Longitudinal trends of per- and polyfluoroalkyl substances in children's serum.
Studies suggest negative health impacts from early life exposure to per- and polyfluoroalkyl substances (PFASs). However, information on longitudinal exposure to PFASs during childhood is scarce for background-exposed individuals. This study sought to fill this gap by investigating children's longitudinal exposure trends through measurement of PFAS serum concentrations and calculation of body burdens (μg, total in body). Blood of 54 Finnish children was sampled 2005-2015 and analyzed for 20 PFASs at 1, 6 and 10.5 years of age. The body burden was calculated by multiplying the serum concentration by the volume of distribution and the bodyweight for each individual. Associations between serum concentrations or body burdens and parameters, such as sex, breastfeeding duration, body mass index as well as indoor dust and air PFAS concentrations, were evaluated. Serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) decreased significantly (p < 0.001) with age. In contrast to serum concentrations, body burdens stayed unchanged or even increased significantly (p < 0.05), except for PFOA in female children. Breastfeeding duration was positively correlated (p < 0.001) with serum concentrations of PFHxS, PFOS, PFOA and PFNA at 1 year of age. Some associations were found at 10.5 years with sex and indoor PFAS concentrations. Observations of longitudinal decreasing trends of serum concentrations can be misleading for understanding exposure levels from external media during childhood, as the serum concentration is influenced by parallel temporal changes and growth dilution. Body burdens account for growth dilution and thus better reflect differences in early-life to adolescence exposure than serum concentrations.


Highly Sensitive and Selective Photoelectrochemical Aptasensor for Cancer Biomarker CA125 Based on AuNPs/GaN Schottky Junction.
A gold nanoparticle (AuNPs)/gallium nitride (GaN) Schottky junction was fabricated by growing AuNPs in situ on the surface of GaN and then etched by H2O2 to appropriate diameter. The photogenerated electrons of GaN can be captured and transferred by the AuNPs to increase the migration efficiency, and the electron-hole pairs were separated, which results in the enhancement of the photoelectric performance of the system. The Fermi energy level of AuNPs and the charge transfer efficiency of the AuNPs/GaN can be adjusted by controlling the size of the AuNPs. Then the AuNPs/GaN Schottky photoelectrode had been applied to develop a novel photoelectrochemical (PEC) aptasensor for the epithelial ovarian cancer marker-CA125 detection. The DNA aptamer of CA125 was modified on the surface of the AuNPs via Au-S bonds. The aptamer can bind with the target with high selectivity, and the photoelectron transfer process of the system can be blocked by the protein, which results in the decrease of the photocurrent of the system. The ratio of photocurrent before and after incubation with CA125 (I1/I0) has a linear with the concentration of CA125 in the range of 1-100 U/mL with a detection limit of 0.3 U/mL. The standard addition recovery rates were between 86.01% and 90.09%. This method showed good sensitivity, selectivity, and reliability in detecting CA125 in serum.


Confined animal feeding operations as amplifiers of influenza.
Influenza pandemics occur when a novel influenza strain, often of animal origin, becomes transmissible between humans. Domestic animal species such as poultry or swine in confined animal feeding operations (CAFOs) could serve as local amplifiers for such a new strain of influenza. A mathematical model is used to examine the transmission dynamics of a new influenza virus among three sequentially linked populations: the CAFO species, the CAFO workers (the bridging population), and the rest of the local human population. Using parameters based on swine data, simulations showed that when CAFO workers comprised 15-45% of the community, human influenza cases increased by 42-86%. Successful vaccination of at least 50% of CAFO workers cancelled the amplification. A human influenza epidemic due to a new virus could be locally amplified by the presence of confined animal feeding operations in the community. Thus vaccination of CAFO workers would be an effective use of a pandemic vaccine.


Liver Transplantation for Patients with Cholestatic Liver Diseases.
Cholestatic liver diseases (CD) account for 11% of all liver transplantations (LT) in the Eurotransplant region. Despite the excellent long-term outcome that is considerably superior to all other indications for LT, transplant surgeons and physicians face nowadays - in the era of MELD (Model of End-Stage Liver Disease)-based allocation, organ shortage, and extended allocation policies - more and more challenges in this patient cohort, especially since there is no curative medical treatment for these entities. Based on a literature review and personal experience in liver transplantation for CD, we show the status quo of indication, allocation, and outcome as well as potential strategies to overcome long waiting times and organ shortage. Concerning graft and patient survival, CD remain the 'best indications' for LT. Since the implementation of MELD-based allocation results in patients with primary sclerosing cholangitis (PSC) could be preserved on good levels only by the implementation and revision of standard exceptions. Recurrence of PSC after LT remains a challenge for transplant surgeons and physicians. New data has kindled a debate on biliary reconstruction in LT for PSC. Promising data on living donor LT motivate to push the boundaries in this direction. CD are excellent indications for liver transplantation since excellent long-term outcomes are achievable when the transplant is performed at the right time. The decisions concerning evaluation, listing, and allocation should be made by an interdisciplinary team of gastroenterologists and transplant surgeons.


Hypoxia-Inducible Factor-1α Target Genes Contribute to Retinal Neuroprotection.
Hypoxia-inducible factor (HIF) is a transcription factor that facilitates cellular adaptation to hypoxia and ischemia. Long-standing evidence suggests that one isotype of HIF, HIF-1α, is involved in the pathogenesis of various solid tumors and cardiac diseases. However, the role of HIF-1α in retina remains poorly understood. HIF-1α has been recognized as neuroprotective in cerebral ischemia in the past two decades. Additionally, an increasing number of studies has shown that HIF-1α and its target genes contribute to retinal neuroprotection. This review will focus on recent advances in the studies of HIF-1α and its target genes that contribute to retinal neuroprotection. A thorough understanding of the function of HIF-1α and its target genes may lead to identification of novel therapeutic targets for treating degenerative retinal diseases including glaucoma, age-related macular degeneration, diabetic retinopathy, and retinal vein occlusions.


Gold nanoparticle-protein agglomerates as versatile nanocarriers for drug delivery.
The fabrication of a versatile nanocarrier based on agglomerated structures of gold nanoparticle (Au NP)-lysozyme (Lyz) in aqueous medium is reported. The carriers exhibit efficient loading capacities for both hydrophilic (doxorubicin) and hydrophobic (pyrene) molecules. The nanocarriers are finally coated with an albumin layer to render them stable and also facilitate their uptake by cancer cells. The interaction between agglomerated structures and the payloads is non-covalent. Cell viability assay in vitro showed that the nanocarriers by themselves are non-cytotoxic, whereas the doxorubicin-loaded ones are cytotoxic, with efficiencies higher than that of the free drug. Transmission electron microscopy and fluorescence microscopy along with flow cytometry analysis confirm the uptake of the drug-loaded nanocarriers by a human cervical cancer HeLa cell line. Field-emission scanning electron microscopy reveals the formation of apoptotic bodies leading to cell death, confirming the release of the payloads from the nanocarriers into the cell. Overall, the findings suggest the fabrication of novel Au NP-protein agglomerate-based nanocarriers with efficient drug-loading and -releasing capabilities, enabling them to act as multimodal drug-delivery vehicles.


Glycosylated flavones as selective inhibitors of topoisomerase IV.
Three flavonoids which promoted Escherichia coli topoisomerase IV-dependent DNA cleavage were isolated from cottonseed flour and identified as quercetin 3-O-beta-D-glucose-[1,6]-O-alpha-L-rhamnose (rutin), quercetin 3-O-beta-D-galactose-[1,6]-O-alpha-L-rhamnose, and quercetin 3-O-beta-D-glucose (isoquercitrin). The most active one (rutin) also inhibited topoisomerase IV-dependent decatenation activity (50% inhibitory concentration, 64 microg/ml) and induced the SOS response of a permeable E. coli strain. Derivatives of quercetin glycosylated at position C-3 were shown to induce two site-specific DNA cleavages of pBR322 DNA, which were mapped by DNA sequence analysis to the gene encoding resistance to tetracycline. Cleavage at these sites was hardly detectable in cleavage reactions with quercetin or fluoroquinolones. None of the three flavonoids isolated from cottonseeds had any stimulatory activity on E. coli DNA gyrase-dependent or calf thymus topoisomerase II-dependent DNA cleavage, and they were therefore specific to topoisomerase IV. These results show that selective inhibitors of topoisomerase IV can be derived from the flavone structure. This is the first report on a DNA topoisomerase inhibitor specific for topoisomerase IV.


Palladium-catalyzed oxidative carbonylation of alkyl and aryl indium reagents with CO under mild conditions.
CO now can react with organoindium reagents. A novel palladium-catalyzed oxidative carbonylation reaction of organoindium reagents by CO gas with desyl chloride as oxidant was developed in supplementation with the classical methods for preparation of carboxylic acid derivatives. Primary, secondary alkyl indium reagents with beta-hydrogens and aryl indium reagents were suitable substrates, and the reaction could be carried out at 60 degrees C under 50 psi CO. Carbonylation of alkyl indium reagents can occur smoothly without additional base. Although the indium reagents were prepared from corresponding Grignard reagents (at low temperature), they displayed full compatibility with various functional groups under the protic reaction conditions. Preliminary mechanistic studies including stoichiometric and catalytic reaction examination provided evidence to support the operation of the mechanism consisted of oxidative addition of deslyl chloride to Pd(0) and quick tautomerization to give a palladium enolate species II (ROPdCl), displacement of the enolate group in II by R(2)OH, followed by CO insertion to give alkoxycarbonyl palladium complex V, which undergoes transmetalation with R(1)(3)In and reductive elimination to afford the product and a Pd(0) species. In this mechanism, the alkoxycarbonyl group was transferred to the palladium center prior to the alkyl group, different from traditional ways initiated from oxidative addition of alkyl halides to a Pd(0) species.


Enamel color changes following orthodontic treatment.
To evaluate and compare the effect of various orthodontic bonding systems and clean up procedures on quantitative enamel colour change. A literature search was done to identify the studies that assessed the quantitative enamel colour change associated with the various bonding systems and cleanup procedures. Electronic database (Pub Med, Cochrane and Google Scholar) were searched. First stage screening was performed and the abstracts were selected according to the initial selection criteria. Full text articles were retrieved and analyzed during second stage screening. The bibliographies were reviewed to identify additional relevant studies. Sixteen full text articles were retrieved. Six were rejected because the methodology was different. There was significant enamel colour change following orthodontic bonding, debonding and clean up procedures. Self-etching primers produce less enamel colour change compared to conventional etching. Resin Modified GIC produces least colour change compared to other light cure and chemical cure systems. Polishing following the clean-up procedure reduces the colour change of the enamel.


[Woolly hair. Apropos of 5 cases].
Five cases of Woolly hair, three generalised, and two localised are reported. On the first two, we carried out trichogrammes which were studied with polarized light, and on all five, SEM (Scanning Electron Microscopy). The data obtained coincided with previous descriptions (Pseudomonilethrix images, Pili torti, Trichorrhexis nodosa, reduced hair diameter, oval section following transversal cut, and a wavy-line disposition), although we emphasize the smaller number of layers of cuticle cells following the transversal cut, and the presence of Trichonodosis, not previously refered.


Liposuction on a lymphedematous arm.
Suction lipectomy is a technique that is being used more and more frequently for both aesthetic and reconstructive purposes. One area in which this technique has only seen limited use heretofore is in the treatment of acquired lymphedema. A patient with longstanding postmastectomy lymphedema recently presented with a large squamous cell carcinoma and multiple smaller suspicious lesions on the lymphedematous forearm. After resection of these lesions, the remaining forearm skin was treated with liposuction to debulk the arm and facilitate wound closure. Most of the forearm wound could be closed after this treatment. The upper arm was then debulked with liposuction as well. Redundant skin from the upper arm was resected and used as a skin graft to the residual defect on the forearm. All wounds healed primarily. The patient has shown no sign of recurrence and has greatly improved function of the arm at 10 months follow-up. Although its exact indications and limitations need to be defined, liposuction can be a useful treatment modality for at least some patients with acquired lymphedema.


The effect of saliva composition on texture perception of semi-solids.
Saliva is expected to be of significance for the perception of food stimuli in the mouth. Mixing the food with saliva, including breakdown and dilution, is considered to be of large importance for semi-solids as these products are masticated without chewing. It is known that there are large variations in composition of saliva originating from different glands and different subjects. In this study we investigated how variations in salivary characteristics affect sensory perception. Eighteen trained subjects participated in the study. Saliva was collected at rest and during three types of stimulation (odour, parafilm chewing and citric acid), and flow rates were determined. The collected saliva was analyzed for protein concentration, buffer capacity, mucin level and alpha-amylase activity. The salivary components measured in this study varied considerably among subjects, but also within subjects as a result of different means of stimulation. Variations in salivary components were correlated with sensory perception of a number of flavour, mouth feel and after feel attributes in the semi-solids mayonnaise and custard dessert. Total protein concentration and alpha-amylase activity were observed to correlate most strongly with texture perception.


Pain Expressions and Inhibitory Control in Patients With Fibromyalgia: Behavioral and Neural Correlates.
Fibromyalgia (FM) is a generalized chronic pain condition associated with a variety of symptoms, including altered cognitive and emotional processing. It has been proposed that FM patients show a preferential allocation of attention to information related to the symptoms of the disease, particularly to pain cues. However, the existing literature does not provide conclusive evidence on the presence of this attentional bias, and its effect on cognitive functions such as inhibitory control. To clarify this issue, we recorded the electroencephalographic activity of 31 women diagnosed with FM and 28 healthy women, while performing an emotional Go/NoGo task with micro-videos of pain, happy, and neutral facial expressions. We analyzed behavioral data, performed EEG time-frequency analyses, and obtained the event-related potentials (ERPs) N2 and P3 components in NoGo trials. A series of self-reports was also administered to evaluate catastrophic thinking and the main symptoms of fibromyalgia. Pain expressions were associated with longer reaction times and more errors, as well as with higher theta and delta power, and P3 amplitude to NoGo stimuli. Thus, behavioral and psychophysiological data suggest that increased attention to pain expressions impairs the performance of an inhibitory task, although this effect was similar in FM patients and healthy controls. N2 amplitude was modulated by type of facial expression (larger to pain faces), but only for the control group. This finding suggests that the presentation of pain faces might represent a smaller conflict for the patients, more used to encounter pain stimuli. No main group effects were found significant for N2 or P3 amplitudes, nor for time-frequency data. Using stimuli with greater ecological validity than in previous studies, we could not confirm a greater effect of attentional bias toward negative stimuli over inhibitory performance in patients with FM. Studying these effects allow us to better understand the mechanisms that maintain pain and develop intervention strategies to modify them.


Management of ischemic coronary disease in patients receiving chemotherapy: an uncharted clinical challenge.
Acute coronary syndrome (ACS) coinciding with active malignancy presents a unique clinical challenge given intersecting pathophysiology and treatment-related effects. There is little established clinical guidance on management strategies, rendering most treatment approaches anecdotal. We present a case highlighting the complexity of managing a patient being treated for malignancy who concurrently suffers from ACS. We then review the literature on co-management of ACS and malignancy, including reports of specific cancer therapies associated with ACS, unique features of clinical presentation and optimal use of dual antiplatelet therapy to minimize risks of bleeding and thrombosis. We also describe gaps in current literature, challenges in systematically studying the clinical intersection of these disease processes and propose alternative methodologies for further research.


Diagnostic modalities in peripheral artery disease.
Peripheral artery disease (PAD) affects approximately one in five persons older than 70 years of age and it is often present in patients with concomitant vascular disease in different body territories (e.g. coronary artery disease). Diagnosis at an early stage is important in order to achieve improvement in patient's symptoms and prognosis. Remarkable improvements in the field of noninvasive and invasive imaging techniques have led to an advanced level the management of patients with PAD. Throughout this review article, the clinically available diagnostic modalities in PAD are presented. Strong and weaker points are stressed out in a manner that elucidates that no perfect diagnostic method exists. Based on the patient's individual profile, as well as on certain aspects of the disease (e.g. morphology of carotid plaque lesions) the attending physician will ultimately decide which diagnostic path will lead to a prompt and correct diagnosis of PAD with the minimum amount of exams and risk for the patient.


Mass media and healthy aging.
Health effects associated with media use have largely focused on children and youth with little attention paid to adults, particularly older adults. However, adults aged 60 years and older report heavy television viewing, and unique health education challenges will be faced as the technically savvy baby-boomer cohort ages. Media health effects relevant to older adults include an established causative link with adiposity and correlations to increased risk of chronic disease, reduced physical activity, and undesirable food choice behaviors. Advertising has targeted older adults as a key market segment promoting anti-aging and health related products, with potential negative body image impacts. Implications for health practitioners and research are discussed in the context of these consequences.


Pharmacogenetics of posttransplant diabetes mellitus.
Many factors (physiological, pathological, environmental or genetic) are associated with variability in drug effect. Most patients respond to a standard treatment but the drug may be ineffective or toxic. In this review, we focused on genetic markers of posttransplant diabetes mellitus (PTDM) after renal transplantation, a frequent complication of immunosuppressive therapy and important risk factor of graft loss and mortality. An initial literature search identified 100 publications and among them 32 association studies were retrieved under 'Pharmacogenetics and PTDM'. Thirty-five variants in 25 genes with an impact on insulin secretion, disposition or effect were significantly associated with PTDM. The population studied, immunosuppressive regimen, follow-up, PTDM diagnostic and genetic variations tested were highly variable between studies. Although pharmacogenetic biomarkers are key tools of great promise for preventing toxicities and improving event-free survival rates, replication studies are required to select validated biomarkers linked to the occurrence of PTDM and select appropriate immusuppressive treatment to improve renal graft and patient outcome.


Radiation safety for pain physicians: principles and recommendations.
C-arm fluoroscopy is a useful tool for interventional pain management. However, with the increasing use of C-arm fluoroscopy, the risk of accumulated radiation exposure is a significant concern for pain physicians. Therefore, efforts are needed to reduce radiation exposure. There are three types of radiation exposure sources: (1) the primary X-ray beam, (2) scattered radiation, and (3) leakage from the X-ray tube. The major radiation exposure risk for most medical staff members is scattered radiation, the amount of which is affected by many factors. Pain physicians can reduce their radiation exposure by use of several effective methods, which utilize the following main principles: reducing the exposure time, increasing the distance from the radiation source, and radiation shielding. Some methods reduce not only the pain physician's but also the patient's radiation exposure. Taking images with collimation and minimal use of magnification are ways to reduce the intensity of the primary X-ray beam and the amount of scattered radiation. It is also important to carefully select the C-arm fluoroscopy mode, such as pulsed mode or low-dose mode, for ensuring the physician's and patient's radiation safety. Pain physicians should practice these principles and also be aware of the annual permissible radiation dose as well as checking their radiation exposure. This article aimed to review the literature on radiation safety in relation to C-arm fluoroscopy and provide recommendations to pain physicians during C-arm fluoroscopy-guided interventional pain management.


Definition of formulation design space, in vitro bioactivity and in vivo biodistribution for hydrophilic drug loaded PLGA/PEO-PPO-PEO nanoparticles using OFAT experiments.
Modified nanoprecipitation method was used for improved incorporation of hydrophilic drug (irinotecan hydrochloride) into the PLGA/PEO-PPO-PEO blended and blended/adsorbed nanoparticles. One factor at a time (OFAT) variation experiments were conducted in order to determine key formulation factors (concentration and volume of drug solution, evaporation rate and PLGA/PEO-PPO-PEO ratio) influencing nanoparticle properties (particle size and size distribution, encapsulation efficiency, drug content, zeta potential, drug dissolution rate, as well as protein binding capacity). The insight into in vivo behavior of prepared nanoparticles and their potential for effective anticancer treatment was gained by performing biodistribution and cell culture studies as part of OFAT experiments. The mean particle size, mainly dependent upon PLGA/PEO-PPO-PEO ratio, was in the range of 112-125 nm, with narrow unimodal distribution (PDI∼0.1). Encapsulation efficiency (32-63%) was impacted by evaporation rate and PLGA/PEO-PPO-PEO ratio. Drug content (0.2-1.51%) and controlled release properties were related to the influence of all tested formulation factors. Structural information for the studied nanoparticles was obtained using DSC and FT-IR spectroscopy. Zeta potential values indicated that presence of PEO-PPO-PEO in the formulations shielded the high surface negative charge of PLGA. PEO-PPO-PEO surface coverage of PLGA/PEO-PPO-PEO blended as well as blended/adsorbed nanoparticles depended upon amount of used PEO-PPO-PEO during preparation procedure and was related to the protein resistant characteristics of nanoparticles. Results from in vivo studies evidenced prolonged blood circulation time of the prepared nanoparticles, while cell culture studies indicated higher in vitro bioefficacy compared to free drug. Performed experiments defined possible design space and justified further optimization of formulation using experimental design studies.


Type 2 diabetes: Gaining insight into the disease process using proteomics.
The incidence of diabetes mellitus is growing rapidly, with an increasing disease related morbidity and mortality. This is caused by macro- and microvascular complications, as a consequence of the often late diagnosis of type 2 diabetes (T2D), but especially by the difficulties to control glucose homeostasis due to the progressive nature of the disease. T2D is moreover a dual disease, with components of beta-cell failure and components of insulin resistance in peripheral organs, such as liver, fat, and muscle. Understanding the pathogenesis of the disease by gaining insight into the molecular pathways involved in both phenomena is one of the major assets of proteomic approaches. Moreover, proteomics and peptidomics may provide us with robust biomarkers for beta-cell failure, insulin resistance in pheripheral organs, but also for the development of diabetic complications. This review focuses on the knowledge gained by use of proteomic and peptidomic techniques in the study of the pathophysiology of T2D and in the attempts to discover new therapeutic targets.


Ester Oils Prepared from Fully Renewable Resources and Their Lubricant Base Oil Properties.
The work reports on the physicochemical and tribological properties of gallate ester oils prepared from fully renewable resources, such as gallic acid and fatty acids. The ester structures were identified by proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR) and high-resolution mass spectra (HRMS) data. The density at 20 °C (d 20), kinematic viscosity (KV), viscosity index (VI), pour point (PP), flash point (FP), thermal and oxidative stabilities, friction-reducing and antiwear properties of gallate ester oils were evaluated. The tribological properties of gallate ester oils as lubricants for steel, copper, and aluminum tribo-pairs can be compared with those of the commercially available lubricating oil tris(2-ethylhexyl) trimellitate (Phe-3Ci8), but their viscosity-temperature characteristics, thermal and oxidative stabilities are better than those of Phe-3Ci8. More importantly, they have much higher biodegradabilities than Phe-3Ci8. The study of the lubrication mechanism shows that the physical and/or chemical adsorption film formed by gallate ester molecules between friction pairs is the key factor for them to obtain friction-reducing and antiwear properties.


Electrochemical analysis of acetaminophen using a boron-doped diamond thin film electrode applied to flow injection system.
The electrochemistry of acetaminophen in phosphate buffer solution (pH 8) was studied at a boron-doped diamond (BDD) thin film electrode using cyclic voltammetry, hydrodynamic voltammetry, and flow injection with amperometric detection. Cyclic voltammetry was used to study the reaction as a function of concentration of analyte. Comparison experiments were performed using a polished glassy carbon (GC) electrode. Acetaminophen undergoes quasi-reversible reaction at both of these two electrodes. The BDD and GC electrodes provided well-resolved cyclic voltammograms but the voltammetric signal-to-background ratios obtained from the diamond electrode were higher than those obtained from the GC electrode. The diamond electrode provided a linear dynamic range from 0.1 to 8 mM and a detection of 10 microM (S/B approximately 3) for voltammetric measurement. The flow injection analysis results at the diamond electrode indicated a linear dynamic range from 0.5 to 50 microM and a detection limit of 10 nM (S/N approximately 4). Acetaminophen in syrup samples has also been investigated. The results obtained in the recovery study (24.68+/-0.26 mg/ml) were comparable to those labeled (24 mg/ml).


Malnutrition and diabetes mellitus are related to hepatic encephalopathy in patients with liver cirrhosis.
Studies on animal models of hepatic encephalopathy (HE) suggest that poor nutritional status may facilitate the development of HE. Insulin resistance and diabetes mellitus have recently been reported to affect cognition in patients with hepatitis C cirrhosis awaiting liver transplantation. Our aim was to investigate the effects of malnutrition and diabetes mellitus on HE in unselected patients with liver cirrhosis. A total of 128 consecutive cirrhotic patients were prospectively evaluated for the presence of HE according to the West-Haven criteria as well as by means of two psychometric tests and fasting plasma ammonium ion concentrations. Nutritional status was assessed by anthropometry and estimation of recent weight change. Fasting plasma glucose was measured, and in a subgroup of 84 patients fasting serum insulin and insulin resistance were also determined. Fifty-one (40%) cirrhotics were malnourished, 33 (26%) had diabetes and 42 (34%) had HE. Patients with vs. without malnutrition had more frequently HE (46 vs. 27%; P=0.031) but did not differ in age, aetiology or severity of liver cirrhosis (P>0.1). Multivariate analysis showed that the time needed to perform number connection test A was independently correlated to age, the Child-Pugh score, diabetes and malnutrition (P<0.05 for all). Plasma ammonium ion levels were related to insulin resistance (r=0.42, P<0.001) and muscle mass (r=0.28, P=0.003). Malnutrition and diabetes mellitus seem to be related to HE in patients with liver cirrhosis. Nutritional status and insulin resistance might be implicated in the pathogenesis of HE.


Ultra-selective high-flux membranes from directly synthesized zeolite nanosheets.
A zeolite with structure type MFI is an aluminosilicate or silicate material that has a three-dimensionally connected pore network, which enables molecular recognition in the size range 0.5-0.6 nm. These micropore dimensions are relevant for many valuable chemical intermediates, and therefore MFI-type zeolites are widely used in the chemical industry as selective catalysts or adsorbents. As with all zeolites, strategies to tailor them for specific applications include controlling their crystal size and shape. Nanometre-thick MFI crystals (nanosheets) have been introduced in pillared and self-pillared (intergrown) architectures, offering improved mass-transfer characteristics for certain adsorption and catalysis applications. Moreover, single (non-intergrown and non-layered) nanosheets have been used to prepare thin membranes that could be used to improve the energy efficiency of separation processes. However, until now, single MFI nanosheets have been prepared using a multi-step approach based on the exfoliation of layered MFI, followed by centrifugation to remove non-exfoliated particles. This top-down method is time-consuming, costly and low-yield and it produces fragmented nanosheets with submicrometre lateral dimensions. Alternatively, direct (bottom-up) synthesis could produce high-aspect-ratio zeolite nanosheets, with improved yield and at lower cost. Here we use a nanocrystal-seeded growth method triggered by a single rotational intergrowth to synthesize high-aspect-ratio MFI nanosheets with a thickness of 5 nanometres (2.5 unit cells). These high-aspect-ratio nanosheets allow the fabrication of thin and defect-free coatings that effectively cover porous substrates. These coatings can be intergrown to produce high-flux and ultra-selective MFI membranes that compare favourably with other MFI membranes prepared from existing MFI materials (such as exfoliated nanosheets or nanocrystals).


[The effect of microstructure on the desulphurization of absorbents].
The microstructure and the pore size distribution of 3 kinds of shell and 1 kind of limestone were measured with electronic scanning microscope and pore master mercury porosimeter, and the desulphurization characteristics of above absorbents were studied with thermal-gravimetric analyzer. As a result, the grains of calcium from shell like tortuous flakes, with pore diameter above 0.2 micron and higher pore volume, while the grains from limestone like particles, with pore diameter between 0.01 to 0.16 micron and lower pore volume, but the surface area were very high. The bigger pore which was above 0.2 micron in shell had many advantages, such as fewer air-blocked pores, lower gas diffusing resistance, almost simultaneous and completed reaction. So, finally the calcium conversation ratio of the shell was greater than that of the limestone. On the other hand, while the gas diffusion was meted, it was effective for desulphurization to reduce the pore size and to increase the surface area.


Visible-pulse generation in gain crystal of near-infrared femtosecond optical parametric oscillator.
An optical parametric oscillator (OPO) based on magnesium-oxide-doped periodically poled lithium niobate (MgO:PPLN) is demonstrated to deliver visible femtosecond pulses, which were created through the intra-cavity nonlinear interactions within the PPLN itself. The signal from the OPO produces femtosecond pulses in the near-infrared region tunable from 1050 to 1600 nm. Visible femtosecond pulses in the range of 522-800 nm and those of 455-540 nm, respectively, were generated via second-harmonic generation (SHG) of signal photons and through sum-frequency generation (SFG) of pump and signal photons. Maximum output efficiencies of 9.2% at 614 nm and 8.0% at 522 nm for the SHG and SFG are attained, respectively, where the efficient visible pulse generation relies on the quasi-phase matching with the aid of the higher-order grating momentum.


Women helping chewers: partner support and smokeless tobacco cessation.
Data from 363 male smokeless tobacco users and their romantic partners were analyzed to discern the role of support in cessation. Women reported playing a part in enrollment (71%), and more than half examined program materials or discussed cessation activities with the chewers. Women's reports of delivered support correlated substantially with men's experience of received support. Men's received positive support predicted abstinence at 6-month follow-up (odds ratio = 1.29, confidence interval = 1.03-1.61) and more than 24 hr of abstinence for those still using tobacco at 6 months (odds ratio = 1.75, confidence interval = 1.30-2.36) and moderated the effect of baseline depression and addiction on abstinence. Women played a major role through all stages of cessation.


Recognition of plosive syllables in noise: comparison of an auditory model with human performance.
Some of the effects of noise on the perception of plosive-vowel syllables have been investigated. It was found that noise added to the syllables for the duration of the speech had a more deleterious effect on perception than noise of the same intensity played continuously. Physiological experiments have shown that the response thresholds of cochlear nerve fibers to tones are raised by continuous background noise but not by short bursts of noise. It is suggested that this may be responsible for the speech perception results. In order to investigate this, an auditory model was developed which incorporated response threshold shifts. This was interfaced to a hidden Markov model recognizer and tested with the same sounds that were employed in the human perception experiments. The recognition scores were greater with the threshold shifts than without them.


Impact of sarcopenia on biliary drainage during neoadjuvant therapy for pancreatic cancer.
Since the usefulness of neoadjuvant chemo(radiation) therapy (NAT) for pancreatic cancer (PC) has been demonstrated, recurrent biliary obstruction (RBO) in patients with PC with a fully covered self-expandable metal stent (FCSEMS) during NAT is expected to increase. This study investigated the impact of sarcopenia on RBO in this setting. Patients were divided into normal and low skeletal muscle index (SMI) groups and retrospectively analyzed. Patient characteristics, overall survival (OS), time to RBO (TRBO), stent-related adverse events, and postoperative complications were compared between the two groups. A Cox proportional hazard model was used to identify the risk factors for short TRBO. A few significant differences were observed in patient characteristics, OS, stent-related adverse events, and postoperative complications between 38 patients in the normal SMI group and 17 in the low SMI group. The median TRBO was not reached in the normal SMI group and was 112 days in the low SMI group (p=0.004). In multivariate analysis, low SMI was the only risk factor for short TRBO, with a hazard ratio of 5.707 (95% confidence interval, 1.148-28.381; p=0.033). Sarcopenia was identified as an independent risk factor for RBO in patients with PC with FCSEMS during NAT.


Imaging and differential diagnosis of the large eye.
The initial step in the differential diagnosis of an enlarged eye is to determine whether an intraocular mass is present. The globe may be expanded by a mass, seen mainly in children with retinoblastoma. Buphthalmos with or without neurofibromatosis also enlarges the eye. Diffuse enlargement may be associated with a connective tissue disorder or be related to axial myopia. Focal enlargement represents staphyloma, which can be unilateral or bilateral. In the presence of one small eye, the normal-sized eye may be incorrectly diagnosed as large.


[Effect of vitamin K2 syrup in neonatal hypoprothrombinemia].
To clarify whether vitamin-K prophylaxis in newborns is effective, a double-blind study with oral vitamin-K2 syrup was performed. There were no side-effects. Various dosages of vitamin K2 or placebo syrup were tried in 148 newborns with thrombotest results below 20%. The efficiency decreased as follows: vit-K2 6 mg greater than vit-K2 2 mg greater than vit-K1 2 mg greater than placebo. The effect of all vitamin K preparations on the coagulation system was significantly different from the placebo effect. With regard to our own results and the literature, general vitamin-K prophylaxis for newborns is not recommended. However, vitamin K 1 X 6 mg orally is helpful in newborns with thrombotest results below 20%, in infants at risk, and in all premature, dystrophic or otherwise underweight infants.


Production of human monoclonal and polyclonal antibodies in TransChromo animals.
We have developed TransChromo (TC) technology, which enables the introduction of megabase-sized segments of DNA into cells. We have used this approach to derive mice that carry megabases of human DNA by the use of a human chromosome fragment (HCF) as a vector. TC technology has been applied to the construction of the TC Mouse,trade mark which incorporates entire human immunoglobulin (hIg) loci. TC Mouse expresses a fully diverse repertoire of hIgs, including all the subclasses of IgGs (IgG1-G4). Immunization of the TC Mouse with various human antigens produced antibody responses comprised of human antibodies. Furthermore, it was possible to obtain hybridoma clones expressing fully human antibodies specific for the target human antigen. However, because of the instability of the Igkappa locus-bearing HCF2, the efficiency of hybridoma production was less than one-tenth of that observed in normal mice. An instant solution to this problem was to cross-breed the Kirin TC Mouse carrying the HCF14, which was stable in mouse cells, with the Medarex YAC-transgenic mouse carrying about 50% of the hIgVkappa gene segments as a region that is stably integrated into the mouse genome. The resulting mouse, dubbed the KM Mouse, performed as well as normal mice with regard to immune responsiveness and efficiency of hybridoma production. Another application of TC technology is the production of polyclonal antibodies in large animals such as chickens and cows. To test the efficacy of human polyclonal antibodies derived from TC animals, feasibility studies were performed using antisera and purified gamma-globulin from TC mice immunized with Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), or Japanese encephalitis virus (JEV). The TC mouse-derived antisera and gamma-globulin showed a much higher titer and efficacy in terms of the neutralizing activity of the pathogens in vitro and in vivo than either human serum or gamma-globulin prepared from human blood.


Release of latent glucuronosyltransferase activity contributes to the sparing of glucuronidation in experimental liver injuries.
In patients with parenchymal liver disease, glucuronidation of drugs is generally preserved but oxidation is impaired. This study explores the effects of liver injuries induced in rats by the administration of acute carbon tetrachloride, chronic bile duct ligation and chronic choline deficiency for 30 weeks on the glucuronidation of p-nitrophenol and 1-naphthol, both before and after solubilization of the microsomes and compares this to three measures of oxidation. Cytochrome P450 content was reduced to 17% of control values after acute carbon tetrachloride and to 35% of control values after bile duct ligation. Cytochrome C reductase fell to 58 and 32% of control and aniline hydroxylase to 46 and 13%, respectively, after acute carbon tetrachloride and bile duct ligation. P-nitrophenol glucuronidation by native microsomes was 206 and 73% of controls in the respective models, while 1-naphthol glucuronidation was 167 and 66% of control. Latent uridine diphosphate-glucuronosyltransferase (UDP-GT) activity, that is, differences between solubilized and native activity, was decreased by each liver injury. Chronic choline deficiency had little effect on the oxidation and native glucuronidation activity, although latent glucuronidation activity was lower. These studies suggest a preservation of glucuronidation compared to oxidation at the microsomal level in these experimental liver injuries. The data also support the hypothesis that a release of latent UDP-GT activity may contribute to this phenomenon.


Dynamic interaction of theory and experiment: total determination of the gas-phase molecular structure of tri-tert-butylphosphine oxide (OPBut3).
A new method to aid the determination of structures of sterically crowded molecules in the gas phase by dynamically linking the gas-phase electron diffraction (GED) refinement process with computational methods has been developed. The procedure involves refining the heavy-atom skeleton of the molecule using the GED data while continually updating the light-atom positions during the refinement using computational methods, in this case molecular mechanics. This removes errors associated with the assumption of local symmetry for the light-atom groups, which can affect the final values of the heavy-atom parameters. The refinement of the molecular structure of tri-tert-butyl phosphine oxide has been used to illustrate this new technique, which we call the DYNAMITE (DYNAMic Interaction of Theory and Experiment) method. Re-examination of the structure using this method has resulted in a shorter P-O distance than was found in a less sophisticated anaylsis, and is consistent with the molecule being regarded as O=PBut3, rather than O(-)-P+But3.


Visual exploration in Parkinson's disease and Parkinson's disease dementia.
Parkinson's disease, typically thought of as a movement disorder, is increasingly recognized as causing cognitive impairment and dementia. Eye movement abnormalities are also described, including impairment of rapid eye movements (saccades) and the fixations interspersed between them. Such movements are under the influence of cortical and subcortical networks commonly targeted by the neurodegeneration seen in Parkinson's disease and, as such, may provide a marker for cognitive decline. This study examined the error rates and visual exploration strategies of subjects with Parkinson's disease, with and without cognitive impairment, whilst performing a battery of visuo-cognitive tasks. Error rates were significantly higher in those Parkinson's disease groups with either mild cognitive impairment (P = 0.001) or dementia (P < 0.001), than in cognitively normal subjects with Parkinson's disease. When compared with cognitively normal subjects with Parkinson's disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cognitive impairment. When compared with control subjects and cognitively normal subjects with Parkinson's disease, saccade amplitudes were significantly reduced in the groups with mild cognitive impairment or dementia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson's disease groups. The strongest predictor of average fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impairment and disease severity contributed to a predictive model for fixation duration [F(2,76) = 12.52, P ≤ 0.001], but medication dose did not (r = 0.18, n = 78, P = 0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson's disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself. The prolongation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson's disease, suggests a disease-specific impact on the networks directing visual exploration, although the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual search.


Evaluation of the frequency of and survival from second primary cancers in North Portugal: a population-based study.
A marked increase in cancer survival and in the frequency of second primary cancers (SPCs) has been observed in the latest decades, propelling the investigation of their burden at a population level. We aimed to quantify the proportion of SPCs among the incident cases in North Portugal and to describe their survival. We identified all SPCs (excluding skin nonmelanoma) registered by the North Region Cancer Registry (RORENO) from 2000 to 2003 according to the International Association of Cancer Registries and the International Agency for Research on Cancer guidelines. We classified tumors diagnosed more than 2 months after a first primary cancer (FPC) as metachronous. The observed survival was computed using vital status in December 2010. A total of 1607 SPCs (3.8% of all cancers) were registered (77.9% metachronous). The most frequent metachronous SPC topographies and the corresponding most frequent FPCs were of the colon (12.2%; FPC: prostate, breast, and stomach), lung (10.5%; FPC: bladder, stomach, and colon), and stomach (9.7%; FPC: prostate, breast, and bladder). The overall 5-year survival of individuals with metachronous SPCs was 47.4%; within the subgroups with higher (63.1%) and lower survival (31.1%), there were no significant differences across groups of FPCs with expectably different survival. The proportion of SPCs was that anticipated for a registry with approximately one decade of activity. The most common cancers in the general population were also frequent metachronous SPCs, whereas the most frequent FPCs were high incidence and survival cancers. The survival of metachronous SPCs did not vary with the survival expected for the FPCs.


A close relationship between verbal memory and SN/VTA integrity in young and older adults.
Age-related dysfunction in dopaminergic neuromodulation is assumed to contribute to age-associated memory impairment. However, to date there are no in vivo data on how structural parameters of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic projections, relate to memory performance in healthy young and older adults. We investigated this relationship in a cross-sectional study including data from the hippocampus and frontal white matter (FWM) and also assessing working memory span and attention. In groups of young and older adults matched for the variance of their age distribution, gender and body mass index, we observed a robust positive correlation between Magnetization Transfer Ratio (MTR)--a measure of structural integrity--of the SN/VTA and FWM with verbal learning and memory performance among older adults, while there was a negative correlation in the young. Two additional imaging parameters, anisotropy of diffusion and diffusion coefficient, suggested that in older adults FWM changes reflected vascular pathology while SN/VTA changes pointed towards neuronal loss and loss of water content. The negative correlation in the young possibly reflected maturational changes. Multiple regression analyses indicated that in both young and older adults, SN/VTA MTR explained more variance of verbal learning and memory than FWM MTR or hippocampal MTR, and contributed less to explaining variance of working memory span. Together these findings indicate that structural integrity in the SN/VTA has a relatively selective impact on verbal learning and memory and undergoes specific changes from young adulthood to older age that qualitatively differ from changes in the FWM and hippocampus.


The Absence of the Transcription Factor Yrr1p, Identified from Comparative Genome Profiling, Increased Vanillin Tolerance Due to Enhancements of ABC Transporters Expressing, rRNA Processing and Ribosome Biogenesis in Saccharomyces cerevisiae.
Enhancing the tolerance of Saccharomyces cerevisiae to inhibitors derived from lignocellulose is conducive to producing biofuel and chemicals using abundant lignocellulosic materials. Vanillin is a major type of phenolic inhibitor in lignocellulose hydrolysates for S. cerevisiae. In the present work, the factors beneficial to vanillin resistance in yeast were identified from the vanillin-resistant strain EMV-8, which was derived from strain NAN-27 by adaptive evolution. We found 450 SNPs and 44 genes with InDels in the vanillin-tolerant strain EMV-8 by comparing the genome sequences of EMV-8 and NAN-27. To investigate the effects of InDels, InDels were deleted in BY4741, respectively. We demonstrated that the deletion of YRR1 improved vanillin tolerance of strain. In the presence of 6 mM vanillin, deleting YRR1 increase the maximum specific growth rate and the vanillin consumption rate by 142 and 51%, respectively. The subsequent transcriptome analysis revealed that deleting YRR1 resulted in changed expression of over 200 genes in the presence of 5 mM vanillin. The most marked changes were the significant up-regulation of the dehydrogenase ADH7, several ATP-binding cassette (ABC) transporters, and dozens of genes involved in ribosome biogenesis and rRNA processing. Coincidently, the crude enzyme solution of BY4741(yrr1Δ) exhibited higher NADPH-dependent vanillin reduction activity than control. In addition, overexpressing the ABC transporter genes PDR5, YOR1, and SNQ2, as well as the RNA helicase gene DBP2, increased the vanillin tolerance of strain. Interestingly, unlike the marked changes we mentioned above, under vanillin-free conditions, there are only limited transcriptional differences between wildtype and yrr1Δ. This indicated that vanillin might act as an effector in Yrr1p-related regulatory processes. The new findings of the relationship between YRR1 and vanillin tolerance, as well as the contribution of rRNA processing and ribosome biogenesis to enhancing S. cerevisiae vanillin tolerance, provide novel targets for genetic engineering manipulation to improve microbes' tolerance to lignocellulose hydrolysate.


Prediction of Bond Vector Autocorrelation Functions from Larmor Frequency-Selective Order Parameter Analysis of NMR Relaxation Data.
Protein molecular dynamics interpretation of the standard R1, R2, and heteronuclear NOE relaxation measurements has typically been limited to a single S2 order parameter which is often insufficient to characterize the rich content of these NMR experiments. In the absence of exchange linebroadening, an optimized reduced spectral density analysis of these measurements can yield spectral density values at three distinct frequencies. Surprisingly, these three discrete spectral density values have proven to be sufficient for a Larmor frequency-selective order parameter analysis of the 223 methine and methylene H-C bonds of the B3 domain of Protein G (GB3) to accurately back-calculate the entire curve of the corresponding bond vector autocorrelation functions upon which the NMR relaxation behavior depends. The 13C relaxation values calculated from 2 μs of CHARMM36 simulation trajectories yielded the corresponding autocorrelation functions to an average rmsd of 0.44% with only three bond vectors having rmsd errors slightly greater than 1.0%. Similar quality predictions were obtained using the CHARMM22/CMAP, AMBER ff99SB, and AMBER ff99SB-ILDN force fields. Analogous predictions for the backbone 15N relaxation values were 3-fold more accurate. Excluding seven residues for which either experimental data is lacking or previous MD studies have indicated markedly divergent dynamics predictions, the CHARMM36-derived and experimentally derived 15N relaxation values for the remaining 48 amides of GB3 agree to an average of 0.016, 0.010, and 0.020 for the fast limit (Sf2) and Larmor frequency-selective (SH2 and SN2) order parameters, respectively. In contrast, for a substantial fraction of side chain positions, the statistical uncertainties obtained in the relaxation value predictions from each force field were appreciably less than the much larger differences predicted among these force fields, indicating a significant opportunity for experimental NMR relaxation measurements to provide structurally interpretable guidance for further optimizing the prediction of protein dynamics.


Results of delayed follow-up imaging in traumatic brain injury.
There is a paucity of scientific evidence available about the benefits of outpatient follow-up imaging for traumatic brain injury patients. In this study, 1 year of consecutive patients at a Level 1 trauma center were analyzed to determine if there is any benefit to routinely obtaining CT of the head at the outpatient follow-up visit. This single-institution retrospective review was performed on all patients with a traumatic brain injury seen at a Level 1 trauma center in 2013. Demographic data, types of injuries, surgical interventions, radiographic imaging in inpatient and outpatient settings, and outcomes were assessed through a review of the institution's trauma registry, patient charts, and imaging. Five hundred twenty-five patients were seen for traumatic brain injury in 2013 at Regional One Health in Memphis, Tennessee. One hundred eighty-five patients (35%) presented for outpatient follow-up, all with CT scans of the head. Seven of these patients (4%) showed worsening of their intracranial injuries on outpatient imaging studies; however, surgical intervention was recommended for only 3 of these patients (2%). All patients requiring an intervention had neurological deterioration prior to their follow-up appointment. These experiences suggest that outpatient follow-up imaging for traumatic brain injury should be done selectively, as it was not helpful for patients who did not exhibit worsening of neurological signs or symptoms. Furthermore, routine outpatient imaging results in unnecessary resource utilization and radiation exposure.


Feasibility of fusing three-dimensional transabdominal and transrectal ultrasound images for comprehensive intraoperative visualization of gynecologic brachytherapy applicators.
In this study, we propose combining three-dimensional (3D) transrectal ultrasound (TRUS) and 3D transabdominal ultrasound (TAUS) images of gynecologic brachytherapy applicators to leverage the advantages of each imaging perspective, providing a broader field-of-view and allowing previously obscured features to be recovered. The aim of this study was to evaluate the feasibility of fusing these 3D ultrasound (US) perspectives based on the applicator geometry in a phantom prior to clinical implementation. In proof-of-concept experiments, 3D US images of application-specific multimodality pelvic phantoms were acquired with tandem-and-ring and tandem-and-ovoids applicators using previously validated imaging systems. Two TRUS images were acquired at different insertion depths and manually fused based on the position of the ring/ovoids to broaden the TRUS field-of-view. The phantom design allowed "abdominal thickness" to be modified to represent different body habitus and TAUS images were acquired at three thicknesses for each applicator. The merged TRUS images were then combined with TAUS images by rigidly aligning applicator components and manually refining the registration using the positions of source channels and known tandem length, as well as the ring diameter for the tandem-and-ring applicator. Combined 3D US images were manually, rigidly registered to images from a second modality (magnetic resonance (MR) imaging for the tandem-and-ring applicator and X-ray computed tomography (CT) for the tandem-and-ovoids applicator (based on applicator compatibility)) to assess alignment. Four spherical fiducials were used to calculate target registration errors (TREs), providing a metric for validating registrations, where TREs were computed using root-mean-square distances to describe the alignment of manually identified corresponding fiducials. An analysis of variance (ANOVA) was used to identify statistically significant differences (p < 0.05) between the TREs for the three abdominal thicknesses for each applicator type. As an additional indicator of geometric accuracy, the bladder was segmented in the 3D US and corresponding MR/CT images, and volumetric differences and Dice similarity coefficients (DSCs) were calculated. For both applicator types, the combination of 3D TRUS with 3D TAUS images allowed image information obscured by the shadowing artifacts under single imaging perspectives to be recovered. For the tandem-and-ring applicator, the mean ± one standard deviation (SD) TREs from the images with increasing thicknesses were 1.37 ± 1.35 mm, 1.84 ± 1.22 mm, and 1.60 ± 1.00 mm. Similarly, for the tandem-and-ovoids applicator, the mean ± SD TREs from the images with increasing thicknesses were 1.37 ± 0.35 mm, 1.95 ± 0.90 mm, and 1.61 ± 0.76 mm. No statistically significant difference was detected in the TREs for the three thicknesses for either applicator type. The mean volume differences for the bladder segmentations were 3.14% and 2.33% and mean DSCs were 87.8% and 87.7% for the tandem-and-ring and tandem-and-ovoids applicators, respectively. In this proof-of-concept study, we demonstrated the feasibility of fusing 3D TRUS and 3D TAUS images based on the geometry of tandem-and-ring and tandem-and-ovoids applicators. This represents a step toward an accessible and low-cost 3D imaging method for gynecologic brachytherapy, with the potential to extend this approach to other intracavitary configurations and hybrid applicators.


[Bacterial flora and mycosis of the vagina in women with symptoms of vaginal inflammation].
To estimate the microbiological profile of vaginal flora in 30 women with gynecologic problems and 20 pregnant women complaining about pathological symptoms {pruritus, burning, vaginal discharge}. The discharge from posterior vaginal vault was examined microbiologically on the Columbia Agar with sheep blood, MacConkey and Sabourand cultures incubated of 48 hours in the temperature of 37 degrees C. Bacterial infections were detected in 33 cases (66%), 12 of these women (24%) lived in urban, 21 (42%) in rural environment. From bacteria isolated from the vagina, most often because at 14 women stepped out Streptococcus agalactiae, at 11 Enterococcus faecalis at 8 Escherichia coli. In 5 cases bacterial inflammation was caused by two kinds of bacterium. At two women stepped out both Enterococcus faecalis and Escherichia coli. In single cases it was Klebsiella pneumoniae and Proteus vulgaris, Escherichia coli and Streptococcus agalactiae. In all cases of inflammation mycosis was called out by from Candida albicans. One ascertained it at 14 among all given an examination women. Mixed inflammations called out both by mycosis and bacterial stepped out in 3 cases in age of 21-30. At two women it was Candida albicans and Streptococcus agalactiae, at one inflammation mycosis accompanied Enterococcus faecalis. The common reason of vaginitis are bacterial infections caused by Streptococcus agalactiae, Enterococcus faecalis, E coli. Both, place of living and women' s age influence the type of etiological factor.


Vinblastine (VLB), bleomycin (BLEO), cis-diamminedichloroplatinum (DDP) in disseminated extragonadal germ cell tumors. A Southwest Oncology Group Study.
Nineteen patients considered to have metastatic primary extragonadal germ cell cancer were entered on a Phase II chemotherapy study using as induction therapy a combination of vinblastine (VLB) 12 mg/m2 day 1, bleomycin (BLEO) 15 U/m2 I.V. or I.M. twice weekly, and cis-diamminedichloroplatinum (DDP) 15 mg/m2 days 1-5, with vinblastine and DDP repeated at 28-day intervals for four months. All complete or partial responders were then placed on a maintenance regimen of vinblastine 12 mg/m2 alternating monthly with actinomycin-D 1.5 mg/m2 day 29, and chlorambucil, 10 mg/m2 P.O. days 32-37. There were three complete remissions (CR's), six partial remissions (PR's), and two stable disease. The response rate (CR's mpr's) was 56%; however the mean duration of response was only two months (range, 1-8 months). Drug toxicity was significant and there was one toxic death. Unlike patients with disseminated testicular cancer, patients with primary metastatic extragonadal germ cell carcinoma appear to do less well on this particular drug regimen. Further investigation using different drug regimens seems necessary.


Medical management of osteomyelitis: considerations for home antibiotic chemotherapy.
Osteomyelitis can result from hematogenous seeding or contiguous infection, especially in association with impaired vascularity. Appropriate antibiotic therapy requires identification of the pathogen or pathogens and confirmation that the pathogens are susceptible to the antibiotic selected. Because of the long duration of parenteral antibiotic therapy required, treatment of osteomyelitis is expensive when patients are kept in the hospital for this reason alone. The development of long-half-life antibiotics that can be administered intramuscularly once a day and that are well tolerated has made outpatient parenteral therapy possible for many such patients. Cefonicid is a long-acting second-generation cephalosporin with activity against many of the microorganisms involved in osteomyelitis. Clinical studies have shown that cefonicid is effective and safe when used in an outpatient treatment program. Such programs have realized considerable savings over the cost of inpatient therapy.


OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF ACUTE MACULAR NEURORETINOPATHY REVEALS DEEP CAPILLARY ISCHEMIA.
To present the multimodal retinal imaging findings, including optical coherence tomography (OCT) angiography, of an atypical case of acute macular neuroretinopathy (AMN). The multimodal retinal imaging findings, including structural OCT and OCT angiography, of an atypical case of AMN are presented. A 23-year old woman, with a history of an unrelenting sinusitis treated with prednisone therapy and decongestants, presented with an acute scotoma of the right eye. Structural OCT illustrated an area of hyperreflectivity in the outer plexiform and outer nuclear layers nasal to the fovea, with associated disruption of the inner segment ellipsoid band consistent with AMN. At the 2-week follow-up visit, intraretinal fluid was noted with repeat OCT, with spontaneous resolution of the fluid at the 2-month follow-up visit. Optical coherence tomography angiography illustrated a flow void in the deep retinal capillary plexus associated with the AMN lesion. Atypical findings of AMN are presented in this case report including the presence and spontaneous resolution of intraretinal fluid. Although OCT angiography illustrated a flow deficit within the deep retinal capillary plexus, the cause of AMN remains elusive.


A versatile transposon-based technology to generate loss- and gain-of-function phenotypes in the mouse liver.
Understanding the contribution of gene function in distinct organ systems to the pathogenesis of human diseases in biomedical research requires modifying gene expression through the generation of gain- and loss-of-function phenotypes in model organisms, for instance, the mouse. However, methods to modify both germline and somatic genomes have important limitations that prevent easy, strong, and stable expression of transgenes. For instance, while the liver is remarkably easy to target, nucleic acids introduced to modify the genome of hepatocytes are rapidly lost, or the transgene expression they mediate becomes inhibited due to the action of effector pathways for the elimination of exogenous DNA. Novel methods are required to overcome these challenges, and here we develop a somatic gene delivery technology enabling long-lasting high-level transgene expression in the entire hepatocyte population of mice. We exploit the fumarylacetoacetate hydrolase (Fah) gene correction-induced regeneration in Fah-deficient livers, to demonstrate that such approach stabilizes luciferase expression more than 5000-fold above the level detected in WT animals, following plasmid DNA introduction complemented by transposon-mediated chromosomal gene transfer. Building on this advancement, we created a versatile technology platform for performing gene function analysis in vivo in the mouse liver. Our technology allows the tag-free expression of proteins of interest and silencing of any arbitrary gene in the mouse genome. This was achieved by applying the HADHA/B endogenous bidirectional promoter capable of driving well-balanced bidirectional expression and by optimizing in vivo intronic artificial microRNA-based gene silencing. We demonstrated the particular usefulness of the technology in cancer research by creating a p53-silenced and hRas G12V-overexpressing tumor model. We developed a versatile technology platform for in vivo somatic genome editing in the mouse liver, which meets multiple requirements for long-lasting high-level transgene expression. We believe that this technology will contribute to the development of a more accurate new generation of tools for gene function analysis in mice.


Review: Effect study of sex hormone in the multiple sclerosis of common neurological disorders.
Multiple sclerosis (MS) is one of most common neurological disorders, mainly affecting women. The central nervous system (CNS) of this autoimmune disease is characterized by intermittent or chronic damage to the myelin sheaths (demyelination), local inflammation and axonal degeneration. During the early relapsing/remitting stages of MS, myelin can regenerate. However, as the disease progresses, both amount and activity of regenerated axons becomes insufficient, leading to impaired axon conduction, neurodegeneration and the worsening symptoms. Epidemiological study found that distinct symptom alleviation of diseases at a certain periods would be shown in women during pregnancy. The following basic researches indicated that sex hormones especially progesterone can significantly reduce the disease severity, moreover, the protective effect of sex hormone on the nervous system has become the research focus.


Relations between performance and subjective ratings of sleepiness during a night awake.
The present study validated the nine-point Karolinska Sleepiness Scale (KSS) and the new Accumulated Time with Sleepiness (ATS) scale against performance of laboratory tasks. The ATS scale was designed as a method for integrating subjective sleepiness over longer time periods. The subjects were asked if certain symptoms of sleepiness had occurred and, if so, for how long. Six subjects participated twice. Each time they were kept awake during the night (except for a short nap occurring during one of the nights in a counterbalanced order) and were tested at 2200, 0200, 0400 and 0600 hours. The tests included a 10-minute rest period, a 28-minute visual vigilance task and an 11-minute single reaction time task. KSS and visual analogue scale (VAS) ratings were given before each test, and ATS ratings were given after. Performance deteriorated clearly, and all three rating scales reflected increased sleepiness with time of night. Scores on the KSS and VAS showed high correlations with performance tasks (mean intraindividual correlations were between 0.49 and 0.71). Performance correlated even higher with the ATS ratings (r = 0.73-0.79). Intercorrelations between rating scales were also high (r = 0.65-0.86). It was concluded that there were strong relations between ratings of sleepiness and performance, that the ATS rating scale was at least as good as the other scales and that the ratings were affected by type of task.


Emergency Visits for Autistic Children and Children With ADHD.
Autistic children and children with attention-deficit/hyperactivity disorder (ADHD) may have more frequent visits to the emergency department (ED). We aim to identify the primary reasons for ED visits among autistic children and children with ADHD, compared to a random sample of visits. Using 2008 to 2017 Nationwide Emergency Department Sample data, we assessed the most frequent primary diagnoses for ED visits among children (ages 3-12 and 13-18 years, separately) (1) with an autism diagnosis, (2) with ADHD, and (3) a random sample (1 000 000 visits). We regressed primary reasons for visits on autism or ADHD diagnosis, controlling for individual characteristics, to assess the odds of presenting for these reasons. Although the 10 most frequent diagnoses among the random sample were physical health conditions, autistic children and children with ADHD often presented for psychiatric conditions. Older children with autism and with ADHD more frequently presented for mood disorders (10%-15% of visits; odds ratios [ORs] = 5.2-8.5) and intentional self-harm (ORs = 3.2-5.0). Younger children with ADHD more commonly presented with mood disorders (6.6% of visits; OR = 18.3) and younger autistic children more often presented with attention-deficit, conduct, and disruptive behavior disorders (9.7% of visits; OR = 9.7). Autistic children and children with ADHD have higher odds of presenting to the ED for psychiatric conditions than a random sample, including for self-harm. Clinicians should treat these populations sensitively, recognize and assess the risk for self-harm, and facilitate continuing psychiatric care.


Central role of Prominin-1 in lipid rafts during liver regeneration.
Prominin-1, a lipid raft protein, is required for maintaining cancer stem cell properties in hepatocarcinoma cell lines, but its physiological roles in the liver have not been well studied. Here, we investigate the role of Prominin-1 in lipid rafts during liver regeneration and show that expression of Prominin-1 increases after 2/3 partial hepatectomy or CCl4 injection. Hepatocyte proliferation and liver regeneration are attenuated in liver-specific Prominin-1 knockout mice compared to wild-type mice. Detailed mechanistic studies reveal that Prominin-1 interacts with the interleukin-6 signal transducer glycoprotein 130, confining it to lipid rafts so that STAT3 signaling by IL-6 is effectively activated. The overexpression of the glycosylphosphatidylinsositol-anchored first extracellular domain of Prominin-1, which is the domain that binds to GP130, rescued the proliferation of hepatocytes and liver regeneration in liver-specific Prominin-1 knockout mice. In summary, Prominin-1 is upregulated in hepatocytes during liver regeneration where it recruits GP130 into lipid rafts and activates the IL6-GP130-STAT3 axis, suggesting that Prominin-1 might be a promising target for therapeutic applications in liver transplantation.


Genome organization of the killer plasmid pGK12 from Kluyveromyces lactis.
We have determined the entire sequence of the plasmid K2 from Kluyveromyces lactis which is involved in the maintenance of both killer plasmids in the cell. K2 shares many of the characteristics of the smaller killer plasmid K1: high A+T content (74.7%) and very compact genomic organization. K2 contains ten open reading frames. Some of them overlap on different strands and some on the same strand. Northern blotting of K2 transcripts shows that at least eight ORFs are transcribed. Analysis of the predicted aminoacid sequence of ORF2 from K2 reveals homology with the aminoacid sequence of ORF 1 from K1 and with several viral DNA polymerases. The sequence of K2 from Saccaromyces cerevisiae F102-2 was also determined. Only one nucleotide difference was found between the K2 sequence from the two yeasts. This mutation does not change the genome organization of the plasmid and has only minimal effect on the structure of the encoded proteins.


Factors Associated with Discharge to Skilled Nursing Facility Following Gunshot Wounds.
Firearm injury is a public health crisis. Most victims are minorities in underserved neighborhoods. Measuring firearm injury by mortality underestimates its impact, as most victims survive to discharge. This study was done to determine if race and insurance status are associated with discharge disposition for gunshot wound (GSW)-related trauma. Using the 2019 Trauma Quality Improvement Program database, we identified GSW patients with Abbreviated Injury Scale (AIS) = 1-3. Exclusion criteria included patients who died in hospital and routine home discharge. We compared discharge patterns of patients based on demographics (age, gender, race, ethnicity, payor, AIS, hospital designation, and length of stay [LOS]) and injury severity. Multivariable logistic regression models identified factors associated with discharge disposition. Our sample included 2437 patients with GSWs. On univariable analysis, Black patients were more likely to discharge to home with home health (64.1% Black versus 34.7% White; P < 0.001). White patients were more likely to discharge to skilled nursing facility (SNF) (51.4% White versus 44.6% Black; P < 0.001). Controlling for age, race, Latin ethnicity, primary payor, LOS, AIS severity, and injury severity score factors independently associated with discharge to SNF included age (0.0462, P < 0.001), Medicaid (1.136, P < 0.0003), Medicare (1.452, P < 0.001), and LOS (0.03745, P < 0.001). Postacute care following traumatic injuries is essential to recovery. Black GSW victims are more likely to be discharged to home health than White patients, who are more likely to be discharged to SNF. Targeted programs to reduce barriers to appropriate aftercare are necessary to eliminate this bias and improve the care of underserved populations.


Levels of HIV RNA are quantitatively related to prior weight loss in HIV-associated wasting.
Thirty-three patients referred to a wasting clinic were evaluated to assess whether levels of HIV RNA were related to the magnitude of prior weight loss. Their median RNA level was 46,887 gene copies/ml (range, <200-510,070 gene copies/ml) at the time of referral. Patients had lost 10.5 +/- 6.4 kg over 461 +/- 304 days. RNA levels were correlated with the absolute amount and percentage of weight lost as well as the difference in body mass index (BMI) at the prior maximal and minimal recorded weights (r = 0.7, 0.67, 0.69; p = .0001 for the comparisons). The magnitude of these changes increased across strata of HIV RNA levels (p < or = .004), previously defined as associated with increasing risk for disease progression. The other parameter that could be associated with weight loss was the CD4 lymphocyte count (r = -0.43; p = .01). Low levels of testosterone and measures of body cell mass, fat free mass, or fat mass within 6 weeks of the RNA level could not be related to weight loss, change in BMI, or RNA levels. Thirty-two of the patients had chronic, relentless weight loss; in 15 of these subjects, no apparent secondary opportunistic complications were associated with weight loss or gastrointestinal symptoms to impair energy intake. Levels of HIV replication appear to be causally related to the magnitude of weight loss in some patients with wasting.


Lung Cancer Screening Participation: Developing a Conceptual Model to Guide Research.
To describe the development of a conceptual model to guide research focused on lung cancer screening participation from the perspective of the individual in the decision-making process. Based on a comprehensive review of empirical and theoretical literature, a conceptual model was developed linking key psychological variables (stigma, medical mistrust, fatalism, worry, and fear) to the health belief model and precaution adoption process model. Proposed model concepts have been examined in prior research of either lung or other cancer screening behavior. To date, a few studies have explored a limited number of variables that influence screening behavior in lung cancer specifically. Therefore, relationships among concepts in the model have been proposed and future research directions presented. This proposed model is an initial step to support theoretically based research. As lung cancer screening becomes more widely implemented, it is critical to theoretically guide research to understand variables that may be associated with lung cancer screening participation. Findings from future research guided by the proposed conceptual model can be used to refine the model and inform tailored intervention development.


Virucidal effect of sodium p-chloromercuribenzoate on influenza viruses attributable to inhibition of virus particle-associated RNA-dependent RNA polymerase.
Sodium p-chloromercuribenzoate (PCMB) caused a noticeable reduction of infectivity of prototype strains of type A and Lee strain of type B influenza viruses at concentrations of 100 and 200 mug/ml, respectively, after an incubation at 37 C for 60 min. The virucidal effect on A/AA/2/60 (H2N2) strain was dependent on the concentration of the drug and temperature as well as on the time of incubation. The reagent exerted this effect at a concentration which induced little change in the hemagglutinating and neuraminidase activities of the virus. PCMB inhibited by 50% the virus particle-associated RNA polymerase activity of all prototype strains of type A influenza virus at about 2 mug/ml and that of Lee strain of type B influenza virus at 8.5 mug/ml. Other sulfhydryl reagent such as phenylmercuric nitrate also exhibited virucidal effect on A/AA/2/60 virus which paralleled their inhibition of the virus particle-associated RNA polymerase activity. From these results it was considered likely that the virucidal action of PCMB on influenza viruses was attributable to inhibition of the virus particle-associated RNA polymerase activity.


Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy.
We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.


A voltage-sensor water pore.
Voltage-sensor (VS) domains cause the pore of voltage-gated ion channels to open and close in response to changes in transmembrane potential. Recent experimental studies suggest that VS domains are independent structural units. This independence is revealed dramatically by a voltage-dependent proton-selective channel (Hv), which has a sequence homologous to the VS domains of voltage-gated potassium channels (Kv). Here we show by means of molecular dynamics simulations that the isolated open-state VS domain of the KvAP channel in a lipid membrane has a configuration consistent with a water channel, which we propose as a common feature underlying the conductance of protons, and perhaps other cations, through VS domains.


New Data on Human Macrophages Polarization by Hymenolepis diminuta Tapeworm-An In Vitro Study.
Helminths and their products can suppress the host immune response to escape host defense mechanisms and establish chronic infections. Current studies indicate that macrophages play a key role in the immune response to pathogen invasion. They can be polarized into two distinct phenotypes: M1 and M2. The present paper examines the impact of the adult Hymenolepis diminuta (HD) tapeworm and its excretory/secretory products (ESP) on THP-1 macrophages. Monocytes were differentiated into macrophages and cultured with a living parasite or its ESP. Our findings indicate that HD and ESP have a considerable impact on human THP-1 macrophages. Macrophages treated with parasite ESP (with or without LPS) demonstrated reduced expression of cytokines (i.e., IL-1α, TNFα, TGFβ, IL-10) and chemokines (i.e., IL-8, MIP-1α, RANTES, and IL-1ra), while s-ICAM and CxCL10 expression rose after ESP stimulation. In addition, inflammatory factor expression rose significantly when macrophages were exposed to living parasites. Regarding induced and repressed pathways, significant differences were found between HD and ESP concerning their influence on the phosphorylation of ERK1/2, STAT2, STAT3, AMPKα1, Akt 1/2/3 S473, Hsp60, and Hck. The superior immunosuppressive properties of ESP compared to HD were demonstrated with lower levels of IL-1β, TNF-α, IL-6, IL-23, and IL-12p70 following stimulation. The presence of HD and its ESP were found to stimulate mixed M1/M2 macrophage phenotypes. Our findings indicate new molecular mechanisms involved in the response of human macrophages to tapeworm infection, this could be a valuable tool in understanding the mechanisms underlying the processes of immune regulation during cestodiasis.


The Prevalence of Restless Legs Syndrome Among Pregnant Women in Saudi Arabia.
Pregnancy has been associated with restless legs syndrome (RLS). RLS is underdiagnosed in most countries. The purpose of this study was to assess the prevalence of RLS among Saudi pregnant women. This cross-sectional study included 459 pregnant women from all Saudi provinces between December 2022 and March 2023. A structured online questionnaire assessing demographic and pregnancy characteristics, medical conditions, sleep quality, and RLS symptoms was conducted. The prevalence of RLS was 26.6% among the participants. Calcium deficiency was significantly associated with RLS (adjusted odds ratio (OR)=2.16, 95% confidence interval (CI)=1.2-3.9, p=0.01), but there was no significant association between RLS and vitamin D and iron deficiencies (p>0.05), according to multivariate binary logistic regression analysis. Moreover, RLS increased the risk of insomnia and frequent waking up (adjusted OR=4.95, 95% CI=2.50-9.83, p<0.001, and adjusted OR=2.87, 95% CI=1.55-5.32, p=0.001, respectively). RLS is common among pregnant women in Saudi Arabia. The study indicates that RLS during pregnancy is linked to calcium deficiency and negatively affects sleep quality.


Effect of endocrine manipulation on anterior pituitary galanin in the rat.
Galanin is widely distributed throughout the rat neural and endocrine system. The highest concentrations are found in the anterior pituitary, and it can influence classical pituitary hormone secretion. The effects of endocrine manipulation on pituitary galanin content, mRNA, and immunostaining have been investigated in the rat. In females, medical (39 +/- 4 fmol/gland), surgical (33 +/- 2), or combined (28 +/- 6) castration resulted in a highly significant decrease in galanin content (control, 223 +/- 14; P less than 0.0001). Estrogen in physiological and pharmacological doses produced a significant increase in galanin content (368 +/- 14 and 373 +/- 13, respectively; P less than 0.01) associated with an increase in galanin mRNA content. In the male, high dose dexamethasone and thyroidectomy caused a fall in galanin content, while galanin mRNA levels showed a rise and fall, respectively. Adrenalectomy caused a rise in galanin content, while adrenalectomy and castration produced a dramatic decrease in tissue galanin content. No change in galanin mRNA was observed in these groups. Galanin immunostaining paralleled the results of tissue content in all groups examined, except in the medically castrated group, in which there was some intragroup variation in staining patterns. In normal and high-dose estrogen-treated females, galanin expression was seen mainly in lactotrophs, with a small number of somatotrophs and thyrotrophs staining. In the male, galanin expression was confined to somatotrophs and thyrotrophs. Galanin mRNA was localized at the cellular level by in situ hybridization. In the normal pituitary only scattered lactotrophs contained message, while in high-dose estrogen-treated animals the number of positive cells, mostly lactotrophs, was vastly increased. Thus, the cellular localization of galanin immunostaining varies between the sexes. Galanin peptide and mRNA levels in the pituitary are powerfully influenced by endocrine status.


Immediate fixed implant rehabilitation of the atrophic edentulous maxilla after bilateral sinus floor augmentation: a 12-month pilot study.
The aims of this study were to evaluate a surgical/prosthetic protocol for the immediate rehabilitation of the augmented edentulous maxilla, and to compare the outcomes of implants placed in grafted (test group) versus native (control group) sites in the same patients. Twenty patients were included in the study. Each patient was treated with a bilateral sinus augmentation procedure using a 50:50 composite graft of autogenous mandibular bone and bovine hydroxyapatite. Four to 5 months later, 155 implants (90 test and 65 control) were placed and restored with screw-retained fixed definitive prostheses supported by titanium frameworks within 1 week. All patients were followed for 1 year. Implant stability quotient (ISQ) measurements and radiographic evaluation of the marginal bone resorption (MBR) were performed. Two test implants failed in two patients, giving a cumulative 1-year success rate of 98.7%; the prostheses success rate was 100%. Insertion torque and ISQ values for test implants were significantly lower than those for control implants (unpaired t-test, p < .0001). The mean MBR around control and test implants at the 1-year evaluation were similar (0.47 ± 0.25 mm and 0.43 ± 0.21 mm, respectively). The combination of implants placed in sinus-grafted and native sites can be immediately loaded with a fixed full-arch prosthesis and yield short-term successful outcomes.


Syntheses, characterization and properties of two new dodeca-niobates presenting unprecedented features.
Two new dodeca-niobate materials, K3[Nb2O2][H7SiNb12O40]·16H2O (1) and [Cu(en)2]9[(VNb12V1.69Nb0.31O42en0.31)2]·20.69H2O (2) (en = ethylenediamine), have been obtained under hydrothermal conditions and characterized by IR, UV-Vis, XRD, and single crystal X-ray diffraction analysis. Single crystal X-ray analysis reveals that compound 1 presents a reasonable bridging layer structure model and that K plays a great role in the three-dimensional structure. Compound 2 is the first capped Keggin POM with organic ligand chelating the capping atom. The photocatalytic hydrogen evolution and styrene epoxidation catalytic properties of the two compounds were also assessed. Additionally, compound 1 is also a good photocatalyst to degrade RhB.


Altered androgen metabolism in carcinoma of the prostate.
Testosterone metabolism was investigated in benign hypertrophied and malignant prostates using a tissue culture technique. The results demonstrated a distinct difference between the two types of tumour. The benign tissue was found to metabolize testosterone via a reductive pathway. The main radiometabolites were found to be dihydrotestosterone and androstanediols. On the other hand, the malignant tumours showed less ability to metabolize testosterone and the metabolism by these tumours was found to be an oxidative one, with the main metabolite being androstenedione.


A genetically encoded near-infrared fluorescent calcium ion indicator.
We report an intensiometric, near-infrared fluorescent, genetically encoded calcium ion (Ca2+) indicator (GECI) with excitation and emission maxima at 678 and 704 nm, respectively. This GECI, designated NIR-GECO1, enables imaging of Ca2+ transients in cultured mammalian cells and brain tissue with sensitivity comparable to that of currently available visible-wavelength GECIs. We demonstrate that NIR-GECO1 opens up new vistas for multicolor Ca2+ imaging in combination with other optogenetic indicators and actuators.


Proliferation and tube formation of periodontal endothelial cells.
Angiogenesis is indispensable to guide a regeneration of good periodontal tissue in the wound healing after periodontal surgery. Hepatocyte growth factor is well known for a strong angiogenic factor and it may play important roles in the periodontal tissue during periodontal wound healing. In exploring the promotion of angiogenesis in the periodontal ligament, proliferative and tubulogenic responses of endothelial cells to hepatocyte growth factor and to soluble factors secreted by fibroblasts were investigated. Pavement-shaped cells isolated from a human periodontal ligament were identified as the endothelial cell by their granular immunoreactivity for factor VIII. The proliferation of the endothelial cells was accelerated by the addition of hepatocyte growth factor or fibroblast-conditioned medium, and far more by adding both than either. The endothelial cells seeded on the agar containing both hepatocyte growth factor and fibroblast products formed a dense network in a shorter time than on the agar containing either. The endothelial cells in the dense network took a tube-like structure with lumen and were covered with laminin. These results suggest that hepatocyte growth factor administered into the regenerating periodontal tissue may promote, synergistically with local factors produced by the activated fibroblast, the proliferation and tubulogenesis of the remaining endothelial cells.


Spectroscopic Approaches to Tracking Metal-based Drugs in Cells and Tissue.
Metal-based drugs with novel targets and modes of action are increasingly being developed as alternatives to classical platinum(ii) chemotherapeutics. Imaging methods in tumour cells and tissues offer valuable insights into the behaviour of these novel complexes; however, mapping the distribution of metal ions and complexes within cellular environments remains challenging. The advantages and limitations of three modes of imaging: synchrotron radiation-induced X-ray fluorescence, mass spectrometry, and fluorescence microscopy are discussed in this review, with particular emphasis on their use in imaging ruthenium-based drugs.


An expedient formal total synthesis of (-)-diazonamide A via a powerful, stereoselective O-aryl to C-aryl migration to form the C10 quaternary center.
During the course of studies on the synthesis of diazonamide A 1, an unusual O-aryl into C-aryl rearrangement was discovered that allows partial control of the absolute stereochemistry of the C-10 quaternary stereogenic center. Treatment of 30 with TBAF/THF gave the O-tyrosine ethers 31 and 32 (1:1), which on heating each separately in chloroform at reflux rearranged to 33 and 34 in ratios of 84:16 and 56:44, respectively. This corresponds to a 70% yield of the correct C-10 stereoisomer 33 and a 30% yield of the wrong C-10 stereoisomer 34. Attempts to convert 34 into 33 by ipso-protonation and equilibration were unsuccessful. Confirmation of the stereochemical outcome of the rearrangement was obtained by converting 33 into 37, an advanced intermediate in the first synthesis of diazonamide A by Nicolaou et al. It was also found that the success of the above rearrangement is sensitive to the protecting group on both the tryptophan nitrogen atom and the tyrosine nitrogen atom.


Clinical effects of cardiac contractility modulation (CCM) as a treatment for chronic heart failure.
Cardiac contractility modulation (CCM) signals are non-excitatory signals applied during the absolute refractory period that have been shown to enhance the strength of left ventricular contraction without increasing myocardial oxygen consumption in studies carried out in animals and humans with heart failure and reduced ejection fraction. Studies from myocardial tissue of animals and humans with heart failure suggest that the mechanisms of these effects is that CCM drives expression of many genes that are abnormally expressed in heart failure towards normal, including proteins involved with calcium cycling and the myocardial contractile machinery. Clinical studies have primarily focused on patients with normal QRS durations in view of the fact that cardiac resynchronization (CRT) is a viable option for patients with prolonged QRS duration. These studies show that CCM improves exercise tolerance as indexed by peak oxygen consumption (VO(2)) and quality of life indexed by the Minnesota Living with Heart Failure Questionnaire. The device is currently available for clinical use in countries recognizing the CE mark and is undergoing additional testing in the USA under a protocol approved by the Federal Drug Administration.


Diabetic nephropathy. The basis for dietary and converting enzyme inhibitor therapy.
Once initiated, renal disease progresses in most patients to end-stage over a matter of months or years. This progressive consumption of renal mass seems to result from maladaptations to the initial insult by the remaining kidney. This review stresses the hemodynamic underpinnings of this progression of renal disease. The evidence is reviewed that indicates that loss of renal mass from surgical reduction in kidney tissue or from diabetes mellitus results in increased blood flow, filtration, and glomerular pressure in the remaining nephrons. Prevention of this glomerular hypertension by reduction in dietary protein or by the addition of converting enzyme inhibitors affords protection. The clinical implications of these observations are reviewed.


The Putative Role of Environmental Mercury in the Pathogenesis and Pathophysiology of Autism Spectrum Disorders and Subtypes.
Exposure to organic forms of mercury has the theoretical capacity to generate a range of immune abnormalities coupled with chronic nitro-oxidative stress seen in children with autism spectrum disorder (ASD). The paper discusses possible mechanisms explaining the neurotoxic effects of mercury and possible associations between mercury exposure and ASD subtypes. Environmental mercury is neurotoxic at doses well below the current reference levels considered to be safe, with evidence of neurotoxicity in children exposed to environmental sources including fish consumption and ethylmercury-containing vaccines. Possible neurotoxic mechanisms of mercury include direct effects on sulfhydryl groups, pericytes and cerebral endothelial cells, accumulation within astrocytes, microglial activation, induction of chronic oxidative stress, activation of immune-inflammatory pathways and impairment of mitochondrial functioning. (Epi-)genetic factors which may increase susceptibility to the toxic effects of mercury in ASD include the following: a greater propensity of males to the long-term neurotoxic effects of postnatal exposure and genetic polymorphisms in glutathione transferases and other glutathione-related genes and in selenoproteins. Furthermore, immune and inflammatory responses to immunisations with mercury-containing adjuvants are strongly influenced by polymorphisms in the human leukocyte antigen (HLA) region and by genes encoding effector proteins such as cytokines and pattern recognition receptors. Some epidemiological studies investigating a possible relationship between high environmental exposure to methylmercury and impaired neurodevelopment have reported a positive dose-dependent effect. Retrospective studies, on the other hand, reported no relationship between a range of ethylmercury-containing vaccines and chronic neuropathology or ASD. On the basis of these results, we would argue that more clinically relevant research is required to examine whether environmental mercury is associated with ASD or subtypes. Specific recommendations for future research are discussed.