The probability of iatrogenic major vascular injury in lumbar discectomy.
Purpose: To estimate the frequency of iatrogenic injury of major vascular structures during lumbar discectomy.Materials and methods: The medical records of patients who underwent surgery for lumbar disc herniation at our neurosurgical clinic between April 2000 and April 2016 were retrospectively reviewed. Patients with intraoperative iatrogenic vascular injury were identified by reading the surgical notes and the post-operative progress records of patients who had undergone lumbar discectomy. The standard calculation of the incidence of iatrogenic major vascular injury in lumbar discectomy was used to analyse the data. The formula for estimating the standard probability by calculating the incidence rate is: [Formula: see text]=n/N, where [Formula: see text] is the estimated probability, n is the number of events and N is the total number of cases. The standard error of this estimate is SE[Formula: see text]=[Formula: see text]Results: During the study period, 2498 patients underwent lumbar discectomy at one or more levels of the lumbar spine. The operations were performed by more than 40 different neurosurgeons or surgical residents. More than 95% of the operations were done under a surgical microscope. Two cases were found to have iatrogenic major vascular injuries. The standard frequentist estimate of the probability, [Formula: see text] (risk-per-case), of iatrogenic major vascular injuries in lumbar discectomy was: [Formula: see text]=2/2498 = 0.0008 (0.08%). The standard error of this estimate was: [Formula: see text]=[Formula: see text]=0.000566 = 10-4 (5.66) (95% confidence interval for true p = 10-4 (801)±(1.96)×10-3 (566)).Conclusions: In this study, the incidence of iatrogenic major vascular injuries in lumbar discectomy was 1 in 1249 operations (0.08%). If utmost care is taken, at least some of these iatrogenic intraoperative vascular complications can be avoided or more rapidly treated, and the lives of such patients can be saved.


[Adenylate kinase activity of phycobilisomes from the blue-green algae Microcystis aerogenosa].
The phycobilisomes (PBS) from the blue-green algae Microcystis aerogenosa was found to possess the adenylate kinase activity. The enzyme activity of PBS is kept for 2 weeks, reaching its maximum on th 2nd-4th day after PBS isolation from the cells, and is retained after passage of freshly isolated PBS through a column with Sephadex G-25. The adenylate kinase activity of PBS is thermostable, depends on the protein concentration in the sample, undergoes activation by white light and is inhibited by glutaric aldehyde. The enzyme activity is presumably determined by the components of the low molecular weight protein fraction of non-pigment origin, which are constituents of PBS.


"A room full of strangers every day": the psychosocial impact of developmental prosopagnosia on children and their families.
Individuals with developmental prosopagnosia ('face blindness') have severe face recognition difficulties due to a failure to develop the necessary visual mechanisms for recognizing faces. These difficulties occur in the absence of brain damage and despite normal low-level vision and intellect. Adults with developmental prosopagnosia report serious personal and emotional consequences from their inability to recognize faces, but little is known about the psychosocial consequences in childhood. Given the importance of face recognition in daily life, and the potential for unique social consequences of impaired face recognition in childhood, we sought to evaluate the impact of developmental prosopagnosia on children and their families. We conducted semi-structured interviews with 8 children with developmental prosopagnosia and their parents. A battery of face recognition tests was used to confirm the face recognition impairment reported by the parents of each child. We used thematic analysis to develop common themes among the psychosocial experiences of the children and their parents. Three themes were developed from the child reports: 1) awareness of their difficulties, 2) coping strategies, such as using non-facial cues to identify others, and 3) social implications, such as discomfort in, and avoidance of, social situations. These themes were paralleled by the parent reports and highlight the unique social and practical challenges associated with childhood developmental prosopagnosia. Our findings indicate a need for increased awareness and treatment of developmental prosopagnosia to help these children manage their face recognition difficulties and to promote their social and emotional wellbeing.


MicroRNA expression profiles differentiate chronic pain condition subtypes.
Chronic pain is a significant health care problem, ineffectively treated because of its unclear etiology and heterogeneous clinical presentation. Emerging evidence demonstrates that microRNAs (miRNAs) regulate the expression of pain-relevant genes, yet little is known about their role in chronic pain. Here, we evaluate the relationship among pain, psychological characteristics, plasma cytokines, and whole blood miRNAs in 22 healthy controls (HCs); 33 subjects with chronic pelvic pain (vestibulodynia, VBD); and 23 subjects with VBD and irritable bowel syndrome (VBD + IBS). VBD subjects were similar to HCs in self-reported pain, psychological profiles, and remote bodily pain. VBD + IBS subjects reported decreased health and function; and an increase in headaches, somatization, and remote bodily pain. Furthermore, VBD subjects exhibited a balance in proinflammatory and anti-inflammatory cytokines, whereas VBD + IBS subjects failed to exhibit a compensatory increase in anti-inflammatory cytokines. VBD subjects differed from controls in expression of 10 miRNAs of predicted importance for pain and estrogen signaling. VBD + IBS subjects differed from controls in expression of 11 miRNAs of predicted importance for pain, cell physiology, and insulin signaling. miRNA expression was correlated with pain-relevant phenotypes and cytokine levels. These results suggest that miRNAs represent a valuable tool for differentiating VBD subtypes (localized pain with apparent peripheral neurosensory disruption vs widespread pain with a central sensory contribution) that may require different treatment approaches.


Coordination between aminoacylation and editing to protect against proteotoxicity.
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ligate amino acids to tRNAs, and often require editing to ensure accurate protein synthesis. Recessive mutations in aaRSs cause various neurological disorders in humans, yet the underlying mechanism remains poorly understood. Pathogenic aaRS mutations frequently cause protein destabilization and aminoacylation deficiency. In this study, we report that combined aminoacylation and editing defects cause severe proteotoxicity. We show that the ths1-C268A mutation in yeast threonyl-tRNA synthetase (ThrRS) abolishes editing and causes heat sensitivity. Surprisingly, experimental evolution of the mutant results in intragenic mutations that restore heat resistance but not editing. ths1-C268A destabilizes ThrRS and decreases overall Thr-tRNAThr synthesis, while the suppressor mutations in the evolved strains improve aminoacylation. We further show that deficiency in either ThrRS aminoacylation or editing is insufficient to cause heat sensitivity, and that ths1-C268A impairs ribosome-associated quality control. Our results suggest that aminoacylation deficiency predisposes cells to proteotoxic stress.


Blastogenesis and interleukin-2 receptor expression assays in the harbor seal (Phoca vitulina).
Two in vitro functional assays were developed to evaluate mitogen-induced responses of peripheral blood mononuclear leukocytes (PBML) from free-ranging harbor seals, Phoca vitulina. Lymphocyte proliferation was measured by a standard blastogenesis assay following optimization of culture conditions including mitogen concentration, cell density, and incubation time. These optimized parameters, with the exception of incubation time, were subsequently employed to measure lymphocyte activation by analytical flow cytometry using fluorochrome-based identification of cell surface interleukin-2 receptor (IL-2r) expression. Baseline values established for free-ranging harbor seals had extensive animal variability; there was evidence that the samples were derived from a group of animals with a normal distribution. Positive correlations were observed between blastogenesis assays, and between blastogenesis and activation assays, when using pokeweed or concanavalin A as the stimulus. However, no relationship was found in the expression of the IL-2r induced by these mitogens. This result supports the contention that the two mitogens stimulate different lymphocyte subpopulations. This was observed only with the IL-2r expression assay because of its unique ability to measure the number of T lymphocytes initially activated rather than the ultimate number of progeny cells identified by blastogenesis. Both assays, used concurrently, should provide a more comprehensive representation of lymphocyte competence and serve as a measure of animal health.


Stillbirth classification in population-based data and role of fetal growth restriction: the example of RECODE.
Stillbirth classifications use various strategies to synthesise information associated with fetal demise with the aim of identifying key causes for the death. RECODE is a hierarchical classification of death-related conditions, which grants a major place to fetal growth restriction (FGR). Our objective was to explore how placement of FGR in the hierarchy affected results from the classification. In the Rhône-Alpes region, all stillbirths were recorded in a local registry from 2000 to 2010 in three districts (N = 969). Small for gestational age (SGA) was defined as a birthweight below the 10th percentile. We applied RECODE and then modified the hierarchy, including FGR as the penultimate category (RECODE-R). 49.0% of stillbirths were SGA. From RECODE to RECODE-R, stillbirths attributable to FGR decreased from 38% to 14%, in favour of other related conditions. Nearly half of SGA stillbirths (49%) were reclassified. There was a non-significant tendency toward moderate SGA, singletons and full-term stillbirths to older mothers being reclassified. The position of FGR in hierarchical stillbirth classification has a major impact on the first condition associated with stillbirth. RECODE-R calls less attention to monitoring SGA fetuses but illustrates the diversity of death-related conditions for small fetuses.


An altered platelet granule glycoprotein in patients with essential thrombocythemia.
The protein profiles of washed platelets from nine patients with essential thrombocythemia were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In four patients, an additional protein band (reduced Mr of 170,000) was clearly identified in both unstimulated platelet preparations and thrombin-released supernatant fractions. This band was also evident, though to a lesser extent, in three more patients, but it could not be located in the two remaining patients nor in any of ten controls. Subsequent characterization of the 170,000 reduced protein in one patient indicated that (a) it was glycosylated, as judged by periodic acid-Schiff staining, and (b) that native protein was a disulfide-linked multimer (possibly trimeric), which (c) partially bound to the activated platelet plasma membrane in the presence of calcium, and (d) was immune precipitated by anti-glycoprotein G antisera. The combined evidence is consistent with the 170,000 reduced protein being a modified form of the normal subunit of the platelet alpha-granule constituent, glycoprotein G (also termed thrombospondin and thrombin-sensitive protein).


Newly reported p.Asp240Asn mutation in UBIAD1 suggests central discoid corneal dystrophy is a variant of Schnyder corneal dystrophy.
To determine whether central discoid corneal dystrophy (CDCD), previously reported as a novel corneal dystrophy, is actually Schnyder corneal dystrophy (SCD) through screening of the UBIAD1 gene in the members of the family in which CDCD was reported. Genetic analysis was performed in 3 affected members and 1 unaffected member of a pedigree with CDCD including the affected 31-year-old proband. All 4 affected members of the described pedigree demonstrated discoid central corneal clouding, with subtle, superficial, crystalline deposits noted in one of the affected individuals. Screening of UBIAD1 in the affected individuals demonstrated a previously unreported missense mutation, p.Asp240Asn, which was not identified in an unaffected family member or in 100 control individuals. The clinical findings of the family reported to have CDCD were indistinguishable from those found in SCD. However, CDCD was originally thought to be distinct from SCD because of the absence of positive lipid staining and the presence of alcian blue staining consistent with glycosaminoglycans in the proband's cornea. Our recent investigation has revealed that corneal specimens from other patients with SCD have also demonstrated staining for glycosaminoglycans. Discovery that mutations in UBIAD1 caused SCD allowed genetic testing of this CDCD family. Our newly reported UBIAD1 mutation suggests that CDCD is actually a variant of SCD. This report underscores the utility of genetic testing in determining whether newly described corneal dystrophies are in fact unique entities or just variants of well-known diseases.


Review of research pertaining to the effect of tumor-derived exosomes on natural killer cells.
Tumor-derived exosomes (TDEs) play critical roles in many aspects of cancer progression. There have been several advances in cancer immunotherapy in recent years. A major challenge, however, has been addressed to the role of TDEs in tumor cell immune escape through their influence on the antitumor immunity of natural killer (NK) cells, a key type of immune cell. In this review, we present our overview of the effects of different TDEs on NK cell activation and NK cell toxicity. Studies on mechanism suggest that TDEs mainly affect the immune response of NK cells by inhibiting activated receptors on the surface of NK cells and downregulating the NK recognition ligand MICA/B on the tumor cell surface. In addition, a summary was documented on how to restore the cytotoxicity of NK cells and improve the drug's ability to recognize tumor cells, and a detailed explanation was also provided on the mechanism of action of the drug.


Patient-Reported Visual Disability in Fuchs' Endothelial Corneal Dystrophy Measured by the Visual Function and Corneal Health Status Instrument.
Measuring patient-reported visual disability in Fuchs' endothelial corneal dystrophy (FECD) may be helpful in determining when to intervene and for understanding the outcomes of intervention. In this study, we aimed to validate a new patient-reported visual disability questionnaire, the Visual Function and Corneal Health Status (V-FUCHS) instrument, in FECD before and after endothelial keratoplasty (EK). Cross-sectional study with instrument readministration at 6 weeks. Patients with a range of severity of FECD, including after EK, and patients with healthy corneas. The V-FUCHS instrument was developed based on patient interviews, expert consultations, and pretesting. Psychometric methods of classic test theory were applied to estimate reliability and validity, including testing V-FUCHS against Catquest-9SF, a cataract-specific visual disability questionnaire. Ordered polytomous Rasch-based partial credit models and item response theory diagnostics were used to define the response patterns. Reliability (primary) and validity (secondary). The final instrument was completed by 65% of patients with a range of severity of FECD (n = 41), after undergoing EK for FECD (n = 70), and with healthy corneas (n = 28). Participants were phakic or pseudophakic. Exploratory factor analysis among FECD and patients who underwent EK showed 2 independent factors of visual disability: 7 items related to visual acuity and 8 items related to glare or diurnal variation. Retest reliability was substantial (intraclass correlation coefficient, ≥0.8, both factors). Among all patients, the visual acuity factor was correlated with Catquest-9SF scores (r = 0.65; P < 0.001; n = 96). The glare or diurnal variation factor increased with FECD severity (P < 0.001, n = 69) and was higher in FECD than healthy participants (P < 0.001). Diagnostics revealed that both factors were well calibrated and met Rasch model expectations. The V-FUCHS instrument is valid and reliable for assessing visual disability in FECD. The instrument allows for standardized, comprehensive, and rapid assessment of disease-specific visual disability and may be useful in clinical practice and research as a patient-reported outcome measure.


Discrimination of different subsets of cytolytic cells in pseudorabies virus-immune and naive pigs.
We previously observed that pseudorabies virus (PRV)-induced, cell-mediated cytolysis in pigs includes killing by natural killer (NK) cells. We also observed that IL-2 stimulation in vitro of naive PBMC expands porcine NK cells. The purpose of this study was to compare the phenotypes of the cytolytic subsets stimulated in vitro by PRV and by IL-2. PBMC were isolated from blood of PRV-immune and naive pigs and stimulated in vitro with PRV or IL-2. After 6 days, the frequency of various lymphocyte subsets in these cultured PBMC was determined by flow cytometry: the cells were separated with a magnet-activated cell sorter and the cytolytic activity of the separated populations was determined. When lymphocytes were separated and analysed with FACScan, the following lymphocyte subsets were discriminated: CD6(+) CD8(bright+) CD4(-) (CTL phenotype), CD6(+) CD8(dull+) CD4(+) (the fraction containing memory T helper cells), CD6(+) CD8(-) CD4(+) (T helper cell phenotype), CD6(-) CD8(dull+) CD4(-) gammadelta-T(+) ( gammadelta-T cell phenotype), CD6(-) CD8(dull+) CD4(-) gammadelta-T(-) (NK phenotype) and CD6(-) CD8(-) CD4(-) gammadelta-T(-) or gammadelta-T(+). Flow cytometry analysis demonstrated that PRV stimulation of immune PBMC resulted in the occurrence of more CD6(+) CD8(+) and CD4(+) CD8(+) and fewer CD6(-) CD8(+) and gammadelta-T(+) CD8(+) lymphocytes than IL-2 stimulation of naive PBMC (P<0.05). It was demonstrated further that killing by PRV-stimulated PBMC was mediated mainly by CD6(+) CD8(+) T lymphocytes. Killing by IL-2-stimulated PBMC was mediated mainly by CD6(-) CD8(+) T lymphocytes. These results demonstrate that both natural killing and killing by classical PRV-specific CTL were detected in PRV-immune pigs, whereas IL-2 stimulation of PBMC isolated from naive pigs mainly induced natural killing.


Skeletal muscle mitochondrial uncoupling in a murine cancer cachexia model.
Approximately half of all cancer patients present with cachexia, a condition in which disease-associated metabolic changes lead to a severe loss of skeletal muscle mass. Working toward an integrated and mechanistic view of cancer cachexia, we investigated the hypothesis that cancer promotes mitochondrial uncoupling in skeletal muscle. We subjected mice to in vivo phosphorous-31 nuclear magnetic resonance (31P NMR) spectroscopy and subjected murine skeletal muscle samples to gas chromatography/mass spectrometry (GC/MS). The mice used in both experiments were Lewis lung carcinoma models of cancer cachexia. A novel 'fragmented mass isotopomer' approach was used in our dynamic analysis of 13C mass isotopomer data. Our 31P NMR and GC/MS results indicated that the adenosine triphosphate (ATP) synthesis rate and tricarboxylic acid (TCA) cycle flux were reduced by 49% and 22%, respectively, in the cancer-bearing mice (p<0.008; t-test vs. controls). The ratio of ATP synthesis rate to the TCA cycle flux (an index of mitochondrial coupling) was reduced by 32% in the cancer-bearing mice (p=0.036; t-test vs. controls). Genomic analysis revealed aberrant expression levels for key regulatory genes and transmission electron microscopy (TEM) revealed ultrastructural abnormalities in the muscle fiber, consistent with the presence of abnormal, giant mitochondria. Taken together, these data suggest that mitochondrial uncoupling occurs in cancer cachexia and thus point to the mitochondria as a potential pharmaceutical target for the treatment of cachexia. These findings may prove relevant to elucidating the mechanisms underlying skeletal muscle wasting observed in other chronic diseases, as well as in aging.


A neurodevelopmental perspective on male violence.
Research is increasingly documenting a neurobiological basis to violence. This review takes a neurodevelopmental perspective on the very small group of males who grow up to become persistent violent offenders. After outlining six criteria for what constitutes a neurodevelopmental disorder, the extent to which chronic violence meets these definitional criteria is examined, covering the fields of genetics, structural and functional brain imaging, and neuropsychology. Early health risk factors for violence are then outlined, including birth complications, minor physical anomalies, prenatal smoking and alcohol exposure, poor nutrition, lead exposure, and traumatic brain injury. Persistent adult violence is argued to originate in aberrant temperamental behavior in early childhood, to have a stable developmental trajectory, and to be associated with impaired education, social, and occupational functioning. Taken together, it is argued that chronic adult violence meets criterion for being conceptualized as having neurodevelopmental origins and that an important, but not sole, source of neural maldevelopment lies in prenatal and early postnatal risk factors. This review concludes with a recognition of the sociopolitical context within which a neurodevelopmental perspective on chronic violence sits, together with directions for future research, including whether a neurodevelopmental hypothesis is best applied to reactive as opposed to proactive aggression.


Evaluation of the Oil-Rich Waste Fillers' Influence on the Tribological Properties of Polylactide-Based Composites.
In recent years, natural-based polymeric composites have gained the attention of researchers and the industry due to their low environmental impact and good applicational properties. A promising example of these materials is polylactide-based composites filled with linseed cake. Even though they can be characterized by reduced brittleness and enhanced crystallization rate, their applicational potential cannot be fully evaluated without knowing their tribological properties. This paper is aimed to analyze the influence of the oil contained by the filler on the mechanical and frictional properties of polylactide-based composites. Specimens of unfilled polylactide and its composites containing 10 wt % of linseed cake with different oil content were prepared by injection molding. Their microhardness was measured by the Vickers method. The softening temperature was determined by the Vicat method. The scratch resistance of the samples was tested with the loading of 10, 20 and 40 N. The coefficient of friction was evaluated by the pin-on-plate method, using CoCrMo alloy as the counter surface. It was found that the oil content in the filler does not directly influence the mechanical and tribological properties, but the composite samples present comparable hardness and lower coefficient of friction than the unfilled polymer, so they can be a good eco-friendly alternative to the unfilled polylactide when the frictional properties are an important factor.


Cecropin A-derived peptides are potent inhibitors of fungal plant pathogens.
Cecropins are naturally occurring peptides that play an important role in the immune response of insects. Cecropin A-derived and cecropin A-melittin hybrid peptides, all smaller than the natural compound cecropin A, were synthesized and tested for their ability to inhibit growth of several agronomically important fungal pathogens. We found that an 11-amino-acid sequence, corresponding to the N-terminal amphipathic alpha-helix domain of cecropin A, exhibited antifungal activity. Differences in susceptibility of the various pathogens were observed, Phytophthora infestans being particularly sensitive to the shortened cecropin A peptides (IC50 = 2 x 10(-6) M). Biotoxicity of the shortest cecropin A-derived peptide was variously affected by the presence of proteins extracted from leaves of tobacco and tomato plants, either total extracts or intercellular fluids (ICFs). Overall, there was a greater tolerance to tomato protein extracts than to tobacco extracts. These findings suggest that tobacco should not be used as a model for testing the possible protective effects of transgenically expressed, cecropin-based genes. The feasibility of tailoring cecropin A genes to enhance crop protection in particular plant/fungus combinations is discussed.


Molecular and histological analysis of a new rat model of experimental knee osteoarthritis.
Articular cartilage degeneration is the most consistently observed feature of osteoarthritis (OA). Animal and human studies have shown that various forms of exercise influence the course of the disease in different ways. In addition, early changes in articular cartilage that influence the progression of OA, such as the expression of cytokines, require further investigation. We have used a surgically induced experimental model of knee OA to address these questions. Here, we discuss our recent studies investigating the effects of an exercise paradigm in surgically induced OA, which determined that the destabilized knee joint is susceptible to enhanced degeneration when subjected to low-intensity, low-impact exercise. Further, we investigated early global changes in gene expression in articular chondrocytes from degenerating cartilage. Identified candidate genes including genes involved in chemokine, endothelin, and transforming growth factor-alpha signaling are discussed in the context of articular cartilage degeneration in early OA.


[Some indices of cellular and humoral immunity in infants with acute purulent otitis media].
The examination of 32 infants with acute otitis media purulenta identified shifts in immunological indices: T-cell immunity appeared 1.5-times weaker (up to 31.5 +/- 2.6%) than in healthy controls, synthesis of serum immunoglobulins intensified (IgA, IgM and IgG levels rose to 161 +/- 18 mg%, 124 +/- 11 mg% and 963 +/- 47 mg%, respectively). Thus, infants with acute otitis media purulenta need not only conventional therapeutic measures but also correction of disturbed cellular and humoral immunity.


Increased sensitivity to angiotensin in uterine arteries from pregnant rabbits.
This study was designed to compare the vascular reactivity intrinsic to uterine and femoral arterial smooth muscle from pregnant (0.92 term) and nonpregnant rabbits to angiotensin II (ANG II), norepinephrine (NE), and potassium chloride (KCl) using the isolated helical strip technique. Comparing dose-response relations, arteries from both groups were equally sensitive to NE and KCl. Uterine arteries from pregnant rabbits, however, exhibited a greater sensitivity to the vasoconstricting effects of ANG II (P less than 0.01). This selective increase in sensitivity to ANG II was not observed in femoral arteries. The altered ANG II response in uterine arteries from pregnant rabbits was unaffected by pretreatment with cocaine or phenoxybenzamine, thus ruling out an adrenergic mechanism mediating the response. In addition, evaluation of saralasin affinity (KB) for the uterine arterial ANG II receptor suggested that it was not altered in pregnancy. However, preincubation of uterine arteries from pregnant rabbits with meclofenamate or indomethacin consistently attenuated the ANG II response (P less than 0.05). Therefore, this study demonstrated that 1) uterine arteries from term pregnant rabbits show a selective and specific enhancement to ANG II vasoconstriction, and 2) this increased response of ANG II results from the local ANG II stimulation of synthesis of prostaglandins by the uterine arterial wall that have a net vasoconstricting action.


FRET detection of cellular alpha4-integrin conformational activation.
Integrins are cell adhesion receptors, expressed on every cell type, that have been postulated to undergo conformational changes upon activation. Here, different affinity states were generated by exposing alpha4-integrins to divalent ions or by inside-out activation using a chemokine receptor. We probed the dynamic structural transformation of the integrin on live cells using fluorescence resonance energy transfer (FRET) between a peptide donor, which specifically binds to the alpha4-integrin, and octadecyl rhodamine B acceptors incorporated into the plasma membrane. We analyzed the data using a model that describes FRET between a random distribution of donors and acceptors in an infinite plane. The distance of closest approach was found to vary with the affinity of the integrin. The change in distance of closest approach was approximately 50 A between resting and Mn2+ activated receptors and approximately 25 A after chemokine activation. We used confocal microscopy to probe the lateral organization of donors and acceptors subsequent to integrin activation. Taken together, FRET and confocal results suggest that changes in FRET efficiencies are primarily due to the vertical extension of the integrin. The coordination between the extension of alpha4-integrin and its affinity provides a mechanism for Dembo's catch-bond concept.


Voltage-Dependent Protonation of the Calcium Pocket Enable Activation of the Calcium-Activated Chloride Channel Anoctamin-1 (TMEM16A).
Anoctamin-1 (ANO1 or TMEM16A) is a homo-dimeric Ca2+-activated Cl- channel responsible for essential physiological processes. Each monomer harbours a pore and a Ca2+-binding pocket; the voltage-dependent binding of two intracellular Ca2+ ions to the pocket gates the pore. However, in the absence of intracellular Ca2+ voltage activates TMEM16A by an unknown mechanism. Here we show voltage-activated anion currents that are outwardly rectifying, time-independent with fast or absent tail currents that are inhibited by tannic and anthracene-9-carboxylic acids. Since intracellular protons compete with Ca2+ for binding sites in the pocket, we hypothesized that voltage-dependent titration of these sites would induce gating. Indeed intracellular acidification enabled activation of TMEM16A by voltage-dependent protonation, which enhanced the open probability of the channel. Mutating Glu/Asp residues in the Ca2+-binding pocket to glutamine (to resemble a permanent protonated Glu) yielded channels that were easier to activate at physiological pH. Notably, the response of these mutants to intracellular acidification was diminished and became voltage-independent. Thus, voltage-dependent protonation of glutamate/aspartate residues (Glu/Asp) located in the Ca2+-binding pocket underlines TMEM16A activation in the absence of intracellular Ca2+.


Interaction of fibrinogen-magnetic nanoparticle bioconjugates with integrin reconstituted into artificial membranes.
Magnetic nanoparticles have a broad spectrum of biomedical applications including cell separation, diagnostics and therapy. One key issue is little explored: how do the engineered nanoparticles interact with blood components after injection? The formation of bioconjugates in the bloodstream and subsequent reactions are potentially toxic due to the ability to induce an immune response. The understanding of the underlying processes is of major relevance to design not only efficient, but also safe nanoparticles for e.g. targeted drug delivery applications. In this study, we report on maghemite nanoparticles functionalized with citrate-, dextran- and polyethylene glycol coatings and their interaction with the clotting protein fibrinogen. Further, we investigate using biophysical tools (e.g. dynamic light scattering, circular dichroism spectroscopy and quartz crystal microbalance) the interaction of the magnetic nanoparticles-fibrinogen bioconjugates with artificial cell membranes as a model system for blood platelets. We found that fibrinogen corona formation provides colloidal stability to maghemite nanoparticles. In addition, bioconjugates of fibrinogen with dextran- and citrate-coated NPs interact with integrin-containing lipid bilayer, especially upon treatment with divalent ions, whereas PEG-coating reveals minor interaction. Our study at the interface of protein-conjugated nanoparticles and artificial cell membranes is essential for engineering safe nanoparticles for drug delivery applications.


Immobilization of inulinase on concanavalin A-attached super macroporous cryogel for production of high-fructose syrup.
In this study, concanavalin A (Con A)-attached poly(ethylene glycol dimethacrylate) [poly(EGDMA)] cryogels were used for immobilization of Aspergillus niger inulinase. For this purposes, the monolithic cryogel column was prepared by radical cryocopolymerization of EGDMA as a monomer and N,N'-methylene bisacrylamide as a crosslinker. Then, Con A was attached by covalent binding onto amino-activated poly(EGDMA) cryogel via glutaraldehyde activation. Characterization of cryogels was performed by FTIR, EDX, and SEM studies. Poly(EGDMA) cryogels were highly porous and pore size was found to be approximately 50-100 μm. Con A-attached poly(EGDMA) cryogels was used in the adsorption of inulinase from aqueous solutions. Adsorption of inulinase on the Con A-attached poly(EGDMA) cryogel was performed in continuous system and the effects of pH, inulinase concentration, and flow rate on adsorption were investigated. The maximum amount of inulinase adsorption was calculated to be 27.85 mg/g cryogel at 1.0 mg/mL inulinase concentration and in acetate buffer at pH 4.0. Immobilized inulinase was effectively used in continuous preparation of high-fructose syrup. Inulin was converted to fructose in a continuous system and released fructose concentration was found to be 0.23 mg/mL at the end of 5 min of hydrolysis. High-fructose content of the syrup was demonstrated by thin layer chromatography.


Discrimination between Alzheimer disease, mild cognitive impairment, and normal aging by using automated segmentation of the hippocampus.
To prospectively evaluate the accuracy of automated hippocampal volumetry to help distinguish between patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and elderly controls, by using established criteria for patients with AD and MCI as the reference standard. The regional ethics committee approved the study and written informed consent was obtained from all participants. The study included 25 patients with AD (11 men, 14 women; mean age +/- standard deviation [SD], 73 years +/- 6; Mini-Mental State Examination (MMSE) score, 24.4 +/- 2.7), 24 patients with amnestic MCI (10 men, 14 women; mean age +/- SD, 74 years +/- 8; MMSE score, 27.2 +/- 1.4) and 25 elderly healthy controls (13 men, 12 women; mean age +/- SD, 64 years +/- 8). For each participant, the hippocampi were automatically segmented on three-dimensional T1-weighted magnetic resonance (MR) images with high spatial resolution. Segmentation was performed by using recently developed software that allows fast segmentation with minimal user input. Group differences in hippocampal volume were assessed by using Student t tests. To obtain robust estimates of P values, the correct classification rate, sensitivity, and specificity, bootstrap methods were used. Significant hippocampal volume reductions were detected in all groups of patients (-32% in AD patients vs controls, P < .001; -19% in MCI patients vs controls, P < .001; and -15% in AD patients vs MCI patients, P < .01). Individual classification on the basis of hippocampal volume resulted in 84% correct classification (sensitivity, 84%; specificity, 84%) between AD patients and controls and 73% correct classification (sensitivity, 75%; specificity, 70%) between MCI patients and controls. This automated method can serve as an alternative to manual tracing and may thus prove useful in assisting with the diagnosis of AD.


Identification of specialized pro-resolving mediator clusters from healthy adults after intravenous low-dose endotoxin and omega-3 supplementation: a methodological validation.
Specialized pro-resolving mediator(s) (SPMs) are produced from the endogenous ω-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and accelerate resolution of acute inflammation. We identified specific clusters of SPM in human plasma and serum using LC-MS/MS based lipid mediator (LM) metabololipidomics in two separate laboratories for inter-laboratory validation. The human plasma cluster consisted of resolvin (Rv)E1, RvD1, lipoxin (LX)B4, 18-HEPE, and 17-HDHA, and the human serum cluster consisted of RvE1, RvD1, AT-LXA4, 18-HEPE, and 17-HDHA. Human plasma and serum SPM clusters were increased after ω-3 supplementation (triglyceride dietary supplements or prescription ethyl esters) and low dose intravenous lipopolysaccharide (LPS) challenge. These results were corroborated by parallel determinations with the same coded samples in a second, separate laboratory using essentially identical metabololipidomic operational parameters. In these healthy subjects, two ω-3 supplementation protocols (Study A and Study B) temporally increased the SPM cluster throughout the endotoxin-challenge time course. Study A and Study B were randomized and Study B also had a crossover design with placebo and endotoxin challenge. Endotoxin challenge temporally regulated lipid mediator production in human serum, where pro-inflammatory eicosanoid (prostaglandins and thromboxane) concentrations peaked by 8 hours post-endotoxin and SPMs such as resolvins and lipoxins initially decreased by 2 h and were then elevated at 24 hours. In healthy adults given ω-3 supplementation, the plasma concentration of the SPM cluster (RvE1, RvD1, LXB4, 18-HEPE, and 17-HDHA) peaked at two hours post endotoxin challenge. These results from two separate laboratories with the same samples provide evidence for temporal production of specific pro-resolving mediators with ω-3 supplementation that together support the role of SPM in vivo in inflammation-resolution in humans.


[Intercellular reabsorption in the general systemic absorption of ethanol in the gastrointestinal tract].
Using the model of different ethanol concentration gradient between gastrointestinal tract (GIT) and blood of white mice, we analyzed kinetics of the intercellular transport of original compound and its metabolites (radioactive material). We showed that with intravenous administration 14C-ethanol (5 mmol/kg), its penetration into various divisions ofGIT (stomach, thin, thick, rectum) was observed. Creating a concentration gradient of ethanol by intravenous injection of ethanol (5 mmol/kg) and peroral intake (5, 10, 20 mmol/kg) led to a reduction in its intake into GIT, which was not entirely restricted under the laws of diffusion. Possible mechanisms for this phenomenon (insufficient gradient of ethanol concentrations in the blood-GIT, intrahepatic circulation, the residual radioactivity in the capillaries) are under discussion. The conclusion was made on possible reabsorption of ethanol in the process of its absorption in GIT.


The application of multiplex fluorimetric sensor for the analysis of flavonoids content in the medicinal herbs family Asteraceae, Lamiaceae, Rosaceae.
The aim of our research work was to quantify total flavonoid contents in the leaves of 13 plant species family Asteraceae, 8 representatives of family Lamiaceae and 9 plant species belonging to family Rosaceae, using the multiplex fluorimetric sensor. Fluorescence was measured using optical fluorescence apparatus Multiplex(R) 3 (Force-A, France) for non-destructive flavonoids estimation. The content of total flavonoids was estimated by FLAV index (expressed in relative units), that is deduced from flavonoids UV absorbing properties. Among observed plant species, the highest amount of total flavonoids has been found in leaves of Helianthus multiflorus (1.65 RU) and Echinops ritro (1.27 RU), Rudbeckia fulgida (1.13 RU) belonging to the family Asteraceae. Lowest flavonoid content has been observed in the leaves of marigold (Calendula officinalis) (0.14 RU) also belonging to family Asteraceae. The highest content of flavonoids among experimental plants of family Rosaceae has been estimated in the leaves of Rosa canina (1.18 RU) and among plant species of family Lamiaceae in the leaves of Coleus blumei (0.90 RU). This research work was done as pre-screening of flavonoids content in the leaves of plant species belonging to family Asteraceae, Lamiaceae and Rosaceae. Results indicated that statistically significant differences (P > 0.05) in flavonoids content were observed not only between families, but also among individual plant species within one family.


Elemental mercury concentrations and fluxes in the tropical atmosphere and ocean.
Air-sea exchange of elemental mercury (Hg(0)) is a critical component of the global biogeochemical Hg cycle. To better understand variability in atmospheric and oceanic Hg(0), we collected high-resolution measurements across large gradients in seawater temperature, salinity, and productivity in the Pacific Ocean (20°N-15°S). We modeled surface ocean Hg inputs and losses using an ocean general circulation model (MITgcm) and an atmospheric chemical transport model (GEOS-Chem). Observed surface seawater Hg(0) was much more variable than atmospheric concentrations. Peak seawater Hg(0) concentrations (∼ 130 fM) observed in the Pacific intertropical convergence zone (ITCZ) were ∼ 3-fold greater than surrounding areas (∼ 50 fM). This is similar to observations from the Atlantic Ocean. Peak evasion in the northern Pacific ITCZ was four times higher than surrounding regions and located at the intersection of high wind speeds and elevated seawater Hg(0). Modeling results show that high Hg inputs from enhanced precipitation in the ITCZ combined with the shallow ocean mixed layer in this region drive elevated seawater Hg(0) concentrations. Modeled seawater Hg(0) concentrations reproduce observed peaks in the ITCZ of both the Atlantic and Pacific Oceans but underestimate its magnitude, likely due to insufficient deep convective scavenging of oxidized Hg from the upper troposphere. Our results demonstrate the importance of scavenging of reactive mercury in the upper atmosphere driving variability in seawater Hg(0) and net Hg inputs to biologically productive regions of the tropical ocean.


Segmentation of polarimetric synthetic aperture radar data.
A statistical image model is proposed for segmenting polarimetric synthetic aperture radar (SAR) data into regions of homogeneous and similar polarimetric backscatter characteristics. A model for the conditional distribution of the polarimetric complex data is combined with a Markov random field representation for the distribution of the region labels to obtain the posterior distribution. Optimal region labeling of the data is then defined as maximizing the posterior distribution of the region labels given the polarimetric SAR complex data (maximum a posteriori (MAP) estimate). Two procedures for selecting the characteristics of the regions are then discussed. Results using real multilook polarimetric SAR complex data are given to illustrate the potential of the two selection procedures and evaluate the performance of the MAP segmentation technique. It is also shown that dual polarization SAR data can yield segmentation resultS similar to those obtained with fully polarimetric SAR data.


Lactococcus garvieae in wild Red Sea wrasse Coris aygula (Labridae).
Lactococcus garvieae infection in wild wrasse Coris aygula is reported, and the serological and molecular characteristics of the isolate are described. This is the first evidence of the presence of this pathogen in the Red Sea, and it follows the recent diagnosis of Mycobacterium marinum and Streptococcus iniae in wild fish from the same region. Whether all 3 pathogens are strains endemic to the Red Sea, or recent introductions into the region, remains to be determined, but their appearance over a period of a few years in wild fish populations in the northern Red Sea is consistent with an emerging trend affecting marine organisms on a global level in areas subjected to intense anthropogenic impacts.


Autism and mitochondrial disease.
Autism spectrum disorder (ASD) as defined by the revised Diagnostic and Statistical Manual of Mental Disorders: DSM IVTR criteria (American Psychiatric Association [2000] Washington, DC: American Psychiatric Publishing) as impairment before the age of 3 in language development and socialization with the development of repetitive behaviors, appears to be increased in incidence and prevalence. Similarly, mitochondrial disorders are increasingly recognized. Although overlap between these disorders is to be expected, accumulating clinical, genetic, and biochemical evidence suggests that mitochondrial dysfunction in ASD is more commonly seen than expected. Some patients with ASD phenotypes clearly have genetic-based primary mitochondrial disease. This review will examine the data linking autism and mitochondria.


Effect of dietary energy on digestibilities, rumen fermentation, urinary purine derivatives and serum metabolites in Tibetan and small-tailed Han sheep.
Tibetan sheep are indigenous to the Qinghai-Tibetan Plateau, graze the grassland all year round without supplementation and are well-adapted to the harsh conditions. Small-tailed Han sheep were introduced to the plateau and are raised mainly in feedlots. Based on their different backgrounds, we hypothesized that the ability to cope with poor diets would be better in Tibetan than in Han sheep. To test our prediction, we examined the effect of dietary energy on apparent digestibilities, rumen fermentation, urinary purine derivatives and serum metabolites by using a 4 × 4 Latin square design in each sheep breed. Four diets were formulated to be low in crude protein (~7%) but to differ in metabolizable energy concentration. Average daily gain was greater in Tibetan than in Han sheep (p < 0.01) and increased linearly with an increase in energy intake (p < 0.001). The digestibilities of dry matter, organic matter, gross energy, and neutral and acid detergent fibres were greater in Tibetan than in Han sheep (p < 0.05). Ruminal pH was lower (p < 0.05), while volatile fatty acids (VFAs), urea-N, ammonia-N and soluble protein-N concentrations were higher (p < 0.05) in Tibetan than in Han sheep. As a molar proportion of total VFA, acetate decreased (p < 0.001) with an increase in dietary energy whereas propionate and butyrate increased (p < 0.05). Urinary purine derivative excretion was greater in Tibetan than in Han sheep (p < 0.01), as was microbial nitrogen production; both parameters increased with dietary energy (p < 0.01). Serum concentrations of glucose, insulin and insulin-like growth factor-1 increased (p < 0.05) as energy level increased, while non-esterified fatty acids and growth hormone decreased (p < 0.05). It was concluded that Tibetan sheep were better able to cope with low-protein, low-energy diets and, consequently, our prediction was supported.


[Dietary behavior disorders: opinions and expectancies on prevention and treatment strategies from the perspective of the several social actors].
The prevalence increase of Eating Disorders in the last decades emphasizes the necessity to develop strategies from the public healthcare system which include the perspective of the principal implicated social actors. The present study aims to know their opinions and expectations regarding the prevention and treatment of Eating Disorders. Realization of 5 focus groups (with relatives, adolescents, professionals from the health and educational sector, representatives from institutions and support groups) and 14 semi-structured interviews (with Eating Disorder patients and relatives) about strengths and weaknesses of actual prevention and treatment programs, expectations of change and suggestions for improvement. Analysis of contents and triangulation of results. The absence of resources and knowledge about Eating Disorders, the scarcity of transversal programs and insufficient coordination were named as the main weaknesses whereas interdisciplinary pilot programs were positively valued. As principal demands, major endowment of human and material resources, increased coverage of specialized services, promotion of specific training and improvement of coordination was asked for. Regarding prevention, preference toward an unspecific approach to the subject in order to hinder imitation between young people was highlighted. The care in Day Hospitals was considered one of the most appropriate treatment modalities for the characteristics of this disease being valued the potentially therapeutic effect of contact between Eating Disorder patients. The support network, the education field and the family were named as other important pillars in a multidisciplinary approach to the disease. There was also a demand for the development of combined programs. The discussion of different psychotherapeutic approaches, the role of support groups in the caring network as well as the post-hospital follow-up were identified as issues open to future research.


DNA Damage, n-3 Long-Chain PUFA Levels and Proteomic Profile in Brazilian Children and Adolescents.
Fatty acids play a significant role in maintaining cellular and DNA protection and we previously found an inverse relationship between blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DNA damage. The aim of this study was to explore differences in proteomic profiles, for 117 pro-inflammatory proteins, in two previously defined groups of individuals with different DNA damage and EPA and DHA levels. Healthy children and adolescents (n = 140) aged 9 to 13 years old in an urban area of Brazil were divided by k-means cluster test into two clusters of DNA damage (tail intensity) using the comet assay (cluster 1 = 5.9% ± 1.2 and cluster 2 = 13.8% ± 3.1) in our previous study. The cluster with higher DNA damage and lower levels of DHA (6.2 ± 1.6 mg/dL; 5.4 ± 1.3 mg/dL, p = 0.003) and EPA (0.6 ± 0.2 mg/dL; 0.5 ± 0.1 mg/dL, p < 0.001) presented increased expression of the proteins CDK8-CCNC, PIK3CA-PIK3R1, KYNU, and PRKCB, which are involved in pro-inflammatory pathways. Our findings support the hypothesis that low levels of n-3 long-chain PUFA may have a less protective role against DNA damage through expression of pro-inflammatory proteins, such as CDK8-CCNC, PIK3CA-PIK3R1, KYNU, and PRKCB.


The psychologizing of Chinese healing practices in the United States.
This paper explores ways in which Chinese healing practices have undergone acculturation in the United States since the early 1970s. Reacting to what is perceived as biomedicine's focus on the physiological, those who describe themselves as favoring a holistic orientation often use the language of "energy blockage" to explain illness, whether thought of as "physical," "emotional," or "spiritual." Acupuncture in particular has been appropriated as one modality with which to "unblock" such conditions, leading to its being used by some practitioners in conjunction with more psychotherapeutic approaches which include valuing the verbalizing of feelings. Some non-Chinese practitioners in the United States, returning to older Chinese texts to develop "an American acupuncture," are reinserting diagnoses eliminated from Traditional Chinese Medicine (TCM) by the People's Republic of China as "superstition." The assumption has been that many such diagnostic categories refer to psychological or spiritual conditions, and therefore may be useful in those American contexts which favor this orientation. Among these categories are those drawn from traditions of demonology in Chinese medicine. What was once a religious category in China turns psychological in the American setting. At the same time, many who use these terms have, since the late 1960s, increasingly conflated the psychological and the religious, the latter being reframed as "spiritual." Thus, this indigenization of Chinese practices is a complex synthesis which can be described as simultaneously medical, psychotherapeutic, and religious.


Identification of retention strategies for neurosurgeons in Iran: Results from expert panels.
Background: The key challenge is how to encourage and retain health professionals in their work location. There is a list of policy options for this purpose but applying an appropriate and effective set of strategies requires a country level research. Our study aimed to identify retention strategies for neurosurgeons and examine both the importance and feasibility of the identified strategies using expert panels' point of view. Methods: First of all, a literature review was conducted to identify retention strategies for physicians. Then to gain consensus on the strategies and determine their importance and feasibility an expert panel was organized and a modified Delphi process was used. Results: A total of 40 strategies were identified by the panel classified in seven categories of income and economic factors, professional/job factors, clinical infrastructure, personal/family factors, living condition and welfare, educational factors and career development, governmental regulations and management policies. Conclusion: Based on the study results, three areas of economic incentives, personal and professional factors got the greatest priority in health professional planning for retention purposes.


Use of GPS ASHTECH Z12T receivers for accurate time and frequency comparisons.
The GPS phase measurements described in this paper were obtained using two similar multichannel GPS ASHTECH Z12T receivers belonging to the Bureau International des Poids et Mesures, BIPM, and the Laboratoire Primaire du Temps et des Frequences, BNM-LPTF. These receivers are based on the conventional geodetic ASHTECH Z12 unit, which has been modified to meet the stability requirements of time and frequency comparisons. Comparison of the two receivers operated side by side in different antenna configurations shows typical short-term noise of 1.1 to 3.5 ps. Longer term variations indicate a temperature sensitivity in the equipment, which limits the performance of the GPS phase method. One of the receivers was successfully operated using a temperature-stabilized antenna TSA from 3S Navigation, and the ASHTECH antenna, which feeds the second receiver, was placed in a home-built oven maintained at a constant temperature. These precautions made it possible to reduce a number of systematic effects. A separate study of frequency comparison was carried out between two hydrogen-masers located at the BNM-LPTF (Paris, France) and the PTB (Braunschweig, Germany) using receivers similar to ASHTECH Z12T receivers. The relative frequency stability obtained was about 3.3x10(-15) for an average time of 15 000 s, an interesting result comparable with the outstanding performance of new ultrastable frequency standards.


Beta-adrenergic receptor subtype is an intrinsic property of the receptor gene product.
The gene encoding the hamster beta-adrenergic receptor (beta AR) was expressed in mouse C6 glioma cells, a cell line which normally expressed the beta 1 subtype of the receptor. Upon transfection with the hamster beta AR gene, the cells expressed increased levels of beta AR, as assessed both by protein immunoblotting and by the binding of the radiolabeled antagonist 125I-cyanopindolol. This newly expressed receptor was of the beta 2 subtype, as determined with a variety of agonists and antagonists. These results suggest that the subtype of the beta AR is an intrinsic property of the gene product and is not the result of a post-translational modification of the receptor by the cell in which it is expressed.


Association of vascular endothelial growth factor and mast cells with angiogenesis in laryngeal squamous cell carcinoma.
We investigated the expression of vascular endothelial growth factor (VEGF) and microvascular density in 54 cases of invasive laryngeal squamous cell carcinoma (SCC) and in ten samples of normal laryngeal tissue using immunohistochemistry methods. The study also focused on the distribution of mast cells in and around the SCCs. The microvascular density in laryngeal carcinoma tissue was higher than that in normal tissue (P = 0.02). VEGF was localized in SCCs, stromal cells, endothelial cells, minor salivary glands, and non-cancer epithelium adjacent to the tumor. VEGF expression in the tumor cells was found in 13 of 54 cases (24.1%), whereas mast cells around the carcinomas were VEGF positive in all 54 cases. Staining of VEGF in SCCs was strong in the area of high microvascular density (P = 0.0002). Using a multi-labeling subtraction immunostaining method, VEGF-positive stromal cells were classified mostly as mast cells and, in a few instances, as macrophages. VEGF staining in SCCs was associated with the mast cell count (P = 0.0001). There was no distinct correlation between VEGF expression and pTNM stage of an SCC. In conclusion, the results suggest that VEGF might be an important angiogenic factor in cancer invasion. Laryngeal cancer cells and mast cells may control the angiogenic response by releasing VEGF.


Evaluation of Chinese medicinal herbs fingerprinting by HPLC-DAD for the detection of toxic aristolochic acids.
Aristolochic acids are known to contribute to various renal disorders; therefore, expanding the availability of analytical methodology to detect these compounds is important in order to assess the quality of Chinese herbal medicines in which they can be found. Twelve medicinal herbal samples were procured from various sources and extracted in duplicate prior to a "fingerprint" analysis using conventional HPLC-DAD. Multivariate analysis was performed on the entire chromatographed fingerprints. The resulting output was a partial least-square discriminant analysis model, which was able to evaluate the potential presence of aristolochic acids I and II as well as providing an individual herbal "fingerprint". The results of this study provide evidence that the presence of aristolochic acids contained within certain herbal extractions could be detected using a simple method, although some limitations apply to this method for quality control, since newly detected samples for aristolochic acid (positives) will need further confirmation with purity checks or MS hyphenation.


Priapus is happier with Venus than with Bacchus.
The relationship between alcohol consumption and erectile function is still not completely clarified. Aims of the present study are to explore a number of biological and clinical correlates of alcohol consumption in a sample of men consulting for sexual dysfunction, and to verify possible associations with the incidence of major adverse cardiovascular events (MACEs). A consecutive series of 1956 (mean age 55 ± 11.9 years old) attending our outpatient clinic for sexual dysfunction was retrospectively studied. A subset of the previous sample (N = 1687) was enrolled in a longitudinal study. Different clinical, biochemical, instrumental (penile Doppler ultrasound [PCDU]), and intrapsychic (Middlesex Hospital Questionnaire [MHQ]) were evaluated. We considered alcohol abuse more than three drinks per day. Among the patients studied 81% reported no or mild (<4 drinks/day) alcohol consumption whereas 14.3% and 3.9% declared a moderate (4-6 drinks/day) or severe (>6 drinks/day) alcohol abuse, respectively. After adjustment for confounders, both moderate or severe alcohol abuse was associated with low perceived partner's sexual desire, worse couple relationship, and smoking abuse. Furthermore, moderate and severe alcohol abuse was associated with low prolactin and thyroid-stimulating hormone levels, as well as an increase in triglycerides and total cholesterol levels. Penile blood flow was reduced in moderate and severe alcohol drinkers even after adjustment for confounders. In the longitudinal study, after adjusting for confounding factors, any kind of alcohol abuse was independently associated with a higher incidence of MACE (hazard ratio = 2.043 [1.059-3.943]; P < 0.0001). Our findings demonstrate that, in subjects consulting for erectile dysfunction, severe alcohol consumption is associated with a worse sexual function and a higher incidence of MACE.


Thyroid status, disability and cognitive function, and survival in old age.
Despite the equivocal outcomes of randomized controlled trials, general clinical opinion favors screening and treatment of elderly individuals with subclinical thyroid disorders. To determine whether subclinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age. A prospective, observational, population-based follow-up study within the Leiden 85-Plus Study of 87% of a 2-year birth cohort (1912-1914) in the municipality of Leiden, the Netherlands. A total of 599 participants were followed up from age 85 years through age 89 years (mean [SD] follow-up, 3.7 [1.4] years). Complete thyroid status at baseline; disability in daily life, depressive symptoms, cognitive function, and mortality from age 85 years through 89 years. Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life, depressive symptoms, and cognitive impairment at baseline or during follow-up. Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status. The hazard ratio (HR) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 (95% confidence interval [CI], 0.63-0.94; P = .009). The HR for mortality per SD increase of 0.21 ng/dL (2.67 pmol/L) of free thyroxine increased 1.16-fold (95% CI, 1.04-1.30; P = .009). In the general population of the oldest old, elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span. However, evidence for not treating elderly individuals can only come from a well-designed, randomized placebo-controlled clinical trial.


Design Optimization of a TOF, Breast PET Scanner.
A dedicated breast positron emission tomography (PET) scanner with limited angle geometry can provide flexibility in detector placement around the patient as well as the ability to combine it with other imaging modalities. A primary challenge of a stationary limited angle scanner is the reduced image quality due to artifacts present in the reconstructed image leading to a loss in quantitative information. Previously it has been shown that using time-of-flight (TOF) information in image reconstruction can help reduce these image artifacts arising due to missing angular projections. Our goal in this work is to optimize the TOF, breast scanner design by performing studies for estimating image uniformity and lesion activity uptake as a function of system timing resolution, scanner angular coverage and shape. Our results show that (i) 1.5 × 1.5 × 15 mm3 lutetium oxy-orthosilicate (LSO) crystals provide a high spatial resolution and system sensitivity relative to clinical scanners, (ii) 2/3 angular coverage scanner design with TOF timing resolution less than 600 ps is appropriate for providing a tomographic image with fewer artifacts and good lesion uptake estimation relative to other partial ring designs studied in this work, (iii) a flat scanner design with 2/3 angular coverage is affected more by larger parallax error than a curved scanner geometry with the same angular coverage, but provides more uniform lesion contrast estimate over the imaging field-of-view (FOV), (iv) 2/3 angular coverage, flat, 300 ps TOF scanner design (for short, practical scan times of ≤ 5 mins per breast) provides similar precision of contrast recovery coefficient (CRC) values to a full curved, non-TOF scanner, and (v) employing depth-of-interaction (DOI) measuring detector and/or implementing resolution modeling (RM) in image reconstruction lead to improved and more uniform spatial resolution and lesion contrast over the whole FOV.


Ultrasound-modulated optical imaging using a powerful long pulse laser.
Ultrasound-modulated optical imaging (or tomography) is an emerging biodiagnostic technique which provides the optical spectroscopic signature and the localization of an absorbing object embedded in a strongly scattering medium. We propose to improve the sensitivity of the technique by using a pulsed single-frequency laser to raise the optical peak power applied to the scattering medium and thereby collect more ultrasonically tagged photons. Moreover, when the detection of tagged photons is done with a photorefractive interferometer, the high optical peak power reduces the response time of the photorefractive crystal below the speckle field decorrelation time. Results obtained with a GaAs photorefractive interferometer are presented for 30- and 60-mm thick scattering media.


The effects of chronic levodopa treatments on the neuronal firing properties of the subthalamic nucleus and substantia nigra reticulata in hemiparkinsonian rhesus monkeys.
Dopamine replacement therapy with levodopa (LD) is currently the most effective pharmacological treatment for Parkinson's disease (PD), a neurodegenerative disorder characterized by dysfunction of basal ganglia electrophysiology. The effects of chronic LD treatments on the electrophysiological activity of the subthalamic nucleus (STN) and the substantia nigra reticulata (SNR) in parkinsonism are not clear. In the present study we examined the effects of chronic LD treatments on the firing rate and firing pattern of STN and SNR neurons in the stable hemiparkinsonian monkey model of PD. We also evaluated local field potentials of both nuclei before and after LD treatments. In a stable hemiparkinsonian state, STN and SNR had a mean firing rate of 42.6 ± 3.5H z (mean ± SEM) and 52.1 ± 5.7 Hz, respectively. Chronic intermittent LD exposure induced marked amelioration of parkinsonism with no apparent drug-induced motor complications. LD treatments did not significantly change the mean firing rate of STN neurons (41.3 ± 3.3 Hz) or bursting neuronal firing patterns. However, LD treatments induced a significant reduction of the mean firing rates of SNR neurons to 36.2 ± 3.3 Hz (p<0.05) and a trend toward increased burstiness. The entropy of the spike sequences from STN and SNR was unchanged by LD treatment, while there was a shift of spectral power into higher frequency bands in the LFPs. The inability of chronic LD treatments to reduce the bursty firing patterns in the STN and SNR should be further examined as a potential pathophysiological mechanism for PD symptoms that are refractory to LD treatments.


Design Optimization of a Gas Turbine Engine for Marine Applications: Off-Design Performance and Control System Considerations.
This paper addresses a design optimization of a gas turbine (GT) for marine applications. A gain-scheduling method incorporating a meta-heuristic optimization is proposed to optimize a thermodynamics-based model of a small GT engine. A comprehensive control system consisting of a proportional integral (PI) controller with additional proportional gains, gain scheduling, and a min-max controller is developed. The modeling of gains as a function of plant variables is presented. Meta-heuristic optimizations, namely a genetic algorithm (GA) and a whale optimization algorithm (WOA), are applied to optimize the designed control system. The results show that the WOA has better performance than that of the GA, where the WOA exhibits the minimum fitness value. Compared to the unoptimized gain, the time to reach the target of the power lever angle is significantly reduced. Optimal gain scheduling shows a stable response compared with a fixed gain, which can have oscillation effects as a controller responds. An effect of using bioethanol as a fuel has been observed. It shows that for the same input parameters of the GT dynamics model, the fuel flow increases significantly, as compared with diesel fuel, because of its low bioethanol heating value. Thus, a significant increase occurs only at the gain that depends on the fuel flow.


Vanadium metabolism in sheep. III. Influence of dietary vanadium on kinetics of 48V administered orally or intravenously and comparison of compartmental and graphical models.
Radiotracer techniques were used to investigate the influence of dietary stable V on the excretion, distribution and blood clearance kinetics of 48V in 14 rams averaging 58 kg body weight. Rams were fed a basal diet with added levels of 0, 50 or 200 mg/kg V as NH4 VO3 for 25 wk before either oral or iv administration of the isotope. A three-compartment model was determined by graphical logarithmic analysis of blood disappearance data from iv-dosed rams and compared with a simultaneous multicompartment model, which made it possible to ascribe physiological processes to the components of the graphical model. The principal route of excretion of 48V administered iv was via urine, whereas the isotope given orally was excreted almost entirely by way of feces, resulting in low tissue and urinary 48V levels. Increasing dietary V increased (P less than .05) the percentage of dose excreted in urine regardless of dosing route, but dietary V had no effect on 48V excreted in feces. Stable dietary V had no effect on blood clearance rates of orally or iv-dosed rams. Dietary V addition decreased 48V concentration in kidney (P less than .01), liver, spleen, testes and muscle (P less than .05) of iv-dosed rams, but had no effect in rams dosed orally. Kidney, bone, liver and spleen retained the highest levels of 48V activity 144 h after dosing. Dietary V appeared to have a minimal effect on V kinetics in rams.


Intraoperative ultrasonographic evaluation of the ascending aorta in 100 consecutive patients undergoing cardiac surgery.
Dislodgement of atheromatous plaque from the ascending aorta following manipulation is one of the principal causes of stroke following cardiac surgery. To define clinical correlates that predict the presence of severe atherosclerosis, we performed ultrasonographic evaluation of the ascending aorta at the time of cardiac surgery in 100 consecutive patients. The ascending aorta was divided into three equal segments for analysis, and the severity of atherosclerosis was determined as mild when intimal thickening (less than 3 mm) was localized to one segment, moderate when intimal thickening (greater than 3 mm) was present in one or two segments, and severe when intimal thickening (greater than 3 mm) was present throughout the entire circumference in all three segments. Thirty-eight percent of the studies were normal, mild atherosclerosis was present in 33%, moderate atherosclerosis in 19%, and severe atherosclerosis in 10% of the patients. Palpation of the ascending aorta to detect atherosclerosis significantly underestimated the presence (p less than 0.001) and severity (p less than 0.001) of atherosclerosis when compared with ultrasonography. Age, carotid artery disease, diabetes, gender, smoking, and hypertension were evaluated for their ability to discriminate between normal and severely atherosclerotic aortas. Stepwise logistic regression analysis showed age (p less than 0.02) and diabetes (p less than 0.04) to be significant independent predictors of the presence of severe atherosclerosis in the ascending aorta. Based on the ultrasonographic findings, the operative procedure was altered to reduce the risk of embolization in 17% of the patients. We conclude that high-resolution images of the ascending aorta for identification of atherosclerosis can be obtained by ultrasonography.(ABSTRACT TRUNCATED AT 250 WORDS)


Inverse association between air pressure and rheumatoid arthritis synovitis.
Rheumatoid arthritis (RA) is a bone destructive autoimmune disease. Many patients with RA recognize fluctuations of their joint synovitis according to changes of air pressure, but the correlations between them have never been addressed in large-scale association studies. To address this point we recruited large-scale assessments of RA activity in a Japanese population, and performed an association analysis. Here, a total of 23,064 assessments of RA activity from 2,131 patients were obtained from the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Detailed correlations between air pressure and joint swelling or tenderness were analyzed separately for each of the 326 patients with more than 20 assessments to regulate intra-patient correlations. Association studies were also performed for seven consecutive days to identify the strongest correlations. Standardized multiple linear regression analysis was performed to evaluate independent influences from other meteorological factors. As a result, components of composite measures for RA disease activity revealed suggestive negative associations with air pressure. The 326 patients displayed significant negative mean correlations between air pressure and swellings or the sum of swellings and tenderness (p = 0.00068 and 0.00011, respectively). Among the seven consecutive days, the most significant mean negative correlations were observed for air pressure three days before evaluations of RA synovitis (p = 1.7 × 10(-7), 0.00027, and 8.3 × 10(-8), for swellings, tenderness and the sum of them, respectively). Standardized multiple linear regression analysis revealed these associations were independent from humidity and temperature. Our findings suggest that air pressure is inversely associated with synovitis in patients with RA.


Exploring the role of telehealth: A novel approach to group-based smoking cessation treatment for men incarcerated in a rural state prison.
Tobacco smoking remains an important public health issue in the United States (US), specifically among people who are incarcerated. There is little to no information about smoking behaviors of incarcerated people in rural areas and there is a lack of resources for smoking cessation interventions in rural settings. Telehealth might be efficient for delivering care to incarcerated people in rural areas. The purpose of this study was to determine the feasibility of delivering group-based smoking cessation treatment via telehealth to incarcerated male smokers in a rural prison. A 6-week group-based smoking cessation treatment program was conducted with 1-month follow up. Video conferencing was used from Weeks 2-5 to deliver treatment. A cross-sectional survey was administered collecting measures including criminal justice experience, smoking behaviors, withdrawal and triggers, mental health, physical health, and substance use. Baseline exhaled carbon monoxide (CO) levels were collected at Session 1, and a final CO level at Session 6 and 1-month follow-up. Twenty (n = 20) incarcerated male smokers were recruited from a rural prison facility. The majority of the inmates were White (85%). Approximately, 80% of the inmates smoked about 20 or more cigarettes per day, and on average smoked for 28 years (SD = 9). Most inmates scored a moderate or high dependence score on the Fagerström Test for Nicotine Dependence. Telehealth programs such as video conferencing smoking cessation treatment ought to be implemented to reduce tobacco-related disparities among incarcerated smokers housed in rural prisons.


Comparative analysis of the site-specific N-glycosylation of human lactoferrin produced in maize and tobacco plants.
We have compared the site-by-site N-glycosylation status of human lactoferrin (Lf) produced in maize, a monocotyledon, and in tobacco, used as a model dicotyledon. Maize and tobacco plants were stably transformed and recombinant Lf was purified from both seeds and leaves. N-glycopeptides were generated by trypsin digestion of recombinant Lf and purified by reverse-phase HPLC. The N-glycosylation pattern of each site was determined by mass spectrometry. Our results indicated that the N-glycosylation patterns of recombinant Lf produced in maize and tobacco share common structural features. In particular, both N-glycosylation sites of each recombinant Lf are mainly substituted by typical plant paucimannose-type N-glycans, with beta1,2-xylose and alpha1,3-linked fucose at the proximal N-acetylglucosamine. However, tobacco Lf shows a significant amount of processed N-glycans with one or two beta1,2GlcNAc linked to the trimannose core, which are weakly expressed in maize Lf. Finally, no Lewisa epitope was observed on tobacco Lf.


Effect of molten sodium nitrate on the decomposition pathways of hydrated magnesium hydroxycarbonate to magnesium oxide probed by in situ total scattering.
The effect of NaNO3 and its physical state on the thermal decomposition pathways of hydrated magnesium hydroxycarbonate (hydromagnesite, HM) towards MgO was examined by in situ total scattering. Pair distribution function (PDF) analysis of these data allowed us to probe the structural evolution of pristine and NaNO3-promoted HM. A multivariate curve resolution alternating least squares (MCR-ALS) analysis identified the intermediate phases and their evolution upon the decomposition of both precursors to MgO. The total scattering results are discussed in relation with thermogravimetric measurements coupled with off-gas analysis. MgO is obtained from pristine HM (N2, 10 °C min-1) through an amorphous magnesium carbonate intermediate (AMC), formed after the partial removal of water of crystallization from HM. The decomposition continues via a gradual release of water (due to dehydration and dehydroxylation) and, in the last step, via decarbonation, leading to crystalline MgO. The presence of molten NaNO3 alters the decomposition pathways of HM, proceeding now through AMC and crystalline MgCO3. These results demonstrate that molten NaNO3 facilitates the release of water (from both water of crystallization and through dehydroxylation) and decarbonation, and promotes the crystallization of MgCO3 and MgO in comparison to pristine HM. MgO formed from the pristine HM precursor shows a smaller average crystallite size than NaNO3-promoted HM and preserves the initial nano-plate-like morphology of HM. NaNO3-promoted HM was decomposed to MgO that is characterized by a larger average crystallite size and irregular morphology. Additionally, in situ SEM allowed visualization of the morphological evolution of HM promoted with NaNO3 at a micrometre scale.


Metastatic breast carcinoma presenting as unilateral pulsatile tinnitus: a case report.
Pulsatile tinnitus is a rare symptom, yet it may herald life-threatening pathology in the absence of other symptoms or signs. Pulsatile tinnitus tends to imply a vascular cause, but metastatic disease also can present in this way. Clinicians should therefore adopt a specific diagnostic algorithm for pulsatile tinnitus and always consider the possibility of metastatic disease. A history of malignant disease and new cranial nerve palsies should raise clinical suspicion for skull base metastases. We describe the case of a 63-year-old woman presenting with unilateral subjective pulsatile tinnitus and a middle ear mass visible on otoscopy. Her background included the diagnosis of idiopathic unilateral vagal and hypoglossal nerve palsies 4 years previously, with normal magnetic resonance imaging (MRI). Repeat MRI and computed tomography imaging were consistent with metastatic breast carcinoma. This case raises important questions about imaging protocols and the role of serial scanning in patients at high risk of metastatic disease.


Kinetic properties of intramembrane charge movement under depolarized conditions in frog skeletal muscle fibers.
Intramembrane charge movement was measured on skeletal muscle fibers of the frog in a single Vaseline-gap voltage clamp. Charge movements determined both under polarized conditions (holding potential, VH = -100 mV; Qmax = 30.4 +/- 4.7 nC/micro(F), V = -44.4 mV, k = 14.1 mV; charge 1) and in depolarized states (VH = 0 mV; Qmax = 50.0 +/- 6.7 nC/micro(F), V = -109.1 mV, k = 26.6 mV; charge 2) had properties as reported earlier. Linear capacitance (LC) of the polarized fibers was increased by 8.8 +/- 4.0% compared with that of the depolarized fibers. Using control pulses measured under depolarized conditions to calculate charge 1, a minor change in the voltage dependence (to V = -44.6 mV and k = 14.5 mV) and a small increase in the maximal charge (to Qmax = 31.4 +/- 5.5 nC/micro(F] were observed. While in most cases charge 1 transients seemed to decay with a single exponential time course, charge 2 currents showed a characteristic biexponential behavior at membrane potentials between -90 and -180 mV. The voltage dependence of the rate constant of the slower component was fitted with a simple constant field diffusion model (alpha m = 28.7 s-1, V = -124.0 mV, and k = 15.6 mV). The midpoint voltage (V) was similar to that obtained from the Q-V fit of charge 2, while the steepness factor (k) resembled that of charge 1. This slow component could also be isolated using a stepped OFF protocol; that is, by hyperpolarizing the membrane to -190 mV for 200 ms and then coming back to 0 mV in two steps. The faster component was identified as an ionic current insensitive to 20 mM Co2+ but blocked by large hyperpolarizing pulses. These findings are consistent with the model implying that charge 1 and the slower component of charge 2 interconvert when the holding potential is changed. They also explain the difference previously found when comparing the steepness factors of the voltage dependence of charge 1 and charge 2.


Binding of the general anesthetics propofol and halothane to human serum albumin. High resolution crystal structures.
Human serum albumin (HSA) is one of the most abundant proteins in the circulatory system and plays a key role in the transport of fatty acids, metabolites, and drugs. For many drugs, binding to serum albumin is a critical determinant of their distribution and pharmacokinetics; however, there have as yet been no high resolution crystal structures published of drug-albumin complexes. Here we describe high resolution crystal structures of HSA with two of the most widely used general anesthetics, propofol and halothane. In addition, we describe a crystal structure of HSA complexed with both halothane and the fatty acid, myristate. We show that the intravenous anesthetic propofol binds at two discrete sites on HSA in preformed pockets that have been shown to accommodate fatty acids. Similarly we show that the inhalational agent halothane binds (at concentrations in the pharmacologically relevant range) at three sites that are also fatty acid binding loci. At much higher halothane concentrations, we have identified additional sites that are occupied. All of the higher affinity anesthetic binding sites are amphiphilic in nature, with both polar and apolar parts, and anesthetic binding causes only minor changes in local structure.


Psychogenic nonepileptic seizures during the COVID-19 pandemic in New York City - A distinct response from the epilepsy experience.
Although psychogenic nonepileptic seizures (PNES) are a common neurologic condition, there remains a paucity of literature on the COVID-19 pandemic's effect on these patients. Using a cross-sectional questionnaire study, our group examined the experience of patients with PNES at a single Comprehensive Epilepsy Center in New York City, the epicenter of the initial COVID-19 outbreak in the United States. Among our cohort of 18 subjects with PNES, 22.2% reported an improvement in seizure control during the peak of the COVID-19 pandemic in New York City. Compared to the cohort of subjects with epilepsy without PNES, subjects with PNES were significantly more likely to report an improvement (p = 0.033). Our findings signal that sleep and stress may be relevant variables in both conditions that should be further investigated and potentially intervened upon. Larger dedicated studies of patients with PNES are needed to understand the impact of the pandemic's widespread societal effects on these patients.


Characterization and prevalence of the different mechanisms of resistance to beta-lactam antibiotics in clinical isolates of Escherichia coli.
A survey of clinical isolates from a hospital laboratory showed that Escherichia coli could be grouped into three classes of beta-lactam-antibiotic resistance by results of routine susceptibility testing to ampicillin, cephalothin, and carbenicillin. E. coli highly resistant to ampicillin and carbenicillin but not to cephalothin (class I) were found to have one of two levels of R factor-mediated, periplasmic-beta-lactamase which resembled R(TEM) and was located behind a permeability barrier to penicillins but not to cephalosporins. This permeability barrier appeared to act synergistically with the beta-lactamase in producing high levels of resistance to penicillins. E. coli highly resistant to ampicillin and cephalothin but not carbenicillin (class II) were found to have a beta-lactamase with predominantly cephalosporinase activity which was neither transferable nor releasable by osmotic shock. E. coli moderately resistant to one or to all three of these antibiotics (class III) were found to have low levels of different beta-lactamases including a transferable beta-lactamase which resembled R(1818). Thus, different mechanisms producing resistance to beta-lactam antibiotics could be deduced from the patterns of resistance to ampicillin, cephalothin, and carbenicillin found on routine susceptibility testing. E. coli of class I were much more prevalent than the other classes and the proportion of E. coli that were class I increased with duration of patient hospitalization. The incidence of class I E. coli rose only slightly over the past 7 years and that of class II E. coli remained constant despite increased usage of both cephalothin and ampicillin. These observations emphasize that the properties of the apparently limited number of individual resistance mechanisms that exist in a bacterial flora, such as their genetic mobility and linkages and the spectrum of their antibiotic inactivating enzymes and permeability barriers, may govern the effect that usage of an antibiotic has upon the prevalence of resistance to it and to other antibiotics.


Examining the rural-urban differentials in yoga and mindfulness practices among middle-aged and older adults in India: secondary analysis of a national representative survey.
Physical activity and mental well-being play an important role in reducing the risk of various diseases and in promoting independence among older adults. Appropriate physical activity, including yoga and mindfulness practices, can help rectify the loss of independence due to aging and have a positive influence on physical health and functional activities. This study assessed rural-urban differences in yoga and mindfulness practices and their associated factors among middle-aged and older Indian adults. The total sample size considered for the current analysis was 72,250 middle-aged and older adults (aged ≥ 45 years). Bivariate and multivariable logistic regression analyses were used to estimate the prevalence of yoga and mindfulness practices and examine the associations of selected variables with yoga and mindfulness practices among the participants. Further, we used the Fairley decomposition technique to determine the factors contributing to rural-urban differences in the prevalence of yoga and mindfulness practices among middle-aged and older adults. More than 9% of middle-aged and older adults in rural areas and 14% in urban areas reported practicing yoga and mindfulness activities more than once per week. Adults aged ≥ 65 years were more likely to practice yoga and mindfulness activities than those who age 45-54 years were. Those with an education of ten years and above were 2.3 and 2.1 times higher likely to practice yoga in rural (AOR: 2.28; CI: 2.07-2.52) and urban (AOR: 2.13; CI: 1.91-2.37) areas compared to their uneducated peers, respectively. The largest contributors in diminishing the gap in yoga practice among participants were education (44.2%), caste (2.5%), chronic diseases such as hypertension (4.53%), diabetes (1.71%), high cholesterol (3.08%), self-reported pain (5.76%), and difficulties in instrumental activities of daily living (1.22%). The findings suggest that middle-aged and older adults in urban areas practice yoga and mindfulness activities more than their peers in rural areas do. Education level, household characteristics, and health outcomes such as chronic conditions, pain, and functional difficulties explain the observed differences in yoga and mindfulness practices across rural and urban areas. Age-appropriate healthy practices such as yoga and mindfulness should be encouraged to enhance the physical and mental well-being of middle-aged and older adults, especially in rural areas.


A case of major form familial hyperekplexia: prenatal diagnosis and effective treatment with clonazepam.
Hyperekplexia (OMIM 149400) is an uncommon neurologic disorder characterized by exaggerated response to sensitive stimuli. It may be sporadic or familial. The disease is usually caused by mutations in the inhibitory glycine receptor alpha1-subunit. The authors report a male patient who is affected by the major form of familial hyperekplexia. He is currently 5 years old and is being successfully treated with clonazepam. Prenatal diagnosis was made owing to prior identification of point mutation K276E in his affected mother. Early diagnosis avoided complex and prolonged differential diagnostic procedures and allowed for early and effective intervention on severe neonatal symptoms: hypertonia, episodes of cyanosis, apneic spells, and massive myoclonic jerks. During his first year of life, the patient was treated with cycles of phenobarbital and diazepam and achieved partial clinical response. Subsequent therapy with low-dose clonazepam was highly effective in reducing myoclonic jerks and exaggerated startle reaction, and unlike previously used drugs, it was decisive in reducing hypertonia.


Monitoring cell detachment by surfactants in a parallel plate flow chamber.
The efficacy of the surfactants SDS and CTAB in detaching P. fluorescens from glass surface was evaluated in a parallel plate flow chamber. This device enables "in situ" determinations of cells detachment following the application of surfactants under well controlled hydrodynamic conditions. The results showed that SDS was able to remove almost all adhering bacteria in a short period of time, whereas CTAB did not promote much cell desorption. On the contrary, this surfactant increased the adhesion strength between cells and glass. Both surfactants promoted different alterations of cell surface properties, which explain their dissimilar effectiveness as cleansing agents.


Photoassociation spectroscopy of cold He(2 3S) atoms
We observe vibrational states by photoassociation spectroscopy of cold He(2 3S) atoms. Photoassociation resonances are detected as peaks in the Penning ionization rate over a frequency range of 20 GHz below the atomic 2 3S1-2 3P2 transition frequency. We have observed three vibrational series, of which two can be identified. A possible mechanism to explain the observed increase of the Penning ionization rate is discussed.


Thymidylate synthase, thymidine phosphorylase, VEGF and p53 protein expression in primary colorectal cancer for predicting response to 5-fluorouracil-based chemotherapy.
In the treatment of advanced metastatic colorectal cancer, several new agents, such as irinotecan and oxaliplatin, have been developed, which have improved both disease free and overall survivals. Among these agents, 5-fluorouracil (5-FU) still remains one of the most active agents, and the selection of patients who can benefit from 5-FU-based chemotherapy is still important, as those unlikely to benefit could be spared the harmful side effects. The expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and p53 have been known to be associated with the clinical response to 5-FU-based therapy as well as the prognosis, and that of vascular endothelial growth factor (VEGF) is associated with poor survival. The relationship between the expressions of TS, TP, VEGF and p53 in primary tumors, using immunohistochemistry, and the response of 45 metastatic colorectal cancer patients (M:F=25:20, median age 59 yrs) to 5-FU-based chemotherapy were evaluated. Thirty-seven patients were treated with 5-FU/LV/irinotecan (FOLFIRI) and 8 with 5-FU/LV/oxaplatin (FOLFOX). The overall response rate was 28.9% (13/45). When immunohistochemically analyzed with monoclonal antibodies against TS, TP, VEGF and p53, 55.6% of the patients (25/45) were positive for TS, 48.9% (22/45) for TP, 82.2% (37/45) for VEGF, and 80% (36/45) for p53. There was a significant difference in the intensity of TS expression between the clinical responders and non-responders (p=0.036). In terms of the staining pattern of TS expression, diffuse staining was correlated with a poor response (p=0.012) and poor survival (p=0.045). However, there was no correlation between the expressions of TP, VEGF or P53 and the response to chemotherapy. These results suggest that the expression of TS in primary colorectal cancer might be an important prognostic factor for chemotherapy response and survival, and might be a useful therapeutic marker for the response of chemotherapy.


Barriers to healthy eating in Switzerland: A nationwide study.
Several barriers can hinder healthy eating in the population. We aimed to assess the prevalence of self-reported barriers to healthy eating in Switzerland and examine their socioeconomic and demographic determinants. Using representative cross-sectional data from the Swiss Health Survey 2012, we assessed, separately by gender, the prevalence of ten barriers and their association with demographic and socioeconomic determinants; we used age- and multivariable-adjusted logistic regression and report the odds ratio for likelihood to identify each barrier according to each demographic and socioeconomic determinant. The most prevalent barriers were "price" (43.2% in women, 35.8% in men), "daily habits, constraints" (39.8%, 37.5%), "fondness of good food" (38.8%, 51.0%), "time constraint" (34.8%, 29.0%) and "lack of willpower" (22.0%, 21.2%). Prevalence of most barriers decreased with age, increased for "fondness of good food" and remained constant for "price." After multivariable adjustment, obese participants were more likely to report "fondness of good food" [Odds ratio (95% confidence interval) for obese vs. normal weight women and men, respectively: 1.63 (1.38-1.91), 2.02 (1.72-2.38)]. Participants with lower education were more likely to report "fondness of good food" [mandatory vs. tertiary women and men, respectively: 1.93 (1.62-2.39), 1.51 (1.26-1.81)], but less likely to report "lack of willpower" [0.45 (0.38-0.55), 0.40 (0.33-0.49)] and "time constraint" [0.61 (0.51-0.73), 0.78 (0.63-0.96)]. Participants with lower income were more likely to report "price" [lowest vs. highest quartile for women and men, respectively, 1.65 (1.43-1.90), 1.47 (1.26-1.71)] but less likely to report "lack of willpower" [0.71 (0.61-0.82), 0.40 (0.33-0.49)]. Smoking, living situation, nationality and living area showed little or no association. Several barriers to healthy eating were highly prevalent regardless of gender; the most important determinants were age, obesity, education, and income, with different effects per barrier. This requires multifaceted interventions to tackle several barriers simultaneously.


Influence of pharmacological manipulation of inhibitory and excitatory neurotransmitter systems on seizure behavior in the Mongolian gerbil.
The purpose of this paper was to study the relationship between different neurotransmitter systems and seizure susceptibility in Mongolian gerbils with genetically determined epilepsy. In these animals, generalized tonic-clonic seizures were induced by stimulation with a blast of compressed air. A variety of drugs that specifically manipulate inhibitory or excitatory neurotransmitter systems proved capable of dose dependently blocking these seizures, i.e., the anticholinergic drug biperiden (ED50 12 mg/kg i.p.), the excitatory amino acid antagonist (+/-)-2-amino-7-phosphonoheptanoic acid (120 mg/kg), the gamma-aminobutyric acid (GABA) agonists muscimol (0.66 mg/kg), 4,5,6,7-tetrahydroisoxazolo(5,4-c) pyridine-3-ol (1.3 mg/kg), progabide (50 mg/kg) and its acidic metabolite SL 75102 (45 mg/kg), the GABA aminotransferase inhibitors aminooxyacetic acid (0.9 mg/kg), gamma-acetylenic GABA (2.1 mg/kg) and ethanolamine-O-sulfate (1000 mg/kg), the GABA uptake inhibitor (-)-nipecotic acid ethyl ester (21 mg/kg), the dopamine agonist apomorphine (approximately 5 mg/kg), the dopamine precursor 3,4-dihydroxy-L-phenylalanine (34 mg/kg), and the alpha-adrenoceptor agonists clonidine (0.38 mg/kg) and xylazine (approximately 10 mg/kg). The anticonvulsant effect of 3,4-dihydroxyl-L-phenylalanine was not significantly affected by pretreatment with the dopamine-beta-hydroxylase inhibitors disulfiram and diethyldithiocarbamate, thus strongly indicating that 3,4-dihydroxyl-L-phenylalanine was acting through increase in dopamine rather than noradrenaline levels in the brain. The (+)-isomer of nipecotic acid ethyl ester, the glycineamide derivative milacemide, the indirect 5-hydroxytryptamine agonist fenfluramine and the 5-hydroxytryptamine antagonist ketanserin exerted no anticonvulsant action. The 5-hydroxytryptamine precursor L-5-hydroxytryptophan and the dopamine agonist lisuride were only weakly active but exerted pronounced side effects in the animals. Weak anticonvulsant effects were also determined for atropine, the noradrenaline precursor DL-threo-3,4-dihydroxyphenylserine and the excitatory amino acid antagonist (+/-)-2-amino-5-phosphonopentanoic acid. Comparison of anticonvulsant potencies of the various drugs in gerbils with potencies reported in other genetic animal models of epilepsy, such as audiogenic seizure-susceptible mice, indicated that drugs that increase GABA and dopamine levels in the brain are strikingly more effective in gerbils than in other species in blocking generalized seizures.(ABSTRACT TRUNCATED AT 400 WORDS)