Cucurbitacin B Diminishes Metastatic Behavior of Cholangiocarcinoma Cells by Suppressing Focal Adhesion Kinase.
Cholangiocarcinoma (CCA) is a malignant tumor with aggressive metastatic property resulted from dysregulation of metastasis-regulated signaling pathways. The aim of this study was to investigate the effect of cucurbitacin B on metastatic behavior of CCA cells through modulation of focal adhesion kinase (FAK) protein. KKU-452 cells were treated with a specific FAK inhibitor, FAK inhibitor-14, or cucurbitacin B at various concentrations for 24 h. Cell viability was assessed by sulforhodamine B assay. The migratory and invasive abilities of the cells were investigated using wound healing and transwell invasion assays, respectively. The fibronectin-coated plate was used for adhesion assay. The effects of the test compounds on FAK activation and the expression of metastasis-associated proteins were determined by Western blot analysis. The amount of MMP-9 was evaluated using a commercial ELISA Kit. FAK inhibitor-14 and cucurbitacin B at concentrations which minimally affected KKU-452 cell viability could suppress FAK activation, evidently by decreased level of phospho-FAK protein after exposure to the compound. At these conditions, cucurbitacin B suppressed metastatic behavior including migration, invasion and adhesion abilities of CCA cells similar to FAK inhibitor-14. Further molecular studies demonstrated that FAK inhibitor-14 and cucurbitacin B downregulated the expression of metastasis-associated proteins including MMP-9, ICAM-1 and VEGF. Consequently, exposure to cucurbitacin B inhibited the production of MMP-9 enzyme in CCA cells similar to FAK inhibitor-14 treatment. FAK participated in regulation of metastatic behavior of KKU-452 CCA cells. Cucurbitacin B suppressed FAK activation in the cells which was associated with inhibition of metastasis essential steps and their related metastatic proteins. The compound may be developed as a novel therapeutic agent for CCA metastasis therapy.<br />.


Effectiveness of an 8-Week Aerobic Exercise Program on Autonomic Function in People Living with HIV Taking Anti-Retroviral Therapy: A Pilot Randomized Controlled Trial.
This study assessed the effectiveness of an 8-week aerobic exercise program on heart rate variability (HRV) in people living with HIV taking antiretroviral therapy. Twenty-six participants were randomly assigned to a control group or an aerobic exercise group. Resting HRV was measured for 5 min in supine position using an electrocardiogram. Estimated maximal oxygen uptake (VO2max) was assessed through a treadmill 6-min walk test. The training program consisted of aerobic exercise thrice per week at 65%-75% of heart rate max for 45 min per session. Repeated measures ANOVA was used to test for differences between groups, and Spearman's rho was used to assess for the correlation between HRV measures and estimated VO2max. There was no significant group by time interactions for any of the HRV indices. However, the standard deviation of normal-to-normal (NN) R-R intervals increased significantly in the aerobic exercise group (pre: 46.97 ± 32.70 ms vs. post: 59.49 ± 37.20 ms, p = .045). There was a strong correlation between the VO2max and the standard deviation of NN intervals (SDNN) (r = 0.617; p = .002). There was a moderate correlation between VO2max and the square root of the mean squared differences of successive normal-to-normal intervals (rMSSD) (r = 0.424; p = .049), the low frequency power (r = 0.506; p = .016), and the standard deviation of differences between successive differences of normal-to-normal intervals (SDSD) (r = 0.424; p = .049). While differences in HRV were not observed between groups, our data suggest that overall autonomic function can improve across time with aerobic exercise, and these changes are associated with greater levels of VO2max. These results advocate the importance of improvements in HRV given their association with lower risk of cardiovascular disease and mortality.


Actin-related proteins in Anabaena spp. and Escherichia coli.
Actin has been described in all eukaryotic cells as the major microfilament cytoskeletal protein. Although prokaryotic cells do not have a cytoskeleton, proteins related to the latter have been found in different prokaryotic species. We have found prokaryotic actin-related proteins in the enterobacterium Escherichia coli and in the cyanobacteria Anabaena cylindrica and Anabaena variabilis. They were identified by the following criteria: (1) by cross-reaction with a fluorescent conjugated anti-actin (rat-brain) mAb by Western blot analysis (in total cellular extracts); (2) specific binding of acetone powder and soluble cellular extracts to DNase I; and (3) specific binding of cells and total cellular extracts to phalloidin. In E coli, specific binding of phalloidin labelled with rhodamine to cells was detected by spectrofluorometry. In total cellular extracts, three bands of 60, 43 and 35 kDa were weakly recognized by the mAb by Western blot analysis; this recognition increased when phalloidin was added to the extracts. Furthermore, three polypeptides of kDa were isolated by binding to DNase I, showing pI values of 6.7, 6.65 and 6.6, less acidic than all reported actin pI values. In A. cylindrica and A. variabilis, specific binding of phalloidin labelled with rhodamine to cells was also detected by spectrofluorometry. In total and soluble cellular extracts, the mAb recognized two bands of 45 and 40 kDa by Western blot analysis, but only the first was purified by binding to DNase I, and it showed three isoforms of pI values 6.8, 6.5 and 6.4. These results suggest the presence, in prokaryotes, of proteins with similar biochemical characteristics to eukaryotic actin.


Case report: herpes simplex encephalitis in cancer patients.
The manifestation of herpes simplex encephalitis in patients can often be interpreted as a possible brain tumor. In order to make a definite diagnosis, subsequent invasive testing is frequently required. In addition to other routine diagnostic measures, particular symptoms, especially those indicating that a patient is immunocompromised, should be considered as possible evidence indicating presence of this central nervous system (CNS) viral infection.


Open abdomen and VAC® in severe diffuse peritonitis.
Currently, the open abdomen technique is the widely recognised method for treatment of life-threatening trauma, intra-abdominal sepsis, abdominal compartment syndrome and wound dehiscence. The techniques for temporary closure using negative pressure have gained increasing popularity. Although negative pressure wound therapy has been proved as an effective method in trauma, the results in diffuse peritonitis are contradictory. Overall, 108 patients with diffuse peritonitis and open abdomen were prospectively enrolled from January 2006 to December 2013--69 treated with mesh-foil laparostomy without negative pressure and 49 with vacuum-assisted closure (VAC(®)) The primary endpoints were the rate of primary fascial closure and mortality. The secondary outcomes were the rate of complications--enteroatmospheric fistulas, intra-abdominal abscesses, wound infection and necrotising fasciitis, intensive care unit (ICU) and overall hospital stay. VAC was associated with higher overall (73% vs 53%) and late primary fascial closure rates (31% vs 7%), lower rates of necrotising fasciitis (2% vs 15%, p=0.012), intra-abdominal abscesses (10% vs 20%), enteroatmospheric fistulas (8% vs 19%), overall mortality (31% vs 53%, p<0.05), shorter ICU (6.1 vs 10.6 days, p=0.002) and hospital stay (15.1 vs 25.9 days, p=0.000). The results clearly suggest the obvious advantage of VAC in comparison to the temporary abdominal closure without negative pressure in the cases with severe diffuse peritonitis. However, to a large extent, our results might be attributed to the combination of VAC with dynamic fascial closure.


Digestive and absorptive phase anomalies associated with the exocrine pancreatic insufficiency of cystic fibrosis.
The pancreas has an enormous reserve capacity, and significant malabsorption usually signals complete absence of exocrine function. However, there is evidence that acid lipases of nonpancreatic origin play an important compensatory role. Complete duodenal hydrolysis of fat requires a series of complex interdependent physicochemical events involving pancreatic lipase, colipase, phospholipase A2, and bile salts in an environment where the pH must be close to neutrality. Lipolytic products must then be shuttled through the unstirred water layer to the surface of the microvillus membrane by ionized bile salts, which must be present in sufficient concentrations to form micelles. In pancreatic insufficiency, there is not only a defective lipolytic phase but also an impaired micellar phase. The output of bile salts is decreased because of increased fecal loss. Furthermore, a significant percentage of bile salts precipitate because the duodenum is acidic and there is a large predominance of glycine conjugates. Although much less work has been done on the absorptive phase of patients with pancreatic insufficiency, there is tentative evidence that defective phospholipid absorption, essential fatty acid deficiency, and protein malnutrition could impair the absorptive phase, particularly chylomicron formation. Although significant advances have been made in our understanding of factors responsible for malabsorption associated with pancreatic insufficiency, much remains to be done for the further delineation of defects. It is hoped that this will lead to further refinements of enzyme preparations and to new strategies of intervention.


A comparison of electrospray ionization, atmospheric pressure chemical ionization, and atmospheric pressure photoionization for the liquid chromatography/tandem mass spectrometric analysis of bisphenols. Application to bisphenols in thermal paper receipts and U.S. currency notes.
Human health concerns have arisen for common bisphenols (BPA and BPS) as well as new structural analogs. While native sulfone bisphenols and sulfone-derivatized bisphenols are amenable to electrospray ionization (ESI), alternative ionization methods such as atmospheric pressure chemical ionization (APCI) and APPI were investigated to analyze non-derivatized, non-sulfone-containing bisphenols. Ionization of bisphenols using negative ion APPI was compared to negative ion ESI and negative ion APCI for their relative abilities to produce [M-H]- precursor ions for subsequent collision-induced dissociation (CID) in a triple quadrupole mass analyzer. Multiple reaction monitoring (MRM) transitions were optimized using the most sensitive ion transitions and coupled with high-performance liquid chromatographic (HPLC) separation to detect and quantify BPA, BPB, BPF, BPZ, BPAP, BPS, and BPSIP. APPI provides a more universal sensitivity over ESI toward the classes of bisphenols studied with detection limits of 20-50 pg on-column. The LC/APPI-MS/MS method was used to examine the levels of these seven bisphenols in thermal paper receipts and in U.S. paper currency. In both receipts and currency, BPA and BPS were the dominant bisphenols found in the paper. The measurement of BPA and bisphenol analogs in thermal paper receipts and transfer of bisphenols from receipts to currency notes is of increasing importance to assess human dermal exposure routes to this class of compounds. Equivalent sensitivity between sulfone- and non-sulfone-containing bisphenols is achievable through the use of alternate ionization sources such as APCI and APPI that circumvents tedious and time-consuming derivatization procedures to render analytical sensitivity by ESI.


Evaluation of the Mechanism of the Gold Cluster Growth during Heating of the Composite Gold-Polytetrafluoroethylene Thin Film.
Nanocomposite films consisting of gold inclusions in the polytetrafluoroethylene (PTFE) matrix were obtained by thermal vacuum deposition. Annealing of the obtained films with different temperatures was used to measure varying of film morphologies. The dependence of optical properties of the films on their morphology was studied. It was established that absorption and profile of the nanocomposite film obtained by thermal vacuum deposition can be changed with annealing owing to the fact that different annealing temperatures lead to different average particle sizes. A method to calculate the optical properties of nanocomposite thin films with inclusions of different sizes was proposed. Thus, comparison of experimental optical spectra with the spectra obtained during the simulation enables estimating average sizes of inclusions. The calculations give the possibility of understanding morphological changes in the structures.


Kinetics of beta-casein hydrolysis by wild-type and engineered trypsin.
Apparent rate constants of tryptic hydrolysis of amide bonds containing Arg and Lys residues in beta-casein were determined by the analysis of kinetics of accumulation of 17 major peptide components revealed by high performance liquid chromatography. When studying pH influence on Arg/Lys bond cleavage preference, averaged rate constants over several Arg&bond;X and Lys&bond;X bonds were used for analysis of kinetics of wild-type trypsin, K188H, K188F, K188Y, K188W, and of K188D/D189K mutants. The pK(a1) value of 6.5 was found for all studied trypsins. For wild-type trypsin and its K188D/D189K mutant, pK(a2) was found to be 10. The lowest among studied engineered trypsins pK(a2) = 9.3 was determined for K188Y mutant. Considerable preference for the cleavage of Arg over Lys containing peptide bonds was demonstrated for all trypsins with engineered S2 site except for K188H and K188F. The comparison of individual rate constants for various bonds showed that during the hydrolysis by wild-type trypsin, the probabilities of splitting depend on secondary specificity and local hydrophobicity of amino acid residues, which are nearest to the hydrolyzed peptide bond (P2 site). The improvement of prediction of hydrolysis rates performed by the used program was achieved after considering the presence of hydrophobic neighborhood of Lys48--Ile49 and Arg202--Gly203 bonds.


Superior cognitive goal maintenance in carriers of genetic markers linked to reduced striatal D2 receptor density (C957T and DRD2/ANKK1-TaqIA).
Maintaining goal representations is a critical component of cognitive control and is required for successful performance in many daily activities. This is particularly important when goal-relevant information needs to be maintained in working memory (WM), updated in response to changing task demands or internal goal states, and protected from interference by inhibiting counter-goal behaviors. Modulation of fronto-striatal dopamine is critical for updating and maintaining goals and representations. Here we test the hypothesis that a genetic predisposition (C957T T+ and DRD2/ANKK1-TaqIA A+) for reduced striatal D2 receptor availability would facilitate goal maintenance using the AX-continuous performance task (AX-CPT), on a sample of 196 adults (25-67 y). We demonstrate that carriers of two polymorphisms that have been linked to reduced striatal D2 receptor density show increased performance on context-dependent (BX) trials, and that the effect of these polymorphisms was only significant for long ISI trials where the demand for goal maintenance is high. The current results add further knowledge to the role of D2 receptor functioning in cognitive stability and flexibility, and could have implications for understanding cognitive deficits in patients characterized by altered dopamine functioning.


Induced systemic resistance (ISR) against pathogens in the context of induced plant defences.
Induced systemic resistance (ISR) of plants against pathogens is a widespread phenomenon that has been intensively investigated with respect to the underlying signalling pathways as well as to its potential use in plant protection. Elicited by a local infection, plants respond with a salicylic-dependent signalling cascade that leads to the systemic expression of a broad spectrum and long-lasting disease resistance that is efficient against fungi, bacteria and viruses. Changes in cell wall composition, de novo production of pathogenesis-related-proteins such as chitinases and glucanases, and synthesis of phytoalexins are associated with resistance, although further defensive compounds are likely to exist but remain to be identified. In this Botanical Briefing we focus on interactions between ISR and induced resistance against herbivores that is mediated by jasmonic acid as a central signalling molecule. While many studies report cross-resistance, others have found trade-offs, i.e. inhibition of one resistance pathway by the other. Here we propose a framework that explains many of the thus far contradictory results. We regard elicitation separately from signalling and from production, i.e. the synthesis of defensive compounds. Interactions on all three levels can act independently from each other.


Microstructure-stiffness relationships of ten European and tropical hardwood species.
Hardwood species exhibit a huge anatomical variability. This makes them perfect study objects for exploring relations between structural features at different length scales and corresponding stiffness properties of wood. We carry out microscopic analysis, nanoindentation tests, as well as macroscale ultrasonic and quasi-static tension tests and build a complete set of microstructural and corresponding micromechanical data of ten different (European and tropical) hardwood species. In addition, we apply micromechanical modeling to further elucidate the individual influences of particular structural features, which might appear only in a superimposed manner in experiments. The test results confirm the dominant influences of the microfibril angle on the stiffness at cell wall level and of density at the macroscopic scale. Vessels and ray cells affect the macroscopic stiffness of the wood tissue not only through their content, but also through their arrangement and shape: A ring-porous structure results in comparably higher longitudinal but lower radial stiffness than a diffuse-porous one. As for ray cells, large and particularly compactly shaped bundles might reduce the stiffness in tangential direction because of the fiber deviations they cause. Moreover, vessel and ray content might affect the relation between nanoindentation modulus and density-corrected macroscopic longitudinal stiffness.


Synthesis and in vitro antibacterial activity of 5-halogenomethylsulfonyl- benzimidazole and benzotriazole derivatives.
A series of 5-halogenomethylsulfonylbenzimidazole and benzotriazole derivatives was synthesized as potential antibacterial agents. A new method of synthesis of benzimidazoles was developed. The antimicrobial activities of these compounds were tested against a series of reference and clinical strains. The reference strains include Gram-positive bacteria (S. aureus, S. epidermidis, B. subtilis, B. cereus, E. hirae, M. luteus) and Gram-negative rods (E. coli, P. vulgaris, P. aeruginosa, B. bronchiseptica). The clinical strains include six methicillin-resistant (MRSA) and two methicillin-sensitive (MSSA) S. aureus strains, one methicillin-resistant S. epidermidis, three E. faecalis and two E. faecium strains. Compound with trifluoromethyl- substituent at C-2 position (4) displayed significant antibacterial activities comparable with nitrofurantoin against four strains, and higher against Micrococcus luteus. MIC values for clinical Staphylococci strains (MRSA) were 12.5-25 μg/mL; for Enterococcus strains these values were 50-100 μg/mL. MIC values for reference and clinical strains of Staphylococcus and Enterococcus group were similar, respectively.


Effective stochastic behavior in dynamical systems with incomplete information.
Complex systems are generally analytically intractable and difficult to simulate. We introduce a method for deriving an effective stochastic equation for a high-dimensional deterministic dynamical system for which some portion of the configuration is not precisely specified. We use a response function path integral to construct an equivalent distribution for the stochastic dynamics from the distribution of the incomplete information. We apply this method to the Kuramoto model of coupled oscillators to derive an effective stochastic equation for a single oscillator interacting with a bath of oscillators and also outline the procedure for other systems.


Covid-19 pandemic effects on food safety - Multi-country survey study.
This study provides an important insight into the response of food safety systems during the first months of the pandemic, elevating the perspective of preventing Covid-19 within conventional food safety management systems. A multi-country survey was conducted in 16 countries involving 825 food companies. Based on the results of the survey, it is obvious that the level of maturity of a food safety system in place is the main trigger in classifying companies and their responses to the pandemic challenge. Staff awareness and hygiene are the two most important attributes in combating Covid-19, opposed to temperature checking of workers in food establishment and health protocols from the World Health Organization, recognized as attributes with limited salience and importance. Companies confirmed implementation of more restrictive hygiene procedures during the pandemic and the need for purchasing more additional personal protective equipment. Retailers were identified as the food supply chain link mostly affected by the pandemic opposed to food storage facilities ranked as least affected. During this challenging period, all companies declared that food safety has not been compromised at any moment. It is important to note that less than a half of the food companies had documented any emergency plans associated with pandemics and health issues in place.


Bragg electrostriction in optical waveguides.
A reverse process of acoustooptic diffraction in thin films is studied. The high optical field concentration in thin films is utilized by mixing two optical guided modes electrostrictively to generate an acoustic surface wave. A theoretical analysis analogous to acoustooptic diffraction is presented by taking the power balance approach. The nonuniform electric and acoustic field distributions are fully taken into account. A relation between electrostriction and diffraction is established, and the published results on Bragg diffraction are applied directly to Bragg electrostriction. Bragg electrostriction is film thickness dependent, and cw operation of acoustic wave generation is possible.


Formation of liquid-crystalline structures in the bile salt-chitosan system and triggered release from lamellar phase bile salt-chitosan capsules.
Nanostructured capsules comprised of the anionic bile salt, sodium taurodeoxycholate (STDC), and the biocompatible cationic polymer, chitosan, were prepared to assess their potential as novel tailored release nanomaterials. For comparison, a previously studied system, sodium dodecyl sulfate (SDS), and polydiallyldimethylammonium chloride (polyDADMAC) was also investigated. Crossed-polarizing light microscopy (CPLM) and small-angle X-ray scattering (SAXS) identified the presence of lamellar and hexagonal phase at the surfactant-polymer interface of the respective systems. The hydrophobic and electrostatic interactions between the oppositely charged components were studied by varying temperature and salt concentration, respectively, and were found to influence the liquid-crystalline nanostructure formed. The hexagonal phase persisted at high temperatures, however the lamellar phase structure was lost above ca. 45 °C. Both mesophases were found to dissociate upon addition of 4% NaCl solution. The rate of release of the model hydrophilic drug, Rhodamine B (RhB), from the lamellar phase significantly increased in response to changes in the solution conditions studied, suggesting that modulating the drug release from these bile salt-chitosan capsules is readily achieved. In contrast, release from the hexagonal phase capsules had no appreciable response to the stimuli applied. These findings provide a platform for these oppositely charged surfactant and polymer systems to function as stimuli-responsive or sustained-release drug delivery systems.


Cutaneous Rosai-Dorfman disease: a case report.
Rosai-Dorfman disease, otherwise known as sinus histiocytosis with massive lymphadenopathy, is a non-Langerhans cell histiocytosis with a benign course and unknown etiology. It was described in 1969 as a painless cervical lymph node enlargement in association with fever, weight loss and sweating. Extranodal disease has been reported in 43% of cases, with involvement of multiple organs. Purely extranodal Rosai-Dorfman disease has been already reported, including forms restricted to the skin. This paper reports a case of purely cutaneous Rosai-Dorfman disease, which is of interest in view of the rarity of this condition.


Bronchial asthma and airway hyperresponsiveness at high altitude.
The mountain climate can modify respiratory function and bronchial responsiveness of asthmatic subjects. Hypoxia, hyperventilation of cold and dry air and physical exertion may worsen asthma or enhance bronchial hyperresponsiveness while a reduction in pollen and pollution may play an important role in reducing bronchial inflammation. At moderate altitude (1,500-2,500 m), the main effect is the absence of allergen and pollutants. We studied bronchial hyperresponsiveness to both hyposmolar aerosol and methacholine at sea level (SL) and at high altitude (HA; 5,050 m) in 11 adult subjects (23-48 years old, 8 atopic, 3 nonatopic) affected by mild asthma. Basal FEV1 at SL and HA were not different (p = 0.09), whereas the decrease in FEV1 induced by the challenge was significantly higher at SL than at HA. (1) Hyposmolar aerosol: at SL the mean FEV1 decreased by 28% from 4.32 to 3.11 liters; at 5,050 m by 7.2% from 4.41 to 4.1 liters (p < 0.001). (2) Methacholine challenge: at SL PD20-FEV1 was 700 micrograms and at HA > 1,600 micrograms (p < 0.005). In 3 asthmatic and 5 nonasthmatic subjects plasma levels of cortisol were also measured. The mean value at SL was 265 nmol and 601 nmol at HA (p < 0.005). We suppose that the reduction in bronchial response might be mainly related to the protective role carried out by the higher levels of cortisol and, as already known, catecholamines.


[Centrioles in the cell cycle of L cells].
The structure of centrosome in non-synchronous L-cells culture during the cell cycle has been studied. In mitosis, mother and daughter centrioles, which differ in their ultrastructure, are located perpendicularly in the pole of the spindle. Microtubules, meeting in the pole area terminate mainly in electron-dense clottings of fibrillar matter surrounding the diplosoma. In telophase, disjunction of mother and daughter centrioles begins. At the beginning of G1-period, centrioles move off from each other for several micron, and then draw together again without forming diplosome. Pericentriolar satellites form on mother centriole of some cells at this time, they disappear at the beginning of S-period, replication of centrioles begins; daughter centrioles reach the size of mother centrioles in anaphase. During growth and maturation, centrioles in L-cells undergo structural changes similar to those described for SPEV cells (Vorob'ev, Chentsov, 1982). Several types of meeting points for microtubules exist in L-cells during the whole interphase: surface of centrioles per se, pericentriolar satellites, free foci.


Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway.
The expression of a number of blood coagulation factors (F) (FX, FIX, FVIII, FVII, alpha-, beta-, gamma-fibrinogen chains, protein C, and antithrombin III [AT III]) was analyzed at RNA and protein level in 5- to 10-week-old human embryos and fetuses. FX, FIX, and FVII were also analyzed at protein level. Total and poly(A)+ RNA, extracted from embryonic-fetal (FL) and adult liver (AL), were analyzed by dot and Northern blot hybridization with specific cDNA probes. The results indicate that: (1) the size of the messenger RNAs of these factors is equivalent in FL and AL; (2) in the 5- to 10-week period, their abundance in FL increases from 30% to 50% of the adult level except for FIX (from 2% to 10%) and FX (always 100% of the adult value). Western blot analysis of FIX, FX, and FVII in 5- to 10-week soluble liver proteins and 6- to 8-week plasma showed a low level of FIX versus a higher concentration of both FVII and FX, when compared with corresponding adult values, ie, a liver protein level of 10% versus 100% and a plasma concentration level of 10% versus 40%. Although little is known so far on the activity and the functional role of the clotting factors in early human ontogenic development, these studies suggest an activation of FX via the FVII/tissue factor activity rather than the FIXa/FVIIIa phospholipid complex in human embryonic and early fetal life.


Diuretic-associated electrolyte disorders in the elderly: risk factors, impact, management and prevention.
Electrolyte and acid-base disorders are commonly encountered adverse effects of various diuretic agents, which are associated with considerable morbidity and mortality especially in elderly patients. Diuretic use is associated with hyponatraemia, hypernatraemia, hypokalaemia, hyperkalaemia, hyperuricaemia and alterations in magnesium, calcium, phosphate and acid-base homeostasis. Clinical studies have provided important data on the relative frequency and risk factors for these diuretic-associated electrolyte and acid-base disorders. Old age is one of the most recognized risk factors for diuretic-associated electrolyte and acid-base disorders. Hyponatraemia and hypokalaemia are the most common electrolyte abnormalities found among the elderly population taking diuretics. Both conditions are associated with short and long-term morbidity as well as mortality. This article presents an overview of the literature on diuretic-associated electrolyte disorders and suggested risk factors for their development especially in elderly patients when evidence is available. The impact of these electrolyte disorders on patients will be discussed. Strategies to prevent adverse outcomes related to these disorders should involve careful consideration of risk factors as well as ongoing clinical and laboratory evaluations in the course of using these diuretics.


In vivo-induced argininosuccinate lyase plays a role in the replication of Brucella abortus in RAW264.7 cells.
Brucellosis caused by Brucella species is a zoonotic disease with a serious impact on public health and the livestock industry. To better understand the pathogenesis of the disease, in vivo-induced antigen technology (IVIAT) was used to investigate the in vivo-induced antigens of Brucella abortus in this study. A genomic expression library of B. abortus was constructed and screened using pooled bovine B. abortus-positive sera by IVIAT. In total, 33 antigens were identified. Five antigens were further expressed and tested for their seroreactivity against 33 individual bovine B. abortus-positive sera by Western blot analysis. The results showed a highest positive rate of 32/33 for argininosuccinate lyase (ASL), indicating that ASL may be used as a candidate marker for serodiagnosis of brucellosis. Furthermore, an asl gene-deleted mutant strain S2308ΔASL was constructed, and the intracellular survival and replication of the mutant strain in RAW264.7 cells were investigated. Interestingly, the numbers of bacteria recovered from cells infected with mutant strain S2308ΔASL were similar at all time points observed from 0 h to 96 h post-infection, suggesting the asl gene plays an important role in the bacterial replication in RAW264.7 cells. Real-time quantitative PCR (qPCR) analysis showed that the mRNA levels in S2308ΔASL were decreased for BvrR, BvrS and virB5 when compared with those in S2308 (P<0.05). Our results not only expand the knowledge of Brucella intracellular replication but also expand the list of candidates for serodiagnostic markers of brucellosis.


Contesting medicalisation, doubting the diagnosis: patients' ambivalence towards the diagnosis of Obstructive Sleep Apnoea.
Whereas social scientific studies have investigated the emergence of the category Obstructive Sleep Apnoea (OSA), the most commonly diagnosed sleep disorder, no study has examined whether and how the ways in which OSA emerged affect patients' reception of the diagnosis. This article fills this gap by drawing upon in-depth interviews with 65 Israelis who received a laboratory diagnosis of OSA. This study finds that many patients doubt the accuracy of their diagnosis, and argues that this scepticism derives from contested macro-level medicalisation processes that preceed and surround the development of OSA as a diagnostic category. Specifically, past and present controversies over the definitions of OSA and its precursor the 'Pickwickian syndrome' created images of 'OSA patients' as sleepy and obese. Consequently, patients whose self-perception conflicted with this image questioned their diagnosis. Other patients argued that one night of sleep at a laboratory could not reflect their quality of sleep at home, thereby implicitly criticising the ways in which OSA was medicalised. This study enhances our understanding of the underexplored dynamics between the macro and micro levels of medicalisation.


Osmium-187 enrichment in some plumes: evidence for core-mantle interaction?
Calculations with data for asteroidal cores indicate that Earth's outer core may have a rhenium/osmium ratio at least 20 percent greater than that of the chondritic upper mantle, potentially leading to an outer core with an osmium-187/osmium-188 ratio at least 8 percent greater than that of chondrites. Because of the much greater abundance of osmium in the outer core relative to the mantle, even a small addition of metal to a plume ascending from the D" layer would transfer the enriched isotopic signature to the mixture. Sources of certain plume-derived systems seem to have osmium-187/osmium-l88 ratios 5 to 20 percent greater than that for chondrites, consistent with the ascent of a plume from the core-mantle boundary.


A candidate gene association analysis identifies SNPs potentially involved in drought tolerance in European beech (Fagus sylvatica L.).
Studies of genetic variation underlying traits related to drought tolerance in forest trees are of great importance for understanding their adaptive potential under a climate change scenario. In this study, using a candidate gene approach, associations between SNPs and drought related traits were assessed in saplings of European beech (Fagus sylvatica L.) representing trees growing along steep precipitation gradients. The saplings were subjected to experimentally controlled drought treatments. Response of the saplings was assessed by the evaluation of stem diameter growth (SDG) and the chlorophyll fluorescence parameters FV/FM, PIabs, and PItot. The evaluation showed that saplings from xeric sites were less affected by the drought treatment. Five SNPs (7.14%) in three candidate genes were significantly associated with the evaluated traits; saplings with particular genotypes at these SNPs showed better performance under the drought treatment. The SNPs were located in the cytosolic class I small heat-shock protein, CTR/DRE binding transcription factor, and isocitrate dehydrogenase genes and explained 5.8-13.4% of the phenotypic variance. These findings provide insight into the genetic basis of traits related to drought tolerance in European beech and could support the development of forest conservation management strategies under future climatic conditions.


Melittin and its potential in the destruction and inhibition of the biofilm formation by Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa isolated from bovine milk.
Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa stand out in veterinary and human medicine for their role in opportunistic infections and their pathogenic mechanisms, including the biofilms formation. It was investigated the antibacterial activity of melittin and antibiofilm of such bacteria. Twelve strains of these microorganisms isolated from bovine milk were used, as well as the strains S. aureus ATCC 12600, E. coli ATCC 8739 and Pseudomonas aeruginosa ATCC 15442. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) were determined by broth microdilution technique. The biofilms were formed in 96-well plates and melittin on these colonies was added at different concentrations and times. Bacteria previously exposed to melittin were evaluated for inhibition of biofilm production. The MIC and MBC were respectively in μg/mL: S. aureus (6-7 and 32-64), E. coli (40-42.5 and 64-128) and P. aeruginosa (65-70 and 64-128). S. aureus biofilms were more sensitive to the action of melittin, since upon exposure to a concentration 10 times lower than the MIC for 4 h, was completely destroyed. In Gram negative bacteria, the pre-formed biofilm was destroyed only when exposed for 4 h under the MIC. With respect to inhibition of biofilm production, S. aureus was the most sensitive again because produced only 37.2% of the biofilm formed by the control (without previous exposure to melittin), when exposed to the MIC, and at a concentration hundred times smaller than MIC, this microorganism produced 75.2% of the biofilm. E. coli was the most resistant bacteria and produced 56.3% of the biofilm, even if previously exposed to melittin MIC. Melittin presents desirable effects in combating microorganisms studied both at your disposal, biofilm destruction and inhibition of the formation, and maybe used in future studies of new strategies to combat infections caused by these pathogens.


Single-molecule electron spin resonance by means of atomic force microscopy.
Understanding and controlling decoherence in open quantum systems is of fundamental interest in science, whereas achieving long coherence times is critical for quantum information processing1. Although great progress was made for individual systems, and electron spin resonance (ESR) of single spins with nanoscale resolution has been demonstrated2-4, the understanding of decoherence in many complex solid-state quantum systems requires ultimately controlling the environment down to atomic scales, as potentially enabled by scanning probe microscopy with its atomic and molecular characterization and manipulation capabilities. Consequently, the recent implementation of ESR in scanning tunnelling microscopy5-8 represents a milestone towards this goal and was quickly followed by the demonstration of coherent oscillations9,10 and access to nuclear spins11 with real-space atomic resolution. Atomic manipulation even fuelled the ambition to realize the first artificial atomic-scale quantum devices12. However, the current-based sensing inherent to this method limits coherence times12,13. Here we demonstrate pump-probe ESR atomic force microscopy (AFM) detection of electron spin transitions between non-equilibrium triplet states of individual pentacene molecules. Spectra of these transitions exhibit sub-nanoelectronvolt spectral resolution, allowing local discrimination of molecules that only differ in their isotopic configuration. Furthermore, the electron spins can be coherently manipulated over tens of microseconds. We anticipate that single-molecule ESR-AFM can be combined with atomic manipulation and characterization and thereby paves the way to learn about the atomistic origins of decoherence in atomically well-defined quantum elements and for fundamental quantum-sensing experiments.


Contact-Lens-Associated Purpureocillium Keratitis: Risk Factors, Microbiologic Characteristics, Clinical Course, and Outcomes.
To study the risk factors, microbiologic characteristics, clinical course, and outcomes of patients with Purpureocillium keratitis at a tertiary eye care center in south Florida. All medical records during a seven-year period starting January 1, 2007, were reviewed. Twenty-eight culture-proven Purpureocillium keratitis cases with complete medical records presenting to our institution were included in this retrospective, observational case series. Data collected included predisposing factors, therapeutic interventions, treatment duration, and visual outcomes. Twenty patients (71.4%) had a history of soft contact lens use, with only two for therapeutic use. Other identified risk factors were trauma and immunosuppression. Fifteen patients (53.6%) received topical corticosteroid treatment prior to the diagnosis of fungal keratitis. Thirteen patients (46.4%) were on Natamycin treatment prior to Purpureocillium identification. As a group, the average best-corrected visual acuity (BCVA) at presentation was 1.1 logMAR; upon the final evaluation, it was 1.0 logMAR. The BCVA on last evaluation for the eight patients presenting to our institution within two weeks of onset of symptoms was 0.3 log MAR, and all patients in this group responded to medical management. The final BCVA for 20 patients presenting two weeks after onset of symptoms was 1.2 logMAR. There was a significant difference in the final BCVA between Group 1 and Group 2 (p = 0.004), but no difference in steroid use or previous treatments. Previous steroid use tended to extend time to presentation and was significantly associated with a worse final visual outcome (1.2 versus 0.6 logMAR; p = 0.0474). Previous Natamycin use was significantly associated with a worse final visual outcome (1.4 versus 0.6 logMAR; p = 0.014). Purpureocillium keratitis can have devastating consequences to visual function and even lead to enucleation. Physicians should make every effort to arrive at an earlier microbiological diagnosis, as this is associated with better outcomes and less need for surgical intervention. The first line use of voriconazole is recommended, and steroid use should be avoided, as their previous use is associated with worse visual outcomes.


SYS-1/beta-catenin inheritance and regulation by Wnt-signaling during asymmetric cell division.
Asymmetric cell division (ACD) allows daughter cells of a polarized mother to acquire different developmental fates. In C. elegans , the Wnt/β-catenin Asymmetry (WβA) pathway oversees many embryonic and larval ACDs; here, a Wnt gradient induces an asymmetric distribution of Wnt signaling components within the dividing mother cell. One terminal nuclear effector of the WβA pathway is the transcriptional activator SYS-1/β-catenin. SYS-1 is sequentially negatively regulated during ACD; first by centrosomal regulation and subsequent proteasomal degradation and second by asymmetric activity of the β-catenin "destruction complex" in one of the two daughter cells, which decreases SYS-1 levels in the absence of WβA signaling. However, the extent to which mother cell SYS-1 influences cell fate decisions of the daughters is unknown. Here, we quantify inherited SYS-1 in the differentiating daughter cells and the role of SYS-1 inheritance in Wnt-directed ACD. Photobleaching experiments demonstrate the GFP::SYS-1 present in daughter cell nuclei is comprised of inherited and de novo translated SYS-1 pools. We used a photoconvertible DENDRA2::SYS-1, to directly observe the dynamics of inherited SYS-1. Photoconversion during mitosis reveals that SYS-1 clearance at the centrosome preferentially degrades older SYS-1, and this accumulation is regulated via dynein trafficking. Photoconversion of the EMS cell during Wnt-driven ACD shows daughter cell inheritance of mother cell SYS-1. Additionally, loss of centrosomal SYS-1 increased inherited SYS-1 and, surprisingly, loss of centrosomal SYS-1 also resulted in increased levels of de novo SYS-1 in both EMS daughter cells. Lastly, we show that daughter cell negative regulation of SYS-1 via the destruction complex member APR-1/APC is key to limit both the de novo and the inherited SYS-1 pools in both the E and the MS cells. We conclude that regulation of both inherited and newly translated SYS-1 via centrosomal processing in the mother cell and daughter cell regulation via Wnt signaling are critical to maintain sister SYS-1 asymmetry during ACD.


A graphene-based biosensing platform based on the release of DNA probes and rolling circle amplification.
We report a versatile biosensing platform capable of achieving ultrasensitive detection of both small-molecule and macromolecular targets. The system features three components: reduced graphene oxide for its ability to adsorb single-stranded DNA molecules nonspecifically, DNA aptamers for their ability to bind reduced graphene oxide but undergo target-induced conformational changes that facilitate their release from the reduced graphene oxide surface, and rolling circle amplification (RCA) for its ability to amplify a primer-template recognition event into repetitive sequence units that can be easily detected. The key to the design is the tagging of a short primer to an aptamer sequence, which results in a small DNA probe that allows for both effective probe adsorption onto the reduced graphene oxide surface to mask the primer domain in the absence of the target, as well as efficient probe release in the presence of the target to make the primer available for template binding and RCA. We also made an observation that the circular template, which on its own does not cause a detectable level of probe release from the reduced graphene oxide, augments target-induced probe release. The synergistic release of DNA probes is interpreted to be a contributing factor for the high detection sensitivity. The broad utility of the platform is illustrated though engineering three different sensors that are capable of achieving ultrasensitive detection of a protein target, a DNA sequence and a small-molecule analyte. We envision that the approach described herein will find useful applications in the biological, medical, and environmental fields.


Biological treatment of a textile effluent after electrochemical oxidation of reactive dyes.
In this work, a synthetic textile effluent containing a reactive dye (C.I. Reactive Orange 4) was treated in an electrochemical cell with titanium covered by platinum oxide (Ti/PtOx) electrodes to remove color. The discolored effluent was mixed with other textile mill process effluents (scouring, bleaching, washing, etc.), according to the rate of each effluent in the mill, and was submitted to biological treatment (activated sludge plant). Two biological plants were run simultaneously to evaluate the influence of oxidant products generated during the electrochemical treatment. The final chemical oxygen demand (COD) removal in both plants was 65 to 72%. The yield of the activated sludge plants was not affected by the addition of 10% of the discolored dyeing effluent (even when oxidants products were not removed), which indicates that the previous electrochemical treatment do not produce inhibition effects on the biological plant. However, in the case of direct addition of the discolored effluent, the biological treatment plant required a longer adaptation period. In addition, the electrolytic respirometry tests showed that all the biodegradable organic matter was removed, which implies that the yield in organic matter removal was the maximum possible for this type of treatment.


A survey of metabolic databases emphasizing the MetaCyc family.
Thanks to the confluence of genome sequencing and bioinformatics, the number of metabolic databases has expanded from a handful in the mid-1990s to several thousand today. These databases lie within distinct families that have common ancestry and common attributes. The main families are the MetaCyc, KEGG, Reactome, Model SEED, and BiGG families. We survey these database families, as well as important individual metabolic databases, including multiple human metabolic databases. The MetaCyc family is described in particular detail. It contains well over 1,000 databases, including highly curated databases for Escherichia coli, Saccharomyces cerevisiae, Mus musculus, and Arabidopsis thaliana. These databases are available through a number of web sites that offer a range of software tools for querying and visualizing metabolic networks. These web sites also provide multiple tools for analysis of gene expression and metabolomics data, including visualization of those datasets on metabolic network diagrams and over-representation analysis of gene sets and metabolite sets.


Serum thyroxine, triiodothyronine, and TSH levels and TSH release after TRH in aging male and female rats.
Serum levels of TSH, T3 and T4, pituitary responsiveness to TRH, and T3-resin uptake were examined in aging male and female rats. Despite normal serum TSH levels, serum T3 and T4 levels were significantly reduced in old male rats (19-26 months of age) when compared to young (120-150 days of age) and middle-aged males (12-1- months of age). In old female rats, serum TSH and T3 levels were not significantly (p greater than 0.05) different from those of young or middle-aged females. Serum T4 levels were significantly lower in old females when compared to younger rats. The T3-resin uptake of old rats was not significantly different from the value of young rats. Serum T4 levels, 3 hours after TRH induced TSH release, were significantly depressed in old male and female rats. Pituitary sensitivity to TRH was unaltered in old rats. These findings suggest that thyroidal release of T4 and T3 is depressed, and that the hypothalamic-pituitary axis is insensitive to diminished thyroid hormone feedback in old rats.


Investigation on the Tool Wear Suppression Mechanism in Non-Resonant Vibration-Assisted Micro Milling.
Excessive tool wear during hard and brittle material processing severely influences cutting performance. As one of the advanced machining technologies, vibration-assisted micro milling adds high-frequency small amplitude vibration on a micro milling tool or workpiece to improve cutting performance, especially for hard and brittle materials. In this paper, the tool wear suppression mechanism in non-resonant vibration-assisted micro milling is studied by using both finite element simulation and experiment methods. A finite element model of vibration-assisted micro milling using ABAQUS is developed based on the Johnson cook material and damage models. The tool-workpiece separation conditions are studied by considering the tool tip trajectories. The machining experiments are carried out on Ti-6Al-4V with a coated micro milling tool (fine-grain tungsten carbide substrate with ZrO2-BaCrO4 (ZB) coating) under different vibration frequencies (high, medium, and low) and cutting states (tool-workpiece separation or non-separation). The results show that tool wear can be reduced effectively in vibration-assisted micro milling due to different wear suppression mechanisms. The relationship between tool wear and cutting performance is studied, and the results indicate that besides tool wear reduction, better surface finish, lower burrs, and smaller chips can also be obtained as vibration assistance is added.


Guidance for RNA-seq co-expression network construction and analysis: safety in numbers.
RNA-seq co-expression analysis is in its infancy and reasonable practices remain poorly defined. We assessed a variety of RNA-seq expression data to determine factors affecting functional connectivity and topology in co-expression networks. We examine RNA-seq co-expression data generated from 1970 RNA-seq samples using a Guilt-By-Association framework, in which genes are assessed for the tendency of co-expression to reflect shared function. Minimal experimental criteria to obtain performance on par with microarrays were >20 samples with read depth >10 M per sample. While the aggregate network constructed shows good performance (area under the receiver operator characteristic curve ∼0.71), the dependency on number of experiments used is nearly identical to that present in microarrays, suggesting thousands of samples are required to obtain 'gold-standard' co-expression. We find a major topological difference between RNA-seq and microarray co-expression in the form of low overlaps between hub-like genes from each network due to changes in the correlation of expression noise within each technology. email@example.com or firstname.lastname@example.com Networks are available at: http://gillislab.labsites.cshl.edu/supplements/rna-seq-networks/ and supplementary data are available at Bioinformatics online.


Numerical analysis of light propagation in image fibers or coherent fiber bundles.
The coupling properties of multi-core fibers are analyzed using the multipole method and coupled mode theory in order to gain insights into the performance of image fibers that are commonly used in flexible endoscopes. It is explained that coherent fiber bundles with high core density are able to transport images because nonuniformity in the pixel size reduces the inter-core coupling that causes crosstalk. The wavelength, average core size and separation, and degree of core size variation determine the strength of coupling between adjacent cores, such that fibers with a smaller core size and separation at longer wavelengths require more nonuniformity in order for reliable image transmission. Guidelines are given for assessing the performance of image fibers in a particular system.


Program of Enhanced Psychiatric Services for Patients With Brain Injury and Neuropsychiatric Disturbances: A Proposed Model of Care.
Neuropsychiatric disturbances associated with brain injury occur frequently and are a common cause of poor quality of life and caregiver burden. These disturbances can disrupt rehabilitation therapies and contribute to functional impairment if they are not appropriately treated. Although some patients can be treated adequately in an outpatient brain injury clinic or rehabilitation clinic, others need a more specialized structured program. Behavioral problems in particular are challenging and often lead to discharge of patients from traditional rehabilitation programs because their behaviors can be disruptive and/or harmful to themselves and others. These patients are often admitted to inpatient general psychiatric units, where they do not receive the comprehensive care they need. In an effort to prevent unnecessary hospitalizations and to provide comprehensive treatment, a community-based, multidisciplinary program was developed to address the physical, cognitive, and psychiatric needs of patients with brain injury. The program is highlighted with two case presentations: (a) a 31-year-old man with severe traumatic brain injury with subsequent cognitive and behavioral symptoms who had improvement in symptoms and quality of life, and (b) a 38-year-old woman with cognitive and mood symptoms after left temporal lobe resection due to medication-refractory epilepsy who had improved mood symptoms and daily life functioning. Brain injury is commonly associated with a host of neuropsychiatric symptoms that wax and wane. There is an urgent need to develop comprehensive programs that can address the multiple needs of this patient population in a community setting.


The biological properties of insulins with tyrosine replaced by phenylalanine at positions 14 and 19 of the A chain.
The tyrosine residues at positions 14 and 19 of the insulin A chain are of both theoretical and practical interest. In order to clarify their roles in insulin function we have studied the biological properties of the two chemically modified insulins in which phenylalanine replaces tyrosine at these sites. In comparison to native bovine insulin the lipogenesis potency (in rat adipocytes) of pheA19-insulin was 33% and of pheA14-insulin was 84%. Metabolic clearance rates (MCR) over a range of plasma concentrations were also reduced compared to native insulin both with pheA19-insulin and pheA14-insulin. Plasma half-disappearance times were 4.6 min for insulin, 5.1 min for pheA14-insulin and 7.3 min for pheA19-insulin. However, as a result of these differences in metabolism, the in vivo hypoglycaemic activity of the modified insulins was not reduced. Both modified insulins conform to the general relationship between lipogenesis potency and MCR. These results confirm the importance of the A19 tyrosine to the activity of insulin and show that manipulation at the A14 position can also influence activity even though this residue is not thought to be directly involved in receptor binding.


Use of an asbestos exposure score and the presence of pleural and parenchymal abnormalities in a lung cancer case series.
To assess whether there was an association between asbestos exposure and abnormalities on chest x-rays or CT scans, chest radiographs and CT scans of 103 asbestos-exposed patients with known lung cancer were reviewed for pleural or parenchymal abnormalities. Asbestos exposure was assessed using an asbestos exposure index that integrated time and intensity of reported exposure via a weighting scheme. Chest CT scans were clearly more sensitive in detecting pleural or parenchymal abnormalities than were standard PA chest x-rays. Furthermore, there was a significant correlation between higher asbestos exposure index scores and abnormalities on CT scans. Multivariable logistic regression models were used to investigate the relationship between the asbestos exposure index score and pleural or parenchymal abnormalities after adjusting for gender, pack-years of smoking, and cell type. None of these variables was associated with abnormalities on chest x-rays or CT scans. An asbestos exposure score > 10 was associated with pleural or parenchymal abnormalities (OR = 4.93; 95%CI 1.05-23.12). The results suggest that assessment of asbestos exposures by means of an algorithm-based index can classify the exposures accurately for epidemiologic studies.


Change in sleep state of the elderly before and after cataract surgery.
It seems likely that the influences of light upon circadian rhythms will decrease with aging, particularly those rhythms that are more influenced by light with a higher color temperature and richer in short wavelengths. More specifically, cataract patients' optical systems transmit light poorly, especially the shorter wavelengths that affect the circadian system more. The present study investigated melatonin secretion profiles and sleep patterns before and after cataract surgery. Fifteen subjects were studied for 3 consecutive weekdays before, and one month after, their cataract surgery. UV-cutting intra-ocular lenses were used for patients after surgery. No statistically significant differences between before and after surgery were observed in the amount of light received and the amount of activity. This means that there were no significant changes in their lifestyle during the experimental period. Considering the group as a whole, no significant differences were present in melatonin secretion, sleep parameters, or sleepiness before and after the surgery. However, individual subjects responded differently. The subjects showed a negative correlation between the wake-up (p=0.067) or retiring times (p=0.017) and sleep efficiency after surgery. The amount of light received during the nighttime influenced sleep more significantly than during the daytime.


Antioxidants in cancer therapy; their actions and interactions with oncologic therapies.
There is a concern that antioxidants might reduce oxidizing free radicals created by radiotherapy and some forms of chemotherapy, and thereby decrease the effectiveness of the therapy. The question has arisen whether concurrent administration of oral antioxidants is contraindicated during cancer therapeutics. Evidence reviewed here demonstrates exogenous antioxidants alone produce beneficial effects in various cancers, and except for a few specific cases, animal and human studies demonstrate no reduction of efficacy of chemotherapy or radiation when given with antioxidants. In fact, considerable data exists showing increased effectiveness of many cancer therapeutic agents, as well as a decrease in adverse effects, when given concurrently with antioxidants.


Assessment of therapeutic plasmapheresis in demyelinating neurologic disorders.
Considerable controversy exists with regard to therapeutic efficacy of plasmapheresis in the immune-mediated demyelinating disorders of the peripheral and central nervous system: acute inflammatory polyneuropathy (Guillain-Barré syndrome), chronic inflammatory demyelinating polyneuropathy, and multiple sclerosis. In an effort to establish specific situations where plasmapheresis was of therapeutic value, we reviewed the experience at Southwestern Medical School, University of Texas Health Science Center at Dallas, and that published in the literature. In acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome), plasmapheresis may prevent progression of the illness, and it significantly increases the rate of recovery. For patients with chronic inflammatory polyneuropathy, plasmapheresis has produced clinical improvement in 50% of corticosteroid-refractory patients. The use of plasmapheresis in patients with acute or chronic progressive multiple sclerosis still remains controversial.


Monolithic active quenching and picosecond timing circuit suitable for large-area single-photon avalanche diodes.
A new integrated active quenching circuit (i-AQC) designed in a standard CMOS process is presented, capable of operating with any available single photon avalanche diode (SPAD) over wide temperature range. The circuit is suitable for attaining high photon timing resolution also with wide-area SPADs. The new i-AQC integrates the basic active-quenching loop, a patented low-side timing circuit comprising a fast pulse pick-up scheme that substantially improves time-jitter performance, and a novel active-load passive quenching mechanism (consisting of a current mirror rather than a traditional high-value resistor) greatly improves the maximum counting rate. The circuit is also suitable for portable instruments, miniaturized detector modules and SPAD-array detectors. The overall features of the circuit may open the way to new developments in diversified applications of time-correlated photon counting in life sciences and material sciences.


Active Wnt signalling is associated with low differentiation and high proliferation in human biliary tract cancer in vitro and in vivo and is sensitive to pharmacological inhibition.
Activation of developmental pathways has been recognized as a key mechanism for tumourigenesis and, hence, might be a valuable target for otherwise difficult to treat tumour entities such as biliary tract cancer (BTC). Therefore, we performed a comprehensive analysis of the Wnt signalling pathway in 9 BTC cell lines on cell blocks, xenograft tumours and on human tissue microarrays by real-time reverse transcription PCR and by immunochemistry. Furthermore, the effects of pharmacological pathway inhibition were investigated. As a result we found a significant positive correlation of Wnt pathway activation with cyclin D1 expression and the proliferation parameters Ki67, cell cycle distribution, and growth kinetics as well as the mesenchymal marker vimentin and an inverse correlation with E-cadherin in BTC cell lines in vitro and in vivo. In human BTC samples loss of membranous beta-catenin, an indicator of active Wnt signalling, correlated with vimentin expression and advanced tumour stage or metastasis, whereas membranous localisation of beta-catenin was associated with the differentiation marker cytokeratin-8/18 and differentiated tumour morphology (ductal or mixed type BTC). In addition, Wnt pathway inhibition by DMAT effectively reduced viability in all cancer cell lines, most effectively in those showing cytoplasmatic beta-catenin localisation, i.e. active Wnt signalling. In summary, activation of the Wnt pathway is associated with high proliferation, dedifferentiation and a solid morphology in human biliary tract cancer cell lines both in vitro and in vivo, and in human BTC tissues. Further investigation of the mechanism(s) of Wnt pathway activation and its inhibition may provide new molecular treatment strategies for biliary tract cancer.


Carcinoids of the common bile duct: a case report and literature review.
Carcinoids of the extrahepatic bile ducts and particularly the common bile duct are extremely rare. A 65-year-old woman presented with obstructive jaundice. Laboratory and imaging studies gave results that were consistent with an obstructing lesion in the common bile duct. In this case, a stent was inserted initially to decompress the bile ducts. Subsequently a laparotomy and pancreaticoduodenectomy were performed and a tissue diagnosis of carcinoid of the common bile duct was made. The patient was well with no evidence of recurrence 17 months postoperatively. The authors believe this is the 19th reported case of an extrahepatic bile duct carcinoid.


The influence of lactic acid bacteria on the viability of the reference strain of Listeria monocytogenes 123 serotype I in plant foods.
Listeria (L.) monocytogenes is the causative agent of human listeriosis, the frequent sourceof which is food of animal origin. The aim of this study was to determine the influence of lactic acid bacteria (LAB) on the viability of Listeria in carrot juice and compound feed inoculated with L. monocytogenes. The effect of homogenous cultures of Streptococcus (Str.) lactis distaticus, Str. thermophilus and Lactobacillus (Lac.) lactis subsp. Cremoris and the combination of Str. thermophilus with Lac. bulgaricus in the carrot juice and compound feed samples on viability of inoculated L. monocytogenes were examined. There were no statistically significant differences in the results between the experimental groups. Regardless of used LAB, the results showed that the mean pH values in the carrot juice samples decreased from an initial pH of 6.7 to a mean value of 3.7 on 15 experimental day. The Listeria concentration in carrot juice samples decreased from average of 4.94 on day 5 to 3.24 log CFU/mL on day 10, and on day 15 achieved <0.01 log CFU/mL. In the compound feed trials, the pH decreased average from initial 6.5 to 3.7 on day 15. The concentration of Listeria decreased, similarly to the carrot juice samples, from average 5.0 on day 5 to 4.68 on day 10, and on day 15 achieved <0.01 log CFU/mL. In control samples, the number of Listeria increased throughout the study period and amounted to 9.2-9.84 log CFU/mL/g in all the samples. The activity of LAB has been shown to be antagonistic to L. monocytogenes. The results of the study did not show any clear differences between the used LAB strains in limiting the L. monocytogenes concentration. Based on the obtained results it can be conducted that the addition of LAB to animal food increases its microbiological safety.


Ricin-like proteins from the castor plant do not influence liquid chromatography-mass spectrometry detection of ricin in forensically relevant samples.
The toxic protein ricin (also known as RCA60), found in the seed of the castor plant (Ricinus communis) is frequently encountered in law enforcement investigations. The ability to detect ricin by analyzing its proteolytic (tryptic) peptides by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is well established. However, ricin is just one member of a family of proteins in R. communis with closely related amino acid sequences, including R. communis agglutinin I (RCA120) and other ricin-like proteins (RLPs). Inferring the presence of ricin from its constituent peptides requires an understanding of the specificity, or uniqueness to ricin, of each peptide. Here we describe the set of ricin-derived tryptic peptides that can serve to uniquely identify ricin in distinction to closely-related RLPs and to proteins from other species. Other ricin-derived peptide sequences occur only in the castor plant, and still others are shared with unrelated species. We also characterized the occurrence and relative abundance of ricin and related proteins in an assortment of forensically relevant crude castor seed preparations. We find that whereas ricin and RCA120 are abundant in castor seed extracts, other RLPs are not represented by abundant unique peptides. Therefore, the detection of peptides shared between ricin and RLPs (other than RCA120) in crude castor seed extracts most likely reflects the presence of ricin in the sample.


Predictors of Local Control of Brain Metastasis Treated With Laser Interstitial Thermal Therapy.
Laser Interstitial Thermal Therapy (LITT) has been used to treat recurrent brain metastasis after stereotactic radiosurgery (SRS). Little is known about how best to assess the efficacy of treatment, specifically the ability of LITT to control local tumor progression post-SRS. To evaluate the predictive factors associated with local recurrence after LITT. Retrospective study with consecutive patients with brain metastases treated with LITT. Based on radiological aspects, lesions were divided into progressive disease after SRS (recurrence or radiation necrosis) and new lesions. Primary endpoint was time to local recurrence. A total of 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence, and 31 radiation necrosis). Freedom from local recurrence at 6 mo was 69.6%, 59.4% at 12, and 54.7% at 18 and 24 mo. Incompletely ablated lesions had a shorter median time for local recurrence (P < .001). Larger lesions (>6 cc) had shorter time for local recurrence (P = .03). Dural-based lesions showed a shorter time to local recurrence (P = .01). Tumor recurrence/newly diagnosed had shorter time to local recurrence when compared to RN lesions (P = .01). Patients receiving systemic therapy after LITT had longer time to local recurrence (P = .01). In multivariate Cox-regression model, the HR for incomplete ablated lesions was 4.88 (P < .001), 3.12 (P = .03) for recurrent tumors, and 2.56 (P = .02) for patients not receiving systemic therapy after LITT. Complication rate was 26.2%. Incompletely ablated and recurrent tumoral lesions were associated with higher risk of treatment failure and were the major predicting factors for local recurrence. Systemic therapy after LITT was a protective factor regarding local recurrence.


English past tense use as a clinical marker in older bilingual children with language impairment.
This study compared the use of English past tense in a group of Spanish-English bilingual children with language impairment (BLI) to younger groups of bilinguals with typical and atypical language development reported in an earlier study. Ten children with BLI enrolled in 3rd-6th grade participated. Children supplied 12 regular, 12 irregular, and 12 novel past tense verbs on an elicitation task. The results demonstrated that despite 2.5 years of school exposure, older children with BLI still lagged in the production of regular and novel past tense verbs when compared to the younger typically developing (TD) controls. Although the rates of productive errors on irregular verbs increased, the older students nonetheless failed to achieve rates of over-regularization comparable to the younger TD group. These data extend earlier findings regarding the exceptional challenge of past tense use, particularly with respect to finite verb morphology in certain children with BLI. These challenges, combined with similarities between monolingual and bilingual impairment, are largely compatible with a linguistic deficit account.


Imaging of tumor angiogenesis: current approaches and future prospects.
Tumor angiogenesis imaging should provide non-invasive assays of tumor vascular characteristics to supplement the now conventional diagnostic imaging goals of depicting tumor location, size, and morphology. This article will review the current status of angiogenesis imaging approaches, considering ultrasound, CT, MR, SPECT, PET and optical techniques with attention to their respective capabilities and limitations. As a group, these imaging methods have some potential to depict and quantify tumor microvascular features, including those considered to be functionally associated with tumor angiogenesis. Additionally, new molecule-specific imaging techniques may serve to depict those biochemical pathways and regulatory events that control blood vessel growth and proliferation. Non-invasive monitoring of anti-angiogenic therapies has great appeal and should find wide application for defining tumor microvascular and metabolic changes, because treatment-related changes in tumor morphology tend to occur rather late and are non-specific. Future developments are likely to include "fusion" or "hybrid" imaging methods. Superimposed data from MR imaging with spectroscopy, PET with CT, and PET with MR should be able to integrate advantages of different modalities yielding comprehensive information about tumor structure, function and microenvironment.


The scaling of postcranial muscles in cats (Felidae) I: forelimb, cervical, and thoracic muscles.
The body masses of cats (Mammalia, Carnivora, Felidae) span a ~300-fold range from the smallest to largest species. Despite this range, felid musculoskeletal anatomy remains remarkably conservative, including the maintenance of a crouched limb posture at unusually large sizes. The forelimbs in felids are important for body support and other aspects of locomotion, as well as climbing and prey capture, with the assistance of the vertebral (and hindlimb) muscles. Here, we examine the scaling of the anterior postcranial musculature across felids to assess scaling patterns between different species spanning the range of felid body sizes. The muscle architecture (lengths and masses of the muscle-tendon unit components) for the forelimb, cervical and thoracic muscles was quantified to analyse how the muscles scale with body mass. Our results demonstrate that physiological cross-sectional areas of the forelimb muscles scale positively with increasing body mass (i.e. becoming relatively larger). Many significantly allometric variables pertain to shoulder support, whereas the rest of the limb muscles become relatively weaker in larger felid species. However, when phylogenetic relationships were corrected for, most of these significant relationships disappeared, leaving no significantly allometric muscle metrics. The majority of cervical and thoracic muscle metrics are not significantly allometric, despite there being many allometric skeletal elements in these regions. When forelimb muscle data were considered in isolation or in combination with those of the vertebral muscles in principal components analyses and MANOVAs, there was no significant discrimination among species by either size or locomotory mode. Our results support the inference that larger felid species have relatively weaker anterior postcranial musculature compared with smaller species, due to an absence of significant positive allometry of forelimb or vertebral muscle architecture. This difference in strength is consistent with behavioural changes in larger felids, such as a reduction of maximal speed and other aspects of locomotor abilities.


Neuropathy-related mutations alter the membrane binding properties of the human myelin protein P0 cytoplasmic tail.
Schwann cells myelinate selected axons in the peripheral nervous system (PNS) and contribute to fast saltatory conduction via the formation of compact myelin, in which water is excluded from between tightly adhered lipid bilayers. Peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT) and Dejerine-Sottas syndrome (DSS), are incurable demyelinating conditions that result in pain, decrease in muscle mass, and functional impairment. Many Schwann cell proteins, which are directly involved in the stability of compact myelin or its development, are subject to mutations linked to these neuropathies. The most abundant PNS myelin protein is protein zero (P0); point mutations in this transmembrane protein cause CMT subtype 1B and DSS. P0 tethers apposing lipid bilayers together through its extracellular immunoglobulin-like domain. Additionally, P0 contains a cytoplasmic tail (P0ct), which is membrane-associated and contributes to the physical properties of the lipid membrane. Six CMT- and DSS-associated missense mutations have been reported in P0ct. We generated recombinant disease mutant variants of P0ct and characterized them using biophysical methods. Compared to wild-type P0ct, some mutants have negligible differences in function and folding, while others highlight functionally important amino acids within P0ct. For example, the D224Y variant of P0ct induced tight membrane multilayer stacking. Our results show a putative molecular basis for the hypermyelinating phenotype observed in patients with this particular mutation and provide overall information on the effects of disease-linked mutations in a flexible, membrane-binding protein segment. Using neutron reflectometry, we additionally show that P0ct embeds deep into a lipid bilayer, explaining the observed effects of P0ct on the physical properties of the membrane.


Products of binding of 7,12-dimethylbenz(a)anthracene to DNA in mouse skin.
7,12-Dimethylbenz(a)anthracene (DMBA):deoxyribonucleoside-adducts, from enzymatic hydrolysis of DNA from mouse skin exposed to [3H]DMBA in vivo, were analyzed by reverse-phase high-pressure liquid chromatography. Double-labeling studies showed that the adducts were qualitatively identical to those formed in mouse embryo cell cultures. These have been tentatively identified as bay-region anti-dihydrodiol epoxide: deoxyguanosine- and :deoxyadenosine adducts and a bay-region syn-dihydrodiol epoxide:deoxyadenosine-adduct (where the terms syn and anti define dihydrodiol-epoxides wherein the benzylic hydroxyl group and epoxide oxygen are cis or trans to one another, respectively). The relative amounts of individual adducts did not vary substantially with time or with the sex of the mice. However, the syn-dihydrodiol-epoxide:deoxyadenosine-adduct did increase with dose and constituted as much as 40% of the total DNA binding at high doses of DMBA. This is in contrast to the much lower (2 to 3%) levels of binding to deoxyadenosine residues in mouse skin reported for the less potent tumor initiator benzo(a)pyrene. The greater reactivity of DMBA with deoxyadenosine residues in mouse skin may play a role in determining its greater tumor initiating potential.


UBE2S promotes the proliferation and survival of human lung adenocarcinoma cells.
Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitination process, is involved in development of various cancers. However, its role in lung adenocarcinoma, has not been well elucidated. In this report, we attempted to investigate expression and function of UBE2S in lung adenocarcinoma. Up-regulation of UBE2S at mRNA, and protein level, was observed in human cancer tissues and lung adenocarcinoma cells. Higher UBE2S expression correlated with poorer prognosis of lung adenocarcinoma patients. UBE2S expression was efficiently suppressed by lentivirus-mediated shRNA strategy in A549 cells, and UBE2S silencing led to reduced cell proliferation, colony formation, and enhanced apoptosis. Inverse results were observed, in UBE2S over-expressed H1299 cells. Microarray analysis indicated that a large number of genes were regulated by UBE2S, and p53 signaling pathway may be critical, to the role of UBE2S in cancer development. Together, UBE2S could be a potential target for lung adenocarcinoma. [BMB Reports 2018; 51(12): 642-647].


[Syndrome of chronic obstruction of the abdominal aorta and its surgical treatment].
The surgical management of 53 patients with high chronic occlusion of the abdominal aorta is reported. The authors unite this pathology under the term "chronic abdominal aorta obstruction syndrome". In 10 patients eversion endarterectomy was performed, in 22--aortofemoral bypass, in 21--prosthetic replacement of the aorta and of the iliac arteries with synthetic grafts. An original techinque of "milking" the thrombus down from the proximal aorta is described; it simplifies the operative procedure and prevents grave complications during surgery in patients with high occlusions of the abdominal aorta. Good results in the immediate postoperative period were achieved in 85% of the cases. Postoperative mortality comprised 12%. Late results were followed-up in 35 patients during 1 to 5 years. In 28 patients the results of surgery proved good.


Neurodegeneration and cellular stress in the retina and optic nerve in rat cerebral ischemia and hypoperfusion models.
Experimental cerebral ischemia induces a stress response in neuronal and non-neuronal cells. In the present study we aimed to evaluate detailed cellular stress responses and neurodegenerative changes in the retinas in rat focal cerebral ischemia and hypoperfusion models involving invasive vascular manipulations. Independent groups of adult male Wistar rats were subjected to i) transient middle cerebral artery occlusion (tMCAO), ii) permanent middle cerebral artery occlusion (pMCAO), iii) cortical photothrombosis of the sensorimotor cortex using Rose Bengal dye or iv) bilateral common carotid artery occlusion (BCCAO). Rats were killed, and their eyes with the optic nerves enucleated and processed for histology, immunohistochemistry for neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), hypoxia-inducible factor 1alpha (HIF-1alpha), c-fos, alphaB-crystallin, heat shock protein (HSP) 27, HSP60 and HSP70, and detection of DNA defragmentation. The total number of the retinal ganglion cell layer (RGCL) neurons and GFAP-immunoreactive astrocytes located in the nerve fiber layer were estimated using unbiased stereological counting. Our findings indicate that although permanent and transient MCAO does not cause detectable morphological alterations in the retina or optic nerve, it evokes ischemic stress as revealed by HIF-1alpha and HSPs expression in the RGCL neurons and reactive gliosis in the Müller cells. Severe neurodegenerative changes in the retina and optic nerve of the BCCAO rats are accompanied by a significant increase in immunoreactivities for the c-fos, HSP27 and HSP70 as compared with the sham-operated animals. The retinas from the ipsilateral side of the Rose Bengal model showed a significant decrease in the total number of NeuN-positive neurons in the RGCL as compared with the contralateral ones. However, these eyes did not differ between each other in the HSPs and HIF-1alpha expression or in the GFAP-immunoreactivity of the Müller cells. In conclusion, our data suggest differential expression of various HSPs in the retina and possibly their distinct roles in the cerebral ischemia-mediated stress response and neurodegeneration.


Racial and Ethnic Differences in Sleep Duration Life Expectancies among Men and Women in Mid-to-Late Life.
This analysis documents U.S. racial/ethnic and gender differences in life expectancies with different self-reported sleep durations among adults aged 50 and older. We used self-reported sleep duration and linked mortality information from the 2004-2015 National Health Interview Survey (n = 145,015) to calculate Sullivan Method Lifetables for life expectancies with different self-reported sleep duration states: short (≤6 hours), optimal (seven to 8 hours), and long (≥9 hours) sleep duration per-day by race/ethnicity and gender. Non-Hispanic Black men (35.8%, 95% CI: 34.8%-36.8%) and women (36.5%, 95% CI: 35.7%-37.1%) exhibited the highest proportion of years lived with short sleep duration followed by Hispanic men (31.1%, 95% CI: 29.9%-32.3%) and women (34.1%, 95% CI: 33.1%-35.1%) and Non-Hispanic White men (25.8%, 95% CI: 25.4%-26.2%) and women (27.4%, 95% CI: 27.0%-27.7%). These results highlight how race/ethnic inequality in sleep duration and life expectancy are intertwined among older adults in the U.S.


A systematic review and quantitative analysis of resting energy expenditure prediction equations in healthy overweight and obese children and adolescents.
Resting energy expenditure (REE) estimates are often needed in young people and can be predicted using prediction equations based on body weight. However, these equations may perform poorly in those who are obese and overweight. The aim of this systematic review was to identify equations based on simple anthropometric and demographic variables that provide the most accurate and precise estimates of REE in healthy obese and overweight young people. Systematic searches for relevant studies in healthy obese and overweight young people aged ≤18 years were undertaken using PubMed, Scopus, Cinahl, OpenGrey and Cochrane Library (completed January 2018). Search terms included metabolism, calorimetry, obesity and prediction equation. Data extraction, study appraisal and synthesis followed PRISMA guidelines. From 390 screened titles, 13 studies met inclusion criteria. The most accurate REE predictions (least biased) were provided by Schofield equations [+0.8% (3-18 years); 0% (11-18 years); +1.1% (3-10 years)]. The most precise REE estimations (percentage of predictions ± 10% of measured) for 11-18 years were provided by Mifflin equations (62%) and, for 7-18 years, by the equations of Schmelzle (57%), Henry (56%) and Harris Benedict (54%). Precision of Schofield predictions was 43% in both age groups. No accuracy data were available for those <3 years or for precision for those <7 years. No single equation provided accurate and precise REE estimations in this population. Schofield equations provided the most accurate REE predictions so are useful for groups. Mifflin equations provided the most precise estimates for individuals aged 11-18 years but tended to underestimate REE.


Factors responsible for pathogenicity in chickens of a low-pathogenic H7N7 avian influenza virus isolated from a feral duck.
Highly pathogenic avian influenza viruses have poly-basic amino acid sequences at the cleavage site in their hemagglutinin (HA). Although this poly-basic region is a prerequisite factor for pathogenicity in chickens, not much is known about additional factors responsible for the acquisition of pathogenicity of the duck influenza virus in chickens. Here, we introduced multiple basic amino acid residues into the HA cleavage site of the A/duck/Hokkaido/Vac-2/2004 (H7N7) strain of avian influenza virus, which has low pathogenicity in chickens; the resultant Vac2sub-P0 strain was not intravenously pathogenic in chickens. In contrast, the Vac2sub-P3 strain, which was recovered from three consecutive passages of Vac2sub-P0 in chicks, was intravenously pathogenic in chickens. Six amino acid substitutions were identified by comparison of the Vac2sub-P3 and Vac2sub-P0 genomic sequences: Lys123Glu in PB2, Asn16Asp in PB1, Glu227Gly and Ile388Thr in HA, Gly228Arg in M1, and Leu46Pro in M2. The results of intravenous inoculations of chickens with recombinant virus indicated that all six amino acid substitutions were required to varying degrees for Vac2sub-P3 pathogenicity, with Glu227Gly and Ile388Thr in HA being particularly essential. These results reveal the roles of additional viral factors in the acquisition of pathogenicity in addition to the previously characterized role of the poly-basic amino acid sequences at the HA cleavage site.


Acting the scapegoat.
THE NATIONAL Health Service has seen the emergence of a new trend of 'customer relations', which has been accompanied by a rising number of complaints about its services.


The Rhynie Chert, Scotland, and the search for life on Mars.
Knowledge of ancient terrestrial hydrothermal systems-how they preserve biological information and how this information can be detected-is important in unraveling the history of life on Earth and, perhaps, that of extinct life on Mars. The Rhynie Chert in Scotland was originally deposited as siliceous sinter from Early Devonian hot springs and contains exceptionally well-preserved fossils of some of the earliest plants and animals to colonize the land. The aim of this study was to identify biomolecules within the samples through Fourier transform infrared (FTIR) spectroscopy and aid current techniques in identification of ancient hot spring deposits and their biological components on Mars. Floral and faunal fossils within the Rhynie Chert are commonly known; but new, FTIR spectroscopic analyses of these fossils has allowed for identification of biomolecules such as aliphatic hydrocarbons and OH molecules that are potentially derived from the fossilized biota and their environment. Gas chromatograph-mass spectrometer (GCMS) data were used to identify n-alkanes; however, this alone cannot be related to the samples' biota. Silicified microfossils are more resistant to weathering or dissolution, which renders them more readily preservable over time. This is of particular interest in astropaleontological research, considering the similarities in the early evolution of Mars and Earth.


Alterations in red blood cells and plasma properties after acute single bout of exercise.
The aim of this study was to investigate alterations in haemoglobin conformation and parameters related to oxidative stress in whole erythrocytes, membranes, and plasma after a single bout of exercise in a group of young untrained men. Venous blood samples from eleven healthy young untrained males (age = 22 ± 2 years, BMI = 23 ± 2.5 kg/m(2)) were taken from the antecubital vein before an incremental cycling exercise test, immediately after exercise, and 1 hour after exercise. Individual heart rate response to this exercise was 195 ± 12 beats/min and the maximum wattage was 292 ± 27 W. Immediately after exercise, significant increase in standard parameters (haemoglobin, haematocrit, lactate levels, and plasma volume) of blood was observed as well as plasma antioxidant capacity one hour after exercise. Reversible conformational changes in haemoglobin, measured using a maleimide spin label, were found immediately following exercise. The concentration of ascorbic acid inside erythrocytes significantly decreased after exercise. A significant decline in membrane thiols was observed one hour after exercise, but simultaneously an increase in plasma thiols immediately after and 1 h after exercise was also observed. This study shows that a single bout of exercise can lead to mobilization of defensive antioxidant systems in blood against oxidative stress in young untrained men.


Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis.
Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m2. Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P < or = .05). Caloric intake decreased (P < .01) and physical activity increased (P < .05) during the year after diagnosis; these factors did not explain the observed weight gain. Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain.


Empirically Derived Profiles of Health-Related Quality of Life in Youth and Young Adults with Sickle Cell Disease.
Determining how the health-related quality of life (HRQOL) is impacted by living with Sickle Cell Disease (SCD) can inform psychosocial interventions. The purpose of the present study is to determine if demographic and treatment variables predict membership into empirically derived subgroups of HRQOL among youth and young adults with SCD. Three hundred and seven youth and young adults with SCD (mean 17.63 years ± 3.74 years, 50.5% female) completed the Pediatric Quality of Life InventoryTM Sickle Cell Disease Module. Latent profile analysis examined subgroups/classes of HRQOL and relationships with demographic and treatment variables. Three distinct classes emerged: High HRQOL (34% of the sample), Moderate HRQOL (44% of the sample), and Low HRQOL (22% of the sample). Being female was associated with increased odds of being in the moderate or low groups. Living with more severe SCD (genotypes HbSS and HbSβ0 thalassemia) was associated with increased odds of being in the Low HRQOL group. Treatment with chronic red blood cell transfusion therapy was associated with increased odds of being in the High HRQOL group. Older age predicted a small increase in the odds of being in the Low versus High HRQOL group. The present study adds to the literature on HRQOL in SCD by exploring person-centered, empirically derived groups of HRQOL. Identification of demographic and treatment factors that predict membership into those groups within a large sample assists in tailoring needed psychosocial interventions for youth with SCD.


Opsonization with C1q and mannose-binding lectin targets apoptotic cells to dendritic cells.
Deficiencies of early components of the classical complement pathway, particularly C1q, are strongly associated with susceptibility to systemic lupus erythematosus. Recent data link this predisposal to autoimmunity to an inappropriate clearance of apoptotic cells, which could lead to a loss of self-tolerance. In the present study, we demonstrate that opsonization of apoptotic cells with C1q and mannose-binding lectin allows and facilitates their uptake not only by macrophages but also by human immature dendritic cells (DCs). Both C1q and mannose-binding lectin enhance the uptake of apoptotic cells by DCs in a dose-dependent way. The uptake of C1q-opsonized apoptotic cells, but not nonopsonized apoptotic cells, by DCs stimulated the production of IL-6, IL-10, and TNF-alpha, without an effect on IL-12p70. We conclude that these recognition molecules of the complement system do not sequester apoptotic cells from DCs, but rather promote their uptake by immature DCs. Therefore, we propose that early complement components support safe clearance of cellular debris by facilitating phagocytosis and possibly by immunomodulatory mechanisms, thus preventing autoimmunity.


Phacoemulsification with the Heslin/Mackool Ocusystem: a follow-up report.
The experience of one surgeon (KBH) with phacoemulsification and the Heslin/Mackool Ocusystem is reported. In a study involving 350 cases with a mean follow-up period of 20.1 months, 88.6% of the patients achieved a visual acuity result of 20/40 or better, and when nonoperative causes of poor vision were eliminated, 97.2% of the study group achieved such a result. The most common complication cited was opacification of the posterior capsule, occurring 20.0% of the time. The authors conclude that the Heslin/Mackool Ocusystem is a safe and efficient instrument for phacoemulsification.