Purification and characterization of vitamin B6-phosphate phosphatase from human erythrocytes.
Human erythrocytes rapidly convert vitamin B6 to pyridoxal-P and contain soluble phosphatase activity which dephosphorylates pyridoxal-P at a pH optimum of 6-6.5. This phosphatase was purified 51,000-fold with a yield of 39% by ammonium sulfate precipitation and chromatography on DEAE-Sepharose, Sephacryl S-200, hydroxylapatite, and reactive yellow 86-agarose. Sephacryl S-200 chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the enzyme was a dimer with a molecular mass of approximately 64 kDa. The phosphatase required Mg2+ for activity. It specifically catalyzed the removal of phosphate from pyridoxal-P, pyridoxine-P, pyridoxamine-P, 4-pyridoxic acid-P, and 4-deoxypyridoxine-P at pH 7.4. Nucleotide phosphates, phosphoamino acids, and other phosphorylated compounds were not hydrolyzed significantly nor were they effective inhibitors of the enzyme. The phosphatase showed Michaelis-Menten kinetics with its substrates. It had a Km of 1.5 microM and a Vmax of 3.2 mumol/min/mg with pyridoxal-P. The Vmax/Km was greatest with pyridoxal-P greater than 4-pyridoxic acid-P greater than pyridoxine-P greater than pyridoxamine-P. The phosphatase was competitively inhibited by the product, inorganic phosphate, with a Ki of 0.8 mM, and weakly inhibited by pyridoxal. It was also inhibited by Zn2+, fluoride, molybdate, and EDTA, but was not inhibited by levamisole, L-phenylalanine, or L(+)-tartrate. These properties of the purified enzyme suggest that it is a unique acid phosphatase that specifically dephosphorylates vitamin B6-phosphates.


Amfonelic acid: similarity to other dopamine agonists.
Rats were trained to discriminate between the stimulus properties of intraperitoneally administered 0.8 mg/kg amfonelic acid and its vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-related decrease in discriminative performance with lower amfonelic acid doses and analysis of the dose-response curve indicated an ED50 of 0.11 mg/kg. Administration of 0.08-0.6 mg/kg d-amphetamine produced a pattern of responding similar to that observed with amfonelic acid, with an ED50 of 0.10 mg/kg and a non-parallel dose-response curve. Likewise, the discriminative stimulus properties of amfonelic acid were shown to generalize to both d,l-cathinone and cocaine but not to apomorphine. The results suggest that amfonelic acid, as well as other non-amphetamine stimulants, acts by a different mechanism of action than does amphetamine and biochemical studies are reviewed to further evidence this observation.


Epigenetic hallmarks in pulmonary fibrosis: New advances and perspectives.
Epigenetics indicates that certain phenotypes of an organism can undergo heritable changes in the absence of changes in the genetic DNA sequence. Many studies have shown that epigenetic patterns play an important role in the lung and lung diseases. Pulmonary fibrosis (PF) is also a type of lung disease. PF is an end-stage change of a large group of lung diseases, characterized by fibroblast proliferation and massive accumulation of extracellular matrix, accompanied by inflammatory injury and histological destruction, that is, structural abnormalities caused by abnormal repair of normal alveolar tissue. It causes loss of lung function in patients with multiple complex diseases, leading to respiratory failure and subsequent death. However, current treatment options for IPF are very limited and no drugs have been shown to significantly prolong the survival of patients. Therefore, based on a systematic understanding of the disease mechanisms of PF, this review integrates the role of epigenetics in the development and course of PF, describes preventive and potential therapeutic targets for PF, and provides a theoretical basis for further exploration of the mechanisms of PF.


Lipid-based nanocarriers for delivery of small interfering RNA for therapeutic use.
Small interfering RNAs (siRNAs) indicate the unprecedented versatility in silencing disease-causing genes. However, the therapeutic use of siRNA is limited by its inherent instability in serum and immunogenicity. Thus, to realize their full therapeutic potential, there is a growing need to develop an efficient siRNA delivery system that targets it towards the localized symptomatic sites. Consequently, nanosized lipid carriers have been utilized for the targeted delivery of therapeutic agents to improve their efficacy in clinical studies. In this review, we attempt to elaborate on the current improvements of chemically diverse lipid carriers for the delivery of siRNAs-based drugs across a wide range of diseases. Finally, we discuss the patents and clinical status of siRNA in lipid formulations, which continue to expand for years to come.


Nucleotide analogue inhibitors of purine nucleoside phosphorylase.
The diphosphate of the antiherpetic agent acyclovir [9-[(2-hydroxyethoxy)methyl]guanine] has been shown to inhibit purine nucleoside phosphorylase with unique potency (Tuttle, J. V., and Krenitsky, T. A. (1984) J. Biol. Chem. 259, 4065-4069). A major factor contributing to the superior inhibition by this diphosphate over the corresponding mono- and triphosphates is revealed here. Homologues of acyclovir mono- and diphosphate that extend the ethoxy moiety by one to four methylene groups were synthesized. These homologues were evaluated for their ability to inhibit human purine nucleoside phosphorylase. Within the diphosphate series, the Ki values increased progressively with increasing chain length. With the monophosphates, the Ki values reached a minimum with the homologue containing a pentoxy moiety. A plot of chain length versus Ki values for both mono- and diphosphates showed that both series had similar optimal distances between the aminal carbon and the terminal oxygen anion. Monophosphates with optimal positioning were somewhat less potent than diphosphates with similar positioning. Nevertheless, it was clear that a major factor in determining potency of inhibition was the distance of the terminal phosphate from the guanine moiety.


Social place as a location of potential core transmitters-implications for the targeted control of sexually transmitted disease transmission in urban areas.
Places are an important determinant of risk for sexually transmitted infection (STI) acquisition and transmission. We sought to identify social places that are critical for targeted STI control activities. The objective of this study was to determine whether sex partner meeting places characterized by drug markets, sex markets, and separately, drug and/or sex markets were more likely to have potential core transmitters as compared with other sex partner meeting places in one urban setting. In 2008-2009, heterosexual sex partner places or venues were identified in Baltimore, MD using a venue-based study approach. A total of 1334 participants aged 18 to 35 years were enrolled at 85 venues. In those participants, 39 potential core transmitters were identified and 31% of venues had at least one potential core transmitter. In final age-adjusted and gender-adjusted models, core transmitters were significantly more likely to be identified at drug markets (OR = 1.37; 95% CI = 1.23-1.53), sex markets (OR = 1.27; 95% CI = 1.14-1.41), and drug and/or sex markets (OR = 1.49; 95% CI = 1.32-1.68). This study identified key characteristics of venues, such as drug and sex market activity, that may be important in identifying places for the targeted control of STI transmission.


Induction of natural killer cell activity by the antitumour compound flavone acetic acid (NSC 347 512).
Flavone acetic acid (FAA), an antitumour drug at present undergoing clinical trial for cancer treatment, has been found to activate natural killer cell activity in spleen cells of mice following in vivo treatment at doses of 45-330 mg/kg. The activity of FAA was measured using a 51Cr-release assay, employing the YAC-1 lymphoma line as a target cell population, and was found to be comparable to that of the interferon inducer polyinosinic acid-polycytidylic acid. The induction of activity was blocked by anti-asialo GM1 antibody. The time course of induction of activity by FAA was similar to that of the induction of haemorrhagic necrosis of the colon 38 tumour in mice, suggesting that natural killer cells or other components of the immune system may be involved in the action of FAA.


Opportunities and challenges of post-pandemic's new normal: Rethinking the contribution of the transport sector to China's carbon neutrality by 2060.
As the post-pandemic world adjusts to a new normal, the deep decarbonization of the transport sector, which is essential for China's carbon neutrality, is likely to be faced with unprecedented challenges and opportunities. This study conducted scenario simulations to understand the role of the transport sector in achieving China's carbon neutral target in the context of the post-pandemic new normal. The simulation results showed that carbon dioxide (CO2) emissions could be significantly reduced by lifestyle changes in a post-pandemic world, while the reduction potential would be partially offset by the negative effects stemming from a decline in public transport and car-sharing services. It was also found that the arrival of the post-pandemic new normal could help reduce the mitigation cost required to meet the carbon neutral target. Because of regional disparities in the reduction potential of CO2 emissions and mitigation costs, transport decarbonization toward carbon neutrality requires region-specific policy packages.


A 12-lead ECG-method for quantifying ischemia-induced QRS prolongation to estimate the severity of the acute myocardial event.
Studies have shown terminal QRS distortion and resultant QRS prolongation during ischemia to be a sign of low cardiac protection and thus a faster rate of myocardial cell death. A recent study introduced a single lead method to quantify the severity of ischemia by estimating QRS prolongation. This paper introduces a 12-lead method that, in contrast to the previous method, does not require access to a prior ECG. QRS duration was estimated in the lead that showed the maximal ST deviation according to a novel method. The degree of prolongation was determined by subtracting the measured QRS duration in the lead that showed the least ST deviation. The method is demonstrated in examples of acute occlusion in two of the major coronary arteries. This paper presents a 12-lead method to quantify the severity of ischemia, by measuring QRS prolongation, without requiring comparison with a previous ECG.


Enhancement of leukotriene D4-induced contraction of guinea-pig isolated trachea by platelet activating factor.
The effect of platelet activating factor (PAF), a potent lipid mediator of inflammation, was examined in the induction of airway hyperreactivity to known mediators of anaphylaxis. Concentration-dependent contractions of the isolated guinea-pig trachea to PAF (10(-7)-10(-5) M) were produced and an EC50 value was found to be 7.5 X 10(-7) M. Pretreatment for 30 min with a known PAF inhibitor, CV-3988 (10(-5) or 10(-4) M), produced significant inhibition of PAF contractions; however, at 10(-6) M, CV-3988 had no effect. In the presence of meclofenamic acid (10(-6) M), the concentration-response curve to PAF was shifted significantly upward and to the left. This potentiation could be reversed by pretreating the tissues with the peptidoleukotriene antagonists, FPL 55712 or SK&F 102922 (10(-5) M). Pretreatment with PAF concentrations having essentially no intrinsic activity (10(-8), 10(-7)) significantly enhanced the contraction of guinea-pig trachea to various concentrations of LTD4 and to certain concentrations of a thromboxane mimic (U-46619). Pretreatment with lyso-PAF failed to potentiate the LTD4 response, while pretreatment with CV-3988 reverse the potentiation by PAF of the lower concentrations of LTD4. However, PAF failed to enhance contractions (with or without the presence of meclofenamic acid) to acetylcholine, histamine, PGD2 or LTC4 (in the presence of serine borate). These results indicate a possible role for PAF as a mediator of airway hyperreactivity.


Revealing the mechanism underlying the effects of γ-aminobutyric acid-dioscorin interactions on dioscorin structure and emulsifying properties by molecular dynamic simulations.
Many studies have shown that γ-aminobutyric acid (GABA) exhibits various beneficial biological activities, including gut-modulating, neuro-stimulating, and cardio-protecting activities. Naturally, GABA exists in small amounts in yam, which is primarily synthesized by the decarboxylation of L-glutamic acid in the presence of glutamate decarboxylase. Dioscorin, the major tuber storage protein of yam, has been shown to have good solubility and emulsifying activity. However, how GABA interacts with dioscorin and affects their properties has yet to be clarified. In this research, the physicochemical and emulsifying properties of GABA-fortified dioscorin, which was dried by spray drying and freeze drying, were studied. As results, the freeze-dried (FD) dioscorin produced more stable emulsions, while the spray-dried (SD) dioscorin adsorbed more rapidly to oil/water (O/W) interface. The fluorescence spectroscopy, ultraviolet spectroscopy and circular dichroism spectroscopy showed that GABA changed the structure of dioscorin, by exposing its hydrophobic groups. The addition of GABA significantly promoted the adsorption of dioscorin to the O/W interface and prevented droplets coalescence. The results of molecular dynamics simulation (MD) showed that GABA destroyed the H-bond network between dioscorin and water, increased surface hydrophobicity and finally improved the emulsifying properties of dioscorin.


Characterization of fibroblast-free CWR-R1ca castration-recurrent prostate cancer cell line.
The previously established CWR-R1 cell line has been used as an in vitro model representing castration-recurrent prostate cancer. Microscopic observation of subconfluent cells demonstrated two distinct cellular morphologies: polygonal closely aggregated epithelial cells surrounded by bipolar fibroblastic cells with long processes. This study sought to establish and characterize a fibroblast-free derivative of the CWR-R1 cell line. The CWR-R1ca cell line was established from CWR-R1 cells by removing fibroblasts using multiple cycles of short-term trypsinization, cloning, and pooling single-cell colonies. Authentication of fibroblast-free CWR-R1ca cells was demonstrated by analyzing the expression of cytodifferentiation and prostate-associated markers, DNA and cytogenetic profiling, and growth pattern in the absence or presence of androgen. CWR-R1ca is an androgen-sensitive cell line that expresses the androgen receptor (AR) and its splice variant 7 and the luminal epithelia markers, CK-8, CK-18, and c-Met. CWR-R1fb fibroblasts isolated from CWR-R1 cells express AR, hepatocyte growth factor-α, and mouse β-actin but not AR-V7 or epithelial markers. Cytogenetic analysis of CWR-R1ca cells revealed a hyperdiploid male with numerical gains in chromosomes 1, 7, 8, 10, 11, and 12, deletion of one chromosome 2 allele, structural abnormalities that include der(1)t(1:4), der(4)t(2:4), der(10)t(4:10), and an unbalanced reciprocal translocation between chromosome 6 and 14. DNA-profiling revealed that CWR-R1ca cells had significant short-tandem repeat marker homology with CWR22Pc and CWR22Rv1 cell lines, which indicated lineage derivation from CWR22 prostate cancer xenografts. CWR-R1ca cells were responsive to the growth stimulatory effects of dihydrotestosterone (DHT) in the femtomolar range. This study establishes CWR-R1ca cells as a fibroblast-free derivative of the castration-recurrent CWR-R1 cell line. Prostate 76:1067-1077, 2016. © 2016 Wiley Periodicals, Inc.


National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy.
This consensus report focuses the presentation, pathophysiology, and management of the hypertensive disorders of pregnancy expanding on recommendations first presented in 1988 by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Practicing physicians should determine whether a patient's hypertension during pregnancy falls into the classification of (1) chronic hypertension, (2) preeclampsia, (3) preeclampsia superimposed on chronic hypertension, or (4) transient hypertension. The distinction, for management considerations, is made between hypertension that is present before pregnancy (chronic and preexisting) and that occurring as part of the pregnancy-specific condition preeclampsia. When maternal blood pressure reaches diastolic levels of 100 mm Hg or greater, treatment should be instituted to avoid hypertensive vascular damage. The report includes a discussion of antihypertensive therapy specific to the chronic or acute hypertension occurring concomitantly with pregnancy. The roles of calcium supplementation and low-dose aspirin to prevent preeclampsia and chronic and transient hypertension are under investigation.


A metabolic derivation of tritium transfer coefficients in animal products.
Tritium is a potentially important environmental contaminant originating from the nuclear industry, and its behaviour in the environment is controlled by that of hydrogen. Animal food products represent a potentially important source of tritium in the human diet and a number of transfer coefficient values for tritium transfer to a limited number of animal products are available. In this paper we present an approach for the derivation of tritium transfer coefficients which is based on the metabolism of hydrogen in animals. The derived transfer coefficients separately account for transfer to and from free (i.e. water) and organically bound tritium. A novel aspect of the approach is that tritium transfer can be predicted for any animal product for which the required metabolic input parameters are available. The predicted transfer coefficients are compared to available independent data. Agreement is good (R2=0.97) with the exception of the transfer coefficient for transfer from tritiated water to organically bound tritium in ruminants. This may be attributable to the particular characteristics of ruminant digestion. We show that tritium transfer coefficients will vary in response to the metabolic status of an animal (e.g. stage of lactation, diet digestibility etc.) and that the use of a single transfer coefficient from diet to animal product is inappropriate. It is possible to derive concentration ratio values from the estimated transfer coefficients which relate the concentration of tritiated water and organically bound tritium in an animal product to their respective concentrations in the animals diet. These concentration ratios are shown to be less subject to metabolic variation and may be more useful radioecological parameters than transfer coefficients. For tritiated water the concentration ratio shows little variation between animal products ranging from 0.59 to 0.82. In the case of organically bound tritium the concentration ratios vary between animal products from 0.15 (goat milk) to 0.67 (eggs).


Advances and challenges of incorporating ecosystem services into impact assessment.
An ecosystem services approach (ESA) to assess the environmental and social impacts of projects is a conceptual innovation that contributes to overcome two widely acknowledged deficiencies of impact assessment (IA): integration of knowledge areas and participation of affected communities. This potential was demonstrated through a practical application to a large mining project, showing evidence of advances in relation to current practice and identifying challenges. Data was obtained from the environmental impact study of the reviewed project and its supplements; additional data to fulfill the needs of the ESA were collected using rapid appraisal techniques. Results show that the ESA provides: (i) a more effective scoping; (ii) a contribution to delimitate the study area; (iii) a more detailed identification of impacts; (iv) a determination of significance inclusive of the perspective of affected communities; (v) a design of mitigation focused on human well-being. The challenges of using the ESA fall into two groups: the limitations inherent to the concept and those that can be overcome by furthering research and advancing practical applications. This research added evidence to previous studies showing that incorporating ecosystem services into IA can improve practice.


The ability of normal human monocytes to phagocytose IgG-coated red blood cells is related to the number of accessible galactosyl and mannosyl residues in the Fc domain of the anti-red blood cell IgG antibody molecules.
The percentage of normal human monocytes (MCs) that are able to form rosettes with, and subsequently phagocytose, IgG-coated red blood cells (RBCs) has been determined in vitro using five batches of anti-RBC IgG antibodies. These antibodies differed from each other by their capacity to bind to lectins recognizing two of the oligosaccharide structures of the Fc domain, namely, peanut agglutinin (PNA) and concanavalin A (ConA) which specifically bind to beta-galactosyl and alpha-mannosyl residues, respectively. The threshold between high (H) and low (L) binding capacities (BC) was arbitrarily fixed at 15% of mean specific binding. For each level of RBC sensitization tested (1500-6000 Ab molecules/one RBC), the percentage of MCs binding at least three IgG-RBCs was similar whatever the IgG Ab preparations used. In contrast, the percentage of MCs capable of phagocytosing at least three IgG-RBCs coated with 3000, 4500 and 6000 IgG/cell, as well as the phagocytosis index (number of IgG-RBCs ingested/100 MCs) of IgG-RBCs coated with 1500, 3000, 4500 and 6000 IgG/cell, were significantly lower (P less than 0.01 at least) using IgG Ab molecules with either [(PNA-H)(ConA-H)] BC, [(PNA-L) (ConA-H)] BC or with [(PNA-L)(ConA-L)] BC than the corresponding values measured using RBCs coated with IgG Ab molecules exhibiting [(PNA-H)(ConA-L)] BC. The binding to MCs of 125I-labelled anti-RBC IgG Ab molecules exhibiting different binding profiles to PNA and to ConA was studied by Scatchard plot analysis. A single class of binding sites was observed in each case. MCs bound a mean of 23,000 IgG molecules with a mean association constant (Ka) for IgG binding of about 1.4 X 10(8) M-1. These data indicate that terminal (and/or accessible) galactosyl and mannosyl residues of IgG Ab molecules play a role in the ingestion of IgG-RBCs by human MCs, despite the fact IgG Ab binding to IgG(Fc) receptors is not significantly affected. Thus, when studying the phagocytosis of IgG-coated RBC by human MC monolayers, the assay should be performed not only using similar RBC/MC ratios and IgG coating values, but also with IgG antibodies having comparable mean PNA and ConA binding capacities.


MicroRNA-16 modulates macrophage polarization leading to improved insulin sensitivity in myoblasts.
Uncontrolled inflammation leads to several diseases such as insulin resistance, T2D and several types of cancers. The functional role of microRNAs in inflammation induced insulin resistance is poorly studied. MicroRNAs are post-transcriptional regulatory molecules which mediate diverse biological processes. We here show that miR-16 expression levels are down-regulated in different inflammatory conditions such as LPS/IFNγ or palmitate treated macrophages, palmitate exposed myoblasts and insulin responsive tissues of high sucrose diet induced insulin resistant rats. Importantly, forced expression of miR-16 in macrophages impaired the production of TNF-α, IL-6 and IFN-β leading to enhanced insulin stimulated glucose uptake in co-cultured skeletal myoblasts. Further, ectopic expression of miR-16 enhanced insulin stimulated glucose uptake in skeletal myoblasts via the up-regulation of GLUT4 and MEF2A, two key players involved in insulin stimulated glucose uptake. Collectively, our data highlight the important role of miR-16 in ameliorating inflammation induced insulin resistance.


Orofacial granulomatosis presenting as bilateral eyelid swelling.
Orofacial granulomatosis (OFG) is an uncommon but increasingly recognized disease of unknown etiology. The typical presentation is chronic swelling of the perioral soft tissue, but eyelid edema can be the sole manifestation. Terminology of this disease can be confusing as it may also be referred to as granulomatous cheilitis and a monosymptomatic presentation of Melkersson-Rosenthal syndrome (MRS). Crohn's disease and sarcoidosis should also be considered in the differential as the histopathology can be similar. Corticosteroids are the mainstay of treatment but can lack efficacy. Atypical presentations and the possibility of systemic disease involvement can further challenge the management. We describe an unusual case in which OFG manifests solely as chronic eyelid swelling. This 69-year old Asian female patient had a delayed diagnosis that responded well to intralesional corticosteroid injection with surgical skin reduction. In addition to describing this unusual presentation of OFG, we review the relevant literature and evaluate the current terminology used to describe this entity.


Bcl-2 overexpression protects the neonatal cerebellum from ethanol neurotoxicity.
The developing nervous system is extremely sensitive to ethanol, and exposure often produces a condition known as the fetal alcohol syndrome. Although mechanisms underlying developmental ethanol toxicity have long been sought, they remain poorly understood. In this study, we examined the ability of the cell death repressor gene bcl-2 to protect against ethanol neurotoxicity. Transgenic mice overexpressing bcl-2 in neurons were exposed to ethanol vapor on postnatal days 4 and 5, which is the peak period of vulnerability of cerebellar Purkinje cells to ethanol. While exposure of wild-type animals to ethanol resulted in significant loss of Purkinje cells by P5, similar exposure of homozygous and heterozygous transgenics had no effect on the number of these neurons. This study suggests that bcl-2 can protect neurons from ethanol neurotoxicity and that modulation of cell death effector or repressor gene products may play a significant role in developmental ethanol neurotoxicity.


[Interventional electrophysiology in cardiac MRI : what is the current status?].
The ablation of simple and complex cardiac arrhythmias has become a first-line therapy in interventional cardiology and is mainly guided by conventional fluoroscopy. Cardiac magnetic resonance imaging (cMRI) allows exact three-dimensional (3D) visualization of complex anatomical structures and serves in the planning and implementation of ablation procedures. Post-procedural lesion visualization using cMRI can assess the success of ablation therapy and may distinguish potential complications. Performing ablation directly in the MRI scanner, with the option of anatomical substrate imagining, exact catheter navigation and real-time lesion visualization, holds the promise of improving success rates and safety in the interventional therapy of simple and complex arrhythmias.


Presence and persistence of SARS-CoV-2 in aquatic environments: A mini-review.
The introduction of SARS-CoV-2 into water bodies via sewage raises public health concerns. For the assessment of public health risks, it is necessary to know the presence and persistence of infectious SARS-CoV-2 in water and wastewater. The present mini-review documents the occurrence and decay rates of viable infectious SARS-CoV-2 and SARS-CoV-2 RNA in different water matrices including wastewater, river water, groundwater, tap water, and seawater. Persistence of viable SARS-CoV-2 is mainly temperature dependent. A rapid inactivation of infectious SARS-CoV-2 is found in river water, sea water, and wastewater compared to tap water. SARS-CoV-2 RNA was found to be considerably more stable than infectious SARS-CoV-2, indicating that the environmental detection of RNA alone does not prove risk of infection. Persistence assays need to consider physicochemical and biological water composition as well as the effect of detergents, enzymes, and filtering particulate matter.


Antagonism of morphine action on brain acetylcholine release by methylxanthines and calcium.
The inhibitory effect of morphine on the release of acetylcholine (ACh) from the rat cerebral cortex was antagonized by theophylline, caffeine and 3-isobutyl-1-methylxanthine (IBMX). Theophylline antagonism of morphine action was dose related and this agent failed to influence a comparable action of chlorpromazine on the release of ACh. Intraventricular injection of calcium also antagonized the anti-release effect of morphine. Neither methylxanthines nor calcium modified the spontaneous release of ACh in the absence of morphine. It is suggested that methylxanthine antagonism of morphine action is selective and that it could be related to the ability of methylxanthines to mobilize bound calcium.


[Electroophthalmologic and fluorescein angiographic studies in a case of exudative retinal detachment with spontaneous healing].
Electroophthalmological and fluorescein angiographic studies were performed on a 13 year old girl with exsudative detachment of the retina during a hypertensive crisis. The ERG showed a significant reduction during the course of the detachment. After healing the ERG values had improved as compared to those values recorded during the acute illness, but never reached normal levels. The lesions of the retina and the pigment epithelium caused by the detachment were responsible for pathological EOG. The fluorescein angiography showed circumscript and conglomerate lesions in the pigment epithelium.


Pesticide analysis in cannabis products.
Pesticide residue analysis in cannabis has become a subject of growing interest in North America since recent legalization in Canada and decriminalization for medicinal or recreational use in most US states. To meet regulatory and quality control standards, cannabis products should be tested for both authorized and unauthorized pesticides. In Canada, testing requirements mandated by Health Canada stipulate pesticide contaminant limits of quantification values of 0.02-3.0 μg/g, 0.01-2.5 μg/g and 0.01-1.5 μg/g for cannabis dried flowers, oil and fresh plants, respectively. Sample preparation and clean up methods reported in the literature for pesticide analysis in cannabis products include liquid-liquid extraction, solid-phase extraction, solid-phase microextraction and QuEChERS whereas separation and detection methods include thin-layer chromatography, capillary electrophoresis, high-performance liquid chromatography and gas chromatography in combination with various detectors such as UV and mass spectrometers. Advantages and disadvantages of the various analytical methods used in pesticide analysis of cannabis products are evaluated in this review. Furthermore, challenges ahead and future directions are discussed.


The anterior olfactory nucleus revisited - An emerging role for neuropathological conditions?
Olfaction is an important sensory modality for many species and greatly influences animal and human behavior. Still, much about olfactory perception remains unknown. The anterior olfactory nucleus is one of the brain's central early olfactory processing areas. Located directly posterior to the olfactory bulb in the olfactory peduncle with extensive in- and output connections and unique cellular composition, it connects olfactory processing centers of the left and right hemispheres. Almost 20 years have passed since the last comprehensive review on the anterior olfactory nucleus has been published and significant advances regarding its anatomy, function, and pathophysiology have been made in the meantime. Here we briefly summarize previous knowledge on the anterior olfactory nucleus, give detailed insights into the progress that has been made in recent years, and map out its emerging importance in translational research of neurological diseases.


Histone 3 lysine 36 to methionine mutations stably interact with and sequester SDG8 in Arabidopsis thaliana.
Post-transcriptional modifications of histones play important roles in various biological processes. Here, we report that Arabidopsis plants overexpressing histone H3 lysine to methionine mutations at histone H3.1K36 (H3.1K36M) and H3.3K36 (H3.3K36M) have serious developmental defects with early-flowering and change in the modifications of endogenous histone H3, including acetylation at lysine 9 (H3K9ac), trimethylation at lysine 27 (H3K27me3), di- and tri-methylation at lysine 36 (H3K36me2 and H3K36me3). In addition, H3K36M mutation alters its subcellular localization and interacts with H3K36 methyltransferase SDG8. Our results support a model in which H3K36M stably interacts with SDG8, and inhibits the activity of SDG8 by sequestering SDG8, resulting in a dominant negative effect to affect the proper expression levels of a variety of genes and plant development.


The epigenome as a target for heritable environmental disruptions of cellular function.
The environment is a well-established source of damaging or disrupting influences on cellular function. In the past, studies of the mechanisms by which such disruptions occur have focused largely on either direct toxic effects on cellular function at the protein or cell signaling level, or mutagenic effects that impact the genome. In recent years there has been a growing appreciation for the potential for environmental influences to disrupt the epigenome and mechanisms of epigenetic regulation within the cell. Indeed, because of the inherent lability of the epigenome, this represents a primary target for environmentally induced disruption. This review summarizes the manner in which the epigenome normally regulates cellular function, the effects of disruptions on this function, and the manner in which such disruptions may or may not be corrected within the organism and/or transmitted to subsequent generations.


Survival after massive pulmonary haemorrhage in the neonatal period.
4 babies with massive pulmonary haemorrhage were seen in an 18 month period. 2 had severe rhesus maemolytic disease, and the other 2 severe respiratory problems. There was evidence of a profound respiratory acidosis and hypoxia prior to the onset of the haemorrhage. 2 babies survived the episode and subsequently developed normally. Adequate ventilation and attendance to the treatment of blood coagulation disorders may have been a factor in their survival.


Cohorting based on nasal methicillin-resistant Staphylococcus aureus status: an opportunity to share more than a room.
Hospital roommates are cohorted with similarly colonized patients to decrease methicillin-resistant Staphylococcus aureus (MRSA) transmission risk. However, little is known about differences in S aureus nasal and extranasal carriage between hospital roommates who are in MRSA or non-MRSA designated rooms. Patients sharing hospital rooms were cultured for S aureus in the nose, throat, and other body sites. Differences in S aureus methicillin and mupirocin susceptibility and USA300 type were evaluated. Eighty-two patients comprising 48 roommate pairs were studied. Among 6 roommate pairs in MRSA rooms, 3 (50%) had differences in carriage based on having methicillin-susceptible S aureus at an extranasal body site. In non-MRSA rooms, 19 (45%) roommate pairs had differences in S aureus carriage. Extranasal colonization was significantly associated with discordance between roommates, P < .001. Antibiotic exposure, ward type, and the duration of room sharing were not associated with discordance. Patients have almost a 50% chance of having differences in S aureus colonization compared with their hospital roommate, even in MRSA-designated rooms. Cohorting by MRSA status at the time of admission may not be as effective a control strategy as horizontal measures that do not rely on known colonization with S aureus or other pathogens.


Coverage by examinations associated with early detection of colorectal neoplasia in the Czech Republic.
Coverage by examinations is a crucial indicator of the future impact on the burden of colorectal cancer (CRC). The study aimed to evaluate coverage by examinations associated with CRC screening and early cancer detection of CRC in the Czech Republic. The burden of CRC was also assessed. The novel nationwide administrative registry with individual data (period 2010-19) was used to evaluate coverage by examinations for screening faecal occult blood test and colonoscopy. In the second step, additional examinations for early CRC detection were included in the coverage calculation (complete coverage). Age-specific trends in CRC incidence (period 1977-2018) were investigated using Joinpoint regression. Coverage by screening examinations within recommended interval was around 30%. Complete coverage reached >37% and >50% at the 3-year interval. The coverage by examinations for the non-screening population aged 40-49 years was almost 4% and 5% (most of them were colonoscopies) at the 3-year interval. In age groups aged ≥50 years, we observed a significant annual decline, especially in the 50-69 age group, with recent annual decreases reaching up to 5-7%. The change in trend and the recent decline were also observed in the age group 40-49. More than half of the target screening population was covered by examinations potentially associated with early detection and subsequent treatment of colorectal neoplasms. The substantial coverage by potentially prophylactic examinations might be an explanation for the considerable decrease in CRC incidence.


Surgical Resident Radiation Knowledge, Attitudes, Practices, and Exposures.
To investigate the level of ionizing radiation exposure among surgical residents and to evaluate resident knowledge, attitudes, and practices regarding exposures. An observational study was conducted using radiation exposure data for surgical residents who wore film badge dosimeters. A cross-sectional survey was electronically administered at the end of the year, examining resident knowledge, attitudes, and practices concerning radiation exposures. Community teaching hospital in the Midwest. Surgical residents who wore a badge for the full calendar year and completed study survey. Excluded were graduating chiefs and interns who only had 6 calendar months of data. A total of 14 surgical residents (100%) were engaged in 168 rotations during study year. Primarily-general surgery (n = 103, 61%), night float (n = 16, 10%), trauma (n = 15, 9%), and vascular (n = 13, 8%). Radiation exposures were greater than a null value during most rotations (i.e., general surgery and night float), with no exposure above occupational thresholds. Certain rotations, namely vascular and trauma, had episodic high exposures. When asked if protective efforts changed during higher-risk rotations, responses revealed they increased (64%) or did not change (36%). A low Cronbach alpha (α = 0.2634) demonstrated that precaution use was not universal and had varied rationale. Percentage of correct radiation knowledge questions was 62%. A multilevel model predicting exposure had a significant multiplicative cross-level interaction term (p < 0.0001) between resident-level exposure and rotation type. Radiation exposure levels for surgical residents have not been previously investigated. Data demonstrated that surgical residents were not at a greater risk than other medical personnel. However, the study demonstrated detectable radiation exposures that were statistically greater than a null value for the most common rotations. Stochastic and dose-response effects of radiation make any exposure a concern. Attempts to lessen exposures are worthwhile, with study results identifying a need for greater safety precaution education and adherence.


Polarographic investigation of beta 2-microglobulin and ferritin thermal denaturation.
A temperature dependence of the corresponding signals, obtained by differential pulse (d.p.) and alternating current (a.c.) polarography, from a buffered aqueous solution of ferritin and beta 2-microglobulin is used for the characterization of a protein thermal denaturation process. The method is based on the significant differences in the interaction of folded and unfolded protein forms with a dropping mercury electrode due to a different accessibility, for the redox process, of protein electroactive groups. From the analysis of the resulting current, or capacitance, signals in function of temperature the thermal transition reversibility of different protein forms in the solution, protein melting points, and the apparent activation energies of the corresponding processes were determined.


Aspertetranones A-D, Putative Meroterpenoids from the Marine Algal-Associated Fungus Aspergillus sp. ZL0-1b14.
Aspertetranones A-D (1-4), four new highly oxygenated putative rearranged triketide-sesquiterpenoid meroterpenes, were isolated from the marine algal-associated fungus Aspergillus sp. ZL0-1b14. On the basis of a comprehensive spectroscopic analysis, the planar structures of aspertetranones were determined to possess an unusual skeleton in the terpenoid part. The relative and absolute configurations of the aspertetranones were assigned on the basis of NOESY analysis, X-ray crystallography, and circular dichroism spectroscopy. Compounds 1-4 were evaluated for anti-inflammatory activity in LPS-stimulated RAW264.7 macrophages. Aspertetranone D exhibited an inhibitory effect against IL-6 production with 69% inhibition at 40 μM.


L-tryptophan-related eosinophilia-myalgia syndrome possibly associated with a chronic B-lymphocytic leukemia.
A female patient presenting with B-CLL and coincident eosinophilia-myalgia syndrome (EMS) after ingestion of L-tryptophan is described. The manifestations of EMS disappeared completely during treatment with cyclophosphamide/prednisone. and there was an intermittent clinical remission of CLL with absence of the monoclonal B-cell population. A few years later, the B-CLL relapsed, but without sign and symptoms of EMS. Whereas other eosinophilic syndromes such as eosinophilic fasciitis, panniculitis, or cellulitis Wells have been found to occur in relation to malignant underlying diseases, only a single patient with malignant fibrous histiocytoma following EMS has been described. There are no reports about an increased occurrence of B-CLL or other non-Hodgkin's lymphomas combined with or following EMS or related to L-tryptophan itself. The variant types of eosinophilic syndromes occurring due to malignant disorders, the differentiation from EMS, and the possible association between B-CLL and L-tryptophan-related EMS are discussed.


Differences on Voice Acoustic Parameters between Colombian College Professors with and without Vocal Fatigue.
To determine which acoustic parameters may be associated with vocal fatigue among college professors in Bogotá-Colombia. This was a cross-sectional study including 27 voice samples of college professors. A gender analysis showed that mean fundamental frequency increased significantly among men and women who reported vocal fatigue compared with the those without fatigue (138.2Hz vs 122.3Hz for males; and 228.7Hz vs 188.9Hz for females; Mann-Whitney U test P value <0.01). Participants with vocal fatigue demonstrated a significantly decreased standard deviation of vocal sound pressure level compared to participants without vocal fatigue (8.7 dB vs 10.2 dB; Mann-Whitney U test P value <0.01). For the males in our sample, fundamental frequency had fair discriminatory value for vocal fatigue (area under the curve = 0.7). Sensitivity and specificity were moderate at a cut-off of 125 Hz (0.7 and 0.6 respectively). For females in this sample, the discriminatory value of fundamental frequency was slightly higher (area under the curve = 0.8). At a cut-off of 200 Hz, sensitivity was high (0.9) and specificity were moderate (0.7). In conclusion, the fundamental frequencies and standard deviations of vocal sound pressure level are good indicators of and may be used to identify college professors with vocal fatigue. Clinically, voice clinicians may aim to train their clients to produce speech with a higher variation of "intensity" in order to avoid vocal fatigue.


Surgical Outcome After Extended Sleeve Lobectomy in Centrally Located Non-small Cell Lung Cancer.
We primarily aimed to evaluate the operative techniques, clinicopathologic characteristics, and surgical outcomes after extended sleeve lobectomy (ESL). Additionally, we evaluated the feasibility of ESL for centrally located non-small cell lung cancer (NSCLC) compared with pneumonectomy (PN). A retrospective review identified 119 patients who underwent pulmonary resections for centrally located NSCLC; of whom, 43 underwent ESLs and 76 underwent PNs. Perioperative morbidity and oncologic outcomes of ESL were analyzed. Postoperative morbidity was evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Overall survival was evaluated using a Cox proportional hazard model. According to the classifications of ESL, 10 patients comprised type A, 8 (19%) type B, 16 (37%) type C, and 9 (21%) type D. Pulmonary artery reconstructions were performed in 5 of type A, 8 of type B, 1 of type C, and 1 of type D, and pulmonary vein reconstructions occurred in 3 of type A and 2 of type C. After ESL, 30-day hospital mortality occurred in 1 patient (2.3%), and grade ≥3 morbidities occurred in 13 patients (30%). In particular, bronchial anastomosis/stump fistula was seen in 4 patients (9.3%) after ESL, and blood perfusion disorders due to the presence of thrombi were seen in 4 (9.3%). The 3-year overall survival was significantly better after ESL compared with that after PN (62.8% vs 45.2%, P = .047). ESLs to preserve lung parenchyma will likely become a promising operative strategy in appropriately selected patients with centrally located NSCLC.


Comparative pharmacokinetics of ifosfamide, 4-hydroxyifosfamide, chloroacetaldehyde, and 2- and 3-dechloroethylifosfamide in patients on fractionated intravenous ifosfamide therapy.
The initial metabolism of the oxazaphosphorine cytostatic ifosfamide (IF) consists of two different pathways: ring oxidation at carbon-4 forms the cytostatically active metabolite 4-hydroxyifosfamide (4-OH-IF, "activated ifosfamide"), whereas side-chain oxidation with liberation of the presumably neurotoxic compound chloroacetaldehyde (CAA) that may also be responsible for IF-associated nephrotoxicity results in the formation of the cytostatically inactive metabolites 2-dechloroethylifosfamide (2-DCE-IF) and 3-dechloroethylifosfamide (3-DCE-IF). The pharmacokinetics of IF and its metabolites were investigated in 11 patients with bronchogenic carcinoma receiving IF on a 5-day divided-dose schedule (1.5 g/m2 daily). Blood samples were drawn on days 1 and 5 for up to 24 h after the start of the IF infusion. IF, 2-DCE-IF, and 3-DCE-IF were simultaneously quantified by gas chromatography (GC) with an NIP flame-ionization detector (NPFID), CAA was determined by GC with an electron-capture detector (ECD), and the highly unstable compound 4-OH-IF was measured using a high-performance liquid chromatography (HPLC) assay with fluorometric detection of 7-OH-quinoline, which is formed by the condensation of 4-OH-IF-derived acrolein with m-aminophenol. As compared with the values obtained on day 1, on day 5 the terminal half-life and AUC values determined for IF were reduced by 30% (6.36 vs 4.06 h and 1781 vs 1204 nmol h ml-1, respectively), whereas the maximal concentration (Cmax) values were not affected significantly (199.1 vs 181.1 nmol ml-1). This known phenomenon is explained by autoinduction of hepatic IF metabolism and was paralleled by increased metabolite levels. The mean Cmax values determined for 4-OH-IF, CAA, 3-DCE-IF, and 2-DCE-IF (on day 1/on day 5) were 1.51/2.59, 2.69/4.85, 12.9/26.5, and 8.6/16.7 nmol ml-1, respectively. The corresponding AUC values were 11.3/16.5, 30.3/34.3, 146/354, and 111/209 nmol h ml-1, respectively. As calculated by intraindividual comparison, the mean Cmax (day 5): Cmax (day 1) ratios for 4-OH-IF, CAA, 3-DCE-IF, and 2-DCE-IF were 1.94*, 2.05*, 2.52*, and 2.33*, respectively; the corresponding AUC (day 5): AUC (day 1) ratios were 1.51*, 1.29, 2.34*, and 2.23*, respectively (* P < 0.05). These data reveal that during fractionated-dose IF therapy the cancerotoxic effect of the drug increases. If the assumed role of CAA in IF-associated neurotoxicity and nephrotoxicity is a dose-dependent phenomenon, the probability of developing these side effects would also increase during prolonged IF application.


Genetics and arrhythmias: diagnostic and prognostic applications.
This review article discusses the genetic bases of cardiac arrest with a specific focus on cardiac channelopathies and right ventricular cardiomyopathy. We review the appropriate use of genetic testing in those patients suspected to have inherited cardiac arrhythmias, highlighting the importance of most genotype-phenotype correlations for risk stratification. The article also presents the most recent views on diagnostic criteria and flowcharts for treatment of patients with inherited arrhythmogenic diseases.


Association between the V Leiden G1691A mutation and sudden sensorineural hearing loss in Italian population: a meta-analysis.
Epidemiological studies have reported inconsistent findings on the association between the V Leiden G1691A mutation and sudden sensorineural hearing loss (SSNHL) in Italian population. The aim of this meta-analysis was to clarify this association. PubMed, Embase, and the China National Knowledge Infrastructure (CNKI) were searched up to April 1, 2015. We used STATA12.0 to calculate summary odds ratios (ORs) with 95 % confidence intervals (CIs). Four studies including 958 patients were identified. Pooled data showed no significant association between V Leiden G1691A mutation and risk of SSNHL in Italian population: A vs. G (OR = 1.660, 95 % CI 0.428-6.446, P OR = 0.464) and AG vs. GG (OR = 1.680, 95 % CI 0.422-6.688, P OR = 0.462). The present meta-analysis suggests that V Leiden G1691A mutation is not significantly associated with increased risk of SSNHL disease in Italian population. Further large and well-designed studies are needed to confirm this association.


Prognostic Significance of Ground-Glass Opacity Components in 5-Year Survivors With Resected Lung Adenocarcinoma.
Reports on the prognosis for 5-year survivors with lung adenocarcinoma after resection are sparse. This study aimed to identify factors associated with overall survival (OS) and cancer-specific survival (CSS) for 5-year survivors with completely resected lung adenocarcinoma, and to determine whether preoperative imaging factors, including the presence of ground-glass opacity (GGO) components, affect late recurrence in long-term survivors. Complete resection of lung adenocarcinoma was performed for 1681 patients between January 2000 and December 2013. Of these patients, 936 who survived 5 years or longer after surgery were identified, and factors associated with OS and CSS were determined using the Cox proportional hazard model. Multivariable analysis demonstrated that lymph node metastasis (p < 0.01) and absence of GGO components (p < 0.01) were independently associated with OS and CSS for the 5-year survivors. The absence of GGO components was significantly associated with OS (p < 0.01) and CSS (p < 0.01) also for the 5-year survivors with stage 1 disease (n = 782) and for the 5-year survivors without recurrence (n = 809). The incidence of recurrence anytime during the 10-year postoperative follow-up period differed significantly between the 5-year survivors with and without GGO components. The absence of GGO components was significantly associated with an unfavorable prognosis for the 5-year survivors with completely resected lung adenocarcinoma regardless whether they had recurrences not.


Contributions of vehicular emissions and secondary formation to nitrous acid concentrations in ambient urban air in Tokyo in the winter.
Nitrous acid (HONO) plays an important role in the formation of OH radicals, which are involved in photochemical oxidation. HONO concentrations in ambient air at urban sites have previously been measured, but very few studies have been performed in central Tokyo. In this study, HONO concentrations in ambient air in southeast central Tokyo (near Tokyo Bay) in winter were determined by incoherent cavity enhanced absorption spectroscopy. The O3, NO, NO2, and SO2 concentrations were simultaneously determined. The NO concentrations were used to classify the parts of the study period into types I (high pollution), II (medium pollution), and III (low pollution). The maximum HONO concentrations in the type I, II, and III periods were 7.1, 4.5, and 3.0ppbv, respectively. These concentrations were comparable to concentrations previously found in other Asian megacities. The mean HONO concentration varied diurnally, and HONO was depleted between 00:00 and 03:00 each day. The sampling site is surrounded by roads with high traffic loads, but vehicular emissions were estimated to contribute <10% of the HONO concentrations. Two positive and negative relative humidity dependences of the HONO to NO2 ratio were confirmed, implying the existence of the two different secondary formation process of HONO. The NO2 to HONO conversion rates at night in the type I, II, and III periods were 6.3×10-3, 7.6×10-3, and 4.2×10-3h-1, respectively.


Histone deacetylase 10: A polyamine deacetylase from the crystal structure to the first inhibitors.
Polyamine deacetylase activity was discovered more than 40 years ago, but the responsible histone deacetylase 10 (HDAC10) was described only recently. HDAC10 is a class IIb HDAC, as is its closest relative, the α-tubulin deacetylase HDAC6. HDAC10 has attracted attention over the last 2 years due to its role in diseases, especially cancer. This review summarises chemical and structural biology approaches to the study of HDAC10. Light will be shed on recent advances in understanding the complex structural biology of HDAC10 and the discovery of the first highly selective HDAC10 inhibitors.


One stage reconstruction of intercalated defect of the thumb using the osteocutaneous radial forearm flap.
A radial forearm flap including a segment of the cortex of the radius, based on the distal pedicle of the radial vessels and the cephalic vein, was used to reconstruct an intercalated defect of the thumb in two cases. In one case it was used as an ipsilateral pedicle flap while in the other case it was used as a free microvascular flap. In both cases, the skin flap as well as the segment of bone survived in toto without any evidence of creeping substitution. The functional result was good in both cases. This flap provides thin skin of good texture together with bone for a one-stage reconstruction.


Thyroxine transport in choroid plexus.
The role of the choroid plexus in thyroid hormone transport between body and brain, suggested by strong synthesis and secretion of transthyretin in this tissue, was investigated in in vitro and in vivo systems. Rat choroid plexus pieces incubated in vitro were found to accumulate thyroid hormones from surrounding medium in a non-saturable process. At equilibrium, the ratio of thyroid hormone concentration in choroid plexus pieces to that in medium decreased upon increasing the concentration of transthyretin in the medium. Fluorescence quenching of fluorophores located at different depths in liposome membranes showed maximal hormone accumulation in the middle of the phospholipid bilayer. Partition coefficients of thyroxine and triiodothyronine between lipid and aqueous phase were about 20,000. After intravenous injection of 125I-labeled thyroid hormones, choroid plexus and parts of the brain steadily accumulated 125I-thyroxine, but not [125I]triiodothyronine, for many hours. The accumulation of 125I-thyroxine in choroid plexus preceded that in brain. The amount of 125I-thyroxine in non-brain tissues and the [125I]triiodothyronine content of all tissues decreased steadily beginning immediately after injection. A model is proposed for thyroxine transport from the bloodstream into cerebrospinal fluid based on partitioning of thyroxine between choroid plexus and surrounding fluids and binding of thyroxine to transthyretin newly synthesized and secreted by choroid plexus.


The Effects of Nativity Status on Well-Being Among Medicare Beneficiaries by Race/Ethnicity: A Multi-group Analysis.
Nativity status is related to stress, health and well-being, but the literature is scant concerning whether these effects differ by race/ethnicity for older adults. We examined direct and indirect effects of nativity status on stress, coping resources, health, and depression/anxiety for the three largest racial/ethnic groups [Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic] in the U.S. using the Transactional Model of Stress and Coping. We obtained the data from Round 1 of the National Health and Aging Trends Study (NHATS; U.S.-born Medicare beneficiaries = 4093, foreign-born Medicare beneficiaries = 382, N = 4475). We used the multi-group analysis function in structural equation modeling to examine similarities and differences in the stress coping processes for the three racial/ethnic groups. The results indicated there are multiple pathways from nativity status to depression or self-rated health. For all three groups, being foreign-born was directly associated with higher stress and indirectly associated with lower self-rated health via stress. Only for Hispanic older adults was being foreign-born directly associated with higher depression/anxiety. For NHWs, being foreign-born was indirectly associated with higher depression/anxiety via less coping resources. Nativity status may have similar effects on self-rated physical health but may exert very different effects on depression/anxiety, depending on race/ethnicity. Nativity status will require special attention for both assessment and management of depression/anxiety as well as self-rated health among older adults of all racial/ethnic backgrounds and especially for older Hispanics.


The effects of aqueous extracts prepared from the leaves of Pistacia lentiscus in experimental liver disease.
In a previous study, we identified Pistacia lentiscus was worthy for further laboratory evaluation because an aqueous extract of the plant suppressed iron-induced lipid peroxidation in rat liver homogenates without affecting mitochondrial respiration in cultured HepG2 and PC12 cells. The present study was undertaken to evaluate the efficacy of an aqueous extract prepared from the dried leaves of Pistacia lentiscus in a rat model of hepatic injury caused by the hepatotoxin, thioacetamide. We assessed the impact of daily dosing on biochemical and morphological indices and the extent of oxidative stress in the livers of healthy and thioacetamide-treated rats. In healthy rats, long-term administration of the extract induced hepatic fibrosis and an inflammatory response, mild cholestasis and depletion of reduced glutathione associated with an increase in its oxidized form. In thioacetamide-treated rats, long-term administration of extract aggravated the inflammatory and fibrotic and glutathione depleting responses without affecting the extent of lipid peroxidation. Although our previous in vitro study established that extracts prepared from the leaves of Pistacia lentiscus had antioxidant activity, this in vivo study establishes these extracts also contains hepatotoxins whose identity may be quite different from those compounds with antioxidant properties. The results of this study suggest complementing in vitro experiments with those involving animals are essential steps in establishing the safety of medicinal plants. Furthermore, these data confirm that complete reliance on data obtained using in vitro methodologies may lead to erroneous conclusions pertaining to the safety of phytopharmaceuticals.


Clinical results and cyclosporine effect on prednisolone metabolism of cadaver kidney transplanted patients.
In the first randomised study of cyclosporine in Denmark 43 cadaveric kidney recipients were treated either with cyclosporine (Cys) and prednisone or azathioprine (Aza) and prednisone. The degradation of prednisolone was examined in 18 of these patients. The 12 month graft survival of the Cys group was not significantly greater than that of the Aza group (68% and 60%, respectively), but fewer rejection episodes occurred in the Cys group (p less than 0.05). The degradation of prednisolone was significantly decreased in the Cys group compared to the Aza group. Accordingly, plasma half-lives of prednisolone were increased in the Cys group compared with the Aza group. As a decreased degradation of prednisolone during Cys treatment may lead to increased steroid activity, we recommend that a reduction of the prednisone dosage during Cys treatment is safe.


The adaptation to temperature of photorespiration and of the photosynthetic carbon metabolism of altitudinal ecotypes of Trifolium repens L.
In altitudinal ecotypes of Trifolium repens L. the oxygen inhibition of photosynthesis, the CO2 compensation point and the sugar content were examined. Excised leaves were exposed to 14CO2 for 20 s and 60 min periods and the radioactivity in different photosynthetic products was studied. In all experiments the temperature during growth and measurement was varied.To some extent, the differences between the ecotypes and the differences between the plants grown under different temperature conditions are similar. These ecotypic differences appear to reflect long-term adaptation to the general temperature conditions at each site. Alpine ecotypes and plants grown at low temperatures show an increased photorespiration. The 14C-labeling of certain photosynthetic products also changes with the ecotypes and the temperatures during growth. Other differences between the ecotypes are interpreted as adaptations to the partial pressure of Co2 and to the length of the growing season, both of which change with altitude.The metabolism of photosynthesis depends greatly on temperature. The 14C-experiments and the study of photorespiration suggest that, to a certain degree, adaptation can compensate for this dependence on temperature.


The dilemma of pilonidal disease: pilonidal cystotomy, reappraisal of an old technique.
A series of 126 patients treated by inhospital pilonidal cystotomy is reviewed. One hundred twenty-four were treated using local anesthesia with supplemental diazepam or Innovar. Most patients spent only three days in the hospital, with healing occurring in less than two months. Recurrences occurred in 20.9 per cent of the patients. The recurrences were treated by office procedures in all but one instance. Most patients were pain-free and back to work within two weeks after operation.


Effect of genetic polymorphism of brain-derived neurotrophic factor and serotonin transporter on smoking phenotypes: A pilot study of Japanese participants.
This study investigated whether a gene polymorphism causing a Val66Met substitution (rs6265) in brain-derived neurotrophic factor (BDNF) is associated with smoking initiation, smoking cessation, nicotine dependence and age of smoking initiation, in Japanese participants. Additionally, this study examined whether the S allele of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) is associated with the BDNF Val66Met polymorphism on smoking phenotypes. The genotypic proportion of the polymorphism responsible for BDNF Val66Met was determined in 148 participants including 88 current smokers, 21 former smokers, and 39 never smokers, and Fisher's exact test was used to investigate the relationship between this polymorphism and smoking cessation and initiation as well as the association between the genotypes of current smokers with a heavy smoking index (HSI) and the age of smoking initiation. In addition to the BDNF Val66Met polymorphism, the 5-HTTLPR polymorphism has also been evaluated in a specific subset of participants. We found statistically significant correlations between the BDNF Val66Met polymorphism and the HSI, both in the whole study sample (P = 0.017) and in the male subgroup (P = 0.049). Moreover, the 5-HTTLPR polymorphism was associated with the age of smoking initiation in current smokers carrying the BDNF Met allele, in both the whole study sample (P = 0.041) and the male subgroup (P = 0.041). On the other hand, no association was observed between the BDNF Val66Met polymorphism, either alone or in combination with the 5-HTTLPR polymorphism, and the age of smoking cessation. Finally, no independent effects of the BDNF Val66Met genotype on the age of smoking initiation were detected. This pilot study provides preliminary findings regarding the influence of BDNF Val66Met on smoking phenotypes and the interacting effect of 5-HTTLPR on the association between BDNF Val66Met and smoking phenotypes in Japanese participants.


In vivo evaluation of the safety of triptolide-loaded hydrogel-thickened microemulsion.
Triptolide (TP) is a major active component of Tripterygium wilfordii Hook F (TWHF), which is used to treat rheumatoid arthritis (RA). TP has a narrow therapeutic window. To increase the therapeutic index of TP, a novel TP-loaded transdermal delivery system, named TP-loaded hydrogel-thickened microemulsion (TP-MTH), has been developed to treat RA. Our previous studies have demonstrated the good efficacy of TP-MTH in animals. This paper evaluated the safety of TP-MTH with several animals. Results demonstrated no obvious toxicities in a series of toxicity tests: acute toxicity study of TP-MTH (1.2mg/kg) in rabbits, 6-month long-term toxicity study of TP-MTH (0.06, 0.18, 0.54mg/kg) in rabbits, safety pharmacology study of TP-MTH (0.03, 0.09, 0.27mg/kg, for 5 d) in mice and beagle dogs, skin irritation study in rabbits, and skin allergic reaction test in guinea pigs. Only mild reversible skin irritation signs were observed on the skin of animals. These studies suggest that topical TP-MTH is a promising drug formulation for the treatment of RA.


Desorption kinetics of antipsychotic drugs from sandy sediments by diffusive gradients in thin-films technique.
Dynamic processes of organic contaminants in sediments can have important toxicological implications in aquatic systems. The current study used diffusive gradients in thin-films (DGT) devices in sandy sediments spiked with nine antipsychotics and in field sandy sediments. Samplers were deployed for 1 to 30 days to determine the flux of these compounds to DGT devices and the exchange rates between the porewater and sediment solid phase. The results showed a continuous removal of antipsychotics to a binding gel and induced a mobile flux from the DGT device to the adjacent sediment solution. A dynamic model, DGT-induced fluxes in soils and sediments, was used to derive rate constants of resupply of antipsychotics from solid phase to aqueous phase (response time, Tc) and distribution coefficients for labile antipsychotics. The largest labile pool was found for lamotrigine and carbamazepine in spiked sediments. Carbamazepine, clozapine, citalopram, and lamotrigine were resupplied rapidly by sediments with Tc (25-30 min). Tc values of bupropion and amitriptyline were the longest (≈5 h), which exhibited slow desorption rates in sediments. In field sediments, high resupply was found for carbamazepine and lamotrigine, which did not show higher labile pool. The Tc values were obviously higher in the filed sediments (52-171 h). Although the adsorption process is dominant for most studied antipsychotics in both spiked sediments and field sediments, the kinetic resupply of antipsychotic compounds may not be accurately estimated by laboratory-controlled incubation experiments. More studies are needed to explore the mechanisms of desorption kinetics by using in situ DGT technique in the field.


Role of the ion channel, transient receptor potential cation channel subfamily V member 1 (TRPV1), in allergic asthma.
Asthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4(+) T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4(+) cells. The aim of these experiments was to demonstrate the importance of CD4(+) T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals. Mice (wild type, CD4 (-/-) or TRPV1 (-/-)) and rats were sensitised with antigen (HDM or OVA) and subsequently topically challenged with the same antigen. Key features associated with an allergic asthma type phenotype were measured: lung function (airway hyperreactivity [AHR] and late asthmatic response [LAR]), allergic status (IgE levels) and airway inflammation. CD4(+) T cells play a central role in both disease model systems with all the asthma-like features attenuated. Targeting TRPV1 using either GM mice or a pharmacological inhibitor tended to decrease IgE levels, airway inflammation and lung function changes. Our data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation.


Predominance of genomically defined A lineage of HPV16 over D lineage in Indian patients from eastern India with squamous cell carcinoma of the cervix in association with distinct oncogenic phenotypes.
Human papillomavirus type-16 (HPV16) is classified into lineages, A, B, C and D and 10 sub-lineages portraying variable infectivity, persistence, and cytological outcomes, however, with geographical variations. Our objective was to delineate the distinctive features of lineages among cervical squamous cell carcinoma (SCC) in the eastern region of India. A total of 145 SCC cases and 24 non-malignant specimens, harboring episomal HPV16, were included. The presence of higher proportion of lineage A over D was observed among SCC cases (86.89% A1, 8.97% D1 and 4.14% D2), while only A1 sub-lineage viruses were found among control specimens. Among the A1 viruses, an association of variants in the E5 (Y44L, I65V), E6 (L83V) genes and LCR: C7577T with SCC, with combined Odd's ratio (95% CI) of 20.5(4.61-91.25) was observed. Network analyses revealed the presence of 10 clades of lineage A viruses comprising of 64 HPV16 genomes harboring the risk alleles. High episomal HPV16 DNA copy numbers (adjusted p-value= 0.0271) and E7 mRNA expression (p-value=0.000017) predominated in SCC with lineage A, over D. Our study highlights the distinctive modalities of oncogenicity among different HPV16 lineages.


MRI features of mucinous adenocarcinoma of the prostate: report of four cases.
We report four patients with mucinous adenocarcinoma of the prostate, focusing on their magnetic resonance imaging (MRI) findings. The lesions appeared hyperintense on T2-weighted images (T2WI) in all four patients. In the two patients in whom the tumors were confined to the peripheral zone (PZ), the lesions were isointense to the surrounding normal PZ, making them difficult to identify. In all three patients who underwent diffusion-weighted imaging (b = 1000), the lesions appeared hyperintense but visually there was little or no decrease in the apparent diffusion coefficient (ADC), with ADC values of 1.02, 1.39, and 1.66 × 10-3 mm2/s, respectively. In the three patients who underwent a dynamic contrast-enhanced MR study, early enhancement was evident in two (partial in one), and gradually increasing enhancement in one. In the four cases in this instance, MRI findings of mucinous adenocarcinoma were very different from the appearance of non-mucinous adenocarcinoma. It is suggested that the conventional interpretation method of MRI for prostate cancer is not suitable for mucinous adenocarcinoma. Those who interpret prostate MRI should be aware of this rare and unique subtype of prostate cancer.


A new approach to apple proliferation detection: a highly sensitive real-time PCR assay.
The present paper describes a new approach for diagnosis of apple proliferation (AP) phytoplasma in plant material using a multiplex real-time PCR assay simultaneously amplifying a fragment of the pathogen 16S rRNA gene and the host, Malus domestica, chloroplast gene coding for tRNA leucine. For the first time, such an approach, with an internal analytical control, is described in a diagnostic procedure for plant pathogenic phytoplasmas enabling distinction between uninfected plant material and false-negative results caused by PCR inhibition. Pathogen detection is based on the highly conserved 16S rRNA gene to ensure amplification of different AP phytoplasma strains. The newly designed primer/probe set allows specific detection of all examined AP strains, without amplifying other fruit tree phytoplasmas or more distantly related phytoplasma strains. Apart from its specificity, real-time PCR with serial dilutions of initial template DNA ranging over almost five orders of magnitude (undiluted to 80,000-fold diluted) demonstrated linear amplification over the whole range, while conventional PCR showed a reliable detection only up to 500-fold or 10,000-fold dilutions, respectively. Compared to existing analytical diagnostic procedures for phytoplasmas, a rapid, highly specific and highly sensitive diagnostic method becomes now available.


Photocrosslinking maleilated hyaluronate/methacrylated poly (vinyl alcohol) nanofibrous mats for hydrogel wound dressings.
Although electrospinning of nanofibrous scaffolds benefit to wound healing have been developed at a fast pace, achieving nanofibrous scaffolds with high absorptivity by green electrospinning and crosslinking techniques is still a great challenge. Here, we developed a maleilated hyaluronate/methacrylated poly (vinyl alcohol) (MHA) (MaPVA) composite nanofibers by electrospinning from pure water solvent and followed by photopolymerization to form crosslinking nanofibers network. Electrospinnability of MHA/MaPVA blend systems were investigated and the results shows that the morphology and diameter of the nanofibers were mainly affected by MHA/MaPVA weight ratios by changing viscosity and conductivity of the blend solutions. The crystalline microstructure of the electrospun fibers was not well developed due to intermolecular hydrogen bonding interaction between the molecules of MHA and MaPVA. The photocrosslinking MHA/MaPVA nanofibrous mats can swell to form fibrous hydrogels with high water absorption, meanwhile it is cytocompatible and capable of promoting the cell attachment, which render it great potential for wound dressings.


Improvement of the Bovine Corneal Opacity and Permeability (BCOP) assay as an in vitro alternative to the Draize rabbit eye irritation test.
Measurement of ocular irritancy is a necessary step in the safety evaluation of both industrial and consumer products. Assessment of the acute eye irritation potential is therefore part of the international regulatory requirements for testing of chemicals. The Bovine Corneal Opacity and Permeability (BCOP) assay is generally accepted as a valid in vitro alternative method to the Draize eye irritation test to detect corrosive and severe eye irritants (category 1), but has not proven sensitive enough to discriminate accurately moderate (category 2A/2B) to mild and non-irritating compounds. In the currently accepted BCOP assay, opacity is determined by the amount of light transmission through the cornea, and permeability is determined by the amount of sodium fluorescein dye that passes through all corneal cell layers. Both measurements are used to assign an In Vitro Irritancy Score (IVIS) for prediction of the in vivo ocular irritation potential of a test substance. Nowadays, opacity is measured by an OP-KIT opacitometer providing a center-weighted reading of light transmission by measuring changes in voltage when the transmission of white light passes through the cornea alters. As a consequence, this may underestimate opacity that develops as spots or heterogeneous opaque areas on the periphery of an isolated cornea. A prototype of a laser light-based opacitometer (PLLBO) allowing better measurement of opacities was developed by Van Goethem et al. (2010). This new device showed improved sensitivity to detect subtle changes in corneal transparency. Furthermore, the new opacitometer allowed the analysis of the complete corneal surface and was able to detect more efficiently opaque spots located along the sides of the excised corneas. A further improved prototype of the PLLBO was constructed in combination with a camera and a speckle noise reducer. Treatment conditions of the corneas in the cornea holders were optimized in order to mimic more the real in vivo situation. A set of test compounds with irritancy potencies especially in the mild and moderate range was tested. The improved LLBO showed some promising features which potentially could improve the usefulness of the BCOP test. Adaptation of cornea holders showed to be of limited value and only restricted to concentrations up to 15% which mimics more test conditions in industry. This 3-year research project was sponsored by the Stavros Niarchos Foundation (Greece).


In vivo cell-mediated immunity in Chinese patients with nasopharyngeal carcinoma.
Delayed hypersensitivity to antigens derived from four EBV-related (KHLY 28, Raji, F265 and NC37) and one EBV-unrelated (Molt) T-lymphoid cell lines and to standard antigens (Trichophyton, Candida albicans and streptokinase/streptodornase) was measured in 104 NPC patients and 24 patients with other cancers. Of the NPC patients with non-disseminated disease, 55/86 (63.2%) had a positive skin reaction to HKLY 28 extract, compared with only 1/18 (5.6%) OC patients with non-disseminated disease. The frequencies of these NPC patients with positive skin reactions to the other cell-line extracts were significantly lower (1.7-5.4%). From the preliminary results of a longitudinal study, skin testing with this particular crude membrane extract from HKLY 28 cells appears to be of little practical value in monitoring the clinical evolution of NPC, although a significant association between clinical evolution and certain patterns of skin reactivity response to the extract was found in about two-thirds of the cases analysed.


Apert syndrome with S252W FGFR2 mutation and characterization using Phenomizer: An Indian case report.
Human genetic disease needs differential diagnosis to optimize clinical management, enable prenatal detection, and genetic counselling. The current methods of robust DNA sequencing also require next generation phenotyping to match with for better interpretation of genotypic and phenotypic heterogeneity commonly observed. We report use of human ontology based phenotypic characterization with Phenomizer that gives statistical score for possible diagnoses based on which, the gene mutation was studied. A case of craniosynostosis which refers to a group of syndromes characterized by a premature fusion of skull was studied. The phenotypic features viz, dental crowding and dental malocclusion, bulbous nose, downslanted palpebral fissures, radial deviation of thumb, syndactyly of fingers, macrocephaly, and oxycephaly were entered to query the web-based tool Phenomizer which indicated high probability of mutation in FGFR2 gene. The proband, a 13-year-old male born to non-consanguineous parents showed mutation on FGFR2 gene at c.755C>G indicative of Apert syndrome. Apert syndrome is one of the most severe craniosynostosis syndromes with two possible mutations in the exon IIIa of FGFR2 gene reported in majority of the cases. This case study shows the importance of Phenomizer and molecular genetic analysis in differential diagnosis of genetic diseases.


Activation of epidermal growth factor receptor mediates receptor axon sorting and extension in the developing olfactory system of the moth Manduca sexta.
During development of the adult olfactory system of the moth Manduca sexta, olfactory receptor neurons extend axons from the olfactory epithelium in the antenna into the brain. As they arrive at the brain, interactions with centrally derived glial cells cause axons to sort and fasciculate with other axons destined to innervate the same glomeruli. Here we report studies indicating that activation of the epidermal growth factor receptor (EGFR) is involved in axon ingrowth and targeting. Blocking the EGFR kinase domain pharmacologically leads to stalling of many axons in the sorting zone and nerve layer as well as abnormal axonal fasciculation in the sorting zone. We also find that neuroglian, an IgCAM known to activate the EGFR through homophilic interactions in other systems, is transiently present on olfactory receptor neuron axons and on glia during the critical stages of the sorting process. The neuroglian is resistant to extraction with Triton X-100 in the sorting zone and nerve layer, possibly indicating its stabilization by homophilic binding in these regions. Our results suggest a mechanism whereby neuroglian molecules on axons and possibly sorting zone glia bind homophilically, leading to activation of EGFRs, with subsequent effects on axon sorting, pathfinding, and extension, and glomerulus development.


Maternal and fetal artery Doppler findings in women with chronic hypertension who subsequently develop superimposed pre-eclampsia.
To carry out a prospective study of Doppler velocimetry of the fetomaternal circulation in women with chronic hypertension, to evaluate whether the subsequent development of superimposed pre-eclampsia can be predicted. Serial Doppler studies of the maternal uterine and renal arteries, and fetal middle cerebral and umbilical arteries, were performed at 16-20 and at 28-32 weeks' gestation in 56 women with chronic hypertension. Pulsatility indices were compared using the Wilcoxon rank sum method. A p value of < 0.05 was considered significant. Uterine artery impedance was significantly elevated as early as 16-20 and at 28-32 weeks' gestation, while the cerebroplacental ratio was lower at 28-32 weeks' gestation, in the 14 women who developed superimposed pre-eclampsia. The maternal renal artery impedance remained constant throughout gestation, regardless of the development of pre-eclampsia. Uterine artery Doppler velocimetry at 16-20 and at 28-32 weeks' gestation showing increased impedance is predictive for the development of superimposed pre-eclampsia in women with chronic hypertension. The cerebroplacental ratio suggested early fetal brain sparing at 28-32 weeks' gestation in these women.


ATP6AP2 knockdown in cardiomyocyte deteriorates heart function via compromising autophagic flux and NLRP3 inflammasome activation.
Moderate autophagy can remove damaged proteins and organelles. In some inflammatory diseases, autophagy plays a protective role by inhibiting the NOD-like receptor family pyrin domain containing 3(NLRP3). (Pro)renin receptor (PRR, or ATP6AP2) is a critical component of the V-ATPase required for autophagy. It remains controversial about ATP6AP2 in the pathological process. The impact of ATP6AP2 on NLRP3 inflammasome and autophagic flux remains unknown under pressure overload stress. This research explores the potential link between ATP6AP2, autophagic flux, and NLRP3. There was upregulation of ATP6AP2 from 5-day post-TAC, and this expression remained at a high level until 8-weeks post-TAC in wild mice. Meanwhile, autophagic flux switched from early compensatory activation to blocking in the heart failure phase. NLRP3 activation can be seen at 8-week post-TAC. Adenovirus-mediated knockdown of ATP6AP2(shR-ATP6AP2) accelerated the progress of heart failure. After TAC was induced, shR-ATP6AP2 significantly deteriorated heart function and fibrosis compared with the shR-Scr group. Meanwhile, there was an elevated expression of NLRP3 and autophagic flux blockage. A transgenic mouse(Tg) with cardio-restricted ATP6AP2/(P)RR overexpression was constructed. Although high expression in cardiac tissue, there were no spontaneous functional abnormalities under the basal state. Cardiac function, fibrosis, hypertrophy remained identical to the control TAC group. However, SQSTM1/P62 was reduced, which indicated the relief of autophagic flux blockage. Further, Neonatal rat ventricular myocyte (NRVMs) transfected with shR-ATP6AP2 showed more susceptibility than sh-Scr NRVMs to phenylephrine-induced cell death. More reactive oxygen species (ROS) or mito-ROS accumulated in the shR-ATP6AP2 group when phenylephrine stimulation. Blocking NLRP3 activation in vivo partly rescued cardiac dysfunction and fibrosis. In conclusion, ATP6AP2 upregulation is a compensatory response to pressure overload. If not effectively compensated, it compromises autophagic flux, leads to dysfunctional mitochondria accumulation, further produces ROS to activate NLRP3, eventually accelerates heart failure.


Influenza-Associated Aspergillosis: Nationwide Trends, Predictors and Outcomes From 2005 to 2014.
Influenza-associated aspergillosis (IAA) has been increasingly reported in the literature in recent years, but contemporary large-scale data on the morbidity and mortality burden of IAA are lacking. The goal of this study was to estimate the predictors, associations, and outcomes of IAA in the United States. This retrospective cohort study was performed by using the National (Nationwide) Inpatient Sample database from 2005 to 2014 to identify influenza and IAA hospitalizations. Baseline variables and outcomes were compared between influenza hospitalizations without IAA and those with IAA. These variables were then used to perform an adjusted analysis for obtaining predictors and associations of the diagnosis and in-hospital mortality of IAA. Of the 477,556 hospitalizations identified with the principal diagnosis of influenza, IAA was identified in 823 (0.17%) hospitalizations. The IAA cohort consisted more commonly of 45- to 65-year-olds in urban teaching hospitals with substance abuse. Yearly trends revealed that both influenza and IAA hospitalizations have increased over time, with a peak observed in 2009, the year of the influenza A(H1N1) pandemic. Mortality was higher (20.58% vs 1.36%), average length of stay was longer (17.94 vs 4.05 days), and mean cost per hospitalization was higher ($194,932 vs $24,286) in the IAA cohort compared with the influenza cohort without IAA (P < .005). Solid-organ transplantation, hematologic malignancies, and use of invasive mechanical ventilation were associated with higher odds of IAA, among other factors. Use of invasive mechanical ventilation (adjusted OR, 13.43; P < .005), longer length of stay (adjusted OR, 5.47; P < .005), utilization of extracorporeal membrane oxygenation (adjusted OR, 4.99; P = .014), and the group aged 45 to 64 years (adjusted OR, 3.03; P = .012) were associated with higher in-hospital mortality in the IAA cohort. Although IAA is a rare complication of influenza hospitalizations, it is associated with increased all-cause mortality, more extended hospital stays, and higher hospital charges compared with influenza without IAA.


[An Elisa stool test to detect Helicobacter pylori infection].
Infection with Helicobacter pylori is frequent in Chile, and a good test for its diagnosis ideally should be non-invasive, fast, easy and inexpensive. To report the use of an immunoassay test, that detects antigens of Helicobacter pylori in stools. One hundred and four patients that required an upper gastrointestinal endoscopy were studied. Stool samples were analyzed using an enzymatic immunoassay. These results were compared with those obtained with the urease test and microscopic examination of smears taken from biopsies obtained during the diagnostic endoscopy. In 81 of 83 patients considered to have the infection according to the endoscopic tests, the antigen was also present in the stools. The test was negative in 16 of 21 patients considered to be without the infection. The resulting sensitivity and specificity for the immunoassay was thus 97.6 and 76.2% respectively, with positive and negative predictive values of 92.4 and 88.9%, respectively. These results are in agreement with those reported in the literature. Further studies are needed to define its usefulness in massive screening, follow up after antibiotic treatments or the detection of coccoid forms of Helicobacter pylori.


High-risk HPV infection modulates the promoter hypermethylation of APC, SFRP1, and PTEN in cervical cancer patients of North India.
Persistent infection with oncogenic HPV and downregulation of tumor suppressor genes play an essential role in the development and progression of cervical cancer. The present study aimed to identify the promoter methylation status of APC, SFRP1, and PTEN which are important regulators of Wnt pathway and their association with high-risk HPV infection and gene expression. Methylation Specific PCR (MSP) and quantitative reverse transcription PCR (RT-qPCR) were used to detect methylation status and gene expression levels of APC, SFRP1, and PTEN in cervical cancer biopsies (110) and paired non-cancerous biopsies (28). APC promoter was methylated in 38%, SFRP1 in 95%, and PTEN in 55% of the cervical cancer biopsies. Our data showed a trend of a higher rate of methylation of the gene promoters in cervical cancer biopsies while; they were majorly un-methylated in non-cancerous biopsies. Corresponding to a higher rate of methylation in cancer biopsies, the gene expression levels of APC, SFRP1, and PTEN were reduced in cervical cancer samples in comparison to normal cervix tissues. Further, we observed that 97% cancer biopsies were HPV infected and high-risk type HPV16 and 18 infections were significantly positively associated with APC (p = 0.008 and p = 0.007), SFRP1 (p = 0.003 and p = 0.0067), and PTEN (p = 0.049 and p = 0.008) promoter methylation. APC, SFRP1, and PTEN promoter hyper-methylation is positively associated with high-risk HPV infection and inversely associated with gene expression. Our findings show that high-risk HPV infection promotes methylation of these genes and further promotes their silencing.


Esophageal and Gastric Motility Disorders in the Elderly.
The elderly are particularly prone to developing upper gastrointestinal disturbances. Changes are due to the aging process, diabetes, cardiovascular risk factors, and neurologic issues. Medications used to treat these underlying conditions can cause gastrointestinal symptoms. Dysphagia is common and can be oropharyngeal and/or esophageal. Gastroparesis is due to either medications such opiates, or due to neurologic sequala of diabetes, cerebrovascular accidents, or neurologic diseases such as Parkinson's disease. Given limitations in many commonly used prokinetics with a wide range of side effect profiles including neurologic and cardiac, the focus of treatment should be on symptom management with dietary changes.


Human rheumatoid factor-producing cell induction by 2-mercaptoethanol: immunomodulation by a simple thiol compound.
Two-mercaptoethanol (2-ME), a simple 2 carbon thiol compound with a wide variety of in vitro and in vivo immunomodulating effects, was evaluated for its usefulness as a molecular probe of human antibody producing cell activation by adding 2-ME to cultures of peripheral blood mononuclear leukocytes from normal human volunteers. Culturing normal human leukocytes with 2-ME induced a significant number of cells producing rheumatoid factor as measured by a hemolytic plaque forming cell (PFC) assay. Dose response studies revealed 5 X 10(-5)M to be the optimum concentration of 2-ME for the induction of rheumatoid factor plaque forming cells (RF-PFC). This concentration of 2-ME also maximally induced PFC making antibodies to sheep red cells coupled to the trinitrophenyl (TNP) hapten demonstrating that 2-ME is a polyclonal inducer of human PFC. The addition of 5 X 10(-5) M 2-ME to cultures containing maximal concentrations of the polyclonal stimulators, pokeweed mitogen and human heat-aggregrated IgG, increased the number of RF-PFC detected in these cultures by approximately 50%, although both lower and higher concentrations of 2-ME suppressed the RF-PFC response. We conclude that 2-ME induces normal human leukocytes to produce rheumatoid factor as part of a polyclonal activation of antibody producing cells. 2-ME also has immunomodulating effects when added to other polyclonal stimulators of antibody producing cells.


[Toxicology screening in paediatrics].
The prevalence of acute or chronic exposure to substances of abuse in paediatric patients, from the neonatal period to adolescence, is not well established as most cases go unnoticed. Regardless of clinical cases of acute poisoning leading to visits to emergency room, the exposure is usually detected by a questionnaire to the parents or children. In the last few years, new validated analytical methodologies have been developed in order to detect parent drugs and their metabolites in different biological matrices. These biological matrices have different time windows for detection of the exposure: acute (i.e., urine, blood, oral fluid), and chronic (i.e., hair, meconium or teeth). The aim of this paper was to review the scenarios where the use of biological matrices is indicated for the detection of acute or chronic exposure to substances of abuse.


Clinical utility of apparent diffusion coefficient values obtained using high b-value when diagnosing prostate cancer using 3 tesla MRI: comparison between ultra-high b-value (2000 s/mm²) and standard high b-value (1000 s/mm²).
To determine whether the apparent diffusion coefficient (ADC) obtained using b = 2000 s/mm(2) upon 3 Tesla (T) diffusion-weighted MRI is superior to b = 1000 s/mm(2) for discriminating malignant from normal prostate tissue and predicting the aggressiveness of prostate cancer, using histopathological findings of radical prostatectomy as a reference. Eighty prostate cancer patients underwent preoperative 3T MRI including diffusion weighted imaging with b-values of 0, 1000, and 2000 s/mm(2) . ADCs were measured for malignant lesions and normal sites on three sets of ADC maps calculated with monoexponential fitting between b = 0 and 1000, 0 and 2000, and 1000 and 2000, respectively. The relationship between the ADC and Gleason score was evaluated. The areas under the ROC curves for b = 0,1000, b = 0,2000, and b = 1000,2000 were 0.896, 0.937, and 0.857, respectively, in the peripheral zone (PZ) and 0.877, 0.889, and 0.731, respectively, in the transition zone (TZ). The difference between b = 0,1000 and b = 0,2000 was significant in PZ (P = 0.033), but not in TZ (P = 0.84). Weak but significant negative correlations were identified between ADCs and Gleason score in both PZ and TZ cancer at b = 0,1000 and b = 0,2000 (r = -0.323 to -0.341). For 3T MRI, ADCs using b = 0,2000 are more accurate than b = 0,1000 for diagnosing PZ cancer, and as accurate for TZ cancer.


Salt stress altered anaerobic microbial community and carbon metabolism characteristics: The trade-off between methanogenesis and chain elongation.
Discharge of saline organic wastewater is increasing worldwide, yet how salt stress disrupts the microbial community's structure and metabolism in bioreactors has not been systematically investigated. The non-adapted anaerobic granular sludge was inoculated into wastewater with varying salt concentration (ranging from 0% to 5%) to examine the effects of salt stress on the structure and function of the anaerobic microbial community. Result indicated that salt stress had a significant impact on the metabolic function and community structure of the anaerobic granular sludge. Specifically, we observed a notable reduction in methane production in response to all salt stress treatments (r = -0.97, p < 0.01), while an unexpected increase in butyrate production (r = 0.91, p < 0.01) under moderate salt stress (1-3%) with ethanol and acetate as carbon sources. In addition, analysis of microbiome structures and networks demonstrated that as the degree of salt stress increased, the networks exhibited lower connectance and increased compartmentalization. The abundance of interaction partners (methanogenic archaea and syntrophic bacteria) decreased under salt stress. In contrast, the abundance of chain elongation bacteria, specifically Clostridium kluyveri, increased under moderate salt stress (1-3%). As a consequence, the microbial carbon metabolism patterns shifted from cooperative mode (methanogenesis) to independent mode (carbon chain elongation) under moderate salt stress. This study provides evidence that salt stress altered the anaerobic microbial community and carbon metabolism characteristics, and suggests potential guidance for steering the microbiota to promote resource conversion in saline organic wastewater treatment.


No evidence for magnetic field effects on the behaviour of Drosophila.
Migratory songbirds have the remarkable ability to extract directional information from the Earth's magnetic field1,2. The exact mechanism of this light-dependent magnetic compass sense, however, is not fully understood. The most promising hypothesis focuses on the quantum spin dynamics of transient radical pairs formed in cryptochrome proteins in the retina3-5. Frustratingly, much of the supporting evidence for this theory is circumstantial, largely because of the extreme challenges posed by genetic modification of wild birds. Drosophila has therefore been recruited as a model organism, and several influential reports of cryptochrome-mediated magnetic field effects on fly behaviour have been widely interpreted as support for a radical pair-based mechanism in birds6-23. Here we report the results of an extensive study testing magnetic field effects on 97,658 flies moving in a two-arm maze and on 10,960 flies performing the spontaneous escape behaviour known as negative geotaxis. Under meticulously controlled conditions and with vast sample sizes, we have been unable to find evidence for magnetically sensitive behaviour in Drosophila. Moreover, after reassessment of the statistical approaches and sample sizes used in the studies that we tried to replicate, we suggest that many-if not all-of the original results were false positives. Our findings therefore cast considerable doubt on the existence of magnetic sensing in Drosophila and thus strongly suggest that night-migratory songbirds remain the organism of choice for elucidating the mechanism of light-dependent magnetoreception.