replicate samples. Despite this, we captured significant changes in bacterial community over diurnal time-scales and find that the extent and pattern of diurnal changes is specific to each sampling location. Further, we find diurnal changes in bacterial community arise due to differences in the presence/absence of the low abundance bacteria and changes in the relative abundance of dominant bacteria. Finally, we show that bacterial community composition is significantly different across sampling sites for time-periods during which there are typically rapid changes in water use. This suggests hydraulic changes (driven by changes in water demand) contribute to shaping the bacterial community in bulk drinking water over diurnal time-scales.


Primerize-2D: automated primer design for RNA multidimensional chemical mapping.
Rapid RNA synthesis of comprehensive single mutant libraries and targeted multiple mutant libraries is enabling new multidimensional chemical approaches to solve RNA structures. PCR assembly of DNA templates and in vitro transcription allow synthesis and purification of hundreds of RNA mutants in a cost-effective manner, with sharing of primers across constructs allowing significant reductions in expense. However, these protocols require organization of primer locations across numerous 96 well plates and guidance for pipetting, non-trivial tasks for which informatics and visualization tools can prevent costly errors. We report here an online tool to accelerate synthesis of large libraries of desired mutants through design and efficient organization of primers. The underlying program and graphical interface have been experimentally tested in our laboratory for RNA domains with lengths up to 300 nucleotides and libraries encompassing up to 960 variants. In addition to the freely available Primerize-2D server, the primer design code is available as a stand-alone Python package for broader applications. http://primerize2d.stanford.edu. email@example.com. Supplementary data are available at Bioinformatics online.


Essential oils showing in vitro anti MRSA and synergistic activity with penicillin group of antibiotics.
This study was planned in order to investigate effective essential oils to inhibit in-vitro growth of Methicillin resistant Staphylococcus aureus (MRSA). In this study using disc diffusion method anti MRSA activity of ten diverse essential oils extracted from traditional plants namely Thymus vulgaris L, Mentha pulegium, Ocimum sanctum, Mentha piperita, Cymbopogon citratus, Rosmarinus officinalis L., Cortex cinnamom, Citrus nobilis x Citrus deliciosa, Origanum vulgare and Mentha sp. was examined. All the essential oils inhibited growth of S. aureus to different extent, by exhibiting moderate to elevated zones of inhibitions. Essential oils of cinnamon (Cortex cinnamomi) and thyme (Thymus vulgaris L) were observed to be the most powerful against MRSA strains used in this study. At lowest concentration of 25μl/ml essential oils comprehensible zone of inhibition was found 9±0.085mm and 8±0.051mm respectively, and at elevated concentrations there was a total decline in growth of MRSA and a very clear zone of inhibition was observed. A synergistic effect of essential oils in amalgamation with amoxicillin a Penicillin group of antibiotic was also examined. Interestingly a strong synergism was observed with oregano (Origanum vulgare) and pennyroyal mint (Mentha pulegium) essential oils, which were not so effective alone driven out to be important synergistic candidate. Our results demonstrated that essential oils of cinnamon and thyme can be used as potential antimicrobial agent against the Methicillin-resistant Staphylococcus aureus infections and Amoxicillin antibacterial activity can be enhanced using active constituents present in oregano and pennyroyal mint essential oils.


Risk Factors for Thyroid Dysfunction among Type 2 Diabetic Patients in a Highly Diabetes Mellitus Prevalent Society.
Diabetes and thyroid dysfunction found to exist simultaneously. In this regard, the present study looked into the prevalence of different forms of thyroid dysfunction and their risk factors among Type 2 diabetic Saudi patients. Methodology. A cross-sectional retrospective randomized hospital-based study of 411 Type 2 diabetic Saudi patients of >25 years of age was conducted to test the prevalence of different types of thyroid dysfunction and their risk factors. Results. The prevalence of different types of thyroid dysfunction is 28.5%, of which 25.3% had hypothyroidism, where 15.3%, 9.5%, and 0.5% are clinical, subclinical, and overt hypothyroidism, respectively. The prevalence of hyperthyroidism is 3.2%, of which subclinical cases accounted for 2.7% and overt hyperthyroidism accounted for 0.5%. Risk factors for thyroid dysfunction among Saudi Type 2 diabetic patients are family history of thyroid disease, female gender, and duration of diabetes of >10 years, while the risk was not significant in patients with history of goiter and patients aged >60 years. Smoking and parity show a nonsignificant reduced risk. Conclusion. Thyroid dysfunction is highly prevalent among Saudi Type 2 diabetic patients, and the most significant risk factors are family history of thyroid disease, female gender, and >10 years duration of diabetes.


Messenger RNA in early sea-urchin embryos: size classes.
Rapidly labeled RNA from four-cell embryos and blastulae of sea urchins was analyzed by sedimentation and for ability to form DNA-RNA hybrids. The RNA was derived from polyribosomes and from the "gel interphase," an extraction compartment resulting from treatment of whole embryos with phenol and known to be enriched with nuclei. The RNA from both sources displayed a high degree of structural complementarity to DNA. This DNA-like RNA of the polyribosomes sedimented in discrete classes, rather than in the sedimentation continuum demonstrable for the labeled RNA of the gel interphase. Thus messenger RNA appears to emerge in the cytoplasm in discrete size classes.


Role of Periostin in Uncontrolled Asthma in Children (DADO study).
Asthma is the most common chronic disease in children. Cases of severe asthma (SA) are underdiagnosed. Periostin is a biomarker for SA in adults, but its role in children is poorly understood. Objectives: The aims of the study were to estimate the percentage of cases of uncontrolled severe asthma (UcSA) in children with poorly controlled asthma and to evaluate the role of periostin as a biomarker. We performed an observational study in children aged 5 to 14 years with poorly controlled asthma. Demographic and clinical data were collected in addition to the results of the lung function test, the fraction of exhaled nitric oxide, the skin prick test, total IgE, specific IgE, blood eosinophil count, serum periostin, treatment, asthma control, and quality of life. Variables were compared between the group with UcSA and the other children. Fifty children with poorly controlled asthma (72% male) were included. Nineteen children (38%) had UcSA. Most children had limitations in their activities of daily living and had visited the emergency department. In addition, 38% were hospitalized. Quality of life was poor. Only 42% of the children received appropriate treatment. The UcSA group was more likely to have a total IgE >500 kUA/mL (52.6% vs 19%, P=.02) and less likely to have serum periostin >1000 ng/mL (31.2% vs 63%, P=.04). In our setting, 38% of children with poorly controlled asthma have UcSA, which is associated with higher levels of total serum IgE and lower levels of serum periostin.


Coffee processing industrial wastewater treatment using batch electrochemical coagulation with stainless steel and Fe electrodes and their combinations, and recovery and reuse of sludge.
The efficiency of chemical oxygen demand (COD) and color removal from raw coffee processing wastewater (CPWW) using batch electrochemical coagulation (BECC) treatment process using stainless steel (SS) and iron (Fe) electrode combinations are investigated. Of the combinations: four SS, four Fe, Fe-Fe-SS-SS, Fe-SS-Fe-SS, SS-SS-Fe-Fe, and SS-Fe-SS-Fe; four SS electrodes operated at 23 V having 120 A/m2 current density was found as a good operating condition to achieve ∼87% COD removal from its initial COD of 1,984 mg/L and corresponding color removal of 97.1% (initial color 7,000 PCU). The second best electrode combination, SS-SS-Fe-Fe, had COD and color removals of 75% and 91%. When using polyaluminum chloride (PAC) as aid with different dosages of 20-100 mg/L, 50 mg/L PAC showed maximum COD and color removals of 80% and 92%. Comparison of proximate and ultimate analyses of various solid fuels with CPWW ECC sludge showed its usefulness as a soil supplement and as an adsorbent for reutilization. The solid residue obtained after BECC was characterized using energy dispersive X-ray spectroscopy and other analyses. Summarizing the results, it was concluded that BECC can be effectively used for maximum removal of organics from raw CPWW with clean water reclamations of up to ∼90% using ECC as a novel treatment technique.


Microfluidic transport in magnetic MEMS and bioMEMS.
Magnetic materials, such as ferrimagnetic and ferromagnetic nanoparticles and microparticles in the form of ferrofluids, can be advantageously used in micro-electro-mechanical systems (MEMS) and bioMEMS applications, as they possess several unique features that provide solutions for major microfluidic challenges. These materials come with a wide range of sizes, tunable magnetic properties and offer a stark magnetic contrast with respect to biological entities. Thus, these magnetic particles are readily and precisely maneuvered in microfluidic and biological environments. The surfaces of these particles offer a relatively large area that can be functionalized with diverse biochemical agents. The useful combination of selective biochemical functionalization and 'action-at-a-distance' that a magnetic field provides makes superparamagnetic particles useful for the application in micro-total analysis systems (micro-TAS). We provide insight into the microfluidic transport of magnetic particles and discuss various MEMS and bioMEMS applications.


Second molar germectomy and third molar eruption. 11 cases of lower second molar enucleation.
Eleven cases followed from enucleation of the unerupted lower second molars through third molar eruption. While results were generally good, three presented third molar malpositions requiring further treatment.


[Particles in the outside air increase the risk of cardiovascular diseases].
Evidence accumulated during the mid-1990 s that ambient particulate air pollution aerosol particles may not only exacerbate respiratory diseases but also be a risk factor for cardiovascular disease exacerbation. The aim of the studies described here was to assess the impact of the 1985 smog episode on the risk factor profile in the randomly selected population-based sample of the MONICA survey 1984/85 (S1). During a 13-day period in January 1985 sulphur dioxide concentrations increased four times and concentrations of total suspended atmospheric particles doubled. The impact of this time period on plasma viscosity, plasma C-reactive protein concentrations, heart rate and blood pressure was investigated. Regression models were used to assess these associations adjusting for individual risk factors such as gender, age, body mass index, serum total cholesterol and HDL-cholesterol, smoking, physical activity and medication for cardiovascular diseases and for weather conditions during the survey period. An increase in plasma viscosity, C-reactive protein and heart rate was estimated during the air pollution episode. There was also an increase in blood pressure, but this appeared to be attributable to the weather conditions during the air pollution episode. All the four outcomes were associated with the sulphur dioxide concentrations and the total suspended particle concentrations during the survey. These results indicate that ambient air pollution, particularly ambient particulate air pollution may induce systemic inflammation and modulate the autonomic function of the heart. These pathomechanisms may contribute to the observed associations between ambient air pollution concentrations and cardiovascular disease exacerbation such as hospitalisation and mortality due to cardiovascular diseases.


Blueprinting macromolecular electronics.
Recently, by mastering either top-down or bottom-up approaches, tailor-made macromolecular nano-objects with semiconducting properties have been fabricated. These engineered nanostructures for organic electronics are based on conjugated systems predominantly made up of sp²-hybridized carbon, such as graphene nanoribbons. Here, we describe developments in a selection of these nanofabrication techniques, which include graphene carving, stimulus-induced synthesis of conjugated polymers and surface-assisted synthesis. We also assess their potential to reproduce chemically and spatially precise molecular arrangements, that is, molecular blueprints. In a broad context, the engineering of a molecular blueprint represents the fabrication of an integrated all-organic macromolecular electronic circuit. In this Perspective, we suggest chemical routes, as well as convergent on-surface synthesis and microfabrication approaches, for the ultimate goal of bringing the field closer to technology.


Reduced Structural Connectivity in Frontostriatal White Matter Tracts in the Associative Loop in Schizophrenia.
The striatum receives segregated and integrative white matter tracts from the cortex facilitating information processing in the cortico-basal ganglia network. The authors examined both types of input tracts in the striatal associative loop in chronic schizophrenia patients and healthy control subjects. Structural and diffusion MRI scans were acquired on a 3-T system from 26 chronic schizophrenia patients and 26 matched healthy control subjects. Using FreeSurfer, the associative cortex was parcellated into ventrolateral prefrontal cortex and dorsolateral prefrontal cortex subregions. The striatum was manually parcellated into its associative and sensorimotor functional subregions. Fractional anisotropy and normalized streamlines, an estimate of fiber counts, were assessed in four frontostriatal tracts (dorsolateral prefrontal cortex-associative striatum, dorsolateral prefrontal cortex-sensorimotor striatum, ventrolateral prefrontal cortex-associative striatum, and ventrolateral prefrontal cortex-sensorimotor striatum). Furthermore, these measures were correlated with a measure of cognitive control, the Trail-Making Test, Part B. Results showed reduced fractional anisotropy and fewer streamlines in chronic schizophrenia patients for all four tracts, both segregated and integrative. Post hoc t tests showed reduced fractional anisotropy in the left ventrolateral prefrontal cortex-associative striatum and left ventrolateral prefrontal cortex-sensorimotor striatum and fewer normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum and in the left and right ventrolateral prefrontal cortex-sensorimotor striatum in chronic schizophrenia patients. Furthermore, normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum negatively correlated with Trail-Making Test, Part B, time spent in healthy control subjects but not in chronic schizophrenia patients. These findings demonstrated that structural connectivity is reduced in both segregated and integrative tracts in the striatal associative loop in chronic schizophrenia and that reduced normalized streamlines in the right-hemisphere dorsolateral prefrontal cortex-sensorimotor striatum predicted worse cognitive control in healthy control subjects but not in chronic schizophrenia patients, suggesting a loss of a "normal" brain-behavior correlation in chronic schizophrenia.


Fecal incontinence in hospitalized patients who are acutely ill.
Information about fecal incontinence experienced by patients in acute-care settings is lacking. The relationship of fecal incontinence to several well-known nosocomial or iatrogenic causes of diarrhea has not been determined. To determine the cumulative incidence of fecal incontinence in hospitalized patients who are acutely ill, and to ascertain the relationship between fecal incontinence and stool consistency, and between diarrhea and two well-known nosocomial or iatrogenic etiologies of diarrhea: Clostridium difficile and tube feeding. The relationship of fecal incontinence and risk factors for diarrhea associated with C. difficile and tube feeding in hospitalized patients was examined. Fecal incontinence, stool frequency and consistency, administration of tube feeding and medications, severity of illness, and nutritional data were prospectively recorded in 152 patients on acute or critical care units of a university-affiliated Veterans' Affairs Medical Center. Rectal swabs and stool specimens from patients were obtained weekly for C. difficile culture. C. difficile culture and cytotoxin assay were performed on diarrheal stools. HindIII restriction endonuclease analysis (REA) was used for typing of C. difficile isolates. In this study, 33% (50/152) of the patients had fecal incontinence. The proportion of total surveillance days with fecal incontinence in these patients was 0.50 +/- 0.06. A greater percentage of patients with diarrhea had fecal incontinence than patients without diarrhea (23/53 [43%] vs. 27/99 [27%]; p = 0.04). Incontinence was more frequent in patients with loose/liquid stool consistency than in patients with hard/soft stool consistency (48/50 [96%] vs. 71/100 [71%]; p < 0.001). The proportion of surveillance days with fecal incontinence was related to the proportion of surveillance days with diarrhea (r = 0.69; p < 0.001) and the proportion of surveillance days with loose/liquid stools (r = 0.64; p < 0.001). Multivariate risk factors for fecal incontinence were unformed/loose or liquid consistency of stool (RR = 11.1; 95% confidence interval [CI] = 2.2, 56.7), severity of illness (RR = 5.7; CI = 2.6, 12.3), and age (RR = 1.1; CI = 1, 1.1). Fecal incontinence is common in hospitalized patients who are acutely ill, but the condition was not associated with any specific cause of diarrhea. Because loose or liquid stool consistency is a risk factor for fecal incontinence, use of treatments that result in a more formed stool may be beneficial in managing fecal incontinence. However, treatments that slow intestinal transit should be avoided in patients with C. difficile-associated diarrhea.


Innate immune memory of tissue-resident macrophages and trained innate immunity: Re-vamping vaccine concept and strategies.
In the past few years, our understanding of immunological memory has evolved remarkably due to a growing body of new knowledge in innate immune memory and immunity. Immunological memory now encompasses both innate and adaptive immune memory. The hypo-reactive and hyper-reactive types of innate immune memory lead to a suppressed and enhanced innate immune protective outcome, respectively. The latter is also named trained innate immunity (TII). The emerging information on innate immune memory has not only shed new light on the mechanisms of host defense but is also revolutionizing our long-held view of vaccination and vaccine strategies. Our current review will examine recent progress and knowledge gaps in innate immune memory with a focus on tissue-resident Mϕs, particularly lung Mϕs, and their relationship to local antimicrobial innate immunity. We will also discuss the impact of innate immune memory and TII on our understanding of vaccine concept and strategies and the significance of respiratory mucosal route of vaccination against respiratory pathogens.


Chloroacetate esterase positivity in acute lymphoblastic leukemia.
Chloroacetate esterase (CAE) reactivity is associated with acute nonlymphocytic leukemia (ANLL) and, to the author's knowledge, has not been reported in acute lymphoblastic leukemia (ALL). The authors have identified a single patient whose blasts displayed CAE reactivity from a review of 400 newly diagnosed patients with ALL. The diagnosis of ALL in this case was based upon morphologic evaluation (FAB:L1), presence of terminal deoxynucleotidyl transferase (TdT), the absence of reactivity with myeloperoxidase, and the failure of leukemic blasts to mark with a panel of anti-myeloid monoclonal antibodies. Remission was induced promptly with standard ALL therapy. This case demonstrates that punctate CAE positivity rarely can occur in ALL, and, therefore, CAE is not entirely specific for ANLL. The authors conclude that CAE positivity should not be used as a sole criterion to diagnose ANLL in the absence of supporting morphologic, cytochemical, immunocytologic, or clinical information.


Actor-network theory and ethnography: Sociomaterial approaches to researching medical education.
Medical education is a messy tangle of social and material elements. These material entities include tools, like curriculum guides, stethoscopes, cell phones, accreditation standards, and mannequins; natural elements, like weather systems, disease vectors, and human bodies; and, objects, like checklists, internet connections, classrooms, lights, chairs and an endless array of others.We propose that sociomaterial approaches to ethnography can help us explore taken for granted, or under-theorized, elements of a situation under study, thereby enabling us to think differently. In this article, we describe ideas informing Actor-Network Theory approaches, and how these ideas translate into how ethnographic research is designed and conducted. We investigate epistemological (what we can know, and how) positioning of the researcher in an actor-network theory informed ethnography, and describe how we tailor ethnographic methods-document and artefact analysis; observation; and interviews-to align with a sociomaterial worldview.Untangling sociomaterial scenarios can offer a novel perspective on myriad contemporary medical education issues. These issues include examining how novel tools (e.g. accreditation standards, assessment tools, mannequins, videoconferencing technologies) and spaces (e.g. simulation suites, videoconferenced lecture theatres) used in medical education impact how teaching and learning actually happen in these settings.


[Development of anti-arrhythmic drugs].
An historical outline of antiarrhythmic therapy is presented. At its beginning treatment was based on empirical data and later on electrophysiologic studies; now it is supported on direct knowledge of ionic currents flowing through the cell membrane during different phases of cellular potentials. It has been possible to reach the present stage of knowledge by starting with clinical observations which permitted the introduction of quinidine in therapy, to the choice of specific agents based upon their effects on ionic movements and the mechanisms maintaining active arrhythmias. These mechanisms can be divided into three groups: circus movement, reentry and discharges of ectopic foci. On these bases, it is justified the use of drugs which prolong the refractory period of myocardial fibers in the first group, of those which enlarge the local block in the second and of those which flatten prepotential or depress systolic depolarization in the third.


[Objective criteria of the severity of the alcohol abstinence syndrome and delirium].
Overall 467 male patients suffering from stage II and stage II-III chronic alcoholism were examined. Of these, 80 patients (17.1%) were with the abstinent syndrome, 66 (14.1%) had the abstinent convulsive syndrome, 251 (53.8%) were with alcoholic delirium and 80 (14.9%) making up a control group were in a state of remission. Noticeable disorders were revealed in enzymatic activity of the liver (hyperfermentemia) coupled with characteristic changes in proteolytic activity. The degree of disorders in enzymic function of the liver and of the proteolytic system correlates with the severity of the psychopathological syndrome, which suggests the existence of the common component underlying the development of the pathogenetic mechanism in abstinent patients and in those with alcoholic delirium. The alcoholic abstinent syndrome and delirium are stages of the common pathological process.


A model for overcoming challenges in academic pediatric medical device innovation.
Technological advancements in medical devices developed for adults far outpace the development of technologies designed for pediatric patients in the USA and other countries. This technology lag was previously reflected in a lack of pediatric-specific innovation within our academic institution. To address the institutional deficit of device innovation around pediatric patients, we formed unique partnerships both within our university and extending to the medical device industry, and developed novel programmatic approaches. The Pediatric Device Innovation Consortium (PDIC) bridges the medical device community and the University of Minnesota. Since 2014, the PDIC has supported 22 pediatric medical technology innovation projects, provided funds totaling more than $500,000, licensed two technologies, and advanced two technologies to patient use. Here, we describe the PDIC model and method, the PDIC approach to common challenges that arise in the development of small-market medical technologies at an academic institution, and iterations to our collaborative, multidisciplinary approach that have matured throughout our experience. The PDIC model continues to evolve to reflect the special needs of innovation for smaller markets and the unique role of clinician innovators. Our approach serves as a successful model for other institutions interested in creating support mechanisms for pediatric or small-market technology development.


Periodic cutaneous blood flow during postocclusive reactive hyperemia.
Forearm cutaneous blood flow was monitored continuously by laser Doppler velocimetry in 10 normal human subjects before, during, and after external brachial artery occlusion for 6 min duration. During the reactive hyperemic response, the cutaneous blood flow exhibited rhythmic oscillatory activity. The amplitude of the oscillations was maximum 30 s postocclusion. Thereafter, the amplitude of the oscillations declined until cutaneous blood flow returned to control values. The mean (+/- SEM) period for the oscillations was 9.26 +/- 0.30 s. Bilateral forearm sites were examined simultaneously in eight studies and demonstrated a progressive loss of synchronicity. Nine additional studies were performed in which two forearm sites only 1.8 cm apart demonstrated a progressive loss of synchronicity resulting from different periodicities of microcirculatory flow patterns. These oscillations in cutaneous blood flow, which occur during postocclusive reactive hyperemia as a normal physiological phenomenon, are not synchronous in adjacent areas of skin. The data suggest an origin of the oscillations in the cutaneous vasculature that is either unrelated to sympathetic vasoconstrictor influences or is due to nonuniform cutaneous sympathetic excitation.


Clinical Value of Natriuretic Peptides in Predicting Time to Dialysis in Stage 4 and 5 Chronic Kidney Disease Patients.
Anticipating the time to renal replacement therapy (RRT) in chronic kidney disease (CKD) patients is an important but challenging issue. Natriuretic peptides are biomarkers of ventricular dysfunction related to poor outcome in CKD. We comparatively investigated the value of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as prognostic markers for the risk of RRT in stage 4 and 5 CKD patients, and in foretelling all-cause mortality and major cardiovascular events within a 5-year follow-up period. Baseline plasma BNP (Triage, Biosite) and NT-proBNP (Elecsys, Roche) were measured at inclusion. Forty-three patients were followed-up during 5 years. Kaplan-Meier analysis, with log-rank testing and hazard ratios (HR), were calculated to evaluate survival without RRT, cardiovascular events or mortality. The independent prognostic value of the biomarkers was estimated in separate Cox multivariate analysis, including estimated glomerular filtration rate (eGFR), creatininemia and comorbidities. During the first 12-month follow-up period, 16 patients started RRT. NT-proBNP concentration was higher in patients who reached endpoint (3221 ng/L vs 777 ng/L, p = 0.02). NT-proBNP concentration > 1345 ng/L proved significant predictive value on survival analysis for cardiovascular events (p = 0.04) and dialysis within 60 months follow-up (p = 0.008). BNP concentration > 140 ng/L was an independent predictor of RRT after 12 months follow-up (p<0.005), and of significant predictive value for initiation of dialysis within 60 months follow-up. Our results indicate a prognostic value for BNP and NT-proBNP in predicting RRT in stage 4 and 5 CKD patients, regarding both short- and long-term periods. NT-proBNP also proved a value in predicting cardiovascular events. Natriuretic peptides could be useful predictive biomarkers for therapeutic guidance in CKD.


A relationship between carotenoid accumulation and the distribution of species of the fungus Neurospora in Spain.
The ascomycete fungus Neurospora is present in many parts of the world, in particular in tropical and subtropical areas, where it is found growing on recently burned vegetation. We have sampled the Neurospora population across Spain. The sampling sites were located in the region of Galicia (northwestern corner of the Iberian peninsula), the province of Cáceres, the city of Seville, and the two major islands of the Canary Islands archipelago (Tenerife and Gran Canaria, west coast of Africa). The sites covered a latitude interval between 27.88° and 42.74°. We have identified wild-type strains of N. discreta, N. tetrasperma, N. crassa, and N. sitophila and the frequency of each species varied from site to site. It has been shown that after exposure to light Neurospora accumulates the orange carotenoid neurosporaxanthin, presumably for protection from UV radiation. We have found that each Neurospora species accumulates a different amount of carotenoids after exposure to light, but these differences did not correlate with the expression of the carotenogenic genes al-1 or al-2. The accumulation of carotenoids in Neurospora shows a correlation with latitude, as Neurospora strains isolated from lower latitudes accumulate more carotenoids than strains isolated from higher latitudes. Since regions of low latitude receive high UV irradiation we propose that the increased carotenoid accumulation may protect Neurospora from high UV exposure. In support of this hypothesis, we have found that N. crassa, the species that accumulates more carotenoids, is more resistant to UV radiation than N. discreta or N. tetrasperma. The photoprotection provided by carotenoids and the capability to accumulate different amounts of carotenoids may be responsible, at least in part, for the distribution of Neurospora species that we have observed across a range of latitudes.


[Dynamics of parameters of variability of processes of repolarization after transluminal balloon angioplasty in patients with ischemic heart disease].
To study dynamics of processes of repolarization after transluminal balloon angioplasty in patients with ischemic heart disease. ECG, Holter ECG monitoring, analysis of parameters of variability of processes of repolarization, echocardiography and treadmill stress echocardiography were carried out in 28 ischemic heart disease patients aged 51.3+/-8.1 years prior to percutaneous coronary intervention, before discharge and in 4.1+/-2.1 months after procedure. Coronary angiography was repeated after intervention when restenosis was suspected because of positive stress echo. Number of vessels with significant stenoses was 1.8+/-0.1, number of implanted stents - 2.0+/-0.2. Analysis of parameters of variability of processes of repolarization at rest and after exercise revealed significant increases of maximal value of QT (MQT(c)) and of its dispersion (QT(cd)). In 3-5 days after procedure significant lowering of these parameters occurred. Development of restenosis during follow-up (in 6 patients, 21.4%) was associated with repeated increases of MQT(c) and QT(cd). MQT(c) and QT(cd) are sensitive to myocardial ischemia and can be used as supplementary markers of myocardial ischemia during exercise tests in patients with ischemic heart disease.


Lithotripsy of gallstones by means of a quality-switched giant-pulse neodymium:yttrium-aluminum-garnet laser. Basic in vitro studies using a highly flexible fiber system.
The quality-switched neodymium:yttrium-aluminum-garnet laser represents a new instrument for athermal fragmentation of gallstones by transformation of optical energy into mechanical energy in the form of shock waves via local plasma formation. A highly flexible 300-micron fiber transmission system was used in basic investigations to determine the influence of varying pulse repetition rates (5-30 Hz) and pulse energies (15 and 20 mJ) on shock wave intensity and stone fragmentation in vitro for 105 biliary calculi of known size and chemical composition. After performance of 1200 shock wave pressure measurements using polyvinylidenefluoride hydrophones, stone fragmentation was analyzed by determination of fragment removal rates (volume of fragments removed per fragmentation time), ablation rates (mean volume removed per laser pulse), and median fragment sizes for each laser setting. With the quality-switched neodymium:yttrium-aluminum-garnet laser system, all concrements could be reliably disintegrated into small fragments (median diameter, 0.7-1.7 mm). Compared with pure cholesterol stones, a significantly higher fragment removal rate was achieved in cholesterol stones containing 30% calcium phosphate (P = 0.039), in cholesterol stones containing 20% pigment (P = 0.015), and in pure pigment stones (P = 0.007). Fragment removal rates, local shock wave pressures, and median grain sizes were significantly higher at a pulse energy of 20 mJ than with 15 mJ. Shock wave pressures showed a distinct dependence on pulse repetition rates at 20 mJ, yet not at 15 mJ. Because there is no evident hazard of thermal damage to tissue using the quality-switched neodymium:yttrium-aluminum-garnet laser, it appears to be a promising device for nonsurgical biliary stone therapy.


Relationship between risk factors and ischaemic heart disease mortality in a representative sample of men aged 45-59 years in Kaunas.
The results of a 7-year prospective follow-up of a representative sample of men aged 45-49 years living in Kaunas, who were initially examined within the framework of the Kaunas-Rotterdam Intervention Study, are presented. The relationship was investigated between systolic and diastolic hypertension, hypercholesterolaemia, smoking impaired glucose tolerance on the one hand, and mortality (total and from ischaemic heart disease) on the other hand. The main cause of death in the studied series were cardiovascular diseases (38.7%); of these, in 62% of cases ischaemic heart disease. Among subjects who had been found healthy at screening, the most unfavourable prognosis as regards mortality from ischaemic heart disease, had men with hypertension.


Optimizing Surveillance for South American Origin Influenza A Viruses Along the United States Gulf Coast Through Genomic Characterization of Isolates from Blue-winged Teal (Anas discors).
Relative to research focused on inter-continental viral exchange between Eurasia and North America, less attention has been directed towards understanding the redistribution of influenza A viruses (IAVs) by wild birds between North America and South America. In this study, we genomically characterized 45 viruses isolated from blue-winged teal (Anas discors) along the Texas and Louisiana Gulf Coast during March of 2012 and 2013, coincident with northward migration of this species from Neotropical wintering areas to breeding grounds in the United States and Canada. No evidence of South American lineage genes was detected in IAVs isolated from blue-winged teal supporting restricted viral gene flow between the United States and southern South America. However, it is plausible that blue-winged teal redistribute IAVs between North American breeding grounds and wintering areas throughout the Neotropics, including northern South America, and that viral gene flow is limited by geographical barriers further south (e.g., the Amazon Basin). Surveillance for the introduction of IAVs from Central America and northern South America into the United States may be further optimized through genomic characterization of viruses resulting from coordinated, concurrent sampling efforts targeting blue-winged teal and sympatric species throughout the Neotropics and along the United States Gulf Coast.


Effects of Atmospheric Gases on Li Metal Cyclability and Solid-Electrolyte Interphase Formation.
For Li-air batteries, dissolved gas can cross over from the air electrode to the Li metal anode and affect the solid-electrolyte interphase (SEI) formation, a phenomenon that has not been fully characterized. In this work, the impact of atmospheric gases on the SEI properties is studied using electrochemical methods and ex situ characterization techniques, including X-ray photoelectron spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. The presence of O2 significantly improved the lithium cyclability; less lithium is consumed to form the SEI or is lost because of electrical disconnects. However, the SEI resistivity and plating overpotentials increased. Lithium cycled in an "air-like" mixed O2/N2 environment also demonstrated improved cycling efficiency, suggesting that dissolved O2 participates in electrolyte reduction, forming a homogeneous SEI, even at low concentrations. The impact of gas environments on Li metal plating and SEI formation represents an additional parameter in designing future Li-metal batteries.


Renal lesion growth in children with tuberous sclerosis complex.
Renal lesions, including angiomyolipoma, renal cysts (simple and polycystic kidney disease) and renal cell carcinoma, develop in patients with tuberous sclerosis complex. While there is limited information that these lesions may grow in adults with tuberous sclerosis complex, the incidence, characterization and growth rate in children have not been reported. Also, the age at which these lesions first appear, thus providing insight into their natural history, is unknown. We present our data from a longitudinal renal surveillance study of children with tuberous sclerosis complex. Since 1985 children with tuberous sclerosis complex at our hospital have undergone periodic renal imaging by ultrasonography or computerized tomography to monitor renal lesions. A total of 35 girls and 25 boys 1 to 18 years old have undergone at least 2 or more annual renal ultrasounds. On initial evaluation 33 of 60 children (55%) (mean age 6.9 years) had an identifiable renal lesion, which increased to 48 of 60 (80%) at followup (mean age 10.5 years). Angiomyolipoma was the most frequent lesion (75%) followed by simple renal cysts (17%). Angiomyolipomas increased in size and/or number in 10 of 18 boys (56%) and 18 of 27 girls (66%). The largest growth rate in 1 year was from 0 to 4 cm. and from 5 to 9 cm. in diameter. The youngest patient demonstrated lesions at age 2 years. The average age at which a normal ultrasound became abnormal was 7.2 years. While a total of 27 patients had a normal ultrasound on entering the study, lesions had developed in 15 at followup (11 with angiomyolipomas, 4 with cysts). Five patients had cysts that had disappeared at followup. A 7-year-old boy had a 9 cm. renal cell carcinoma removed. One patient has renal lesions characteristic of autosomal dominant polycystic kidney disease. Renal involvement in patients with tuberous sclerosis complex begins in infancy, and angiomyolipoma is the most common lesion (75%). Angiomyolipomas are more likely to grow than remain stable, although the rate of growth varies. Simple renal cysts may appear or disappear with time but angiomyolipomas do not disappear. An initially normal renal ultrasound does not rule out future development of lesions. Periodic surveillance is indicated in children with tuberous sclerosis complex.


Isolating Neural Indices of Continuous Speech Processing at the Phonetic Level.
The human ability to understand speech across an enormous range of listening conditions is underpinned by a hierarchical auditory processing system whose successive stages process increasingly complex attributes of the acoustic input. In order to produce a categorical perception of words and phonemes, it has been suggested that, while earlier areas of the auditory system undoubtedly respond to acoustic differences in speech tokens, later areas must exhibit consistent neural responses to those tokens. Neural indices of such hierarchical processing in the context of continuous speech have been identified using low-frequency scalp-recorded electroencephalography (EEG) data. The relationship between continuous speech and its associated neural responses has been shown to be best described when that speech is represented using both its low-level spectrotemporal information and also the categorical labelling of its phonetic features (Di Liberto et al., Curr Biol 25(19):2457-2465, 2015). While the phonetic features have been proven to carry extra-information not captured by the speech spectrotemporal representation, the causes of this EEG activity remain unclear. This study aims to demonstrate a framework for examining speech-specific processing and for disentangling high-level neural activity related to intelligibility from low-level activity in response to spectrotemporal fluctuations of speech. Preliminary results suggest that neural measure of processing at the phonetic level can be isolated.


Acquired segmental neuromas.
Neuromas are benign hyperplastic proliferations of normal peripheral nerve components. These can be associated with some genodermatoses, namely Cowden syndrome and multiple endocrine neoplasia (MEN) 2B, especially when numerous lesions are present. Given the potential for malignancy (such as breast cancer, pheochromocytoma, and thyroid cancer) associated with these syndromes, other features indicative of either syndrome should be evaluated in patients presenting with multiple cutaneous neuromas. The evaluation should include a thorough family history and complete physical, dermatologic, and ophthalmologic exams as well as thyroid studies. We report, herein, the case of an 8-year-old female with cutaneous neuromas distributed segmentally with no other associated finding suggestive of an underlying syndrome.


Phylogeography of the salmonid fish, Dolly Varden Salvelinus malma: multiple glacial refugia in the North Pacific Rim.
The geographic distribution pattern of mitochondrial DNA (control region) sequence polymorphisms from 73 populations of a salmonid fish, Dolly Varden Salvelinus malma, over most of its range in the North Pacific rim, was examined to assess how its spatial population genetic structure has been molded. The observed 68 haplotypes were grouped into three main lineages, which correspond to western, central, and eastern regions in the North Pacific. The two outlier-haplotype groups gave close agreement with DNA types from two congeneric species, white-spotted charr S. leucomaenis and Arctic charr S. alpinus, respectively. These results suggest that the present-day genetic structure of S. malma reflects historical patterns of isolation and re-colonization, and also historical hybridization with co-distributed species. We also placed the haplotypes of S. malma within our study areas into a pre-existing evolutionary relationship of S. alpinus and S. malma throughout the Northern Hemisphere. Phylogenetic analysis revealed that the Western Lineage S. malma was basal to all other lineages of S. malma and S. alpinus. Our data serve as a biogeographic hypothesis for salmonid fishes that the Sea of Japan and/or Sea of Okhotsk regions represents a place of origin for S. malma and S. alpinus groups currently distributed in circumpolar regions.


Serum FGF23 levels in normal and disordered phosphorus homeostasis.
We investigated if the circulating levels of the phosphaturic factor FGF23 are elevated in subjects with XLH. Although we failed to find a statistically significant increase, FGF23 levels were significantly correlated with the degree of hypophosphatemia in XLH. In contrast, FGF23 levels were markedly increased in subjects with ESRD and correlated inversely with the degree of hyperphosphatemia. Inactivating mutations of PHEX cause renal phosphate wasting in X-linked hypophosphatemic rickets (XLH) because of the accumulation of a phosphaturic hormone called phosphatonin. The recent discovery that FGF23 is the circulating phosphaturic factor in autosomal dominant hypophosphatemia raises the possibility that FGF23 is phosphatonin. Fasting serum FGF23 levels and serum biochemical parameters were measured using a human FGF23 (C-terminal) ELISA assay in 11 subjects with XLH and 42 age-matched controls, 5 subjects with hypophosphatemia of unknown cause, and 14 hyperphosphatemic subjects with end stage renal disease (ESRD). Associations between variables were examined using the Spearman's correlation coefficient and linear regression analysis. FGF23 (RU/ml) concentrations were not different (p = 0.11) between control and hypophosphatemic XLH subjects, but were significantly increased in hyperphosphatemic subjects with ESRD (p < 0.001). Western blot analysis found the presence of both full-length and C-terminal FGF23 fragments in serum from ESRD subjects. There was a strong inverse correlation between FGF23 and serum phosphorus (r = -0.60) and calcium and phosphorus (Ca x P) product (r = -0.65) in XLH, and a strong positive relationship between FGF23 and Pi (r = 0.50) and Ca x P product (r = 0.62) in ESRD. FGF23 levels were variably elevated in subjects with hypophosphatemia of unknown cause, one of which had tumor-induced osteomalacia (TIO). Removal of the tumor resulted in rapid reduction in serum FGF23 levels. These findings suggest that FGF23 has a possible role in mediating hypophosphatemia in XLH and TIO, but the overlapping levels of FGF23 in hypophosphatemic disorders and normal subjects indicate that serum phosphorus and FGF23 can also be independently regulated.


The eating disorder assessment for DSM-5 (EDA-5): Development and validation of a structured interview for feeding and eating disorders.
Existing measures for DSM-IV eating disorder diagnoses have notable limitations, and there are important differences between DSM-IV and DSM-5 feeding and eating disorders. This study developed and validated a new semistructured interview, the Eating Disorders Assessment for DSM-5 (EDA-5). Two studies evaluated the utility of the EDA-5. Study 1 compared the diagnostic validity of the EDA-5 with the Eating Disorder Examination (EDE) and evaluated the test-retest reliability of the new measure. Study 2 compared the diagnostic validity of an EDA-5 electronic application ("App") with clinician interview and self-reported assessments. In Study 1, the kappa for EDE and EDA-5 eating disorder diagnoses was 0.74 across all diagnoses (n = 64), with a range of κ = 0.65 for other specified feeding or eating disorder/unspecified feeding or eating disorder to κ = 0.90 for binge eating disorder. The EDA-5 test-retest kappa coefficient was 0.87 across diagnoses. For Study 2, clinical interview versus App conditions revealed a kappa of 0.83 for all eating disorder diagnoses (n = 71). Across individual diagnostic categories, kappas ranged from 0.56 for other specified feeding or eating disorder/unspecified feeding or eating disorder to 0.94 for BN. High rates of agreement were found between diagnoses by EDA-5 and the EDE, and EDA-5 and clinical interviews. Because this study supports the validity of the EDA-5 to generate DSM-5 eating disorders and the reliability of these diagnoses, the EDA-5 may be an option for the assessment of anorexia nervosa, bulimia nervosa, and binge eating disorder. Additional research is needed to evaluate the utility of the EDA-5 in assessing DSM-5 feeding disorders.


Cognitive function in postmenopausal women receiving adjuvant letrozole or tamoxifen for breast cancer in the BIG 1-98 randomized trial.
Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant (A) 5-years tamoxifen, (B) 5-years letrozole, (C) 2-years tamoxifen followed by 3-years letrozole, or (D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B+C; N=65) vs. tamoxifen (A+D; N=55). The patients taking letrozole had better overall cognitive function than those taking tamoxifen (difference in mean composite z-scores=0.28, P=0.04, 95% CI: 0.02, 0.54, Cohen's D=0.40 indicating small to moderate effect). In this substudy, breast cancer patients taking adjuvant letrozole during the fifth year of treatment had better cognitive function than those taking tamoxifen, suggesting aromatase inhibitors do not adversely impact cognition compared with tamoxifen.


Bullying and Being Bullied in Childhood Are Associated With Different Psychosocial Risk Factors for Poor Physical Health in Men.
Bullying and being bullied in childhood are both linked with later adjustment problems. The impact of childhood bullying on risk for poor physical health in adulthood is understudied. Black and White men ( n = 305; mean age = 32.3 years) enrolled in the Pittsburgh Youth Study since the first grade underwent a comprehensive assessment of psychosocial, behavioral, and biological risk factors for poor health. Indices of bullying and being bullied were created by averaging annual ratings collected from participants and their caregivers when the participants were 10 to 12 years old. Results showed that being a bully in childhood was associated with greater stress and aggression and poorer health behaviors in adulthood, whereas being a victim of bullies in childhood was associated with lower socioeconomic resources, less optimism, and greater unfair treatment in adulthood. Unexpectedly, neither bullying nor being bullied in childhood was related to inflammation or metabolic syndrome. Bullying and being bullied in childhood were associated with distinct domains of psychosocial risk in adulthood that may later lead to poor physical health.


Direct determination of lead in urine by flameless atomic absorption spectrophotometry with platform atomisation.
A direct method of urinary lead assay by flameless atomic absorption spectrophotometry is described for routine use in the clinical laboratory. It employs a simple sample pre-treatment procedure preceding automated analysis. Reproducibility, linearity and recovery were satisfactory without the need of standard addition. Mean and reference intervals of normal urine were similar to values reported in the literature.


Classification of Atretic Small Antral Follicles in the Human Ovary.
The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition. Our findings revealed that atresia spreads in the follicle with wave-like dynamics, initiating away from the cumulus granulosa cells. We also observed an enrichment of CD68+ macrophages in the antrum during the progression of follicular atresia. This work not only provides criteria for classifying three stages of follicular atresia in small antral follicles in the human ovary but also serves as a foundation for understanding follicular degeneration and ultimately preventing or treating premature ovarian failure. Understanding follicular remodeling in the ovary could provide a means to increase the number of usable follicles and delay the depletion of the follicular reserve, increasing the reproductive lifespan.


Elevated maternal androgen is associated with dysfunctional placenta and lipid disorder in newborns of mothers with polycystic ovary syndrome.
To investigate the placental morphology alterations and identify the clinical characteristics of women with polycystic ovary syndrome (PCOS) and their newborns. Pregnant women with PCOS (n = 12) and pregnant women without PCOS (n = 11) were recruited. Then, the placenta, maternal blood and cord blood were collected after delivery. Clinical observational study. Not applicable. In the present study, pregnant women with PCOS and healthy pregnant women were recruited from the clinic of the Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, China, between February 2015 and October 2015. None. A proteomic analysis was performed on the placenta in women with PCOS and healthy women. The maternal testosterone, androstenedione, dehydroepiandrosterone sulfate, free androgen index, cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A-I levels were significantly higher in the PCOS group than in the control group, and the offspring in the PCOS group had higher dehydroepiandrosterone sulfate, high-density lipoprotein, and cholesterol levels, when compared with the control group. The placenta in the PCOS group demonstrated infarction, calcification, and a greater intervillous space, when compared with the control group. A higher level of estrogen receptor-β protein was observed in the placenta of women with PCOS, when compared with women without PCOS. A total of 258 proteins in the placenta were identified to be significantly different, when the PCOS and control groups were compared, and fibronectin 1 exhibited the closest relationship with other differential proteins. The overexposure to hyperandrogenism and hyperlipidemia affects the functions of the placenta, which are associated with the development of metabolic disorders in newborns.


cIAP1/2 inhibition synergizes with TNF inhibition in autoimmunity by down-regulating IL-17A and inducing Tregs.
IL-17 and TNF-α are major effector cytokines in chronic inflammation. TNF-α inhibitors have revolutionized the treatment of rheumatoid arthritis (RA), although not all patients respond, and most relapse after treatment withdrawal. This may be due to a paradoxical exacerbation of TH17 responses by TNF-α inhibition. We examined the therapeutic potential of targeting cellular inhibitors of apoptosis 1 and 2 (cIAP1/2) in inflammation by its influence on human TH subsets and mice with collagen-induced arthritis. Inhibition of cIAP1/2 abrogated CD4+ IL-17A differentiation and IL-17 production. This was a direct effect on T cells, mediated by reducing NFATc1 expression. In mice, cIAP1/2 inhibition, when combined with etanercept, abrogated disease activity, which was associated with an increase in Tregs and was sustained after therapy retraction. We reveal an unexpected role for cIAP1/2 in regulating the balance between TH17 and Tregs and suggest that combined therapeutic inhibition could induce long-term remission in inflammatory diseases.


An alternative model for psychiatric service delivery for people with intellectual disabilities in a vocational rehabilitation center.
The prevalence of mental illness in the intellectually disabled (ID) population is high. Because of their special characteristics, such as involvement of multiple carers (family, social services, protected housing staff, vocational instructors), linguistic limitations and the need for a familiar and steady environment, these patients require special therapeutic consideration. In Israel, as in many other countries, people with ID (PWID) receive psychiatric services from general psychiatric outpatient clinics and hospitals; their treatment is generally not specifically tailored to their needs, and hence often suboptimal. In this article we will review some models of psychiatric service delivery for PWID and present an alternative model that we have developed. Our service has been operating since December 1998; it is based upon cooperation between the municipal social services and the local psychiatric outpatient clinic, and is provided in a vocational rehabilitation center where most mild to moderate ID individuals in our area, the city of Bat Yam, are employed. During the first five years (1999-2004) of the operation of the service, 42 people (about half the total number of clients passing through the vocational rehabilitation center during this period) were examined by the psychiatrist; 37 of them (88%) had at least one psychiatric diagnosis. There were especially high rates of adjustment disorder (26% of all principal diagnoses) and of behavior disorder (24% of all principal diagnoses). This model for psychiatric service delivery for PWID in a vocational-rehabilitation center, based as it is on cooperation between the different care agencies, facilitates more accurate psychiatric diagnosis and hence the provision of more appropriate treatment, which in practice usually consists of a combination of pharmacological and behavioral treatment together with educational programs and support for families and staff. Based on our positive experience with this model, we believe that it is the most suitable framework of treatment for adults with dual diagnosis, and that it should be adopted in other areas.


Estimation of the contemporary effective population size from SNP data while accounting for mating structure.
A new method is developed to estimate the contemporary effective population size (Ne ) from linkage disequilibrium (LD) between SNPs without information on their location, which is the usual scenario in non-model species. The general theory of linkage disequilibrium is extended to include the contribution of full-sibs to the measure of LD, leading naturally to the estimation of Ne in monogamous and polygamous mating systems, as well as in multiparous species, and with non-random distributions of full-sib family size due to selection or other causes. Prediction of confidence intervals for Ne estimates was solved using a small artificial neural network trained on a dataset of over 105 simulation results. The method, implemented in a user-friendly and fast software (currentNe), is able to estimate Ne even in problematic scenarios with large population sizes or small sample sizes and provides confidence intervals that are more consistent than resampling methods.


Coordinated regulation of platelet actin filament barbed ends by gelsolin and capping protein.
Exposure of cryptic actin filament fast growing ends (barbed ends) initiates actin polymerization in stimulated human and mouse platelets. Gelsolin amplifies platelet actin assembly by severing F-actin and increasing the number of barbed ends. Actin filaments in stimulated platelets from transgenic gelsolin-null mice elongate their actin without severing. F-actin barbed end capping activity persists in human platelet extracts, depleted of gelsolin, and the heterodimeric capping protein (CP) accounts for this residual activity. 35% of the approximately 5 microM CP is associated with the insoluble actin cytoskeleton of the resting platelet. Since resting platelets have an F-actin barbed end concentration of approximately 0.5 microM, sufficient CP is bound to cap these ends. CP is released from OG-permeabilized platelets by treatment with phosphatidylinositol 4,5-bisphosphate or through activation of the thrombin receptor. However, the fraction of CP bound to the actin cytoskeleton of thrombin-stimulated mouse and human platelets increases rapidly to approximately 60% within 30 s. In resting platelets from transgenic mice lacking gelsolin, which have 33% more F-actin than gelsolin-positive cells, there is a corresponding increase in the amount of CP associated with the resting cytoskeleton but no change with stimulation. These findings demonstrate an interaction between the two major F-actin barbed end capping proteins of the platelet: gelsolin-dependent severing produces barbed ends that are capped by CP. Phosphatidylinositol 4,5-bisphosphate release of gelsolin and CP from platelet cytoskeleton provides a mechanism for mediating barbed end exposure. After actin assembly, CP reassociates with the new actin cytoskeleton.


Systemic lupus erythematosus and pregnancy at the Royal Women's Hospital, Brisbane 1979-1989.
The management and obstetric outcome of 17 patients with systemic lupus erythematosus (SLE) complicating 42 pregnancies is presented. Similar to world figures there was a 14.3% incidence of therapeutic abortion, a 4.8% incidence of ectopic pregnancy, a 16.7% incidence of spontaneous abortion, a 23.8% incidence of prematurity, a 4.8% incidence of fetal death in utero (FDIU) and a 9.5% incidence of intrauterine growth retardation (IUGR). In patients with antiphospholipid antibodies the obstetric outcome was significantly worse. Pregnancies complicated by preexisting renal compromise all concluded with an adverse outcome to the conceptus. In light of the experiences at the Royal Women's Hospital and a review of the world literature, the need for a standardized approach to SLE in pregnancy and more importantly the need for a large, prospective randomized trial of low dose aspirin in these pregnancies is highlighted.


Dynamic systems analysis for better hospital bed operation: using time series model.
Achieving high efficiency in hospital bed operations becomes an important aim of hospital management, as managerial environment of hospitals has been increasingly competitive in Korea. Many authors have made studies on higher occupancies, but very few about systems characteristics of the time serial data as well as decision behavior on bed operations. For those topics overlooked, this paper applies Wu's Dynamic Data Systems Analysis, for which an ARMA model is developed and its characteristic roots are analyzed. The results include such information as periodic nature of data, strength and effects of disturbances, based on which interpretations are provided tuned to the target system's operational aspects. For this work, data were collected and processed for two different periods of time, October 1990 to April 1991 and October 1993 to April 1994. While the average occupancies between two periods are not statistically different, the effect of error disturbances was managed better in 1990 than in 1993. And the restoring forces from fluctuations are almost the same between the periods of comparison. With this analysis, conclusions are summarized: in both periods, short-term flexibility in patient admissions and discharges are good, but long-term management of hospital census trend needs to be improved by developing the system of controlling patient admissions and discharges. For the improvement, some possible approaches are suggested for future studies.


Personalized medicine in oncology: tailoring the right drug to the right patient.
Despite advances in the management of many human cancers over the past few decades, improvements in survival are marginal, and the overall diagnosis and prognosis for cancer patients remain poor. Tailoring therapy to the individual patient has become a promising approach for maximizing efficacy and minimizing drug toxicity. Aided by major technological advances, the field of personalized medicine has become extremely active in the identification of predictive biomarkers that can guide treatment decisions and, ultimately, improve treatment outcomes. Genomics and proteomics have provided a means for molecular profiling that allows tailoring of therapy. Although implementing genomic and proteomic testing into clinical practice is still in its infancy, the rapid development of newer technologies and platforms provides hope for personalized medicine.


The effect of songwriting on knowledge of coping skills and working alliance in psychiatric patients: a randomized clinical effectiveness study.
The purpose of this study was to determine the effects of a songwriting intervention on psychiatric patients' knowledge of coping skills and working alliance. Participants were randomly assigned to scripted and manualized experimental (n=48) or control (n=41) conditions. The experimental condition was a group psychoeducational music therapy songwriting session concerning coping skills while the control condition was a group psychoeducational session concerning coping skills. Both conditions were single-session therapy with patients on an acute adult psychiatric unit. Results indicated no significant between group differences in measures of knowledge of coping skills, consumer working alliance, or perception of enjoyment (p>.05), although the experimental condition tended to have slightly higher mean scores than the control group for these measures. There was a significant between group difference in measures of therapist working alliance (p<.001), with the therapist scoring the experimental group higher than the control group. Although the music therapy group had a higher mean rate of previous psychiatric hospitalizations, their perception of enjoyment scores were still higher than those of the control condition, a finding incongruent in the literature. Furthermore, despite the increased number of previous hospitalizations, the music therapy condition had higher attendance rates than the control condition, thus possibly providing incentives for funding. It seems that group songwriting about coping skills can be as effective a psychosocial intervention as traditional talk-based psychoeducation to teach psychiatric inpatients how to proactively manage their illness. Additionally, music therapy can be as effective as talk-based psychoeducation in establishing working alliance. Implications for clinical practice, limitations, and suggestions for future research are provided.


Defective ferrocene-based metal-organic frameworks for efficient solar-powered water oxidation via the ligand competition and etching effect.
Two-dimensional metal-organic frameworks are considered to be promising electrocatalytic materials due to their ultrathin lamellar structure, ultrahigh porosity and large surface area, but there are still many challenges such as the embedding of organic ligands leading to low density of active sites and poor conductivity. Herein, we synthesize two-dimensional ferrocene-based metal-organic frameworks nanosheet electrocatalysts via the one-step hydrothermal hydrogen peroxide etching method. The prepared FcNi-BDC-H2O2/NF exhibits excellent oxygen evolution reaction performance with a current density of 100 mA·cm-2 at only 258 mV and a small driving potential of 1.542 V (10 mA·cm-2) is required to achieve overall water splitting. Significantly, an overall water-cracked cell using a solar cell assembly achieves the solar hydrogen conversion efficiency of 19.5%. The introduction of high electronegativity ferrocene and the etching of H2O2 increase the Ni3+ content of FcNi-BDC-H2O2, and expose more unsaturated active sites, which improve the intrinsic activity of the catalysts and the mass transfer rate during the catalytic process. Moreover, the FcNi-BDC-H2O2/NF demonstrates significant urea oxidation reaction performance, achieving a potential of 1.35 V and producing 10 mA·cm-2. This study presents a viable approach to investigating highly efficient electrocatalysts for oxygen evolution reaction and urea oxidation reaction using MOF-based bifunctional catalysts.


Development of an injectable formulation for the novel lipid A analog E5531 using a 'pH-jump method'.
In order to design an injectable formulation of E5531, a novel synthetic disaccharide analog of novel lipid A, for the treatment of septic shock, a 'pH-jump method' was developed. In this method, E5531 was dispersed in 0.003 mol/l NaOH (pH 11.0, above pK(a2)) at 50 degrees C (above phase transition temperature) and then mixed with a buffer to neutralize the pH to 7.3. E5531 was dispersed as particles, and the size was approximately 20 nm. The structure of the particles was vesicular. After dispersal, the solution was sterilized using a filter, filled aseptically into vials, and lyophilized. The size of the particles did not change before and after lyophilization. The relationship between the physicochemical properties of the particles and the pharmacokinetics in rats after intravenous administration was investigated. The membrane fluidity of the particles was affected by the dispersal methods, the dispersal time in 0.003 mol/l NaOH in the pH-jump method, and the addition of Ca(2+) to the solution. The membrane fluidity was correlated with the pharmacokinetics in rats.


Effects of chronic intraventricular infusion of heparin glycosaminoglycan on learning and brain acetylcholine parameters in aged rats.
We reported previously that the glycosaminoglycan heparin (HP) has the facility to improve learning in adult rodents when administered into the nucleus basalis of the ventral pallidum. Here we gauged the effects of chronic intraventricular infusion of HP (20 ng per day over 28 days) in 26-month-old rats in terms of Morris water maze performance, habituation to a novel open field, retention of a step-through inhibitory avoidance task and changes in forebrain acetylcholine (ACh) levels. Control groups included vehicle-infused old and adult (3-month-old) rats. The chronic infusion of HP did not significantly influence the performance of the old animals in any of the learning and memory tasks employed. HP only slightly facilitated the retention of the inhibitory avoidance task and the rate of habituation in the open-field paradigm. In the water maze, the glycosaminoglycan did not counteract the navigation deficits observed for aged controls and even impaired performance during the initial place-learning trials. After behavioural testing, tissue levels of ACh were determined in frontal cortex, ventral striatum, neostriatum and hippocampus without detecting any obvious neurochemical differences between groups. The current results, together with our previous work, indicate that HP differentially affects learning and memory parameters in adult and aged rats. Thus, whereas the glycosaminoglycan proved effective in facilitating mnemonic functions in normal adult animals, no such a clear-cut beneficial effect was observed in behaviourally impaired old rats.


Clinical, pathologic, and immunohistochemical characteristics of gastrointestinal stromal tumors of the colon and rectum: implications for surgical management and adjuvant therapies.
This study was designed to review the clinical characteristics of surgically treated gastrointestinal stromal tumors of the colon and rectum, evaluate their immunohistochemical and pathologic features based on the current National Institutes of Health criteria, and correlate clinicopathologic findings with the subsequent clinical course. Patient and disease characteristics at presentation, pathologic features, surgical management, and clinical outcomes of 18 patients with gastrointestinal stromal tumors (4 colon and 14 rectum) diagnosed and primarily treated at our institution between 1979 and 2004 were evaluated. Tumors were classified on basis of size and mitotic rate according to current National Institutes of Health recommendations: 67 percent (n = 12) were high-risk, 5 percent (n = 1) were intermediate-risk, 17 percent (n = 3) were low-risk, and 11 percent (n = 2) were very low-risk gastrointestinal stromal tumors. Fifteen of 18 tumors were KIT-positive. The three KIT-negative tumors were platelet-derived growth factor receptor alpha positive. All patients with colonic gastrointestinal stromal tumors (n = 4) underwent segmental resection, whereas patients with rectal gastrointestinal stromal tumors had local excision (n = 5) or radical resection (n = 9). Sixty-six percent (8/12) of patients with high-risk colorectal gastrointestinal stromal tumors developed metastases. None of the patients (n = 6) with intermediate-risk, low-risk, or very low-risk gastrointestinal stromal tumors died of their disease after a median follow-up of 65 (range, 15-266) months. The majority of gastrointestinal stromal tumors of the colon and rectum are high-risk. Patients with high-risk colorectal gastrointestinal stromal tumors have a significant likelihood of developing metastases that is associated with poor prognosis. These patients need to be closely followed for an extended period and should be considered for adjuvant therapy with tyrosine kinase inhibitors.